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Sample records for exhibit antiviral activity

  1. Amphipathic DNA polymers exhibit antiviral activity against systemic Murine Cytomegalovirus infection

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    Juteau Jean-Marc

    2009-12-01

    Full Text Available Abstract Background Phosphorothioated oligonucleotides (PS-ONs have a sequence-independent, broad spectrum antiviral activity as amphipathic polymers (APs and exhibit potent in vitro antiviral activity against a broad spectrum of herpesviruses: HSV-1, HSV-2, HCMV, VZV, EBV, and HHV-6A/B, and in vivo activity in a murine microbiocide model of genital HSV-2 infection. The activity of these agents against animal cytomegalovirus (CMV infections in vitro and in vivo was therefore investigated. Results In vitro, a 40 mer degenerate AP (REP 9 inhibited both murine CMV (MCMV and guinea pig CMV (GPCMV with an IC50 of 0.045 μM and 0.16 μM, respectively, and a 40 mer poly C AP (REP 9C inhibited MCMV with an IC50 of 0.05 μM. Addition of REP 9 to plaque assays during the first two hours of infection inhibited 78% of plaque formation whereas addition of REP 9 after 10 hours of infection did not significantly reduce the number of plaques, indicating that REP 9 antiviral activity against MCMV occurs at early times after infection. In a murine model of CMV infection, systemic treatment for 5 days significantly reduced virus replication in the spleens and livers of infected mice compared to saline-treated control mice. REP 9 and REP 9C were administered intraperitoneally for 5 consecutive days at 10 mg/kg, starting 2 days prior to MCMV infection. Splenomegaly was observed in infected mice treated with REP 9 but not in control mice or in REP 9 treated, uninfected mice, consistent with mild CpG-like activity. When REP 9C (which lacks CpG motifs was compared to REP 9, it exhibited comparable antiviral activity as REP 9 but was not associated with splenomegaly. This suggests that the direct antiviral activity of APs is the predominant therapeutic mechanism in vivo. Moreover, REP 9C, which is acid stable, was effective when administered orally in combination with known permeation enhancers. Conclusion These studies indicate that APs exhibit potent, well tolerated

  2. Hsp90 inhibitors exhibit resistance-free antiviral activity against respiratory syncytial virus.

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    Ron Geller

    Full Text Available Respiratory syncytial virus (RSV is a major cause of respiratory illness in young children, leading to significant morbidity and mortality worldwide. Despite its medical importance, no vaccine or effective therapeutic interventions are currently available. Therefore, there is a pressing need to identify novel antiviral drugs to combat RSV infections. Hsp90, a cellular protein-folding factor, has been shown to play an important role in the replication of numerous viruses. We here demonstrate that RSV requires Hsp90 for replication. Mechanistic studies reveal that inhibition of Hsp90 during RSV infection leads to the degradation of a viral protein similar in size to the RSV L protein, the viral RNA-dependent RNA polymerase, implicating it as an Hsp90 client protein. Accordingly, Hsp90 inhibitors exhibit antiviral activity against laboratory and clinical isolates of RSV in both immortalized as well as primary differentiated airway epithelial cells. Interestingly, we find a high barrier to the emergence of drug resistance to Hsp90 inhibitors, as extensive growth of RSV under conditions of Hsp90 inhibition did not yield mutants with reduced sensitivity to these drugs. Our results suggest that Hsp90 inhibitors may present attractive antiviral therapeutics for treatment of RSV infections and highlight the potential of chaperone inhibitors as antivirals exhibiting high barriers to development of drug resistance.

  3. Anticancer molecule AS1411 exhibits low nanomolar antiviral activity against HIV-1.

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    Métifiot, Mathieu; Amrane, Samir; Mergny, Jean-Louis; Andreola, Marie-Line

    2015-11-01

    During clinical trials, a number of fully characterized molecules are dropped along the way because they do not provide enough benefit for the patient. Some of them show limited side effects and might be of great use for other applications. AS1411 is a nucleolin-targeting aptamer that underwent phase II clinical trials as anticancer agent. Here, we show that AS1411 exhibits extremely potent antiviral activity and is therefore an attractive new lead as anti-HIV agent. Copyright © 2015 Elsevier B.V. and Société Française de Biochimie et Biologie Moléculaire (SFBBM). All rights reserved.

  4. Dextrans produced by lactic acid bacteria exhibit antiviral and immunomodulatory activity against salmonid viruses.

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    Nácher-Vázquez, Montserrat; Ballesteros, Natalia; Canales, Ángeles; Rodríguez Saint-Jean, Sylvia; Pérez-Prieto, Sara Isabel; Prieto, Alicia; Aznar, Rosa; López, Paloma

    2015-06-25

    Viral infections in the aquaculture of salmonids can lead to high mortality and substantial economic losses. Thus, there is industrial interest in new molecules active against these viruses. Here we describe the production, purification, and the physicochemical and structural characterization of high molecular weight dextrans synthesized by Lactobacillus sakei MN1 and Leuconostoc mesenteroides RTF10. The purified dextrans, and commercial dextrans with molecular weights ranging from 10 to 2000kDa, were assayed in infected BF-2 and EPC fish cell-line monolayers for antiviral activity. Only T2000 and dextrans from MN1 and RTF10 had significant antiviral activity. This was similar to results obtained against infectious pancreatic necrosis virus. However the dextran from MN1 showed ten-fold higher activity against hematopoietic necrosis virus than T2000. In vivo assays using the MN1 polymer confirmed the in vitro results and revealed immunomodulatory activity. These results together with the high levels of dextran production (2gL(-1)) by Lb. sakei MN1, indicate the compounds potential utility as an antiviral agent in aquaculture. Copyright © 2015 Elsevier Ltd. All rights reserved.

  5. Nanoparticulate vacuolar ATPase blocker exhibits potent host-targeted antiviral activity against feline coronavirus

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    Hu, Che-Ming Jack; Chang, Wei-Shan; Fang, Zih-Syun; Chen, You-Ting; Wang, Wen-Lin; Tsai, Hsiao-Han; Chueh, Ling-Ling; Takano, Tomomi; Hohdatsu, Tsutomu; Chen, Hui-Wen

    2017-01-01

    Feline infectious peritonitis (FIP), caused by a mutated feline coronavirus, is one of the most serious and fatal viral diseases in cats. The disease remains incurable, and there is no effective vaccine available. In light of the pathogenic mechanism of feline coronavirus that relies on endosomal acidification for cytoplasmic entry, a novel vacuolar ATPase blocker, diphyllin, and its nanoformulation are herein investigated for their antiviral activity against the type II feline infectious per...

  6. Resveratrol exhibits a strong cytotoxic activity in cultured cells and has an antiviral action against polyomavirus: potential clinical use

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    Galati Gaspare

    2009-07-01

    Full Text Available Abstract Background Resveratrol is a non flavonoid polyphenol compound present in many plants and fruits and, at especially high concentrations, in the grape berries of Vitis vinifera. This compound has a strong bioactivity and its cytoprotective action has been demonstrated, however at high concentrations the drug exhibits also an effective anti-proliferative action. We recently showed its ability to abolish the effects of oxidative stress in cultured cells. In this work we assayed the bioactivity of resveratrol as antiproliferative and antiviral drug in cultured fibroblasts. Studies by other Authors showed that this natural compound inhibits the proliferation of different viruses such as herpes simplex, varicella-zoster and influenza A. The results presented here show an evident toxic activity of the drug at high concentrations, on the other hand at sub-cytotoxic concentrations, resveratrol can effectively inhibit the synthesis of polyomavirus DNA. A possible interpretation is that, due to the damage caused by resveratrol to the plasma membrane, the transfer of the virus from the endoplasmic reticulum to the nucleus, may be hindered thus inhibiting the production of viral DNA. Methods The mouse fibroblast line 3T6 and the human tumor line HL60 were used throughout the work. Cell viability and vital cell count were assessed respectively, by the MTT assay and Trypan Blue staining. Cytotoxic properties and evaluation of viral DNA production by agarose gel electrophoresis were performed according to standard protocols. Results Our results show a clear dose dependent both cytotoxic and antiviral effect of resveratrol respectively at high and low concentrations. The cytotoxic action is exerted towards a stabilized cell-line (3T6 as well as a tumor-line (HL60. Furthermore the antiviral action is evident after the phase of virion entry, therefore data suggest that the drug acts during the synthesis of the viral progeny DNA. Conclusion Resveratrol is

  7. Chebulagic Acid, a Hydrolyzable Tannin, Exhibited Antiviral Activity in Vitro and in Vivo against Human Enterovirus 71

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    Lianfeng Zhang

    2013-05-01

    Full Text Available Human enterovirus 71 is one of the major causative agents of hand, foot and mouth disease in children under six years of age. Presently, no vaccines or antiviral drugs have been clinically available to employ against EV71. In this study, we demonstrate that treatment with chebulagic acid reduced the viral cytopathic effect on rhabdomyosarcoma cells with an IC50 of 12.5 μg/mL. The utilization of the chebulagic acid treatment on mice challenged with a lethal dose of enterovirus 71 was able to efficiently reduce mortality and relieve clinical symptoms through the inhibition of viral replication. Chebulagic acid may represent a potential therapeutic agent to control infections to enterovirus 71.

  8. Plants with antiviral activity

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    Eduardo Orrego Escobar

    2013-11-01

    Full Text Available Introduction. Antiviral drugs are the only medicines currently in use in viral conditions in spite of the described risk of adverse health effects such as phlebitis, hematuria, hypocalcaemia, increased creatinine and, in the worst cases, mutagenicity and teratogenicity. Aim. The purpose of this article is to provide a descriptive overview of global research on the antiviral properties of complementary medicinal plants to treat diseases such as hepatitis, HIV, human papilloma virus, among others. Discussion. Plants continue to provide answers to current public health problems, such as microbial resistance to antibiotics and antifungal agents, or recalcitrant conditions present in Latin America such as malaria and tuberculosis. However, research in this area is still incipient. More studies are needed on pharmacological properties, identification of active ingredients, characterization of therapeutic spectrum and toxicological risks.

  9. Naphthyridines with Antiviral Activity - A Review.

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    Singh, Inder P; Kumar, Sanjay; Gupta, Shiv

    2017-01-01

    Naphthyridine scaffold is an important pharmacophore in compounds which have shown various biological activities like antiviral, antimicrobial, anticancer, antiinflammatory and analgesic. This scaffold is also reported to exhibit activity against HIV, HCMV, HSV, HPV and HCV. Antiviral activity displayed by many naphthyridine analogs is in nM range. Only few review articles are available in literature which describe about various biological activities of naphthyridines, but there is no comprehensive compilation particularly for antiviral activities. The objective of this review is to compile the literature on anti-viral activities of naphthyridine analogs. SciFinder, Google Scholar and PubMed database were searched with keyword "naphthyridine" and the references obtained were further sorted using keywords "antihiv", "antiviral" and "virus", separately. References obtained were considered to review the antiviral literature of naphthyridines. Literature search using SciFinder database with different keywords gave several references. Only references of antiviral activities of naphthyridine compounds were reviewed. References to in-silico studies alone or on formulation development or on patents were excluded. This review will be helpful for future researches to design and synthesize naphthyridine analogs with improved antiviral activities. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  10. Antiviral drug research proposal activity.

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    Injaian, Lisa; Smith, Ann C; Shipley, Jennifer German; Marbach-Ad, Gili; Fredericksen, Brenda

    2011-01-01

    The development of antiviral drugs provides an excellent example of how basic and clinical research must be used together in order to achieve the final goal of treating disease. A Research Oriented Learning Activity was designed to help students to better understand how basic and clinical research can be combined toward a common goal. Through this project students gained a better understanding of the process of scientific research and increased their information literacy in the field of virology. The students worked as teams to research the many aspects involved in the antiviral drug design process, with each student becoming an "expert" in one aspect of the project. The Antiviral Drug Research Proposal (ADRP) culminated with students presenting their proposals to their peers and local virologists in a poster session. Assessment data showed increased student awareness and knowledge of the research process and the steps involved in the development of antiviral drugs as a result of this activity.

  11. Antiviral Drug Research Proposal Activity

    Directory of Open Access Journals (Sweden)

    Lisa Injaian

    2011-03-01

    Full Text Available The development of antiviral drugs provides an excellent example of how basic and clinical research must be used together in order to achieve the final goal of treating disease. A Research Oriented Learning Activity was designed to help students to better understand how basic and clinical research can be combined toward a common goal. Through this project students gained a better understanding of the process of scientific research and increased their information literacy in the field of virology. The students worked as teams to research the many aspects involved in the antiviral drug design process, with each student becoming an "expert" in one aspect of the project. The Antiviral Drug Research Proposal (ADRP culminated with students presenting their proposals to their peers and local virologists in a poster session. Assessment data showed increased student awareness and knowledge of the research process and the steps involved in the development of antiviral drugs as a result of this activity.

  12. Antiviral activities of heated dolomite powder.

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    Motoike, Koichi; Hirano, Shozo; Yamana, Hideaki; Onda, Tetsuhiko; Maeda, Takayoshi; Ito, Toshihiro; Hayakawa, Motozo

    2008-12-01

    The effect of the heating conditions of dolomite powder on its antiviral activity was studied against the H5N3 avian influenza virus. Calcium oxide (CaO) and magnesium oxide (MgO), obtained by the thermal decomposition of dolomite above 800 degrees C, were shown to have strong antiviral activity, but the effect was lessened when the heating temperature exceeded 1400 degrees C. Simultaneous measurement of the crystallite size suggested that the weakening of the activity was due to the considerable grain growth of the oxides. It was found that the presence of Mg in dolomite contributed to the deterrence of grain growth of the oxides during the heating process. Although both CaO and MgO exhibited strong antiviral activity, CaO had the stronger activity but quickly hydrated in the presence of water. On the other hand, the hydration of MgO took place gradually under the same conditions. Separate measurements using MgO and Mg(OH)2 revealed that MgO had a higher antiviral effect than Mg(OH)2. From the overall experiments, it was suggested that the strong antiviral activity of dolomite was related to the hydration reaction of CaO.

  13. Hibiscus sabdariffa L. and Its Bioactive Constituents Exhibit Antiviral Activity against HSV-2 and Anti-enzymatic Properties against Urease by an ESI-MS Based Assay.

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    Hassan, Sherif T S; Švajdlenka, Emil; Berchová-Bímová, Kateřina

    2017-04-30

    For decades, Hibiscus sabdariffa L. and its phytochemicals have been shown to possess a wide range of pharmacologic properties. In this study, aqueous extract of Hibiscus sabdariffa (AEHS) and its bioactive constituent protocatechuic acid (PCA), have been evaluated in vitro for their antiviral activity against HSV-2 clinical isolates and anti-enzymatic activity against urease. Antiherpetic activity was evaluated by the titer reduction assay in infected Vero cells, and cytotoxicity was evaluated by the neutral red dye-uptake method. Anti-urease activity was determined by a developed Electrospray Ionization-Mass Spectrometry (ESI-MS)-based assay. PCA showed potent anti-HSV-2 activity compared with that of acyclovir, with EC50 values of 0.92 and 1.43 µg∙mL(-1), respectively, and selectivity indices > 217 and > 140, respectively. For the first time, AEHS was shown to exert anti-urease inhibition activity, with an IC50 value of 82.4 µg∙mL(-1). This, combined with its safety, could facilitate its use in practical applications as a natural urease inhibitor. Our results present Hibiscus sabdariffa L. and its bioactive compound PCA as potential therapeutic agents in the treatment of HSV-2 infection and the treatment of diseases caused by urease-producing bacteria.

  14. Hibiscus sabdariffa L. and Its Bioactive Constituents Exhibit Antiviral Activity against HSV-2 and Anti-enzymatic Properties against Urease by an ESI-MS Based Assay

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    Sherif T. S. Hassan

    2017-04-01

    Full Text Available For decades, Hibiscus sabdariffa L. and its phytochemicals have been shown to possess a wide range of pharmacologic properties. In this study, aqueous extract of Hibiscus sabdariffa (AEHS and its bioactive constituent protocatechuic acid (PCA, have been evaluated in vitro for their antiviral activity against HSV-2 clinical isolates and anti-enzymatic activity against urease. Antiherpetic activity was evaluated by the titer reduction assay in infected Vero cells, and cytotoxicity was evaluated by the neutral red dye-uptake method. Anti-urease activity was determined by a developed Electrospray Ionization-Mass Spectrometry (ESI-MS-based assay. PCA showed potent anti-HSV-2 activity compared with that of acyclovir, with EC50 values of 0.92 and 1.43 µg∙mL−1, respectively, and selectivity indices > 217 and > 140, respectively. For the first time, AEHS was shown to exert anti-urease inhibition activity, with an IC50 value of 82.4 µg∙mL−1. This, combined with its safety, could facilitate its use in practical applications as a natural urease inhibitor. Our results present Hibiscus sabdariffa L. and its bioactive compound PCA as potential therapeutic agents in the treatment of HSV-2 infection and the treatment of diseases caused by urease-producing bacteria.

  15. Ribonuclease, deoxyribonuclease, and antiviral activity of Escherichia coli-expressed Bougainvillea xbuttiana antiviral protein 1.

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    Choudhary, N L; Yadav, O P; Lodha, M L

    2008-03-01

    A full-length cDNA encoding ribosome-inactivating/antiviral protein from the leaves of Bougainvillea xbuttiana was recently isolated. The coding region of cDNA was cloned and expressed in Escherichia coli, and the protein product was designated as BBAP1 (Bougainvillea xbuttiana antiviral protein 1). BBAP1 showed ribonuclease activity against Torula yeast RNA. It also exhibited depurination activity against supercoiled pBlueScript SK+ plasmid DNA in a concentration dependent manner, and was found to convert nicked circular DNA into linear form only at higher concentration. On bioassay, BBAP1 exhibited antiviral activity against sunnhemp rosette virus infecting Cyamopsis tetragonoloba leaves in which 95% inhibition of local lesion formation was observed.

  16. High Expression of Antiviral Proteins in Mucosa from Individuals Exhibiting Resistance to Human Immunodeficiency Virus.

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    Gonzalez, Sandra Milena; Taborda, Natalia Andrea; Feria, Manuel Gerónimo; Arcia, David; Aguilar-Jiménez, Wbeimar; Zapata, Wildeman; Rugeles, María Teresa

    2015-01-01

    Several soluble factors have been reported to have the capacity of inhibiting HIV replication at different steps of the virus life cycle, without eliminating infected cells and through enhancement of specific cellular mechanisms. Yet, it is unclear if these antiviral factors play a role in the protection from HIV infection or in the control of viral replication. Here we evaluated two cohorts: i) one of 58 HIV-exposed seronegative individuals (HESNs) who were compared with 59 healthy controls (HCs), and ii) another of 13 HIV-controllers who were compared with 20 HIV-progressors. Peripheral blood, oral and genital mucosa and gut-associated lymphoid tissue (GALT) samples were obtained to analyze the mRNA expression of ELAFIN, APOBEC3G, SAMHD1, TRIM5α, RNase 7 and SerpinA1 using real-time PCR. HESNs exhibited higher expression of all antiviral factors in peripheral blood mononuclear cells (PBMCs), oral or genital mucosa when compared with HCs. Furthermore, HIV-controllers exhibited higher levels of SerpinA1 in GALT. These findings suggest that the activity of these factors is compartmentalized and that these proteins have a predominant role depending on the tissue to avoid the infection, reduce the viral load and modulate the susceptibility to HIV infection.

  17. High Expression of Antiviral Proteins in Mucosa from Individuals Exhibiting Resistance to Human Immunodeficiency Virus.

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    Sandra Milena Gonzalez

    Full Text Available Several soluble factors have been reported to have the capacity of inhibiting HIV replication at different steps of the virus life cycle, without eliminating infected cells and through enhancement of specific cellular mechanisms. Yet, it is unclear if these antiviral factors play a role in the protection from HIV infection or in the control of viral replication. Here we evaluated two cohorts: i one of 58 HIV-exposed seronegative individuals (HESNs who were compared with 59 healthy controls (HCs, and ii another of 13 HIV-controllers who were compared with 20 HIV-progressors. Peripheral blood, oral and genital mucosa and gut-associated lymphoid tissue (GALT samples were obtained to analyze the mRNA expression of ELAFIN, APOBEC3G, SAMHD1, TRIM5α, RNase 7 and SerpinA1 using real-time PCR.HESNs exhibited higher expression of all antiviral factors in peripheral blood mononuclear cells (PBMCs, oral or genital mucosa when compared with HCs. Furthermore, HIV-controllers exhibited higher levels of SerpinA1 in GALT.These findings suggest that the activity of these factors is compartmentalized and that these proteins have a predominant role depending on the tissue to avoid the infection, reduce the viral load and modulate the susceptibility to HIV infection.

  18. Antiviral Drug Research Proposal Activity

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    Injaian, Lisa; Smith, Ann C.; Shipley, Jennifer German; Marbach-Ad, Gili; Fredericksen, Brenda

    2011-01-01

    The development of antiviral drugs provides an excellent example of how basic and clinical research must be used together in order to achieve the final goal of treating disease. A Research Oriented Learning Activity was designed to help students to better understand how basic and clinical research can be combined toward a common goal. Through this project students gained a better understanding of the process of scientific research and increased their information literacy in the field of virology. The students worked as teams to research the many aspects involved in the antiviral drug design process, with each student becoming an “expert” in one aspect of the project. The Antiviral Drug Research Proposal (ADRP) culminated with students presenting their proposals to their peers and local virologists in a poster session. Assessment data showed increased student awareness and knowledge of the research process and the steps involved in the development of antiviral drugs as a result of this activity. PMID:23653735

  19. Novel cycloalkylthiophene-imine derivatives bearing benzothiazole scaffold: synthesis, characterization and antiviral activity evaluation.

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    Ke, Shaoyong; Wei, Yanhong; Yang, Ziwen; Wang, Kaimei; Liang, Ying; Shi, Liqiao

    2013-09-15

    A series of novel cycloalkylthiophene-imine derivatives containing benzothiazole unit were designed, synthesized and evaluated for their anti-viral activities. The bio-evaluation results indicated that some of the target compounds (such as 5g, 5i, 5u) exhibited good to moderate antiviral effect on CVB5, ADV7 and EV71 viruses, however, these compounds did not have inhibition activity against H1N1 virus. Especially, the compounds 4c and 4d also exhibited high antiviral activities, which provide a new and efficient approach to evolve novel multi-functional antiviral agents by rational integration of active pharmacophores. Copyright © 2013 Elsevier Ltd. All rights reserved.

  20. Screening of Brazilian medicinal plants for antiviral activity against rotavirus.

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    Cecílio, Alzira Batista; de Faria, Déborah Behr; Oliveira, Pollyana de Carvalho; Caldas, Sérgio; de Oliveira, Dario Alves; Sobral, Marcos Eduardo Guerra; Duarte, Maria Gorette Resende; Moreira, Carolina Paula de Souza; Silva, Cláudia Gontijo; de Almeida, Vera Lúcia

    2012-06-14

    Brazilian medicinal plants traditionally used for the treatment of diarrhoea were investigated for their in vitro antiviral activity against the simian rotavirus SA11. The ethanolic crude extracts of plants collected in the cerrado of Minas Gerais, Brazil were submitted to phytochemical screening. The cytotoxicity of the extracts was inferred by cellular morphologic alterations. Antiviral activity was assessed by the ability of the extracts to inhibit the cytopathic effect (CPE) of rotavirus on the treated cells. RT-PCR was performed to confirm and/or confront antiviral assay data. The maximum non-toxic concentration ranged from 50 to 500 μg/mL. All extracts were toxic at a concentration of 5000 μg/mL but no extract showed cytotoxicity at 50 μg/mL. The species Byrsonima verbascifolia, Myracrodruon urundeuva, Eugenia dysenterica and Hymenaea courbaril exhibited the strongest in vitro activity against rotavirus. Their extracts prevented the formation of CPE, and RT-PCR analysis detected no amplification of genetic material from rotavirus. Tannins, flavonoids, saponins, coumarins and terpenes were the major classes of natural products found in the leaf extracts that showed antiviral activity. Among the species studied, Byrsonima verbascifolia, Eugenia dysenterica, Hymenaea courbaril and Myracrodruon urundeuva showed potential activity against rotavirus and are worthy of further study. The present study corroborates ethnopharmacological data as a valuable source in the selection of plants with antiviral activity and to some extent validates their traditional uses. Published by Elsevier Ireland Ltd.

  1. Screening for Antiviral Activities of Isolated Compounds from Essential Oils

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    Akram Astani

    2011-01-01

    Full Text Available Essential oil of star anise as well as phenylpropanoids and sesquiterpenes, for example, trans-anethole, eugenol, β-eudesmol, farnesol, β-caryophyllene and β-caryophyllene oxide, which are present in many essential oils, were examined for their antiviral activity against herpes simplex virus type 1 (HSV-1 in vitro. Antiviral activity was analyzed by plaque reduction assays and mode of antiviral action was determined by addition of the drugs to uninfected cells, to the virus prior to infection or to herpesvirus-infected cells. Star anise oil reduced viral infectivity by >99%, phenylpropanoids inhibited HSV infectivity by about 60–80% and sesquiterpenes suppressed herpes virus infection by 40–98%. Both, star anise essential oil and all isolated compounds exhibited anti-HSV-1 activity by direct inactivation of free virus particles in viral suspension assays. All tested drugs interacted in a dose-dependent manner with herpesvirus particles, thereby inactivating viral infectivity. Star anise oil, rich in trans-anethole, revealed a high selectivity index of 160 against HSV, whereas among the isolated compounds only β-caryophyllene displayed a high selectivity index of 140. The presence of β-caryophyllene in many essential oils might contribute strongly to their antiviral ability. These results indicate that phenylpropanoids and sesquiterpenes present in essential oils contribute to their antiviral activity against HSV.

  2. ANTI-VIRAL ACTIVITY OF GLYCIRRHETINIC AND GLYCIRRHIZIC ACIDS

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    V. V. Zarubaev

    2016-01-01

    Full Text Available Influenza is a highly contagious human disease. In the course of use of antiviral drugs drug-resistant strains of the virus are formed, resulting in reduced efficiency of the chemotherapy. The review describes the biological activity of glycirrhetinic (GLA and glycirrhizic (GA acids in terms of their use as a therapeutic agent for viral infections. So, these compounds are against a broad spectrum of viruses, including herpes, corona-, alphaand flaviviruses, human immunodeficiency virus, vaccinia virus, poliovirus type I, vesicular stomatitis virus and influenza A virus. These data indicate that anti-viral effect of these compounds is due to several types of activity — direct antiviral effects, effects on cellular proand anti-viral and immunomodulating pathways, in particular by activation of innate immunity system. GA interferes with early steps of the viral reproductive cycle such as virus binding to its receptor, the absorption of the virus by endocytosis or virus decapsidation in the cytoplasm. This is due to the effect of GA-induced reduction of membrane fluidity. Thus, one mechanism for the antiviral activity of GA is that GA molecule increases the rigidity of cellular and viral membranes after incorporation in there. This results in increasing of energy threshold required for the formation of negative curvature at the fusion zones, as well as difficult lateral migration of the virus-receptor complexes. In addition, glycyrrhizin prevents interaction of viral nucleoprotein with cellular protein HMGB1, which is necessary for the viral life cycle. Glycyrrhizin also inhibits the induction of oxidative stress during influenza infection, exhibiting antioxidant properties, which leads to a reduction of virus-induced production of cytokines/chemokines, without affecting the replication of the virus. A wide spectrum of biological activity and effect on various aspects of the viral pathogenesis substantiate the effect of GA and GLA as a component

  3. Antimicrobial and antiviral activity of hydrolysable tannins.

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    Buzzini, Pietro; Arapitsas, Panagiotis; Goretti, Marta; Branda, Eva; Turchetti, Benedetta; Pinelli, Patrizia; Ieri, F; Romani, Annalisa

    2008-10-01

    Hydrolysable tannins (HTs), secondary metabolites widely distributed in the plant kingdom, are generally multiple esters of gallic acid with glucose. HTs have been shown to be effective antagonists against viruses, bacteria and eukaryotic microorganisms. The present review examines the antimicrobial and antiviral activity of HTs, the mechanism(s) of action, and some structure-activity relationships.

  4. Novel antiviral activity of baicalein against dengue virus

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    Zandi Keivan

    2012-11-01

    Full Text Available Abstract Background Dengue is a serious arboviral disease currently with no effective antiviral therapy or approved vaccine available. Therefore, finding the effective compound against dengue virus (DENV replication is very important. Among the natural compounds, bioflavonoids derived mainly from plants are of interest because of their biological and medicinal benefits. Methods In the present study, antiviral activity of a bioflavonoid, baicalein, was evaluated against different stages of dengue virus type 2 (DENV-2 replication in Vero cells using focus forming unit reduction assay and quantitative RT-PCR. Results Baicalein inhibited DENV-2 replication in Vero cells with IC50= 6.46 μg/mL and SI= 17.8 when added after adsorption to the cells. The IC50 against DENV-2 was 5.39 μg/mL and SI= 21.3 when cells were treated 5 hours before virus infection and continuously up to 4 days post infection. Baicalein exhibited direct virucidal effect against DENV-2 with IC 50= 1.55 μg/mL and showed anti-adsorption effect with IC50 = 7.14 μg/mL. Conclusions Findings presented here suggest that baicalein exerts potent antiviral activity against DENV. Baicalein possesses direct virucidal activity against DENV besides its effects against dengue virus adsorption and intracellular replication of DENV-2. Baicalein, hence, should be considered for in vivo evaluation in the development of an effective antiviral compound against DENV.

  5. Evaluation of in vitro antiviral activity of a brown alga ( Cystoseira ...

    African Journals Online (AJOL)

    The hot water extract of a brown marine alga, Cystoseira myrica, from the Persian Gulf was evaluated as an antiviral compound against KOS strain of HSV-1 in cell culture. The extract exhibited antiviral activity against herpes simplex virus type 1 (HSV-1) not only during absorption of virus to the cells, but also on post ...

  6. Antiviral Drug Research Proposal Activity

    OpenAIRE

    Lisa Injaian; Smith, Ann C.; Jennifer German Shipley; Gili Marbach-Ad; Brenda Lee Fredericksen

    2011-01-01

    The development of antiviral drugs provides an excellent example of how basic and clinical research must be used together in order to achieve the final goal of treating disease. A Research Oriented Learning Activity was designed to help students to better understand how basic and clinical research can be combined toward a common goal. Through this project students gained a better understanding of the process of scientific research and increased their information literacy in the field of virol...

  7. Evaluation of Antiviral Activity ofZanthoxylumSpecies Against Picornaviruses.

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    Choi, Hwa-Jung

    2016-12-01

    Human rhinoviruses and enteroviruses (family Picornaviridae) infect millions of people worldwide each year, but little is known about effective therapeutical treatment for the infection caused by these viruses. We sought to determine whether or not Zanthoxylum (Rutaceae) species can exhibit antiviral activity against picornaviruses. The leaf parts of four Zanthoxylum species were extracted with methanol, and the extracts were investigated for their antiviral activity against picornaviruses using cytopathic effects by cytopathic effect reduction. Leaf extracts of Zanthoxylum piperitum among four Zanthoxylum species were found to possess only broad-spectrum antipicornavirus activity against human rhninovirus 2 with a 50% inhibitory concentration (IC 50 ) value of 59.48 μg/mL, human rhinovirus 3 with an IC 50 value of 39.94 μg/mL, coxsackie A16 virus with an IC 50 value of 45.80 μg/mL, coxsackie B3 virus with an IC 50 value of 68.53 μg/mL, coxsackie B4 virus with an IC 50 value of 93.58 μg/mL, and enterovirus 71 virus with an IC 50 value of 4.48 μg/mL. However, ribavirin did not possess antiviral activity against human rhinovirus 3 and four enteroviruses. Therefore, leaves of Z. piperitum showed broad-spectrum antipicornavirus activity, and may be useful as a candidate for studying picornavirus agents and development of pharmaceuticals.

  8. Development of a Broad-Spectrum Antiviral Agent with Activity ...

    African Journals Online (AJOL)

    Purpose: To evaluate the broad-spectrum antiviral activity of peptide H9 (H9) in vitro in order to gain insight into its underlying molecular mechanisms. Method: Antiviral activity against Herpes simplex virus type 1 (HSV-1) was determined using thiazolyl blue (MTT) assay. Polymerase Chain Reaction (PCR) was employed to ...

  9. Comparison of different methods for extraction of Cinnamomi ramulus: yield, chemical composition and in vitro antiviral activities.

    Science.gov (United States)

    Zhou, Jing; Yuan, Xiurong; Li, Ling; Zhang, Tong; Wang, Bing

    2017-03-21

    Hydrodistillation (HD), supercritical fluid extraction (SFE) and reflux extraction (RE) were applied to obtain Cinnamomi ramulus extracts. The yields, chemical compositions and antiviral activities of the extracts were investigated. Extracts were analysed using gas chromatography-mass spectrometry and the antiviral activities were evaluated using cytopathic effect inhibition assay. HD, SFE and RE afforded 0.376, 1.227 and 5.914% yields, respectively. Cinnamaldehyde (CA), SFE and ethanol extracts exhibited antiviral activities against herpes simplex virus type 1. Moreover, CA and other three extracts had inhibition efficacy against respiratory syncytial virus. The most efficient antiviral activities were obtained with SFE.

  10. Antiviral Activity of Graphene Oxide: How Sharp Edged Structure and Charge Matter.

    Science.gov (United States)

    Ye, Shiyi; Shao, Kang; Li, Zhonghua; Guo, Nan; Zuo, Yunpeng; Li, Qin; Lu, Zhicheng; Chen, Lu; He, Qigai; Han, Heyou

    2015-09-30

    Graphene oxide and its derivatives have been widely explored for their antimicrobial properties due to their high surface-to-volume ratios and unique chemical and physical properties. However, little information is available on their effects on viruses. In this study, we report the broad-spectrum antiviral activity of GO against pseudorabies virus (PRV, a DNA virus) and porcine epidemic diarrhea virus (PEDV, an RNA virus). Our results showed that GO significantly suppressed the infection of PRV and PEDV for a 2 log reduction in virus titers at noncytotoxic concentrations. The potent antiviral activity of both GO and rGO can be attributed to the unique single-layer structure and negative charge. First, GO exhibited potent antiviral activity when conjugated with PVP, a nonionic polymer, but not when conjugated with PDDA, a cationic polymer. Additionally, the precursors Gt and GtO showed much weaker antiviral activity than monolayer GO and rGO, suggesting that the nanosheet structure is important for antiviral properties. Furthermore, GO inactivated both viruses by structural destruction prior to viral entry. The overall results suggest the potential of graphene oxide as a novel promising antiviral agent with a broad and potent antiviral activity.

  11. Antiviral Activity of Isatis indigotica Extract and Its Derived Indirubin against Japanese Encephalitis Virus

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    Shu-Jen Chang

    2012-01-01

    Full Text Available Isatis indigotica is widely used in Chinese Traditional Medicine for clinical treatment of virus infection, tumor, and inflammation, yet its antiviral activities remain unclear. This study probed antiviral activity of I. indigotica extract and its marker compounds against Japanese encephalitis virus (JEV. I. indigotica methanol extract, indigo, and indirubin proved less cytotoxic than other components, showing inhibitory effect (concentration-dependent on JEV replication in vitro. Time-of-addition experiments proved the extract, indigo, and indirubin with potent antiviral effect by pretreatment (before infection or simultaneous treatment (during infection, but not posttreatment (after entry. Antiviral action of these agents showed correlation with blocking virus attachment and exhibited potent virucidal activity. In particular, indirubin had strong protective ability in a mouse model with lethal JEV challenge. The study could yield anti-JEV agents.

  12. Antiviral and antifungal activity of some dermaseptin S4 analogues ...

    African Journals Online (AJOL)

    terminus is necessary for the antifungal activity of peptide, but antiviral effect is determined by C-terminal domain and/or entire peptide sequence. Key words: Antimicrobial peptides, dermaseptin, structure-activity relationship, peptide synthesis.

  13. E. fischeriana Root Compound Dpo Activates Antiviral Innate Immunity

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    Jingxuan Chen

    2017-10-01

    Full Text Available E. fischeriana has long been used as a traditional Chinese medicine. Recent studies reported that some compounds of E. fischeriana exhibited antimicrobial and immune enhance activity. Innate immune system is essential for the immune surveillance of inner and outer threats, initial host defense responses and immune modulation. The role of natural drug compounds, including E. fischeriana, in innate immune regulation is largely unknown. Here we demonstrated that E. fischeriana compound Dpo is involved in antiviral signaling. The genome wide RNA-seq analysis revealed that the induction of ISGs by viral infection could be synergized by Dpo. Consistently, Dpo enhanced the antiviral immune responses and protected the mice from death during viral infection. Dpo however was not able to rescue STING deficient mice lethality caused by HSV-1 infection. The enhancement of ISG15 by Dpo was also impaired in STING, IRF3, IRF7, or ELF4 deficient cells, demonstrating that Dpo activates innate immune responses in a STING/IRFs/ELF4 dependent way. The STING/IRFs/ELF4 axis is therefore important for Dpo induced ISGs expression, and can be used by host to counteract infection.

  14. Antiviral activity and mode of action of propolis extracts and selected compounds.

    Science.gov (United States)

    Schnitzler, Paul; Neuner, Annett; Nolkemper, Silke; Zundel, Christine; Nowack, Hans; Sensch, Karl Heinz; Reichling, Jürgen

    2010-01-01

    Aqueous and ethanol extracts of propolis were analysed phytochemically and examined for their antiviral activity in vitro. Different polyphenols, flavonoids and phenylcarboxylic acids were identified as major constituents. The antiviral effect of propolis extracts and selected constituents, e.g. caffeic acid (1), p-coumaric acid (2), benzoic acid (3), galangin (4), pinocembrin (5) and chrysin (6) against herpes simplex virus type 1 (HSV-1) was analysed in cell culture. The 50% inhibitory concentration (IC(50)) of aqueous and ethanol propolis extracts for HSV-1 plaque formation was determined at 0.0004% and 0.000035%, respectively. Both propolis extracts exhibited high levels of antiviral activity against HSV-1 in viral suspension tests, plaque formation was significantly reduced by >98%. In order to determine the mode of antiviral action of propolis, the extracts were added at different times during the viral infection cycle. Both propolis extracts exhibited high anti-HSV-1 activity when the viruses were pretreated with these drugs prior to infection. Among the analysed compounds, only galangin and chrysin displayed some antiviral activity. However, the extracts containing many different components exhibited significantly higher antiherpetic effects as well as higher selectivity indices than single isolated constituents. Propolis extracts might be suitable for topical application against herpes infection.

  15. Antiviral activity of the crude extracts and phytochemical fractions of ...

    African Journals Online (AJOL)

    The three fractions used contained the major peaks within which the main compounds had been identified as aloenin, aloin and an aloinoside derivatives. The crude Aloe extract at 400 mg/ml exhibited antiviral effects at 100%, While 200 mg/ml resulted to 30% reduction in viral multiplication. Fraction containing aloenin (4 ...

  16. Antiviral Activities and Putative Identification of Compounds in Microbial Extracts from the Hawaiian Coastal Waters

    Science.gov (United States)

    Tong, Jing; Trapido-Rosenthal, Hank; Wang, Jun; Wang, Youwei; Li, Qing X.; Lu, Yuanan

    2012-01-01

    Marine environments are a rich source of significant bioactive compounds. The Hawaiian archipelago, located in the middle of the Pacific Ocean, hosts diverse microorganisms, including many endemic species. Thirty-eight microbial extracts from Hawaiian coastal waters were evaluated for their antiviral activity against four mammalian viruses including herpes simplex virus type one (HSV-1), vesicular stomatitis virus (VSV), vaccinia virus and poliovirus type one (poliovirus-1) using in vitro cell culture assay. Nine of the 38 microbial crude extracts showed antiviral potencies and three of these nine microbial extracts exhibited significant activity against the enveloped viruses. A secosteroid, 5α(H),17α(H),(20R)-beta-acetoxyergost-8(14)-ene was putatively identified and confirmed to be the active compound in these marine microbial extracts. These results warrant future in-depth tests on the isolation of these active elements in order to explore and validate their antiviral potential as important therapeutic remedies. PMID:22611351

  17. Antiviral Activities and Putative Identification of Compounds in Microbial Extracts from the Hawaiian Coastal Waters

    Directory of Open Access Journals (Sweden)

    Yuanan Lu

    2012-02-01

    Full Text Available Marine environments are a rich source of significant bioactive compounds. The Hawaiian archipelago, located in the middle of the Pacific Ocean, hosts diverse microorganisms, including many endemic species. Thirty-eight microbial extracts from Hawaiian coastal waters were evaluated for their antiviral activity against four mammalian viruses including herpes simplex virus type one (HSV-1, vesicular stomatitis virus (VSV, vaccinia virus and poliovirus type one (poliovirus-1 using in vitro cell culture assay. Nine of the 38 microbial crude extracts showed antiviral potencies and three of these nine microbial extracts exhibited significant activity against the enveloped viruses. A secosteroid, 5α(H,17α(H,(20R-beta-acetoxyergost-8(14-ene was putatively identified and confirmed to be the active compound in these marine microbial extracts. These results warrant future in-depth tests on the isolation of these active elements in order to explore and validate their antiviral potential as important therapeutic remedies.

  18. Synthesis and Broad-Spectrum Antiviral Activity of Some Novel Benzo-Heterocyclic Amine Compounds

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    Da-Jun Zhang

    2014-01-01

    Full Text Available A series of novel unsaturated five-membered benzo-heterocyclic amine derivatives were synthesized and assayed to determine their in vitro broad-spectrum antiviral activities. The biological results showed that most of our synthesized compounds exhibited potent broad-spectrum antiviral activity. Notably, compounds 3f (IC50 = 3.21–5.06 μM and 3g (IC50 = 0.71–34.87 μM showed potent activity towards both RNA viruses (influenza A, HCV and Cox B3 virus and a DNA virus (HBV at low micromolar concentrations. An SAR study showed that electron-withdrawing substituents located on the aromatic or heteroaromatic ring favored antiviral activity towards RNA viruses.

  19. Cherry Valley ducks mitochondrial antiviral-signaling protein (MAVS mediated signaling pathway and antiviral activity research

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    Ning Li

    2016-09-01

    Full Text Available Mitochondrial antiviral-signaling protein (MAVS, an adaptor protein of retinoic acid-inducible gene I (RIG-I like receptors (RLRs-mediated signal pathway, is involved in innate immunity. In this study, Cherry Valley duck MAVS (duMAVS was cloned from the spleen and analyzed. duMAVS was determined to have a caspase activation and recruitment domain at N-terminal, followed by a proline rich domain and a transmembrane domain at C-terminal. Quantitative real time PCR indicated that duMAVS was expressed in all tissues tested across a broad expression spectrum. The expression of duMAVS was significantly up-regulated after infection with duck Tembusu virus. Overexpression of duMAVS could drive the activation of interferon-β, nuclear factor-κB, interferon regulatory factor 7, and many downstream factors (such as Mx, PKR, OAS, and IL-8 in duck embryo fibroblast cells. What’s more, RNA interference further confirmed that duMAVS was an important adaptor for IFN-β activation. The antiviral assay showed that duMAVS could suppress the various viral replications (duck Tembusu virus, novel reovirus, and duck plague virus at early stages of infection. Overall, these results showed that the main signal pathway mediated by duMAVS and it had a broad-spectrum antiviral ability. This research will be helpful to better understanding the innate immune system of ducks.

  20. Phytochemistry, cytotoxicity and antiviral activity of Eleusine indica (sambau)

    Science.gov (United States)

    Iberahim, Rashidah; Yaacob, Wan Ahmad; Ibrahim, Nazlina

    2015-09-01

    Goose grass also known as Eleusine indica (EI) is a local medicinal plant that displays antioxidant, antimicrobial and anticancer activities. The present study is to determine the phytochemical constituents, cytotoxicity and antiviral activities for both crude extract and fraction obtained from the plant. The crude extract contained more secondary metabolites compared to the hexane fraction as gauged using standard phytochemical tests. Cytotoxicity screening against Vero cells using MTT assay showed that the CC50 values for crude extract and hexane fraction were 2.07 and 5.62 mg/ml respectively. The antiviral activity towards Herpes Simplex Virus type 1 (HSV-1) was determined using plaque reduction assay. The selective indices (SI = CC50 / EC50) for both methanol extract and hexane fraction were 12.2 and 6.2 respectively. These results demonstrate that the extract prepared from E. indica possesses phytochemical compound that was non cytotoxic to the cell with potential antiviral activity.

  1. Mechanisms of virus resistance and antiviral activity of snake venoms

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    JVR Rivero

    2011-01-01

    Full Text Available Viruses depend on cell metabolism for their own propagation. The need to foster an intimate relationship with the host has resulted in the development of various strategies designed to help virus escape from the defense mechanisms present in the host. Over millions of years, the unremitting battle between pathogens and their hosts has led to changes in evolution of the immune system. Snake venoms are biological resources that have antiviral activity, hence substances of significant pharmacological value. The biodiversity in Brazil with respect to snakes is one of the richest on the planet; nevertheless, studies on the antiviral activity of venom from Brazilian snakes are scarce. The antiviral properties of snake venom appear as new promising therapeutic alternative against the defense mechanisms developed by viruses. In the current study, scientific papers published in recent years on the antiviral activity of venom from various species of snakes were reviewed. The objective of this review is to discuss the mechanisms of resistance developed by viruses and the components of snake venoms that present antiviral activity, particularly, enzymes, amino acids, peptides and proteins.

  2. Synthesis and biological activity of hydroxycinnamoyl containing antiviral drugs

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    Chochkova Maya G.

    2014-01-01

    Full Text Available Seven N-hydroxycinnamoyl amides were synthesized by EDC/HOBt coupling of the corresponding substituted cinnamic acids (p-coumaric-, ferulic-, sinapic- and caffeic acids with influenza antivirals (amantadine, rimantadine and oseltamivir. DPPH (1,1-diphenyl-2-picrylhydrazyl scavenging abilities and the inhibitory effect on mushroom tyrosinase activity (using L-tyrosine as the substrate were investigated in vitro. Amongst the synthesized compounds, N-[(E-3-(3’,4’-dihydroxyphenyl-2-propenoyl]oseltamivir (1 and N-[(E-3-(3’,4’-dihydroxyphenyl-2-propenoyl]rimantadine (4, containing catechol moiety, exhibited the most potent DPPH radical-scavenging activity. Amide (1 displayed also tyrosinase inhibitory effect toward L-tyrosine as the substrate (~50%. Due to its biological activities revealed so far compound (1 can be considered as a promising candidate for a cosmetic ingredient. The synthesized compounds were also investigated for their in vitro inhibitory activity against the replication of influenza virus A (H3N2.

  3. Induction of IFN-α subtypes and their antiviral activity in mumps virus infection.

    Science.gov (United States)

    Markušić, Maja; Šantak, Maja; Košutić-Gulija, Tanja; Jergović, Mladen; Jug, Renata; Forčić, Dubravko

    2014-12-01

    Human type I interferons (IFNs) comprise one IFN-β, -ω, -κ, and -ɛ and 12 different IFN-α subtypes, which play an important role in early host antiviral response. Despite their high structural homology and signaling through the same receptor, IFN-α subtypes exhibit different antiviral, antiproliferative, and immunomodulatory activities. Differences in the production of IFN-α subtypes therefore determine the quality of an antiviral response. In this study, we investigated the pattern of IFN-α subtypes induced in infection with different mumps virus (MuV) strains and examined the MuV sensitivity to the action of IFN-α subtypes. We found that all IFN-α subtypes are being expressed in response to MuV infection with a highly similar IFN-α subtype pattern between the virus strains. We assessed an antiviral activity of several IFN-α subtypes: IFN-α1, IFN-α2, IFN-α4, IFN-α6, IFN-α8, IFN-α14, IFN-α17, and IFN-α21. Although they were all effective in suppressing MuV replication, the intensity and pattern of their action varied between MuV strains. Our results indicate that the overall IFN antiviral activity as well as the activity of specific IFN-α subtypes against MuV depend on a virus strain.

  4. Antiviral activity of carnosic acid against respiratory syncytial virus

    Science.gov (United States)

    2013-01-01

    Background Human respiratory syncytial virus (hRSV) is a leading cause of severe lower respiratory infection and a major public health threat worldwide. To date, no vaccine or effective therapeutic agent has been developed. In a screen for potential therapeutic agents against hRSV, we discovered that an extract of Rosmarinus officinalis exerted a strong inhibitory effect against hRSV infection. Subsequent studies identified carnosic acid as a bioactive constituent responsible for anti-hRSV activity. Carnosic acid has been shown to exhibit potent antioxidant and anti-cancer activities. Anti-RSV activity of carnosic acid was further investigated in this study. Methods Effects of extracts from various plants and subfractions from R. officinalis on hRSV replication were determined by microneutralization assay and plaque assay. Several constituents were isolated from ethyl acetate fraction of R. officinalis and their anti-RSV activities were assessed by plaque assay as well as reverse-transcription quantitative PCR to determine the synthesis of viral RNAs. Results Among the tested bioactive constituents of R. officinalis, carnosic acid displayed the most potent anti-hRSV activity and was effective against both A- and B-type viruses. Carnosic acid efficiently suppressed the replication of hRSV in a concentration-dependent manner. Carnosic acid effectively suppressed viral gene expression without inducing type-I interferon production or affecting cell viability, suggesting that it may directly affect viral factors. A time course analysis showed that addition of carnosic acid 8 hours after infection still effectively blocked the expression of hRSV genes, further suggesting that carnosic acid directly inhibited the replication of hRSV. Conclusions The current study demonstrates that carnosic acid, a natural compound that has already been shown to be safe for human consumption, has anti-viral activity against hRSV, efficiently blocking the replication of this virus. Carnosic

  5. Antiviral Activity of Baicalein and Quercetin against the Japanese Encephalitis Virus

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    Jefree Johari

    2012-12-01

    Full Text Available Japanese encephalitis (JE, a mosquito-borne viral disease, is endemic to the entire east and southeast Asia, and some other parts of the world. Currently, there is no effective therapeutic available for JE; therefore, finding the effective antiviral agent against JEV replication is crucial. In the present study, the in vitro antiviral activity of baicalein and quercetin, two purportedly antiviral bioflavonoids, was evaluated against Japanese encephalitis virus (JEV replication in Vero cells. Anti-JEV activities of these compounds were examined on different stages of JEV replication cycle. The effects of the compounds on virus replication were determined by foci forming unit reduction assay (FFURA and quantitative RT-PCR. Baicalein showed potent antiviral activity with IC50 = 14.28 µg/mL when it was introduced to the Vero cells after adsorption of JEV. Quercetin exhibited weak anti-JEV effects with IC50 = 212.1 µg/mL when the JEV infected cells were treated with the compound after virus adsorption. However, baicalein exhibited significant effect against JEV adsorption with IC50 = 7.27 µg/mL while quercetin did not show any anti-adsorption activity. Baicalein also exhibited direct extracellular virucidal activity on JEV with IC50 = 3.44 µg/mL. However, results of quantitative RT-PCR experiments confirmed the findings from FFURA. This study demonstrated that baicalein should be considered as an appropriate candidate for further investigations, such as the study of molecular and cellular mechanism(s of action and in vivo evaluation for the development of an effective antiviral compound against Japanese encephalitis virus.

  6. In vitro characterization of the antiviral activity of fucoidan from Cladosiphon okamuranus against Newcastle Disease Virus

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    Elizondo-Gonzalez Regina

    2012-12-01

    Full Text Available Abstract Background Newcastle Disease Virus (NDV causes a serious infectious disease in birds that results in severe losses in the worldwide poultry industry. Despite vaccination, NDV outbreaks have increased the necessity of alternative prevention and control measures. Several recent studies focused on antiviral compounds obtained from natural resources. Many extracts from marine organisms have been isolated and tested for pharmacological purposes, and their antiviral activity has been demonstrated in vitro and in vivo. Fucoidan is a sulfated polysaccharide present in the cell wall matrix of brown algae that has been demonstrated to inhibit certain enveloped viruses with low toxicity. This study evaluated the potential antiviral activity and the mechanism of action of fucoidan from Cladosiphon okamuranus against NDV in the Vero cell line. Methods The cytotoxicity of fucoidan was determined by the MTT assay. To study its antiviral activity, fusion and plaque-forming unit (PFU inhibition assays were conducted. The mechanism of action was determined by time of addition, fusion inhibition, and penetration assays. The NDV vaccine strain (La Sota was used in the fusion inhibition assays. PFU and Western blot experiments were performed using a wild-type lentogenic NDV strain. Results Fucoidan exhibited antiviral activity against NDV La Sota, with an obtained IS50 >2000. In time of addition studies, we observed viral inhibition in the early stages of infection (0–60 min post-infection. The inhibition of viral penetration experiments with a wild-type NDV strain supported this result, as these experiments demonstrated a 48% decrease in viral infection as well as reduced HN protein expression. Ribavirin, which was used as an antiviral control, exhibited lower antiviral activity than fucoidan and high toxicity at active doses. In the fusion assays, the number of syncytia was significantly reduced (70% inhibition when fucoidan was added before cleavage of

  7. In vitro Cytotoxic, Antibacterial and Antiviral Activities of Triterpenes ...

    African Journals Online (AJOL)

    Purpose: To study the phytochemical composition of Siphonochalina siphonella sponge from the western coast of the Red Sea and to evaluate the isolates for possible in vitro cytotoxic, antibacterial and antiviral activities. Methods: The compounds obtained were isolated and purified by different chromatographic means.

  8. Antiviral activities of streptomycetes against tobacco mosaic virus ...

    African Journals Online (AJOL)

    Madina (M) areas in Saudi Arabia. Among these strains, six were selected for antiviral activity screening which are K1, K2, K3, M1, M2 and M3. All the selected strains were characterized morphologically to be under the genus Streptomyces. Primary ...

  9. Development of a Broad-Spectrum Antiviral Agent with Activity ...

    African Journals Online (AJOL)

    Development of a Broad-Spectrum Antiviral Agent with. Activity Against Herpesvirus Replication .... deviation. The data were analyzed by SPSS software, version 16. Significant differences (p <. 0.01) between groups were determined using unpaired Student's t-test. RESULTS. Cytotoxic and optimum drug concentrations.

  10. Antiviral activity of Conyza canadensis (L.) Cronquist extracts grown ...

    African Journals Online (AJOL)

    Ethyl acetate, chloroform, butanol and methanol extracts of the aerial parts of Conyza Canadensis L. Cronquist were investigated for their antiviral activity against human cytomegalovirus (HCMV) AD-169 and Cox-B3 viruses by modification of the widely used shell-vial assay. The results showed that butanol and methanol ...

  11. Antiviral activity of exopolysaccharides from Arthrospira platensis against koi herpesvirus.

    Science.gov (United States)

    Reichert, M; Bergmann, S M; Hwang, J; Buchholz, R; Lindenberger, C

    2017-10-01

    Although koi herpesvirus (KHV) has a history of causing severe economic losses in common carp and koi farms, there are still no treatments available on the market. Thus, the aim of this study was to test exopolysaccharides (EPS) for its antiviral activity against KHV, by monitoring inhibition and cytotoxic effects in common carp brain cells. These substances can be easily extracted from extracellular algae supernatant and were identified as groups of sulphated polysaccharides. In order to reach this aim, Arthrospira platensis, which is well known for its antiviral activity of intra- and extracellular compounds towards mammalian herpesviruses, was investigated as standard organism and compared to commercial antiviral drug, ganciclovir, which inhibits the viral DNA polymerization. The antiviral activity of polysaccharides of A. platensis against KHV was confirmed in vitro using qualitative assessment of KHV life cycle genes, and it was found by RT-PCR that EPS, applied at a concentration of >18 μg mL(-1) and a multiplicity of infection (MOI) of 0.45 of KHV, suppressed the viral replication in common carp brain (CCB) cells even after 22 days post-infection, entirely. Further, this study presents first data indicating an enormous potential using polysaccharides as an additive for aquacultures to lower or hinder the spread of the KHV and koi herpesvirus disease (KHVD) in future. © 2017 John Wiley & Sons Ltd.

  12. Antiviral activity of maca (Lepidium meyenii) against human influenza virus.

    Science.gov (United States)

    Del Valle Mendoza, Juana; Pumarola, Tomàs; Gonzales, Libertad Alzamora; Del Valle, Luis J

    2014-09-01

    To investigate antiviral activity of maca to reduce viral load in Madin-Darby canine kidney (MDCK) cells infected with influenza type A and B viruses (Flu-A and Flu-B, respectively). Maca were extracted with methanol (1:2, v/v). The cell viability and toxicity of the extracts were evaluated on MDCK cells using method MTT assay. Antiviral activity of compounds against Flu-A and Flu-B viruses was assayed using a test for determining the inhibition of the cytopathic effect on cell culture and multiplex RT-PCR. The methanol extract of maca showed low cytotoxicity and inhibited influenza-induced cytopathic effect significantly, while viral load was reduced via inhibition of viral growth in MDCK infected cells. Maca contains potent inhibitors of Flu-A and Flu-B with a selectivity index [cytotoxic concentration 50%/IC50] of 157.4 and 110.5, respectively. In vitro assays demonstrated that maca has antiviral activity not only against Flu-A (like most antiviral agents) but also Flu-B viruses, providing remarkable therapeutic benefits. Copyright © 2014 Hainan Medical College. Published by Elsevier B.V. All rights reserved.

  13. A 2,5-Dihydroxybenzoic Acid-Gelatin Conjugate: The Synthesis, Antiviral Activity and Mechanism of Antiviral Action Against Two Alphaherpesviruses.

    Science.gov (United States)

    Lisov, Alexander; Vrublevskaya, Veronika; Lisova, Zoy; Leontievsky, Alexey; Morenkov, Oleg

    2015-10-15

    Various natural and synthetic polyanionic polymers with different chemical structures are known to exhibit potent antiviral activity in vitro toward a variety of enveloped viruses and may be considered as promising therapeutic agents. A water-soluble conjugate of 2,5-dihydroxybezoic acid (2,5-DHBA) with gelatin was synthesized by laccase-catalyzed oxidation of 2,5-DHBA in the presence of gelatin, and its antiviral activity against pseudorabies virus (PRV) and bovine herpesvirus type 1 (BoHV-1), two members of the Alphaherpesvirinae subfamily, was studied. The conjugate produced no direct cytotoxic effect on cells, and did not inhibit cell growth at concentrations up to 1000 µg/mL. It exhibited potent antiviral activity against PRV (IC50, 1.5-15 µg/mL for different virus strains) and BoHV-1 (IC50, 0.5-0.7 µg/mL). When present during virus adsorption, the conjugate strongly inhibited the attachment of PRV and BoHV-1 to cells. The 2,5-DHBA-gelatin conjugate had no direct virucidal effect on the viruses and did not influence their penetration into cells, cell-to-cell spread, production of infectious virus particles in cells, and expression of PRV glycoproteins E and B. The results indicated that the 2,5-DHBA-gelatin conjugate strongly inhibits the adsorption of alphaherpesviruses to cells and can be a promising synthetic polymer for the development of antiviral formulations against alphaherpesvirus infections.

  14. Bilirubin: an endogenous molecule with antiviral activity in vitro.

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    Rosaria eSantangelo

    2012-03-01

    Full Text Available Bilirubin-IX-alpha (BR is the final product of heme metabolism through the heme oxygenase/biliverdin reductase (HO/BVR system. Previous papers reported on the microbicidal effects of the HO by-products biliverdin-IX-alpha, carbon monoxide and iron, through either direct or indirect mechanisms. In this paper the evidence of a virucidal effect of BR against human herpes simplex virus type 1 (HSV-1 and the enterovirus EV71 was provided. Bilirubin-IX-alpha, at concentrations 1-10 µM, close to those found in blood and tissues, significantly reduced HSV-1 and EV71 replication in Hep-2 and Vero cell lines, respectively. Bilirubin-IX-alpha inhibited viral infection of Hep-2 and Vero cells when given 2 hours before, concomitantly and 2 hours after viral infection. Furthermore, BR retained its antiviral activity even complexed with a saturating concentration of human serum-albumin. Moreover, 10 µM BR increased the formation of nitric oxide and the phosphorylation of JNK in Vero and Hep-2 cell lines, respectively, thus implying a role of these two pathways in the mechanism of antiviral activity of the bile pigment. In conclusion, these results support the antiviral effect of BR against HSV-1 and enterovirus in vitro, and put the basis for further basic and clinical studies to understand the real role of BR as an endogenous antiviral molecule.

  15. Antiviral and Antitumor Activity of Licorice Root Extracts.

    Science.gov (United States)

    Fukuchi, Kunihiko; Okudaira, Noriyuki; Adachi, Kazunori; Odai-Ide, Reina; Watanabe, Shigeru; Ohno, Hirokazu; Yamamoto, Masaji; Kanamoto, Taisei; Terakubo, Shigemi; Nakashima, Hideki; Uesawa, Yoshihiro; Kagaya, Hajime; Sakagami, Hiroshi

    In the search for anti-viral and antitumor substances from natural resources, antiviral and antitumor activities of licorice root extract and purified ingredients were investigated. Viability of cells was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide method. Antiviral activity was quantified by the selectivity index, defined as the ratio of the 50% cytotoxic concentration (CC50) to the 50% effective concentration against human immunodeficiency virus (HIV) or herpes simplex virus (HSV)-infected cells (EC50). The tumor specificity was calculated by the ratio of CC50 against human normal oral cells to that against human oral squamous cell carcinoma cell lines. Licorice flavonoids and lower molecular polyphenols were subjected to quantitative structure-activity relationship analysis. Alkaline extract of licorice root had higher anti-HIV activity than did water extracts, confirming our previous reports. On the other hand, water extract, especially the flavonoid-rich fraction, had higher anti-HSV activity than did the alkaline extract. The flavonoid-rich fraction was more cytotoxic against human oral squamous cell carcinoma cell lines compared to normal oral cells, suggesting their tumor-specific cytotoxicity. The present study suggests that water and alkaline extracts of licorice root exert different mechanisms of actions against these two viruses. Physicochemical properties, rather than the category of compounds, may be important in determining their anti-HSV activity. Copyright © 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  16. Antiviral activity of shikonin ester derivative PMM-034 against enterovirus 71 in vitro

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    Y. Zhang

    2017-08-01

    Full Text Available Human enterovirus 71 (EV71 is the major causative agent of hand, foot, and mouth disease (HFMD, particularly in infants and children below 4 years of age. Shikonin is a bioactive compound with anti-inflammatory, antiviral, and antibacterial activities derived from the roots of the Chinese medicinal herb Lithospermum erythrorhizon. This study aimed to examine the antiviral activity of PMM-034, a shikonin ester derivative, against EV71 in rhabdomyosarcoma (RD cells. Cytotoxicity of PMM-034 on RD cells was determined using WST-1 assay. Dose- and time-dependent effects of PMM-034 on EV71 replication in RD cells were determined using plaque reduction assay. mRNA expression levels of EV71/VP1 and pro-inflammatory cytokines (IL-1β, IL-6, IL-8, and TNF-α were determined by real-time RT-PCR, and EV71/VP1 and phospho-p65 protein expressions were determined by western blot analysis. PMM-034 exhibited only weak cytotoxicity against RD cells. However, PMM-034 exhibited significant antiviral activity against EV71 in RD cells with 50% inhibitory concentration of 2.31 μg/mL. The VP1 mRNA and protein levels were significantly reduced in cells treated with PMM-034. Furthermore, relative mRNA expression levels of IL-1β, IL-6, IL-8, and TNF-α significantly decreased in the cells treated with PMM-034, while the phospho-p65 protein expression was also significantly lower in the treated cells. These results indicated that PMM-034 suppressed the expressions of pro-inflammatory cytokines in RD cells, exhibiting antiviral activity against EV71, as evidenced by the reduced VP1 mRNA and protein levels in PMM-034-treated cells. Thus, PMM-034 is a promising candidate for further development as an EV71 inhibitor.

  17. Antiviral activity of lauryl gallate against animal viruses.

    Science.gov (United States)

    Hurtado, Carolina; Bustos, Maria Jose; Sabina, Prado; Nogal, Maria Luisa; Granja, Aitor G; González, Maria Eugenia; Gónzalez-Porqué, Pedro; Revilla, Yolanda; Carrascosa, Angel L

    2008-01-01

    Antiviral compounds are needed in the control of many animal and human diseases. We analysed the effect of the antitumoural drug lauryl gallate on the infectivity of the African swine fever virus among other DNA (herpes simplex and vaccinia) and RNA (influenza, porcine transmissible gastroenteritis and Sindbis) viruses, paying attention to its effect on the viability of the corresponding host cells. Viral production was strongly inhibited in different cell lines at non-toxic concentrations of the drug (1-10 microM), reducing the titres 3->5 log units depending on the multiplicity of infection. In our model system (African swine fever virus in Vero cells), the addition of the drug 1 h before virus adsorption completely abolished virus productivity in a one-step growth virus cycle. Interestingly, no inhibitory effect was observed when lauryl gallate was added after 5-8 h post-infection. Both cellular and viral DNA synthesis and late viral transcription were inhibited by the drug; however, the early viral protein synthesis and the virus-mediated increase of p53 remained unaffected. Activation of the apoptotic effector caspase-3 was not detected after lauryl gallate treatment of Vero cells. Furthermore, the presence of the drug abrogated the activation of this protease induced by the virus infection. Lauryl gallate is a powerful antiviral agent against several pathogens of clinical and veterinary importance. The overall results indicate that a cellular factor or function might be the target of the antiviral action of alkyl gallates.

  18. RNase and DNase activities of antiviral proteins from leaves of Bougainvillea xbuttiana.

    Science.gov (United States)

    Bhatia, Shikha; Lodha, M L

    2005-06-01

    Antiviral proteins (AVPs) purified from the leaves of Bougainvillea xbuttiana cv Mahara exhibited RNase activity against viral RNA of the tobamoviruses, Tobacco mosaic virus (TMV) and Sunnhemp rosette virus (SRV). They caused complete degradation of viral RNAs in a concentration-dependent manner. RNase activity gel assay ruled out the possibility of the presence of contaminating nucleases. AVPs also showed DNase activity, as indicated by conversion of supercoiled form of plasmid DNA into relaxed and linear forms. The implications of these activities in controlling plant viruses are discussed.

  19. Antiviral activity of a Bacillus sp: P34 peptide against pathogenic viruses of domestic animals

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    Débora Scopel e Silva

    2014-09-01

    Full Text Available P34 is an antimicrobial peptide produced by a Bacillus sp. strain isolated from the intestinal contents of a fish in the Brazilian Amazon basin with reported antibacterial activity. The aim of this work was to evaluate the peptide P34 for its in vitro antiviral properties against canine adenovirus type 2 (CAV-2, canine coronavirus (CCoV, canine distemper virus (CDV, canine parvovirus type 2 (CPV-2, equine arteritis virus (EAV, equine influenza virus (EIV, feline calicivirus (FCV and feline herpesvirus type 1 (FHV-1. The results showed that the peptide P34 exhibited antiviral activity against EAV and FHV-1. The peptide P34 inhibited the replication of EAV by 99.9% and FHV-1 by 94.4%. Virucidal activity was detected only against EAV. When P34 and EAV were incubated for 6 h at 37 °C the viral titer reduced from 10(4.5 TCID50 to 10(2.75 TCID50, showing a percent of inhibition of 98.6%. In conclusion, our results demonstrated that P34 inhibited EAV and FHV-1 replication in infected cell cultures and it showed virucidal activity against EAV. Since there is documented resistance to the current drugs used against herpesviruses and there is no treatment for equine viral arteritis, it is advisable to search for new antiviral compounds to overcome these infections.

  20. A 2,5-Dihydroxybenzoic Acid–Gelatin Conjugate: The Synthesis, Antiviral Activity and Mechanism of Antiviral Action Against Two Alphaherpesviruses

    Science.gov (United States)

    Lisov, Alexander; Vrublevskaya, Veronika; Lisova, Zoy; Leontievsky, Alexey; Morenkov, Oleg

    2015-01-01

    Various natural and synthetic polyanionic polymers with different chemical structures are known to exhibit potent antiviral activity in vitro toward a variety of enveloped viruses and may be considered as promising therapeutic agents. A water-soluble conjugate of 2,5-dihydroxybezoic acid (2,5-DHBA) with gelatin was synthesized by laccase-catalyzed oxidation of 2,5-DHBA in the presence of gelatin, and its antiviral activity against pseudorabies virus (PRV) and bovine herpesvirus type 1 (BoHV-1), two members of the Alphaherpesvirinae subfamily, was studied. The conjugate produced no direct cytotoxic effect on cells, and did not inhibit cell growth at concentrations up to 1000 µg/mL. It exhibited potent antiviral activity against PRV (IC50, 1.5–15 µg/mL for different virus strains) and BoHV-1 (IC50, 0.5–0.7 µg/mL). When present during virus adsorption, the conjugate strongly inhibited the attachment of PRV and BoHV-1 to cells. The 2,5-DHBA–gelatin conjugate had no direct virucidal effect on the viruses and did not influence their penetration into cells, cell-to-cell spread, production of infectious virus particles in cells, and expression of PRV glycoproteins E and B. The results indicated that the 2,5-DHBA–gelatin conjugate strongly inhibits the adsorption of alphaherpesviruses to cells and can be a promising synthetic polymer for the development of antiviral formulations against alphaherpesvirus infections. PMID:26501311

  1. A 2,5-Dihydroxybenzoic Acid–Gelatin Conjugate: The Synthesis, Antiviral Activity and Mechanism of Antiviral Action Against Two Alphaherpesviruses

    Directory of Open Access Journals (Sweden)

    Alexander Lisov

    2015-10-01

    Full Text Available Various natural and synthetic polyanionic polymers with different chemical structures are known to exhibit potent antiviral activity in vitro toward a variety of enveloped viruses and may be considered as promising therapeutic agents. A water-soluble conjugate of 2,5-dihydroxybezoic acid (2,5-DHBA with gelatin was synthesized by laccase-catalyzed oxidation of 2,5-DHBA in the presence of gelatin, and its antiviral activity against pseudorabies virus (PRV and bovine herpesvirus type 1 (BoHV-1, two members of the Alphaherpesvirinae subfamily, was studied. The conjugate produced no direct cytotoxic effect on cells, and did not inhibit cell growth at concentrations up to 1000 µg/mL. It exhibited potent antiviral activity against PRV (IC50, 1.5–15 µg/mL for different virus strains and BoHV-1 (IC50, 0.5–0.7 µg/mL. When present during virus adsorption, the conjugate strongly inhibited the attachment of PRV and BoHV-1 to cells. The 2,5-DHBA–gelatin conjugate had no direct virucidal effect on the viruses and did not influence their penetration into cells, cell-to-cell spread, production of infectious virus particles in cells, and expression of PRV glycoproteins E and B. The results indicated that the 2,5-DHBA–gelatin conjugate strongly inhibits the adsorption of alphaherpesviruses to cells and can be a promising synthetic polymer for the development of antiviral formulations against alphaherpesvirus infections.

  2. Design, Synthesis and Antiviral Activity Studies of Schizonepetin Derivatives

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    Anwei Ding

    2013-08-01

    Full Text Available A series of schizonepetin derivatives have been designed and synthesized in order to obtain potent antivirus agents. The antiviral activity against HSV-1 and influenza virus H3N2 as well as the cytotoxicity of these derivatives was evaluated by using cytopathic effect (CPE inhibition assay in vitro. Compounds M2, M4, M5 and M34 showed higher inhibitory activity against HSV-1 virus with the TC50 values being in micromole. Compounds M28, M33, and M35 showed higher inhibitory activity against influenza virus H3N2 with their TC50 values being 96.4, 71.0 and 75.4 μM, respectively. Preliminary biological activity evaluation indicated that the anti-H3N2 and anti-HSV-1 activities improved obviously through the introduction of halogen into the structure of schizonepetin.

  3. Epimedium koreanum Nakai Displays Broad Spectrum of Antiviral Activity in Vitro and in Vivo by Inducing Cellular Antiviral State

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    Won-Kyung Cho

    2015-01-01

    Full Text Available Epimedium koreanum Nakai has been extensively used in traditional Korean and Chinese medicine to treat a variety of diseases. Despite the plant’s known immune modulatory potential and chemical make-up, scientific information on its antiviral properties and mode of action have not been completely investigated. In this study, the broad antiviral spectrum and mode of action of an aqueous extract from Epimedium koreanum Nakai was evaluated in vitro, and moreover, the protective effect against divergent influenza A subtypes was determined in BALB/c mice. An effective dose of Epimedium koreanum Nakai markedly reduced the replication of Influenza A Virus (PR8, Vesicular Stomatitis Virus (VSV, Herpes Simplex Virus (HSV and Newcastle Disease Virus (NDV in RAW264.7 and HEK293T cells. Mechanically, we found that an aqueous extract from Epimedium koreanum Nakai induced the secretion of type I IFN and pro-inflammatory cytokines and the subsequent stimulation of the antiviral state in cells. Among various components present in the extract, quercetin was confirmed to have striking antiviral properties. The oral administration of Epimedium koreanum Nakai exhibited preventive effects on BALB/c mice against lethal doses of highly pathogenic influenza A subtypes (H1N1, H5N2, H7N3 and H9N2. Therefore, an extract of Epimedium koreanum Nakai and its components play roles as immunomodulators in the innate immune response, and may be potential candidates for prophylactic or therapeutic treatments against diverse viruses in animal and humans.

  4. NICTABA and UDA, two GlcNAc-binding lectins with unique antiviral activity profiles.

    Science.gov (United States)

    Gordts, Stephanie C; Renders, Marleen; Férir, Geoffrey; Huskens, Dana; Van Damme, Els J M; Peumans, Willy; Balzarini, Jan; Schols, Dominique

    2015-01-01

    This study aimed to assess the antiviral properties of a unique lectin (NICTABA) produced by the tobacco plant, Nicotiana tabacum. Cellular assays were used to investigate the antiviral activity of NICTABA and Urtica dioica agglutinin (UDA). Surface plasmon resonance (SPR) studies were performed to study the sugar specificity and the interactions of both lectins with the envelope glycoproteins of HIV-1. The N-acetyl-d-glucosamine (GlcNAc)-binding lectins exhibited broad-spectrum activity against several families of enveloped viruses including influenza A/B, Dengue virus type 2, herpes simplex virus types 1 and 2 and HIV-1/2. The IC50 of NICTABA for various HIV-1 strains, clinical isolates and HIV-2 assessed in PBMCs ranged from 5 to 30 nM. Furthermore, NICTABA inhibited syncytium formation between persistently HIV-1-infected T cells and uninfected CD4+ T lymphocytes and prevented DC-SIGN-mediated HIV-1 transmission to CD4+ target T lymphocytes. However, unlike many other antiviral carbohydrate-binding agents (CBAs) described so far, NICTABA did not block HIV-1 capture to DC-SIGN+ cells and it did not interfere with the binding of the human monoclonal antibody 2G12 to gp120. SPR studies with HIV-1 envelope glycoproteins showed that the affinity of NICTABA for gp120 and gp41 was in the low nanomolar range. The specific binding of NICTABA to gp120 could be prevented in the presence of a GlcNAc trimer, but not in the presence of mannose trimers. NICTABA displayed no antiviral activity against non-enveloped viruses. Since CBAs possess a high genetic barrier for the development of viral resistance and NICTABA shows a broad antiviral activity profile, this CBA may qualify as a potential antiviral candidate with a pleiotropic mode of action aimed at targeting the entry of enveloped viruses. © The Author 2015. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  5. Engineering a Therapeutic Lectin by Uncoupling Mitogenicity from Antiviral Activity

    Science.gov (United States)

    Swanson, Michael D.; Boudreaux, Daniel M.; Salmon, Loïc; Chugh, Jeetender; Winter, Harry C.; Meagher, Jennifer L.; André, Sabine; Murphy, Paul V.; Oscarson, Stefan; Roy, René; King, Steven; Kaplan, Mark H.; Goldstein, Irwin J.; Tarbet, E. Bart; Hurst, Brett L.; Smee, Donald F.; de la Fuente, Cynthia; Hoffmann, Hans-Heinrich; Xue, Yi; Rice, Charles M.; Schols, Dominique; Garcia, J. Victor; Stuckey, Jeanne A.; Gabius, Hans-Joachim; Al-Hashimi, Hashim M.; Markovitz, David M.

    2015-01-01

    Summary A key effector route of the Sugar Code involves lectins that exert crucial regulatory controls by targeting distinct cellular glycans. We demonstrate that a single amino acid substitution in a banana lectin, replacing histidine 84 with a threonine, significantly reduces its mitogenicity while preserving its broad-spectrum antiviral potency. X-ray crystallography, NMR spectroscopy, and glycocluster assays reveal that loss of mitogenicity is strongly correlated with loss of pi-pi stacking between aromatic amino acids H84 and Y83, which removes a wall separating two carbohydrate binding sites, thus diminishing multivalent interactions. On the other hand, monovalent interactions and antiviral activity are preserved by retaining other wild-type conformational features and possibly through unique contacts involving the T84 side chain. Through such fine-tuning, target selection and downstream effects of a lectin can be modulated so as to knock down one activity while preserving another, thus providing tools for therapeutics and for understanding the Sugar Code. PMID:26496612

  6. SYNTHESIS AND ANTIVIRAL ACTIVITY OF NEW THIAZOLE, 1,2,4-TRIAZOL AND OXINDOLE DERIVATIVES

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    Oleg Radul

    2011-06-01

    Full Text Available The synthesis and antiviral activity evaluation of new derivatives of 2-aminothiazole, 1,2,4-triazole, as well as oxindoles has been realized. The synthesized compounds exhibited different cytotoxicity, in particular, oxindols 4 , 5 , 7 , 8 , 9, 10, 11, 12, 13, 58 as well as thiazole/triazole 73 and 75 turned out to be the most cytotoxic for MT-4 cell lines. The compounds 11, 12, 73, and 75 are more toxic than reference compound Efavirenz. As far as the antiviral activity is concerned, none of the title compounds turned out active against Reo-1, Sb-1, VSV, RSV, YFV and VV viruses. The results obtained against Bovine Viral Diarrhoea Virus (BVDV showed that nine compounds (six from oxindol’s seria 6, 12, 13, 52, 56, 58 and three 73, 75, 77 of triazole homologues resulted moderate active. Among all of them, the most potent compound was 52, with EC50 of 6.6 μM. Studies of effect of synthesized compounds against Coxsakie Virus (CVB-2 revealed that only two compounds, 13 and 73 exhibit moderate activity (EC50 >40 and >18 μM, respectively. It should be noticed that eleven compounds, 4, 5, 7, 8, 9, 10, 11, 12, 13, 58, and 75 showed moderate activity against HIV-1 (EC50 >16 – m >59μM.

  7. Antiviral activity of four types of bioflavonoid against dengue virus type-2

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    Zandi Keivan

    2011-12-01

    Full Text Available Abstract Background Dengue is a major mosquito-borne disease currently with no effective antiviral or vaccine available. Effort to find antivirals for it has focused on bioflavonoids, a plant-derived polyphenolic compounds with many potential health benefits. In the present study, antiviral activity of four types of bioflavonoid against dengue virus type -2 (DENV-2 in Vero cell was evaluated. Anti-dengue activity of these compounds was determined at different stages of DENV-2 infection and replication cycle. DENV replication was measured by Foci Forming Unit Reduction Assay (FFURA and quantitative RT-PCR. Selectivity Index value (SI was determined as the ratio of cytotoxic concentration 50 (CC50 to inhibitory concentration 50 (IC50 for each compound. Results The half maximal inhibitory concentration (IC50 of quercetin against dengue virus was 35.7 μg mL-1 when it was used after virus adsorption to the cells. The IC50 decreased to 28.9 μg mL-1 when the cells were treated continuously for 5 h before virus infection and up to 4 days post-infection. The SI values for quercetin were 7.07 and 8.74 μg mL-1, respectively, the highest compared to all bioflavonoids studied. Naringin only exhibited anti-adsorption effects against DENV-2 with IC50 = 168.2 μg mL-1 and its related SI was 1.3. Daidzein showed a weak anti-dengue activity with IC50 = 142.6 μg mL-1 when the DENV-2 infected cells were treated after virus adsorption. The SI value for this compound was 1.03. Hesperetin did not exhibit any antiviral activity against DENV-2. The findings obtained from Foci Forming Unit Reduction Assay (FFURA were corroborated by findings of the qRT-PCR assays. Quercetin and daidzein (50 μg mL-1 reduced DENV-2 RNA levels by 67% and 25%, respectively. There was no significant inhibition of DENV-2 RNA levels with naringin and hesperetin. Conclusion Results from the study suggest that only quercetin demonstrated significant anti-DENV-2 inhibitory activities. Other

  8. In-vitro antiviral activity of Solanum nigrum against Hepatitis C Virus

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    Rehman Sidra

    2011-01-01

    Full Text Available Abstract Background Hepatitis C is a major health problem causes liver cirrhosis, hepatocellular carcinoma and death. The current treatment of standard interferon in combination with ribavirin, has limited benefits due to emergence of resistant mutations during long-term treatment, adverse side effects and high cost. Hence, there is a need for the development of more effective, less toxic antiviral agents. Results The present study was designed to search anti-HCV plants from different areas of Pakistan. Ten medicinal plants were collected and tested for anti-HCV activity by infecting the liver cells with HCV 3a innoculum. Methanol and chloroform extracts of Solanum nigrum (SN seeds exhibited 37% and more than 50% inhibition of HCV respectively at non toxic concentration. Moreover, antiviral effect of SN seeds extract was also analyzed against HCV NS3 protease by transfecting HCV NS3 protease plasmid into liver cells. The results demonstrated that chloroform extract of SN decreased the expression or function of HCV NS3 protease in a dose- dependent manner and GAPDH remained constant. Conclusion These results suggest that SN extract contains potential antiviral agents against HCV and combination of SN extract with interferon will be better option to treat chronic HCV.

  9. Evaluation ofin vitro antiviral activity ofVitex Negundo L., Hyptis suaveolens (L poit., Decalepis hamiltonii Wight & Arn., to Chikungunya virus

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    Sangeetha Kothandan

    2014-02-01

    Full Text Available Objective: To screen the three Indian plants for the antiviral activity to chikungunya virus since chikungunya infections are treated symptomatically without specific drugs till date. Methods: In vitro cytotoxicity assay of the lyophilised extracts was assessed in vero cells for the determination of maximum non toxic concentration and in vitro antiviral assay was evaluated by the inhibition of virus induced cytopathic effect. Results: Aqueous and aqueous ethanolic extracts of Hyptis suaveolens exhibited partial inhibition to Asian strain of chikungunya virus. Conclusion: Of all the three plants tested for antiviral activity to both the lineages of chikungunya virus, Hyptis suaveolens were found to be effective to Asian strain of chikungunya virus.

  10. Structure-Activity Relationships of Acyclic Selenopurine Nucleosides as Antiviral Agents

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    Pramod K. Sahu

    2017-07-01

    Full Text Available A series of acyclic selenopurine nucleosides 3a–f and 4a–g were synthesized based on the bioisosteric rationale between oxygen and selenium, and then evaluated for antiviral activity. Among the compounds tested, seleno-acyclovir (4a exhibited the most potent anti-herpes simplex virus (HSV-1 (EC50 = 1.47 µM and HSV-2 (EC50 = 6.34 µM activities without cytotoxicity up to 100 µM, while 2,6-diaminopurine derivatives 4e–g exhibited significant anti-human cytomegalovirus (HCMV activity, which is slightly more potent than the guanine derivative 4d, indicating that they might act as prodrugs of seleno-ganciclovir (4d.

  11. In vitro evaluation of antiviral and virucidal activity of a high molecular weight hyaluronic acid

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    Blasi Elisabetta

    2011-03-01

    Full Text Available Abstract Background hyaluronic acid (HA, a non-sulphated glycosaminoglycan, is present in synovial fluid, vitreous humour serum and many connective tissues. Pharmaceutical preparations of HA are used in clinical practice for wound healing, joint pain, kerato-conjunctivitis, asthma, mouth care, oesophageal-reflux, and gastritis. Moreover, it is used as a filler to counteract ageing and facial lipoatrophy. Our study aims at investigating the in vitro antiviral activity of a high molecular weight HA. Methods the MTT test was used to rule out the potential toxic effects of HA on the different cell lines used in the antiviral assays. The antiviral activity of HA against Coxsackievirus B5, Herpes Simplex Virus-1, Mumps Virus, Adenovirus-5, Influenza Virus A/H1N1, Human Herpesvirus-6, Porcine Parvovirus, Porcine Reproductive and Respiratory Syndrome Virus was assessed by virus yield assays. Results the most effective inhibition was observed against Coxsackievirus B5, with 3Log reduction of the virus yield at 4 mg/ml, and a reduction of 3.5Log and 2Log, at 2 mg/ml and 1 mg/ml, respectively: the selectivity index was 16. Mumps virus was highly inhibited too showing a reduction of 1.7Log at 1 mg/ml and 1Log at 4 mg/ml and 2 mg/ml (selectivity index = 12. The selectivity index for Influenza Virus was 12 with the highest inhibition (1Log observed at 4 mg/ml. Herpes Simplex Virus-1 and Porcine Parvovirus were mildly inhibited, whereas no antiviral activity was observed with respect to Adenovirus-5, Human Herpesvirus-6, Porcine Reproductive and Respiratory Syndrome Virus. No HA virucidal activity was ever observed against any of the viruses tested. Kinetic experiments showed that both Coxsackievirus B5 and Herpes simplex virus-1 replication were consistently inhibited, not influenced by the time of HA addition, during the virus replication cycle. Conclusions the spectrum of the antiviral activity exhibited by HA against both RNA and DNA viruses, known to have

  12. Weurotoxicologic profile of new adenine substances with antiviral activity

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    D.G. Kovalev

    2010-06-01

    Full Text Available The aim of the research is to study pharmacological properties and to determine safety effect diapason, toxico-logical properties of new adenine substances 9-[2-(4-isopropylphenopxy aethyl] adenine under laboratory code VMA-99-82 which obtains antiviral activity in vitro. the results of the research of neurotoxicologic profile of combination of VMA-99-82 are presented in the work using technique of multistage testing according to «S.lrvin». while performing the research it has been established that safety level of substance VMA-99-82 refers to the class of low toxic combination. the diapason of doses (from 18,7 to 300 mg/kg of substance evident therapeutic effect has been determined. Side-effects are not expressed significantly. therapeutic effect of the combination VMA-99-82 has behavioral reactions. thus the given substance must be further studied for psychotropic effect and its mechanism action

  13. Antiviral activity of Aloe vera against herpes simplex virus type 2: An ...

    African Journals Online (AJOL)

    In this study we tested the antiviral activity of a crude hot glycerine extract of Aloe vera gel which was grown in Bushehr (Southwest of Iran) against HSV-2 replication in Vero cell line. The extract showed antiviral activity against HSV-2 not only before attachment and entry of virus to the Vero cells but also on post attachment ...

  14. In Vitro Evaluation of Antiprotozoal and Antiviral Activities of Extracts from Argentinean Mikania Species

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    Laura C. Laurella

    2012-01-01

    Full Text Available The aim of this study was to investigate the antiprotozoal and antiviral activities of four Argentinean Mikania species. The organic and aqueous extracts of Mikania micrantha, M. parodii, M. periplocifolia, and M. cordifolia were tested on Trypanosoma cruzi epimastigotes, Leishmania braziliensis promastigotes, and dengue virus type 2. The organic extract of M. micrantha was the most active against T. cruzi and L. braziliensis exhibiting a growth inhibition of 77.6±4.5% and 84.9±6.1%, respectively, at a concentration of 10 μg/ml. The bioguided fractionation of M. micrantha organic extract led to the identification of two active fractions. The chromatographic profile and infrared analysis of these fractions revealed the presence of sesquiterpene lactones. None of the tested extracts were active against dengue virus type 2.

  15. VSV infection is sensed by Drosophila, attenuates nutrient signaling, and thereby activates antiviral autophagy.

    Science.gov (United States)

    Cherry, Sara

    2009-10-01

    Innate immune mechanisms are the first line of defense against pathogens including viruses. This work identifies autophagy, an innate intracellular degradative pathway, as antiviral against Vesicular Stomatitis Virus (VSV) in Drosophila. VSV is sensed by cells via the surface glycoprotein leading to the attenuation of the nutrient signaling pathway thereby activating an antiviral autophagic program.

  16. Antiviral activity of human lactoferrin : Inhibition of alphavirus interaction with heparan sulfate

    NARCIS (Netherlands)

    Waarts, Barry-Lee; Aneke, Onwuchekwa J.C.; Smit, Jolanda; Kimata, Koji; Bittman, Robert; Meijer, Dirk K.F.; Wilschut, Jan

    2005-01-01

    Human lactoferrin is a component of the non-specific immune system with distinct antiviral properties. We used alphaviruses, adapted to interaction with heparan sulfate (HS), as a tool to investigate the mechanism of lactoferrin's antiviral activity. Lactoferrin inhibited infection of BHK-21 cells

  17. Salidroside exhibits anti-dengue virus activity by upregulating host innate immune factors.

    Science.gov (United States)

    Sharma, Navita; Mishra, K P; Ganju, Lilly

    2016-12-01

    Dengue is an arboviral disease with no effective therapy available. Therefore, there is an urgent need to find a potent antiviral agent against dengue virus (DENV). In the present study, salidroside, a main bioactive compound of Rhodiola rosea, was evaluated for its antiviral potential against DENV serotype-2 infection and its effect on host innate immune factors. Antiviral effects of salidroside were examined in DENV-infected cells by western blotting, flow cytometry and real-time PCR. Its underlying mechanism involved in antiviral action was determined by evaluating expression of host innate immune factors including RIG-I, IRF-3, IRF-7, PKR, P-eIF2α and NF-κB. Salidroside potently inhibited DENV infection by decreasing DENV envelope protein expression more than tenfold. Salidroside exerts its antiviral activity by increasing expression of RNA helicases such as RIG-I, thereby initiating a downstream signaling cascade that induces upregulation of IRF-3 and IRF-7. It prevents viral protein synthesis by increasing the expression of PKR and P-eIF2α while decreasing NF-κB expression. It was also found to induce the expression of IFN-α. In addition, the number of NK cells and CD8(+) T cells were also found to be increased by salidroside treatment in human PBMCs, which are important in limiting DENV replication during early stages of infection. The findings presented here suggest that salidroside exhibits antiviral activity against DENV by inhibiting viral protein synthesis and boosting host immunity by increasing the expression of host innate immune factors and hence could be considered for the development of an effective therapeutic agent against DENV infection.

  18. Antiviral activity of leaf-bud gum-resin of Tarenna asiatica

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    Vatsavaya Ramabharathi

    2014-08-01

    Full Text Available The leaf-bud exudate of Tarenna asiatica (Rubiaceae: Ixoroideae, Pavetteae is investigated for its biological activity. The crude benzene extract and corymbosin (pure compound isolated were screened for antiviral activity by using ELISA and PCR methods against animal (blue tongue and chikungunya and plant (papaya ring spot, sesbania mosaic and common bean mosaic viruses. Both corymbosin and benzene extract showed significant antiviral activity though corymbosin was found relatively more potent against the animal and plant viruses tested. This is the first report of antiviral activity for the gum-resin of T. asiatica, so also for the compound corymbosin, against the plant viruses.

  19. Design, synthesis, antiviral bioactivity and three-dimensional quantitative structure-activity relationship study of novel ferulic acid ester derivatives containing quinazoline moiety.

    Science.gov (United States)

    Wu, Zengxue; Zhang, Jian; Chen, Jixiang; Pan, Jianke; Zhao, Lei; Liu, Dengyue; Zhang, Awei; Chen, Jin; Hu, Deyu; Song, Baoan

    2017-10-01

    Ferulic acid and quinazoline derivatives possess good antiviral activities. In order to develop novel compounds with high antiviral activities, a series of ferulic acid ester derivatives containing quinazoline were synthesized and evaluated for their antiviral activities. Bioassays indicated that some of the compounds exhibited good antiviral activities in vivo against tobacco mosaic virus (TMV) and cucumber mosaic virus (CMV). One of the compounds demonstrated significant curative and protective activities against TMV and CMV, with EC50 values of 162.14, 114.61 and 255.49, 138.81 mg L-1 , respectively, better than those of ningnanmycin (324.51, 168.84 and 373.88, 272.70 mg L-1 ). The values of q2 and r2 for comparative molecular field analysis and comparative molecular similarity index analysis in the TMV (0.508, 0.663 and 0.992, 0.930) and CMV (0.530, 0.626 and 0.997, 0.981) models presented good predictive abilities. Some of the title compounds demonstrated good antiviral activities. Three-dimensional quantitative structure-activity relationship models revealed that the antiviral activities depend on steric and electrostatic properties. These results could provide significant structural insights for the design of highly active ferulic acid derivatives. © 2017 Society of Chemical Industry. © 2017 Society of Chemical Industry.

  20. Epigenetic reprogramming of the type III interferon response potentiates antiviral activity and suppresses tumor growth.

    Directory of Open Access Journals (Sweden)

    Siyuan Ding

    2014-01-01

    Full Text Available Type III interferon (IFN-λ exhibits potent antiviral activity similar to IFN-α/β, but in contrast to the ubiquitous expression of the IFN-α/β receptor, the IFN-λ receptor is restricted to cells of epithelial origin. Despite the importance of IFN-λ in tissue-specific antiviral immunity, the molecular mechanisms responsible for this confined receptor expression remain elusive. Here, we demonstrate that the histone deacetylase (HDAC repression machinery mediates transcriptional silencing of the unique IFN-λ receptor subunit (IFNLR1 in a cell-type-specific manner. Importantly, HDAC inhibitors elevate receptor expression and restore sensitivity to IFN-λ in previously nonresponsive cells, thereby enhancing protection against viral pathogens. In addition, blocking HDAC activity renders nonresponsive cell types susceptible to the pro-apoptotic activity of IFN-λ, revealing the combination of HDAC inhibitors and IFN-λ to be a potential antitumor strategy. These results demonstrate that the type III IFN response may be therapeutically harnessed by epigenetic rewiring of the IFN-λ receptor expression program.

  1. Identification of a novel multiple kinase inhibitor with potent antiviral activity against influenza virus by reducing viral polymerase activity

    Energy Technology Data Exchange (ETDEWEB)

    Sasaki, Yutaka; Kakisaka, Michinori; Chutiwitoonchai, Nopporn [Viral Infectious Diseases Unit, RIKEN, 2-1 Hirosawa, Wako, Saitama 351-0198 (Japan); Tajima, Shigeru [Department of Virology I, National Institute of Infectious Diseases, 1-23-1 Toyama, Shinjuku, Tokyo 162-8640 (Japan); Hikono, Hirokazu; Saito, Takehiko [Influenza and Prion Disease Research Center, National Institute of Animal Health, National Agriculture and Food Research Organization (NARO), 3-1-5 Kannondai, Tsukuba, Ibaraki 305-0856 (Japan); Aida, Yoko, E-mail: aida@riken.jp [Viral Infectious Diseases Unit, RIKEN, 2-1 Hirosawa, Wako, Saitama 351-0198 (Japan)

    2014-07-18

    Highlights: • Screening of 50,000 compounds and subsequent lead optimization identified WV970. • WV970 has antiviral effects against influenza A, B and highly pathogenic viral strains. • WV970 inhibits viral genome replication and transcription. • A target database search suggests that WV970 may bind to a number of kinases. • KINOMEscan screening revealed that WV970 has inhibitory effects on 15 kinases. - Abstract: Neuraminidase inhibitors are the only currently available influenza treatment, although resistant viruses to these drugs have already been reported. Thus, new antiviral drugs with novel mechanisms of action are urgently required. In this study, we identified a novel antiviral compound, WV970, through cell-based screening of a 50,000 compound library and subsequent lead optimization. This compound exhibited potent antiviral activity with nanomolar IC{sub 50} values against both influenza A and B viruses but not non-influenza RNA viruses. Time-of-addition and indirect immunofluorescence assays indicated that WV970 acted at an early stage of the influenza life cycle, but likely after nuclear entry of viral ribonucleoprotein (vRNP). Further analyses of viral RNA expression and viral polymerase activity indicated that WV970 inhibited vRNP-mediated viral genome replication and transcription. Finally, structure-based virtual screening and comprehensive human kinome screening were used to demonstrate that WV970 acts as a multiple kinase inhibitor, many of which are associated with influenza virus replication. Collectively, these results strongly suggest that WV970 is a promising anti-influenza drug candidate and that several kinases associated with viral replication are promising drug targets.

  2. Matrix Metalloproteinase 9 Exerts Antiviral Activity against Respiratory Syncytial Virus.

    Directory of Open Access Journals (Sweden)

    Abdoulaye J Dabo

    Full Text Available Increased lung levels of matrix metalloproteinase 9 (MMP9 are frequently observed during respiratory syncytial virus (RSV infection and elevated MMP9 concentrations are associated with severe disease. However little is known of the functional role of MMP9 during lung infection with RSV. To determine whether MMP9 exerted direct antiviral potential, active MMP9 was incubated with RSV, which showed that MMP9 directly prevented RSV infectivity to airway epithelial cells. Using knockout mice the effect of the loss of Mmp9 expression was examined during RSV infection to demonstrate MMP9's role in viral clearance and disease progression. Seven days following RSV infection, Mmp9-/- mice displayed substantial weight loss, increased RSV-induced airway hyperresponsiveness (AHR and reduced clearance of RSV from the lungs compared to wild type mice. Although total bronchoalveolar lavage fluid (BALF cell counts were similar in both groups, neutrophil recruitment to the lungs during RSV infection was significantly reduced in Mmp9-/- mice. Reduced neutrophil recruitment coincided with diminished RANTES, IL-1β, SCF, G-CSF expression and p38 phosphorylation. Induction of p38 signaling was required for RANTES and G-CSF expression during RSV infection in airway epithelial cells. Therefore, MMP9 in RSV lung infection significantly enhances neutrophil recruitment, cytokine production and viral clearance while reducing AHR.

  3. Antiviral activities of purified compounds from Youngia japonica (L.) DC (Asteraceae, Compositae).

    Science.gov (United States)

    Ooi, Linda S M; Wang, Hua; He, Zhendan; Ooi, Vincent E C

    2006-06-30

    The ethanol extract of a biannual medicinal herb, Youngia japonica (commonly known as Oriental hawk's beard) was reported previously to have potent antiviral activity against respiratory syncytial virus (RSV) cultured in HEp-2 cells. Three anti-microbial agents, namely 3,4-dicaffeoylquinic acid, 3,5-dicaffeoylquinic acid, and luteolin-7-O-glucoside were subsequently purified and chemically characterized from the ethanol extract of Youngia japonica. The two dicaffeoylquinic acids exhibited prominent anti-RSV with 50% inhibitory concentration (IC50) of 0.5 microg/ml in vitro. Luteolin-7-O-glucoside together with the two dicaffeoylquinic acids were also manifested to have some antibacterial activity towards the causal agents of food-borne disease, namely Vibrio cholerae and Vibrio parahaemolyticus at the concentration of 2mg/ml. Bacillus cereus was sensitive to 3,4-dicaffeoylquinic acid and 3,5-dicaffeoylquinic acid only, but not to luteolin-7-O-glucoside.

  4. Phenolic compounds from Origanum vulgare and their antioxidant and antiviral activities.

    Science.gov (United States)

    Zhang, Xiao-Li; Guo, Yu-Shan; Wang, Chun-Hua; Li, Guo-Qiang; Xu, Jiao-Jiao; Chung, Hau Yin; Ye, Wen-Cai; Li, Yao-Lan; Wang, Guo-Cai

    2014-01-01

    In the present study, six new phenolic compounds (1-6) along with five known ones were isolated from the ethanol extract of the whole plants of Origanum vulgare. The structures of the new compounds were identified on the basis of extensive spectroscopic analyses (UV, IR, NMR, and HRESIMS) and acid hydrolysis. Twenty-one phenolic compounds isolated from O. vulgare in our previous and present studies were evaluated for their in vitro antioxidant activity using 2,2-diphenyl-1-picryhydrazyl (DPPH) radical-scavenging and ferric-reducing antioxidant power (FRAP) assays; twelve of them including two new compounds exhibited significant antioxidant activity comparable to that of ascorbic acid. In addition, the antiviral effects against respiratory syncytial virus (RSV), Coxsackie virus B3 (CVB3) and herpes simplex virus type 1 (HSV-1) were tested by cytopathic effect (CPE) reduction assay. Copyright © 2013 Elsevier Ltd. All rights reserved.

  5. Antiviral activity of leaf-bud gum-resin of Tarenna asiatica

    OpenAIRE

    Vatsavaya Ramabharathi; Divi Venkata Ramana Saigopal; Galla Rajitha

    2014-01-01

    The leaf-bud exudate of Tarenna asiatica (Rubiaceae: Ixoroideae, Pavetteae) is investigated for its biological activity. The crude benzene extract and corymbosin (pure compound isolated) were screened for antiviral activity by using ELISA and PCR methods against animal (blue tongue and chikungunya) and plant (papaya ring spot, sesbania mosaic and common bean mosaic) viruses. Both corymbosin and benzene extract showed significant antiviral activity though corymbosin was found relatively more p...

  6. Antiviral Activity of 4'-thioIDU and Thymidine Analogs against Orthopoxviruses

    Directory of Open Access Journals (Sweden)

    Mark N. Prichard

    2010-09-01

    Full Text Available The search for effective therapies for orthopoxvirus infections has identified diverse classes of molecules with antiviral activity. Pyrimidine analogs, such as 5-iodo-2'-deoxyuridine (idoxuridine, IDU were among the first compounds identified with antiviral activity against a number of orthopoxviruses and have been reported to be active both in vitro and in animal models of infection. More recently, additional analogs have been reported to have improved antiviral activity against orthopoxviruses including several derivatives of deoxyuridine with large substituents in the 5 position, as well as analogs with modifications in the deoxyribose moiety including (north-methanocarbathymidine, and 5-iodo-4'-thio-2'-deoxyuridine (4'-thioIDU. The latter molecule has proven to have good antiviral activity against the orthopoxviruses both in vitro and in vivo and has the potential to be an effective therapy in humans.

  7. In vitro antiviral activity of antimicrobial peptides against herpes simplex virus 1, adenovirus, and rotavirus

    National Research Council Canada - National Science Library

    Carriel-Gomes, Márcia Cristina; Kratz, Jadel Müller; Barracco, Margherita Anna; Bachére, Evelyne; Barardi, Célia Regina Monte; Simões, Cláudia Maria Oliveira

    2007-01-01

    .... This paper describes the in vitro evaluation of the cytotoxicity and antiviral activity of nine peptides with different structures and origins against herpes simplex virus type 1, human adenovirus...

  8. Baicalin, a metabolite of baicalein with antiviral activity against dengue virus

    National Research Council Canada - National Science Library

    Moghaddam, Ehsan; Teoh, Boon-Teong; Sam, Sing-Sin; Lani, Rafidah; Hassandarvish, Pouya; Chik, Zamri; Yueh, Andrew; Abubakar, Sazaly; Zandi, Keivan

    2014-01-01

    .... We previously reported the antiviral activity of baicalein against dengue virus (DENV). Here, we examined the anti-DENV properties of baicalin in vitro, and described the inhibitory potentials of baicalin at different steps of DENV-2...

  9. Antiviral activity and host gene induction by tamarin and marmoset interferon-alpha and interferon-gamma in the GBV-B primary hepatocyte culture model.

    Science.gov (United States)

    Chavez, Deborah; Guerra, Bernadette; Lanford, Robert E

    2009-08-01

    GBV-B induces hepatitis in tamarins and marmosets and is a surrogate model for HCV infections. Here, we cloned and characterized the antiviral activity of tamarin and marmoset interferon (IFN)alpha and IFN gamma. Potent antiviral activity was observed for tamarin and marmoset IFN alpha in primary hepatocyte cultures infected with GBV-B. The antiviral activity was greater in cultures exposed to IFN alpha prior to GBV-B infection, suggesting that either GBV-B was capable of inhibition of the antiviral activity of exogenous IFN alpha or that the preexisting endogenous IFN response to the virus reduced efficacy to exogenous IFN alpha. IFN gamma also exhibited antiviral activity in GBV-B infected hepatocytes. The transcriptional response to IFN alpha in marmoset hepatocytes was characterized using human genome microarrays. Since the GBV-B hepatocyte culture model possesses a functional innate immune response, it will provide opportunities to explore the nature of the antiviral response to a virus closely related to HCV.

  10. Synthesis and Antiviral Activity of 3-Aminoindole Nucleosides of 2-Acetamido-2-deoxy-D-glucose

    Energy Technology Data Exchange (ETDEWEB)

    Abdelrahman, Adel A. H.; Elessawy, Farag A.; Barakat, Yousif A. [Menoufia Univ., Shebin El-Koam (Egypt); Ellatif, Mona M. Abd [The British Univ. in Egypt, Cairo (Egypt)

    2012-10-15

    A new method for the construction of 3-aminoindole nucleosides of 2-acetamido-2-deoxy-D-glucose based is presented. Nitration and acetylation of the indole nucleosides by acetic anhydride-nitric acid mixture followed by reduction using silver catalyst (SNSM) impregnated on silica gel, afforded the corresponding amino indole nucleosides. The nucleosides were tested for antiviral activity against hepatitis B virus (HBV) to show different degrees of antiviral activities or inhibitory actions.

  11. Antiviral activity of bovine uterus and placenta induced by Newcastle disease virus Atividade antiviral do útero e da placenta bovina induzida pelo vírus da doença de Newcastle

    Directory of Open Access Journals (Sweden)

    J.B. Barreto Filho

    2007-06-01

    Full Text Available The antiviral activity profile of the uterus and fetal membranes from bovine placenta, induced by the Newcastle disease virus (NDV throughout gestation, was investigated. Explants of the endometrium and caruncles were collected from the uterus, and amniochorion, allantochorion and cotyledons, from fetal placenta. Tissue cultures were induced with ~6.0 hemagglutinating units (HU of NDV. Supernatants were concentrated 20 fold, filtered in 100kDa cut-off membranes and antiviral activity was titrated in MDBK x VSV system. Tissues of the uterus did not exhibit antiviral activity, while allantochorion and amniochorion produced antiviral factors throughout gestation. Antiviral factors were not related with IFN-alpha, gamma, tau or TNF-alpha. The antiviral activity pattern observed showed to be related with the development of fetal membranes and increased at the end of pregnancy. Such data suggest that IFN genes inducible by virus are present in fetal membranes of the cow placenta and their expression is dependent on the age of gestation.Investigou-se a atividade antiviral do útero e da placenta bovina, ao longo da gestação, induzidos pelo vírus da doença de Newcastle (NDV. Explantes do endométrio e carúnculas foram colhidos do útero. Os tecidos corioamniótico, corioalantóide e cotilédones foram dissecados da placenta fetal. Os cultivos celulares foram induzidos com aproximadamente 6,0 unidades hemaglutinantes do NDV. Os sobrenadantes foram concentrados 20 vezes, filtrados em dispositivos com superfície de separação de 100kDa e a atividade antiviral foi titulada em células MDBK e vírus da estomatite vesicular (VSV. Endométrio, carúnculas e cotilédones não apresentaram atividade antiviral. Corioamniótico e corioalantóide produziram fatores antivirais ao longo da gestação. Estes fatores não foram relacionados aos IFN - alfa, gama ou tau e nem ao TNF - alfa. O padrão de produção de fatores antivirais acompanhou o desenvolvimento

  12. Determination of antioxidant activity, phenolic contents and antiviral ...

    African Journals Online (AJOL)

    extracted by methanol and that the antiviral effect of this genus is due to these secondary metabolites [14,25-27]. Thus, inhibition of HSV-1 replication seen in the present study may probably be due to the action of these secondary metabolites of E. spinidens. CONCLUSION. Based on our results, crude methanol extract of.

  13. Antiviral activity and mechanism of action of arbidol against Hantaan ...

    African Journals Online (AJOL)

    and then further diluted with maintaining medium. Experimental design. The cytotoxicity of arbidol on HUVEC cells was determined by quantitative colorimetric MTT assay as described previously [7]. To investigate .... affecting RIG-I and IFN signaling pathway [8], which implied other antiviral mechanisms of arbidol besides ...

  14. Antiviral and immune stimulant activities of glycyrrhizin against duck ...

    African Journals Online (AJOL)

    This study was conducted to investigate the effect of glycyrrhizin as an immune stimulant against duck hepatitis virus (DHV). In vitro study was carried out to determine cytotoxic and antiviral effects of glycyrrhizin in VERO cells. In vivo study was performed on 40 one-day-old White Pekin ducklings. –and the birds weres ...

  15. Exhibition

    CERN Multimedia

    Staff Association

    2017-01-01

    A Look of Hope Islam Mahmoud Sweity From 19 to 30 June 2017 CERN Meyrin, Main Building Islam Mahmoud Sweity Islam Mahmoud Sweity was born in 1997 at Beit Awwa, Palestine. She is currently following a course to get an Art diploma of Painting at the college of Fine Arts at An-Najah National University under the supervision of Esmat Al As'aad. Her portraits, landscapes and still life paintings are full of life and shining colours. Charged of emotional empathy they catch the attention of the viewer and are reminding us that life is beautiful and worth living in spite of all difficulties we have to go through. She participated in many exhibitions and has exposed her drawings in 2015 at CERN and in France in the framework of the exhibition "The Origin“, and in 2017 in the Former Yugoslav Republic of Macedonia, Palestina and Jordan. In this exhibition the oil paintings made in the past year will be presented. For more information : staff.association@cern.ch | T&eacu...

  16. Antiviral Activity of Graphene–Silver Nanocomposites against Non-Enveloped and Enveloped Viruses

    Directory of Open Access Journals (Sweden)

    Yi-Ning Chen

    2016-04-01

    Full Text Available The discovery of novel antiviral materials is important because many infectious diseases are caused by viruses. Silver nanoparticles have demonstrated strong antiviral activity, and graphene is a potential antimicrobial material due to its large surface area, high carrier mobility, and biocompatibility. No studies on the antiviral activity of nanomaterials on non-enveloped viruses have been reported. To investigate the antiviral activity of graphene oxide (GO sheets and GO sheets with silver particles (GO-Ag against enveloped and non-enveloped viruses, feline coronavirus (FCoV with an envelope and infectious bursal disease virus (IBDV without an envelope were chosen. The morphology and sizes of GO and GO-Ag were characterized by transmission, scanning electron microscopy, and X-ray diffraction. A virus inhibition assay was used to identify the antiviral activity of GO and GO-Ag. Go-Ag inhibited 25% of infection by FCoV and 23% by IBDV, whereas GO only inhibited 16% of infection by FCoV but showed no antiviral activity against the infection by IBDV. Further application of GO and GO-Ag can be considered for personal protection equipment to decrease the transmission of viruses.

  17. Exhibition

    CERN Multimedia

    Staff Association

    2016-01-01

    Encounters Hanne Blitz From February 1st to 12th 2016 CERN Meyrin, Main Building What is our reaction to a first encounter with a tourist attraction? Contemporary Dutch painter Hanne Blitz captures visitors' responses to art and architecture, sweeping vistas and symbolic memorials. Encounters, a series of oil paintings curated specially for this CERN exhibition, depicts tourists visiting cultural highlights around the world. A thought-provoking journey not to be missed, and a tip of the hat to CERN's large Hadron Collider.

  18. Tyrosinase inhibitory components from Aloe vera and their antiviral activity.

    Science.gov (United States)

    Kim, Jang Hoon; Yoon, Ju-Yeon; Yang, Seo Young; Choi, Seung-Kook; Kwon, Sun Jung; Cho, In Sook; Jeong, Min Hee; Ho Kim, Young; Choi, Gug Seoun

    2017-12-01

    A new compound, 9-dihydroxyl-2'-O-(Z)-cinnamoyl-7-methoxy-aloesin (1), and eight known compounds (2-9) were isolated from Aloe vera. Their structures were elucidated using 1D/2D nuclear magnetic resonance and mass spectra. Compound 9 exhibited reversible competitive inhibitory activity against the enzyme tyrosinase, with an IC50 value of 9.8 ± 0.9 µM. A molecular simulation revealed that compound 9 interacts via hydrogen bonding with residues His244, Thr261, and Val283 of tyrosinase. Additionally, compounds 3 and 7 were shown by half-leaf assays to exhibit inhibitory activity towards Pepper mild mottle virus.

  19. Positive selection and increased antiviral activity associated with the PARP-containing isoform of human zinc-finger antiviral protein.

    Directory of Open Access Journals (Sweden)

    Julie A Kerns

    2008-01-01

    Full Text Available Intrinsic immunity relies on specific recognition of viral epitopes to mount a cell-autonomous defense against viral infections. Viral recognition determinants in intrinsic immunity genes are expected to evolve rapidly as host genes adapt to changing viruses, resulting in a signature of adaptive evolution. Zinc-finger antiviral protein (ZAP from rats was discovered to be an intrinsic immunity gene that can restrict murine leukemia virus, and certain alphaviruses and filoviruses. Here, we used an approach combining molecular evolution and cellular infectivity assays to address whether ZAP also acts as a restriction factor in primates, and to pinpoint which protein domains may directly interact with the virus. We find that ZAP has evolved under positive selection throughout primate evolution. Recurrent positive selection is only found in the poly(ADP-ribose polymerase (PARP-like domain present in a longer human ZAP isoform. This PARP-like domain was not present in the previously identified and tested rat ZAP gene. Using infectivity assays, we found that the longer isoform of ZAP that contains the PARP-like domain is a stronger suppressor of murine leukemia virus expression and Semliki forest virus infection. Our study thus finds that human ZAP encodes a potent antiviral activity against alphaviruses. The striking congruence between our evolutionary predictions and cellular infectivity assays strongly validates such a combined approach to study intrinsic immunity genes.

  20. Exhibition

    CERN Multimedia

    Staff Association

    2017-01-01

    Sintropie Flavio Pellegrini From 13 to 24 March 2017 CERN Meyrin, Main Building Energia imprigionata - Flavio Pellegrini. The exhibition is composed by eleven wood artworks with the expression of movement as theme. The artworks are the result of harmonics math applied to sculpture. The powerful black colour is dominated by the light source, generating reflexes and modulations. The result is a continuous variation of perspective visions. The works generate, at a first approach, an emotion of mystery and incomprehension, only a deeper contemplation lets one discover entangling and mutative details, evidencing the elegance of the lines and letting the meaning emerge. For more information : staff.association@cern.ch | Tél: 022 766 37 38

  1. In vitro antiviral activity of plant extracts from Asteraceae medicinal plants

    OpenAIRE

    Visintini Jaime, María Florencia; Redko, Flavia del Carmen; Muschietti, Liliana Victoria; Campos, Rodolfo Hector; Martino, Virginia Susana; Cavallaro, Lucia Vicenta

    2015-01-01

    Due to the high prevalence of viral infections having no specific treatment and the constant appearance of resistant viral strains, the development of novel antiviral agents is essential. The aim of this study was to evaluate the antiviral activity against bovine viral diarrhea virus, herpes simplex virus type 1 (HSV-1), poliovirus type 2 (PV-2) and vesicular stomatitis virus of organic (OE) and aqueous extracts (AE) from: Baccharis gaudichaudiana, B. spicata, Bidens subalternans, Pluchea sag...

  2. In vitro antiviral activity of plant extracts from Asteraceae medicinal plants

    Science.gov (United States)

    2013-01-01

    Background Due to the high prevalence of viral infections having no specific treatment and the constant appearance of resistant viral strains, the development of novel antiviral agents is essential. The aim of this study was to evaluate the antiviral activity against bovine viral diarrhea virus, herpes simplex virus type 1 (HSV-1), poliovirus type 2 (PV-2) and vesicular stomatitis virus of organic (OE) and aqueous extracts (AE) from: Baccharis gaudichaudiana, B. spicata, Bidens subalternans, Pluchea sagittalis, Tagetes minuta and Tessaria absinthioides. A characterization of the antiviral activity of B. gaudichaudiana OE and AE and the bioassay-guided fractionation of the former and isolation of one active compound is also reported. Methods The antiviral activity of the OE and AE of the selected plants was evaluated by reduction of the viral cytopathic effect. Active extracts were then assessed by plaque reduction assays. The antiviral activity of the most active extracts was characterized by evaluating their effect on the pretreatment, the virucidal activity and the effect on the adsorption or post-adsorption period of the viral cycle. The bioassay-guided fractionation of B. gaudichaudiana OE was carried out by column chromatography followed by semipreparative high performance liquid chromatography fractionation of the most active fraction and isolation of an active compound. The antiviral activity of this compound was also evaluated by plaque assay. Results B. gaudichaudiana and B. spicata OE were active against PV-2 and VSV. T. absinthioides OE was only active against PV-2. The corresponding three AE were active against HSV-1. B. gaudichaudiana extracts (OE and AE) were the most selective ones with selectivity index (SI) values of 10.9 (PV-2) and >117 (HSV-1). For this reason, both extracts of B. gaudichaudiana were selected to characterize their antiviral effects. Further bioassay-guided fractionation of B. gaudichaudiana OE led to an active fraction, FC (EC50

  3. Antiviral Activity of Resveratrol against Human and Animal Viruses

    Directory of Open Access Journals (Sweden)

    Yusuf Abba

    2015-01-01

    Full Text Available Resveratrol is a potent polyphenolic compound that is being extensively studied in the amelioration of viral infections both in vitro and in vivo. Its antioxidant effect is mainly elicited through inhibition of important gene pathways like the NF-κβ pathway, while its antiviral effects are associated with inhibitions of viral replication, protein synthesis, gene expression, and nucleic acid synthesis. Although the beneficial roles of resveratrol in several viral diseases have been well documented, a few adverse effects have been reported as well. This review highlights the antiviral mechanisms of resveratrol in human and animal viral infections and how some of these effects are associated with the antioxidant properties of the compound.

  4. In vitro evaluation of marine-microorganism extracts for anti-viral activity

    Directory of Open Access Journals (Sweden)

    Yasuhara-Bell Jarred

    2010-08-01

    Full Text Available Abstract Viral-induced infectious diseases represent a major health threat and their control remains an unachieved goal, due in part to the limited availability of effective anti-viral drugs and measures. The use of natural products in drug manufacturing is an ancient and well-established practice. Marine organisms are known producers of pharmacological and anti-viral agents. In this study, a total of 20 extracts from marine microorganisms were evaluated for their antiviral activity. These extracts were tested against two mammalian viruses, herpes simplex virus (HSV-1 and vesicular stomatitis virus (VSV, using Vero cells as the cell culture system, and two marine virus counterparts, channel catfish virus (CCV and snakehead rhabdovirus (SHRV, in their respective cell cultures (CCO and EPC. Evaluation of these extracts demonstrated that some possess antiviral potential. In sum, extracts 162M(4, 258M(1, 298M(4, 313(2, 331M(2, 367M(1 and 397(1 appear to be effective broad-spectrum antivirals with potential uses as prophylactic agents to prevent infection, as evident by their highly inhibitive effects against both virus types. Extract 313(2 shows the most potential in that it showed significantly high inhibition across all tested viruses. The samples tested in this study were crude extracts; therefore the development of antiviral application of the few potential extracts is dependent on future studies focused on the isolation of the active elements contained in these extracts.

  5. Enteromorpha compressa Exhibits Potent Antioxidant Activity

    Directory of Open Access Journals (Sweden)

    Sanaa M. M. Shanab

    2011-01-01

    Full Text Available The green macroalgae, Enteromorpha compressa (Linnaeus Nees, Ulva lactuca, and E. linza, were seasonally collected from Abu Qir bay at Alexandria (Mediterranean Sea This work aimed to investigate the seasonal environmental conditions, controlling the green algal growth, predominance, or disappearance and determining antioxidant activity. The freshly collected selected alga (E. compressa was subjected to pigment analysis (chlorophyll and carotenoids essential oil and antioxidant enzyme determination (ascorbate oxidase and catalase. The air-dried ground alga was extracted with ethanol (crude extract then sequentially fractionated by organic solvents of increasing polarity (petroleum ether, chloroform, ethyl acetate, and water. Antioxidant activity of all extracts was assayed using different methods (total antioxidant, DPPH [2, 2 diphenyl-1-picrylhydrazyl], ABTS [2, 2 azino-bis ethylbenzthiazoline-6-sulfonic acid], and reducing power, and β-carotene linoleic acid bleaching methods. The results indicated that the antioxidant activity was concentration and time dependent. Ethyl acetate fraction demonstrated higher antioxidant activity against DPPH method (82.80% compared to the synthetic standard butylated hydroxyl toluene (BHT, 88.5%. However, the crude ethanolic extract, pet ether, chloroform fractions recorded lower to moderate antioxidant activities (49.0, 66.0, and 78.0%, resp.. Using chromatographic and spectroscopic analyses, an active compound was separated and identified from the promising ethyl acetate fraction.

  6. Soluble factors with antiviral activity: searching for new therapeutic targets to HIV-1 infection

    Directory of Open Access Journals (Sweden)

    Urquijo Sánchez, Susana

    2015-01-01

    Full Text Available Antiviral innate mechanisms have a potential use in developing preventive and therapeutic strategies against HIV. Specifically, antiviral soluble factors have been evaluated in multiple investigations, based on their capacity to inhibit different steps of the viral cycle, and to increase the host immune response. Among these factors, TRIM-5α, APOBEC3G, SAMHD1, ELAFIN, SERPINA1 and SLPI are of particular interest, as they can act directly on the viral particle or the cell, or promote the production of molecules related to the viral immune response. Some of these factors have been associated with a low risk of HIV infection or slow progression to AIDS. Evaluation of mechanisms exhibited by antiviral proteins is a requirement for developing new therapeutic alternatives.

  7. Antiviral Activity of Natural Products Extracted from Marine Organisms

    Directory of Open Access Journals (Sweden)

    Sobia Tabassum

    2011-11-01

    Full Text Available Many epidemics have broken out over the centuries. Hundreds and thousands of humans have died over a disease. Available treatments for infectious diseases have always been limited. Some infections are more deadly than the others, especially viral pathogens. These pathogens have continuously resisted all kinds of medical treatment, due to a need for new treatments to be developed. Drugs are present in nature and are also synthesized in vitro and they help in combating diseases and restoring health. Synthesizing drugs is a hard and time consuming task, which requires a lot of man power and financial aid. However, the natural compounds are just lying around on the earth, may it be land or water. Over a thousand novel compounds isolated from marine organisms are used as antiviral agents. Others are being pharmacologically tested. Today, over forty antiviral compounds are present in the pharmacological market. Some of these compounds are undergoing clinical and pre-clinical stages. Marine compounds are paving the way for a new trend in modern medicine.

  8. Dimerization of tetherin is not essential for its antiviral activity against Lassa and Marburg viruses.

    Directory of Open Access Journals (Sweden)

    Toshie Sakuma

    Full Text Available Tetherin (also known as BST2, CD317 or HM1.24 has recently been reported to inhibit a wide range of viruses. However, the antiviral mechanism of action of tetherin has not been determined. Both ends of the tetherin molecule are associated with the plasma membrane and it forms a homodimer. Therefore, a model in which progeny virions are retained on the cell surface by dimer formation between tetherin molecules on the viral envelope and plasma membrane has been proposed as the antiviral mechanism of action of this molecule. To investigate this possibility, we examined the correlation between dimerization and antiviral activity of tetherin in Lassa and Marburg virus-like particle production systems using tetherin mutants deficient in dimer formation. However, the tetherin mutant with complete loss of dimerization activity still showed apparent antiviral activity, indicating that dimerization of tetherin is not essential for its antiviral activity. This suggests that tetherin retains progeny virions on the cell surface by a mechanism other than dimerization.

  9. Antiviral activity of the Lippia graveolens (Mexican oregano essential oil and its main compound carvacrol against human and animal viruses

    Directory of Open Access Journals (Sweden)

    Marciele Ribas Pilau

    2011-12-01

    Full Text Available Mexican oregano (Lippia graveolens is a plant found in Mexico and Central America that is traditionally used as a medicinal herb. In the present study, we investigated the antiviral activity of the essential oil of Mexican oregano and its major component, carvacrol, against different human and animal viruses. The MTT test (3-4,5-dimethythiazol-2yl-2,5-diphenyl tetrazolium bromide was conducted to determine the selectivity index (SI of the essential oil, which was equal to 13.1, 7.4, 10.8, 9.7, and 7.2 for acyclovir-resistant herpes simplex virus type 1 (ACVR-HHV-1, acyclovir-sensitive HHV-1, human respiratory syncytial virus (HRSV, bovine herpesvirus type 2 (BoHV-2, and bovine viral diarrhoea virus (BVDV, respectively. The human rotavirus (RV and BoHV-1 and 5 were not inhibited by the essential oil. Carvacrol alone exhibited high antiviral activity against RV with a SI of 33, but it was less efficient than the oil for the other viruses. Thus, Mexican oregano oil and its main component, carvacrol, are able to inhibit different human and animal viruses in vitro. Specifically, the antiviral effects of Mexican oregano oil on ACVR-HHV-1 and HRSV and of carvacrol on RV justify more detailed studies.

  10. Antiviral activity of the dichloromethane extracts from Artocarpus heterophyllus leaves against hepatitis C virus

    OpenAIRE

    Achmad Fuad Hafid; Chie Aoki-Utsubo; Adita Ayu Permanasari; Myrna Adianti; Lydia Tumewu; Aty Widyawaruyanti; Sri Puji Astuti Wahyuningsih; Tutik Sri Wahyuni; Maria Inge Lusida; Soetjipto; Hak Hotta

    2017-01-01

    Objective: To determine anti-viral activities of three Artocarpus species: Artocarpus altilis, Artocarpus camansi, and Artocarpus heterophyllus (A. heterophyllus) against Hepatitis C Virus (HCV). Methods: Antiviral activities of the crude extracts were examined by cell culture method using Huh7it-1 cells and HCV genotype 2a strain JFH1. The mode of action for anti-HCV activities was determined by time-of-addition experiments. The effect on HCV RNA replication and HCV accumulation in cells ...

  11. [Polysuccinimide exhibited antitumor activity in the experiment].

    Science.gov (United States)

    Ostrovskaya, L A; Korman, D B; Varfolomeev, S D; Goldberg, V A; Fomina, M M; Bluhterova, N V; Rikova, V A

    2015-01-01

    Antitumor activity of the novel for oncology compound, such as polysuccinimide, against some of experimental tumor models (Lewis lung carcinoma, Acatol adenocarcinoma, Ca-755 adenocarcinoma) has been established. This drug induced 60-80% tumor growth inhibition of these murine solid tumor strains. Polysuccinimide is also effective (60%) against development of metastatic process in lung (Lewis lung carcinoma). Polysuccinimide causes no changes in pH level in tumor tissue (P-388 leukemia, Acatol adenocarcinoma). This agent may be recommended for further profound preclinical study.

  12. ANTIMICROBIAL, ENTOMOPATHOGENIC AND ANTIVIRAL ACTIVITY OF GAUPSIN BIOPREPARATION CREATED ON THE BASIS OF Pseudomonas chlororaphis STRAINS

    Directory of Open Access Journals (Sweden)

    E. A. Kiprianova

    2017-02-01

    Full Text Available The aim of this review was to present the results of more than ten-year study of gaupsin biopreparation created on the basis of two strains Pseudomonas chlororaphis subsp. aureofaciens UCM В-111 and UCM В-306 with antifungal, entomopathogenic and antiviral activities. Data about antibiotic substances produced by these strains — phenazine and phenylpyrrole derivatives — are presented. Entomocidal properties against the wide spectrum of insect pests have been found out in the strains-producers. Antiviral activity of gaupsin due to the production of thermostable exopolymers containing neutral monosaccharides has been shown using the tobacco mosaic virus as a model. Lipopolysaccharides of the strains В-111 and В-306 also appeared to be highly active antiviral agents. Structure of their O-specific polysaccharides has been established. The last one are structurally heterogenic, presented by linear tri-and tetrasaccharide repeated links and have specific structure that has not been described previously.

  13. Cytotoxic, Virucidal, and Antiviral Activity of South American Plant and Algae Extracts

    Directory of Open Access Journals (Sweden)

    Paula Faral-Tello

    2012-01-01

    Full Text Available Herpes simplex virus type 1 (HSV-1 infection has a prevalence of 70% in the human population. Treatment is based on acyclovir, valacyclovir, and foscarnet, three drugs that share the same mechanism of action and of which resistant strains have been isolated from patients. In this aspect, innovative drug therapies are required. Natural products offer unlimited opportunities for the discovery of antiviral compounds. In this study, 28 extracts corresponding to 24 plant species and 4 alga species were assayed in vitro to detect antiviral activity against HSV-1. Six of the methanolic extracts inactivated viral particles by direct interaction and 14 presented antiviral activity when incubated with cells already infected. Most interesting antiviral activity values obtained are those of Limonium brasiliense, Psidium guajava, and Phyllanthus niruri, which inhibit HSV-1 replication in vitro with 50% effective concentration (EC50 values of 185, 118, and 60 μg/mL, respectively. For these extracts toxicity values were calculated and therefore selectivity indexes (SI obtained. Further characterization of the bioactive components of antiviral plants will pave the way for the discovery of new compounds against HSV-1.

  14. Antiviral Activity and Constituents of the Nepalese Medicinal Plant Astilbe rivularis

    Directory of Open Access Journals (Sweden)

    Meena Rajbhandari

    2011-01-01

    Full Text Available During the screening of Nepalese ethnomedicinal plants for antiviral activities, Astilbe rivularis Buch.-Ham. , Saxifragaceae, was identified as a promising species. Bioassay-guided fractionation led to the isolation of arbutin, bergenin and a bergenin derivative. The structures were established by NMR studies. Except bergenin, the two compounds were found in this plant for the first time. A dimer of bergenin has not been described as a natural product before. The compounds showed in vitro antiviral activity against herpes simplex virus type-1 in non cytotoxic concentrations.

  15. Antiviral activity of Acacia nilotica against Hepatitis C Virus in liver infected cells

    Directory of Open Access Journals (Sweden)

    Javed Tariq

    2011-05-01

    Full Text Available Abstract Hepatitis C virus (HCV belonging to the family Flaviviridae has infected 3% of the population worldwide and 6% of the population in Pakistan. The only recommended standard treatment is pegylated INF-α plus ribavirin. Due to less compatibility of the standard treatment, thirteen medicinal plants were collected from different areas of Pakistan on the basis of undocumented antiviral reports against different viral infections. Medicinal plants were air dried, extracted and screened out against HCV by infecting HCV inoculums of 3a genotype in liver cells. RT-PCR results demonstrate that acetonic and methanolic extract of Acacia nilotica (AN showed more than 50% reduction at non toxic concentration. From the above results, it can be concluded that by selecting different molecular targets, specific structure-activity relationship can be achieved by doing mechanistic analysis. So, additional studies are required for the isolation and recognition of antiviral compound in AN to establish its importance as antiviral drug against HCV. For further research, we will scrutinize the synergistic effect of active antiviral compound in combination with standard PEG INF-α and ribavirin which may be helpful in exploring further gateways for antiviral therapy against HCV.

  16. Structural characterization and antiviral activity of a novel heteropolysaccharide isolated from Grifola frondosa against enterovirus 71.

    Science.gov (United States)

    Zhao, Chao; Gao, Luying; Wang, Chunyang; Liu, Bin; Jin, Yu; Xing, Zheng

    2016-06-25

    A novel heteropolysaccharide from Grifola frondosa mycelia was extracted and purified using DEAE Sephadex A-50 and Sephadex G-200 chromatography. Fourier transform infrared (FT-IR) spectroscopy and nuclear magnetic resonance ((1)H NMR and (13)C NMR) spectroscopy were used to decipher the structure of the purified G. frondosa polysaccharide (GFP1). Chemical and spectral analysis revealed that GFP1, with an average molecular weight of 40.5kDa, possessed a 1,6-β-d-glucan backbone with a single 1,3-α-d-fucopyranosyl side-branching unit. Enterovirus 71 (EV71) is the causative pathogen of hand-foot-and-mouth disease. GFP1 was tested for its anti-EV71 activity in cultured cells, which showed that EV71 viral replication was blocked and viral VP1 protein expression and genomic RNA synthesis were suppressed. Moreover, GFP1 exhibited apoptotic and other activities by suppressing the EV71-induced caspase-3 cleavage and IκBα down regulation. Our results demonstrate that the novel G. frondosa polysaccharide has antiviral activity, which could be valuable as a potentially new anti-EV71 therapeutic compound. Copyright © 2016. Published by Elsevier Ltd.

  17. A mastoparan-derived peptide has broad-spectrum antiviral activity against enveloped viruses.

    Science.gov (United States)

    Sample, Christopher J; Hudak, Kathryn E; Barefoot, Brice E; Koci, Matthew D; Wanyonyi, Moses S; Abraham, Soman; Staats, Herman F; Ramsburg, Elizabeth A

    2013-10-01

    Broad-spectrum antiviral drugs are urgently needed to treat individuals infected with new and re-emerging viruses, or with viruses that have developed resistance to antiviral therapies. Mammalian natural host defense peptides (mNHP) are short, usually cationic, peptides that have direct antimicrobial activity, and which in some instances activate cell-mediated antiviral immune responses. Although mNHP have potent activity in vitro, efficacy trials in vivo of exogenously provided mNHP have been largely disappointing, and no mNHP are currently licensed for human use. Mastoparan is an invertebrate host defense peptide that penetrates lipid bilayers, and we reasoned that a mastoparan analog might interact with the lipid component of virus membranes and thereby reduce infectivity of enveloped viruses. Our objective was to determine whether mastoparan-derived peptide MP7-NH2 could inactivate viruses of multiple types, and whether it could stimulate cell-mediated antiviral activity. We found that MP7-NH2 potently inactivated a range of enveloped viruses. Consistent with our proposed mechanism of action, MP7-NH2 was not efficacious against a non-enveloped virus. Pre-treatment of cells with MP7-NH2 did not reduce the amount of virus recovered after infection, which suggested that the primary mechanism of action in vitro was direct inactivation of virus by MP7-NH2. These results demonstrate for the first time that a mastoparan derivative has broad-spectrum antiviral activity in vitro and suggest that further investigation of the antiviral properties of mastoparan peptides in vivo is warranted. Copyright © 2013 Elsevier Inc. All rights reserved.

  18. Phytochemical screening, cytotoxicity and antiviral activity of hexane fraction of Phaleria macrocarpa fruits

    Science.gov (United States)

    Ismaeel, Mahmud Yusef Yusef; Yaacob, Wan Ahmad; Tahir, Mariya Mohd.; Ibrahim, Nazlina

    2015-09-01

    Phaleria macrocarpa fruits have been widely used in the traditional medicine for the treatment of several infections. The current study was done to determine the phytochemical content, cytotoxicity and antiviral activity of the hexane fraction (HF) of P. macrocarpa fruits. In the hexane fraction of P. macarocarpa fruits, phytochemical screening showed the presence of terpenoids whereas saponins, alkaloids, tannins and anthraquinones were not present. Evaluation on Vero cell lines by using MTT assay showed that the 50% cytotoxic concentration (CC50) value was 0.48 mg/mL indicating that the fraction is not cytotoxic. Antiviral properties of the plant extracts were determined by plaque reduction assay. The effective concentration (EC50) was 0.18 mg/mL. Whereas the selective index (SI = CC50/EC50) of hexane fraction is 2.6 indicating low to moderate potential as antiviral agent.

  19. Cytotoxicity and antiviral activities of Asplenium nidus, Phaleria macrocarpa and Eleusine indica

    Science.gov (United States)

    Tahir, Mariya Mohd; Ibrahim, Nazlina; Yaacob, Wan Ahmad

    2014-09-01

    Three local medicinal plants namely Asplenium nidus (langsuyar), Eleusine indica (sambau) and Phaleria macrocarpa (mahkota dewa) were screened for the cytotoxicity and antiviral activities. Six plant extracts were prepared including the aqueous and methanol extracts from A. nidus leaf and root, aqueous extract from dried whole plant of E. indica and methanol extract from P. macrocarpa fruits. Cytotoxicity screening in Vero cell line by MTT assay showed that the CC50 values ranged from 15 to 60 mg/mL thus indicating the safety of the extracts even at high concentrations. Antiviral properties of the plant extracts were determined by plaque reduction assay. The EC50 concentrations were between 3.2 to 47 mg/mL. The selectivity indices (SI = CC50/EC50) of each tested extracts ranged from 4.3 to 63.25 indicating the usefulness of the extracts as potential antiviral agents.

  20. A systemic resistance inducing antiviral protein with N-glycosidase activity from Bougainvillea xbuttiana leaves.

    Science.gov (United States)

    Narwal, S; Balasubrahmanyam, A; Sadhna, P; Kapoor, H; Lodha, M L

    2001-06-01

    An antiviral protein from Bougainvillea xbuttiana leaves induced systemic resistance in host plants N. glutinosa and Cyamopsis tetragonoloba against TMV and SRV, respectively which was reversed by actinomycin D, when applied immediately or shortly after antiviral protein treatment. When the inhibitor was applied to the host plant leaves post inoculation, it was effective if applied upto 4 h after virus infection. It also delayed the expression of symptoms in systemic hosts of TMV. The inhibitor showed characteristic N-glycosidase activity on 25S rRNA of tobacco ribosomes, suggesting that it could also be interfering with virus multiplication through ribosome-inactivation process.

  1. Coxsackievirus cloverleaf RNA containing a 5' triphosphate triggers an antiviral response via RIG-I activation.

    Directory of Open Access Journals (Sweden)

    Qian Feng

    Full Text Available Upon viral infections, pattern recognition receptors (PRRs recognize pathogen-associated molecular patterns (PAMPs and stimulate an antiviral state associated with the production of type I interferons (IFNs and inflammatory markers. Type I IFNs play crucial roles in innate antiviral responses by inducing expression of interferon-stimulated genes and by activating components of the adaptive immune system. Although pegylated IFNs have been used to treat hepatitis B and C virus infections for decades, they exert substantial side effects that limit their use. Current efforts are directed toward the use of PRR agonists as an alternative approach to elicit host antiviral responses in a manner similar to that achieved in a natural infection. RIG-I is a cytosolic PRR that recognizes 5' triphosphate (5'ppp-containing RNA ligands. Due to its ubiquitous expression profile, induction of the RIG-I pathway provides a promising platform for the development of novel antiviral agents and vaccine adjuvants. In this study, we investigated whether structured RNA elements in the genome of coxsackievirus B3 (CVB3, a picornavirus that is recognized by MDA5 during infection, could activate RIG-I when supplied with 5'ppp. We show here that a 5'ppp-containing cloverleaf (CL RNA structure is a potent RIG-I inducer that elicits an extensive antiviral response that includes induction of classical interferon-stimulated genes, as well as type III IFNs and proinflammatory cytokines and chemokines. In addition, we show that prophylactic treatment with CVB3 CL provides protection against various viral infections including dengue virus, vesicular stomatitis virus and enterovirus 71, demonstrating the antiviral efficacy of this RNA ligand.

  2. Antiviral activity of Dianthus superbusn L. against hepatitis B virus in ...

    African Journals Online (AJOL)

    Antiviral activity of Dianthus superbusn L. against hepatitis B virus in vitro and in vivo. ... Journal Home > Vol 13, No 5 (2016) > ... The PDF file you selected should load here if your Web browser has a PDF reader plug-in installed (for example, ...

  3. Antiviral activity of Petiveria alliacea against the bovine viral diarrhea virus.

    Science.gov (United States)

    Ruffa, M J; Perusina, M; Alfonso, V; Wagner, M L; Suriano, M; Vicente, C; Campos, R; Cavallaro, L

    2002-07-01

    Natural products are a relevant source of antiviral drugs. Five medicinal plants used in Argentina have been assayed to detect inhibition of viral growth. Antiviral activity of the infusions and methanolic extracts of Aristolochia macroura, Celtis spinosa, Plantago major, Schinus areira, Petiveria alliacea and four extracts obtained from the leaves and stems of the last plant were evaluated by the plaque assay. P. alliacea, unlike A. macroura, C. spinosa, P. major and S. areira, inhibited bovine viral diarrhea virus (BVDV) replication. Neither P. alliacea nor the assays of the other plants were active against herpes simplex virus type 1, poliovirus type 1, adenovirus serotype 7 and vesicular stomatitis virus type 1. Four extracts of P. alliacea were assayed to detect anti-BVDV activity. Ethyl acetate (EC(50) of 25 microg/ml) and dichloromethane (EC(50) of 43 microg/ml) extracts were active; moreover, promising SI (IC(50)/EC(50)) values were obtained. BVDV is highly prevalent in the cattle population, there are no antiviral compounds available; additionally, it is a viral model of the hepatitis C virus. For these reasons and in view of the results obtained, the isolation and characterization of the antiviral components present in the P. alliacea extracts is worth carrying out in the future. Copyright 2002 S. Karger AG, Basel

  4. In-ovo evaluation of the antiviral activity of methanolic root-bark ...

    African Journals Online (AJOL)

    User

    2011-05-16

    May 16, 2011 ... root-bark extract of the African Baobab tree (Adansonia digitata Lin) against Newcastle disease virus. One hundred and ... Key words: Ethnoveterinary, African Baobab, antiviral activity, Newcastle disease virus. INTRODUCTION .... water and dimethylsulfoxide (DMSO) extract of the leaf, stem and pulp of A.

  5. Antiviral activity of ovine interferon tau 4 against foot-and-mouth disease virus.

    Science.gov (United States)

    Usharani, Jayaramaiah; Park, Sun Young; Cho, Eun-Ju; Kim, Chungsu; Ko, Young-Joon; Tark, Dongseob; Kim, Su-Mi; Park, Jong-Hyeon; Lee, Kwang-Nyeong; Lee, Myoung-Heon; Lee, Hyang-Sim

    2017-07-01

    Foot-and-mouth disease (FMD) is an economically important disease in most parts of the world and new therapeutic agents are needed to protect the animals before vaccination can trigger the host immune response. Although several interferons have been used for their antiviral activities against Foot-and-mouth disease virus (FMDV), ovine interferon tau 4 (OvIFN-τ4), with a broad-spectrum of action, cross-species antiviral activity, and lower incidence of toxicity in comparison to other type І interferons, has not yet been evaluated for this indication. This is the first study to evaluate the antiviral activity of OvIFN-τ4 against various strains of FMDV. The effective anti-cytopathic concentration of OvIFN-τ4 and its effectiveness pre- and post-infection with FMDV were tested in vitro in LFBK cells. In vivo activity of OvIFN-τ4 was then confirmed in a mouse model of infection. OvIFN-τ4 at a concentration of 500 ng, protected mice until 5days post-FMDV challenge and provided 90% protection for 10 days following FMDV challenge. These results suggest that OvIFN-τ4 could be used as an alternative to other interferons or antiviral agents at the time of FMD outbreak. Copyright © 2017. Published by Elsevier B.V.

  6. In vitro anti-viral activity of aqueous extracts of Kenyan Carissa ...

    African Journals Online (AJOL)

    Vahl (Apocynaceae), Prunus africana (Hook.f.) Kalkm (Rosaceae) and Melia azedarach L. (Meliaceae) have shown significant reduction in the replication of human cytomegalovirus (HCMV) in human embryonic lung (HEL) fibroblasts cells in vitro. Using the plaque inhibition assay for the determination of anti-viral activity, ...

  7. Synthesis and antiviral activity of new dimeric inhibitors against HIV-1

    DEFF Research Database (Denmark)

    Danel, Krzysztof; Larsen, Louise M.; Pedersen, Erik Bjerreg.

    2008-01-01

    This paper describes the synthesis and the antiviral activities of dimeric compounds derived from homo and asymmetric combinations of N-1 propynyloxymethyl analogues 1a,b of MKC-442, an N-1 4-iodobenzyloxymethyl analogue of TNK-651 5, potent contraceptive norgestrel and AZT. They were obtained by...

  8. Antiviral activity of Dianthus superbusn L. against hepatitis B virus in ...

    African Journals Online (AJOL)

    Background: Hepatitis is a viral infection of hepatitis B virus (HBV). Limitations of drug used in the management of it opens the interest related to alternative medicine. The given study deals with the antiviral activity of Dianthus superbusn L. (DSL) against HBV in vitro & in vivo. Material and Methods: In vitro study liver cell line ...

  9. Neuraminidase activity provides a practical read-out for a high throughput influenza antiviral screening assay

    Directory of Open Access Journals (Sweden)

    Wu Meng

    2008-09-01

    Full Text Available Abstract Background The emergence of influenza strains that are resistant to commonly used antivirals has highlighted the need to develop new compounds that target viral gene products or host mechanisms that are essential for effective virus replication. Existing assays to identify potential antiviral compounds often use high throughput screening assays that target specific viral replication steps. To broaden the search for antivirals, cell-based replication assays can be performed, but these are often labor intensive and have limited throughput. Results We have adapted a traditional virus neutralization assay to develop a practical, cell-based, high throughput screening assay. This assay uses viral neuraminidase (NA as a read-out to quantify influenza replication, thereby offering an assay that is both rapid and sensitive. In addition to identification of inhibitors that target either viral or host factors, the assay allows simultaneous evaluation of drug toxicity. Antiviral activity was demonstrated for a number of known influenza inhibitors including amantadine that targets the M2 ion channel, zanamivir that targets NA, ribavirin that targets IMP dehydrogenase, and bis-indolyl maleimide that targets protein kinase A/C. Amantadine-resistant strains were identified by comparing IC50 with that of the wild-type virus. Conclusion Antivirals with specificity for a broad range of targets are easily identified in an accelerated viral inhibition assay that uses NA as a read-out of replication. This assay is suitable for high throughput screening to identify potential antivirals or can be used to identify drug-resistant influenza strains.

  10. Antiviral activities of compounds from aerial parts of Salvia plebeia R. Br.

    Science.gov (United States)

    Bang, Sunghee; Quy Ha, Thi Kim; Lee, Changyeol; Li, Wei; Oh, Won-Keun; Shim, Sang Hee

    2016-11-04

    Salvia plebeia R. Br. is an edible plant widely spread in many countries. It has been used as a traditional medicine to treat common cold, flu, cough, hepatitis, hemorrhoids, etc. The purpose of the study is to explicate antiviral compounds responsible for its traditional use for the common cold or flu. The methanolic extract of the aerial parts of S. plebeia was extracted with CHCl3, EtOAc, and n-BuOH, successively. The EtOAc and CHCl3 fractions were subjected to a successive of chromatographic method, which led to the isolation of fourteen compounds. Inhibition activities of the isolated compounds were evaluated against influenza A (H1N1) neuraminidase. Chemical investigation of the methanolic extracts of S. plebeia resulted in the isolation of two novel benzoylated monoterpene glycosides, named as plebeiosides A (1) and B (2), together with twelve known compounds including four flavonoids (4-5, 7, 10), two sesquiterpenoids (8, 12), four phenolics (9-10, 13-14), a steroid (6), and a triterpenoid (3). Their chemical structures were elucidated based on spectroscopic data and absolute stereochemistries of 1 and 2 were determined by comparison of optical rotations of their hydrolysates with literature values. Compounds 5, 7, 9, and 11 exhibited potent enzymatic inhibition against H1N1 neuraminidase (IC50 values ranging from 11.18±1.73 to 19.83±2.28μM). Furthermore, two flavonoids (5 and 7) and one rosmarinic acid methyl ester (9) reduced cytopathic effects of the H1N1 virus during replication. The antiviral activities of the flavonoids and phenolics isolated from the extracts of S. plebeia supported the traditional application of this medicine on common cold or flu. In this study, benzoylated monoterpene glycosides were first found to exist in this species. Moreover, the present study suggested potential of three compounds (5, 7, and 9) to be new lead structures for the development of new neuraminidase inhibitors in the future. Copyright © 2016 Elsevier Ireland

  11. Cloning and characterization of the antiviral activity of feline Tetherin/BST-2.

    Directory of Open Access Journals (Sweden)

    Aiko Fukuma

    Full Text Available Human Tetherin/BST-2 has recently been identified as a cellular antiviral factor that blocks the release of various enveloped viruses. In this study, we cloned a cDNA fragment encoding a feline homolog of Tetherin/BST-2 and characterized the protein product. The degree of amino acid sequence identity between human Tetherin/BST-2 and the feline homolog was 44.4%. Similar to human Tetherin/BST-2, the expression of feline Tetherin/BST-2 mRNA was inducible by type I interferon (IFN. Exogenous expression of feline Tetherin/BST-2 efficiently inhibited the release of feline endogenous retrovirus RD-114. The extracellular domain of feline Tetherin/BST-2 has two putative N-linked glycosylation sites, N79 and N119. Complete loss of N-linked glycosylation by introduction of mutations into both sites resulted in almost complete abolition of its antiviral activity. In addition, feline Tetherin/BST-2 was insensitive to antagonism by HIV-1 Vpu, although the antiviral activity of human Tetherin/BST-2 was antagonized by HIV-1 Vpu. Our data suggest that feline Tetherin/BST-2 functions as a part of IFN-induced innate immunity against virus infection and that the induction of feline Tetherin/BST-2 in vivo may be effective as a novel antiviral strategy for viral infection.

  12. Biologically active heteroarotinoids exhibiting anticancer activity and decreased toxicity.

    Science.gov (United States)

    Benbrook, D M; Madler, M M; Spruce, L W; Birckbichler, P J; Nelson, E C; Subramanian, S; Weerasekare, G M; Gale, J B; Patterson, M K; Wang, B; Wang, W; Lu, S; Rowland, T C; DiSivestro, P; Lindamood, C; Hill, D L; Berlin, K D

    1997-10-24

    A series of retinoids, containing heteroatoms in a cyclic ring and called heteroarotinoids, were synthesized, and their biological activity was evaluated using tissue culture lines that have measurable responses to trans-retinoic acid (t-RA). Transglutaminase (TGase) was assessed in the human erythroleukemia cell line (GMO6141A) as an indicator of differentiation and apoptosis. Proliferation was evaluated in a human cervical cell line, CC-1, which exhibits dose-dependent alterations in growth rate in response to treatment with trans-retinoic acid. Activation of nuclear retinoic acid receptors was determined in a reporter cell line established from CC-1. The reporter line, called CC-B, contains a reporter gene controlled by a retinoic acid responsive element (RARE) and a thymidine kinase (tk) promoter. Treatment of the CC-B line with the heteroarotinoids resulted in a dose-responsive and retinoid-dependent regulation of reporter gene expression. The heteroarotinoids exhibited activity in all assays and correlated in a statistically significant manner between assays. RARE transactivation activity in CC-B cells correlated with induction of TGase in GMO6141A (R = 0.96) and with a decrease in the growth rate of CC-1 cells (R = -0.90). The ability of the selected heteroarotinoids to induce differentiation, inhibit proliferation, and activate nuclear receptors demonstrates the chemotherapeutic potential of these agents. In view of the biological activity cited, an in vivo toxicity study was conducted on male B6D2F1 mice with three heteroarotinoids, namely 8 [(2E,4E,6E)-3,7-dimethyl-7-(1,2,3,4-tetrahydro-4,4-dimeth ylthiochroman-6-yl)-2,4,6-heptatrienoic acid], 10 [(2E,4E,6E)-3,7-dimethyl-7-(1,2,3,4-tetrahydro-4,4-dimeth ylchroman-6-yl)-2, 4,6-heptatrienoic acid], and 13 [(E)-p-[2-(4,4-dimethylchroman-6-yl)propenyl]benzoic acid]. The mice were used with gavage of heteroarotinoids in corn oil [0.1, 0.2, 0.4, or 0.8 mg/kg] and with 0.01 or 0.05 mg/kg of TTNPB (5) [(E)-4

  13. Molecular characterization and antiviral activity test of common drugs against echovirus 18 isolated in Korea

    Directory of Open Access Journals (Sweden)

    Park KwiSung

    2011-11-01

    Full Text Available Abstract Genetic diversity and antiviral activity for five common antiviral drugs of echovirus (ECV 5 isolated in Korea have been described. The present study extended these tests to a Korean ECV 18 isolate. An outbreak of aseptic meningitis caused by the ECV 18 isolate was reported in Korea in 2005, marking the first time this virus had been identified in the country since enterovirus surveillance began in 1993. Using a sample isolated from stool specimen of a 5-year-old male patient with aseptic meningitis, the complete genome sequence was obtained and was compared it with the Metcalf prototype strain. Unlike the ECV5 isolate, the 3' untranslated region had the highest identity value (94.2% at the nucleotide level, while, at the amino acid level, the P2 region displayed the highest identity value (96.9%. These two strains shared all cleavage sites, with the exception of the 2B/2C site, which was RQ/NN in the Metcalf strain but RQ/NS in the Korean ECV 18 isolate. In Vero cells infected with the Korean ECV 18 isolate, no cytotoxicity was observed in the presence of azidothymidine, acyclovir, amantadine, lamivudine, or ribavirin, when the drugs were administered at a CC50 value >100 μg/mL. Of the five drugs, only amantadine (IC50: 4.97 ± 0.77 μg/mL, TI: 20.12 and ribavirin (IC50: 7.63 ± 0.87 μg/mL, TI: 13.11 had any antiviral activity against the Korean ECV 18 isolate in the five antiviral drugs. These antiviral activity effects were similar with results of the Korean ECV5 isolate.

  14. [Antiviral activity of recombinant interferon-alpha-2b in combination with certain antioxidant].

    Science.gov (United States)

    Vasil'ev, A N; Deriabin, P G; Galegov, G A

    2011-01-01

    In vitro activity of interferon-alpha-2b in combination with various antioxidants against the influenza virus and Herpes simplex was studied. The standard strains and a clinical strain of Herpes simplex isolated from a patient with resistance to acyclovir were used. The in vitro studie showed that antioxidants, such as alpho-tocoferol acetate (vitamin E), Unithiol and ascorbic acid had a significant antiinfluenzae and antiherpetic action on the influenza virus A/H5N1 and Herpes simplex variants. They protected up to 100% of the cell monolayer from the virus cytopathic effect. The taurin solutions had no antiviral activity irrespective of the infection dose. Combinations of interferon-alpha-2b with alpha-tocopherol acetate (vitamin E), Unithiol or ascorbic acid showed a significant synergistic effect: the antiviral activity of interferon increased several times. The antiinfluenza activity of interferon-a-2b in the presence of various concentrations of taurin did not change.

  15. Presentation and exhibition activities for promoting theexportof transport services

    Directory of Open Access Journals (Sweden)

    Darya Vladimirovna Nesterova

    2012-03-01

    Full Text Available Development of presentation and exhibition activities is considered as an important factor in providing new competitive advantages at the strategic markets for exporting of transportation services. A specific role for exhibition activities as a factor to overcome market failures arose from imperfect information and incomplete markets is displayed. Exhibitions are considered as a true reflection of most market parameters, as a means to get correct information concerning market capacity and its borders, as an instrument to access to new markets. At the firm level presentation and branding activities should be considered as a modern technology (especially it concerns Russian companies which provide to hold up already existed markets and to conquer new ones. Presentation and branding activities are an effective technology to promote company trade-mark, competitive advantages for market demand increasing. Comparative analysis of the main exhibitions on transport and logistics issues is fulfilled on the data basecollected by authors. Data observes geographical distribution of transport exhibition and exhibition facilities development at several regions for the last years. The analyses allow to revealing a geographical structure of the exhibitions and its distribution by type of transport. The most promising and economically favorable exhibition areas for the promotion of Russian transport services are shown.

  16. Synthesis and Antiviral Activity of Novel 1,4-Pentadien-3-one Derivatives Containing a 1,3,4-Thiadiazole Moiety

    Directory of Open Access Journals (Sweden)

    Lu Yu

    2017-04-01

    Full Text Available 1,4-Pentadien-3-one derivatives derived from curcumin possess excellent inhibitory activity against plant viruses. On the basis of this finding, a series of novel 1,4-pentadien-3-one derivatives containing a 1,3,4-thiadiazole moiety were designed and synthesized, and their structures confirmed by IR, 1H-NMR, and 13C-NMR spectroscopy and elemental analysis. The antiviral activities of the title compounds were evaluated against tobacco mosaic virus (TMV and cucumber mosaic virus (CMV in vivo. The assay results showed that most of compounds had remarkable antiviral activities against TMV and CMV, among which compounds 4b, 4h, 4i, 4k, 4o, and 4q exhibited good curative, protection, and inactivation activity against TMV. Compounds 4h, 4i, 4k, 4l, 4o, and 4q exhibited excellent protection activity against TMV, with EC50 values of 105.01, 254.77, 135.38, 297.40, 248.18, and 129.87 μg/mL, respectively, which were superior to that of ribavirin (457.25 µg/mL. In addition, preliminary SARs indicated that small electron-withdrawing groups on the aromatic ring were favorable for anti-TMV activity. This finding suggests that 1,4-pentadien-3-one derivatives containing a 1,3,4-thiadiazole moiety may be considered as potential lead structures for discovering new antiviral agents.

  17. Antiviral activity and mechanism of action of arbidol against Hantaan ...

    African Journals Online (AJOL)

    Purpose: To investigate the activity and mechanism of action of arbidol against Hantaan virus (HTNV) activity by modulating inflammation via TLR-4 pathway. Methods: HUVEC cells infected with HTNV 76-118 were treated with serially diluted arbidol solutions at. -2h (2 h before viral infection, pre-treatment mode), 0 h (at the ...

  18. Activation of the Antiviral Kinase PKR and Viral Countermeasures

    Directory of Open Access Journals (Sweden)

    Bianca Dauber

    2009-10-01

    Full Text Available The interferon-induced double-stranded (dsRNA-dependent protein kinase (PKR limits viral replication by an eIF2α-mediated block of translation. Although many negative-strand RNA viruses activate PKR, the responsible RNAs have long remained elusive, as dsRNA, the canonical activator of PKR, has not been detected in cells infected with such viruses. In this review we focus on the activating RNA molecules of different virus families, in particular the negative-strand RNA viruses. We discuss the recently identified non-canonical activators 5’-triphosphate RNA and the vRNP of influenza virus and give an update on strategies of selected RNA and DNA viruses to prevent activation of PKR.

  19. [Adenovirus-mediated canine interferon-gamma expression and its antiviral activity against canine parvovirus].

    Science.gov (United States)

    Zhang, Kao; Jin, Huijun; Zhong, Fei; Li, Xiujin; Neng, Changai; Chen, Huihui; Li, Wenyan; Wen, Jiexia

    2012-11-04

    To construct recombinant adenovirus containing canine interferon-gamma (cIFN-gamma) gene and to investigate its antiviral activity against canine parvovirus in Madin-Darby canine kidney cells (MDCK). [Methods] The cIFN-gamma gene was inserted into adenovirus shuttle plasmid to construct pShuttle3-cIFN-gamma expression vector, from which the cIFN-gamma expression cassette was transferred into the adenovirus genomic plasmid pAdeno-X by specific restriction sites to generate recombinant adenovirus genomic plasmid pAd-cIFN-gamma. The pAd-cIFN-gamma plasmid was linearized by digestion and transfected into human embryonic kidney (HEK) 293T cells to generate the replication-defective cIFN-gamma recombinant adenovirus (Ad-cIFN-gamma). To analyze its anti-canine parvovirus activity, the MDCK cells were pre-infected by Ad-cIFN-gamma recombinant adenovirus, and then infected by canine parvovirus. The antiviral activity of the Ad-cIFN-gamma recombinant adenovirus against parvovirus was analyzed. The recombinant adenovirus containing cIFN-gamma gene was constructed by the ligation method. The recombinant adenovirus could mediates recombinant cIFN-gamma secretory expression in MDCK cells. The Ad-cIFN-gamma recombinant adenovirus could significantly inhibit canine parvovirus replication in MDCK cells pre-infected with the recombinant adenovirus. These results indicate that the Ad-cIFN-gamma recombinant adenovirus has the potent antiviral activity against canine parvovirus. The Ad-cIFN-gamma recombinant adenovirus was successfully constructed by the ligation method and possessed a powerful antiviral activity against canine parvovirus.

  20. Antiviral Activity of Hatay Propolis Against Replication of Herpes Simplex Virus Type 1 and Type 2.

    Science.gov (United States)

    Yildirim, Ayse; Duran, Gulay Gulbol; Duran, Nizami; Jenedi, Kemal; Bolgul, Behiye Sezgin; Miraloglu, Meral; Muz, Mustafa

    2016-02-09

    BACKGROUND Propolis is a bee product widely used in folk medicine and possessing many pharmacological properties. In this study we aimed to investigate: i) the antiviral activities of Hatay propolis samples against HSV-1 and HSV-2 in HEp-2 cell line, and ii) the presence of the synergistic effects of propolis with acyclovir against these viruses. MATERIAL AND METHODS All experiments were carried out in HEp-2 cell cultures. Proliferation assays were performed in 24-well flat bottom microplates. We inoculated 1x105 cells per ml and RPMI 1640 medium with 10% fetal calf serum into each well. Studies to determine cytotoxic effect were performed. To investigate the presence of antiviral activity of propolis samples, different concentrations of propolis (3200, 1600, 800, 400, 200, 100, 75, 50, and 25 μg/mL) were added into the culture medium. The amplifications of HSV-1 and HSV-2 DNA were performed by real-time PCR method. Acyclovir (Sigma, USA) was chosen as a positive control. Cell morphology was evaluated by scanning electron microscopy (SEM). RESULTS The replication of HSV-1 and HSV-2 was significantly suppressed in the presence of 25, 50, and 100 μg/mL of Hatay propolis. We found that propolis began to inhibit HSV-1 replication after 24 h of incubation and propolis activity against HSV-2 was found to start at 48 h following incubation. The activity of propolis against both HSV-1 and HSV-2 was confirmed by a significant decrease in the number of viral copies. CONCLUSIONS We determined that Hatay propolis samples have important antiviral effects compared with acyclovir. In particular, the synergy produced by antiviral activity of propolis and acyclovir combined had a stronger effect against HSV-1 and HSV-2 than acyclovir alone.

  1. Antiviral Activity of Hatay Propolis Against Replication of Herpes Simplex Virus Type 1 and Type 2

    Science.gov (United States)

    Yildirim, Ayse; Duran, Gulay Gulbol; Duran, Nizami; Jenedi, Kemal; Bolgul, Behiye Sezgin; Miraloglu, Meral; Muz, Mustafa

    2016-01-01

    Background Propolis is a bee product widely used in folk medicine and possessing many pharmacological properties. In this study we aimed to investigate: i) the antiviral activities of Hatay propolis samples against HSV-1 and HSV-2 in HEp-2 cell line, and ii) the presence of the synergistic effects of propolis with acyclovir against these viruses. Material/Methods All experiments were carried out in HEp-2 cell cultures. Proliferation assays were performed in 24-well flat bottom microplates. We inoculated 1×105 cells per ml and RPMI 1640 medium with 10% fetal calf serum into each well. Studies to determine cytotoxic effect were performed. To investigate the presence of antiviral activity of propolis samples, different concentrations of propolis (3200, 1600, 800, 400, 200, 100, 75, 50, and 25 μg/mL) were added into the culture medium. The amplifications of HSV-1 and HSV-2 DNA were performed by real-time PCR method. Acyclovir (Sigma, USA) was chosen as a positive control. Cell morphology was evaluated by scanning electron microscopy (SEM). Results The replication of HSV-1 and HSV-2 was significantly suppressed in the presence of 25, 50, and 100 μg/mL of Hatay propolis. We found that propolis began to inhibit HSV-1 replication after 24 h of incubation and propolis activity against HSV-2 was found to start at 48 h following incubation. The activity of propolis against both HSV-1 and HSV-2 was confirmed by a significant decrease in the number of viral copies. Conclusions We determined that Hatay propolis samples have important antiviral effects compared with acyclovir. In particular, the synergy produced by antiviral activity of propolis and acyclovir combined had a stronger effect against HSV-1 and HSV-2 than acyclovir alone. PMID:26856414

  2. Antitumor and Antiviral Activity of Colombian Medicinal Plant Extracts

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    Betancur-Galvis LA

    1999-01-01

    Full Text Available Extracts of nine species of plants traditionally used in Colombia for the treatment of a variety of diseases were tested in vitro for their potential antitumor (cytotoxicity and antiherpetic activity. MTT (Tetrazolium blue and Neutral Red colorimetric assays were used to evaluate the reduction of viability of cell cultures in presence and absence of the extracts. MTT was also used to evaluate the effects of the extracts on the lytic activity of herpes simplex virus type 2 (HSV-2. The 50% cytotoxic concentration (CC50 and the 50% inhibitory concentration of the viral effect (EC50 for each extract were calculated by linear regression analysis. Extracts from Annona muricata, A. cherimolia and Rollinia membranacea, known for their cytotoxicity were used as positive controls. Likewise, acyclovir and heparin were used as positive controls of antiherpetic activity. Methanolic extract from Annona sp. on HEp-2 cells presented a CC50 value at 72 hr of 49.6x103mg/ml. Neither of the other extracts examined showed a significant cytotoxicity. The aqueous extract from Beta vulgaris, the ethanol extract from Callisia grasilis and the methanol extract Annona sp. showed some antiherpetic activity with acceptable therapeutic indexes (the ratio of CC50 to EC50. These species are good candidates for further activity-monitored fractionation to identify active principles.

  3. Antiprotozoan and Antiviral Activities of Non-Cytotoxic Truncated and Variant Analogues of Mussel Defensin

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    Philippe Roch

    2004-01-01

    Full Text Available We previously reported the crucial role displayed by loop 3 of defensin isolated from the Mediterranean mussel, Mytilus galloprovincialis, in antibacterial and antifungal activities. We now investigated antiprotozoan and antiviral activities of some previously reported fragments B, D, E, P and Q. Two fragments (D and P efficiently killed Trypanosoma brucei (ID50 4–12 μM and Leishmania major (ID50 12–45 μM in a time/dose-dependent manner. Killing of T. brucei started as early as 1 h after initiation of contact with fragment D and reached 55% mortality after 6 h. Killing was temperature dependent and a temperature of 4°C efficiently impaired the ability to kill T. brucei. Fragments bound to the entire external epithelium of T. brucei. Prevention of HIV-1 infestation was obtained only with fragments P and Q at 20 μM. Even if fragment P was active on both targets, the specificity of fragments D and Q suggest that antiprotozoan and antiviral activities are mediated by different mechanisms. Truncated sequences of mussel defensin, including amino acid replacement to maintain 3D structure and increased positive net charge, also possess antiprotozoan and antiviral capabilities. New alternative and/or complementary antibiotics can be derived from the vast reservoir of natural antimicrobial peptides (AMPs contained in marine invertebrates.

  4. Antiviral activity of polysaccharide extract from Laminaria japonica against respiratory syncytial virus.

    Science.gov (United States)

    Cao, Yin-Guang; Hao, Yu; Li, Zhi-Hui; Liu, Shun-Tao; Wang, Le-Xin

    2016-12-01

    This study was designed to investigate the inhibition activity of polysaccharide extract from Laminaria japonica against RSV. The polysaccharide from Laminaria japonica was isolated by ethanol precipitation. HEK293 cells were infected with RVS, and the antiviral activity of polysaccharide extract against RSV in host cells was tested. By using ELISA and western blot assay, the expression level of IFN-α and IRF3 and their functional roles in polysaccharide-mediated antiviral activity against RSV were investigated. The polysaccharide extract from Laminaria japonica had low toxicity to HEK293 cell. The TC50 to HEK293 cells was up to 1.76mg/mL. Furthermore, the EC50 of polysaccharide extract to RSV was 5.27μg/mL, and TI was 334. The polysaccharide extract improved IRF-3 expression which promoted the level of IFN-α. Polysaccharide extract from Laminaria japonica elicits antiviral activity against RSV by up-regulation of IRF3 signaling-mediated IFN-α production. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  5. Antiviral activity of the EB peptide against zoonotic poxviruses

    Directory of Open Access Journals (Sweden)

    Altmann Sharon E

    2012-01-01

    Full Text Available Abstract Background The EB peptide is a 20-mer that was previously shown to have broad spectrum in vitro activity against several unrelated viruses, including highly pathogenic avian influenza, herpes simplex virus type I, and vaccinia, the prototypic orthopoxvirus. To expand on this work, we evaluated EB for in vitro activity against the zoonotic orthopoxviruses cowpox and monkeypox and for in vivo activity in mice against vaccinia and cowpox. Findings In yield reduction assays, EB had an EC50 of 26.7 μM against cowpox and 4.4 μM against monkeypox. The EC50 for plaque reduction was 26.3 μM against cowpox and 48.6 μM against monkeypox. A scrambled peptide had no inhibitory activity against either virus. EB inhibited cowpox in vitro by disrupting virus entry, as evidenced by a reduction of the release of virus cores into the cytoplasm. Monkeypox was also inhibited in vitro by EB, but at the attachment stage of infection. EB showed protective activity in mice infected intranasally with vaccinia when co-administered with the virus, but had no effect when administered prophylactically one day prior to infection or therapeutically one day post-infection. EB had no in vivo activity against cowpox in mice. Conclusions While EB did demonstrate some in vivo efficacy against vaccinia in mice, the limited conditions under which it was effective against vaccinia and lack of activity against cowpox suggest EB may be more useful for studying orthopoxvirus entry and attachment in vitro than as a therapeutic against orthopoxviruses in vivo.

  6. Short hairpin RNA targeting 2B gene of coxsackievirus B3 exhibits potential antiviral effects both in vitro and in vivo

    Directory of Open Access Journals (Sweden)

    Yao Hailan

    2012-08-01

    Full Text Available Abstract Background Coxsackievirus B3 is an important infectious agent of viral myocarditis, pancreatitis and aseptic meningitis, but there are no specific antiviral therapeutic reagents in clinical use. RNA interference-based technology has been developed to prevent the viral infection. Methods To evaluate the impact of RNA interference on viral replication, cytopathogenicity and animal survival, short hairpin RNAs targeting the viral 2B region (shRNA-2B expressed by a recombinant vector (pGCL-2B or a recombinant lentivirus (Lenti-2B were tansfected in HeLa cells or transduced in mice infected with CVB3. Results ShRNA-2B exhibited a significant effect on inhibition of viral production in HeLa cells. Furthermore, shRNA-2B improved mouse survival rate, reduced the viral tissues titers and attenuated tissue damage compared with those of the shRNA-NC treated control group. Lenti-2B displayed more effective role in inhibition of viral replication than pGCL-2B in vivo. Conclusions Coxsackievirus B3 2B is an effective target of gene silencing against coxsackievirus B3 infection, suggesting that shRNA-2B is a potential agent for further development into a treatment for enterviral diseases.

  7. A Review on Antibacterial, Antiviral, and Antifungal Activity of Curcumin

    Directory of Open Access Journals (Sweden)

    Soheil Zorofchian Moghadamtousi

    2014-01-01

    Full Text Available Curcuma longa L. (Zingiberaceae family and its polyphenolic compound curcumin have been subjected to a variety of antimicrobial investigations due to extensive traditional uses and low side effects. Antimicrobial activities for curcumin and rhizome extract of C. longa against different bacteria, viruses, fungi, and parasites have been reported. The promising results for antimicrobial activity of curcumin made it a good candidate to enhance the inhibitory effect of existing antimicrobial agents through synergism. Indeed, different investigations have been done to increase the antimicrobial activity of curcumin, including synthesis of different chemical derivatives to increase its water solubility as well ass cell up take of curcumin. This review aims to summarize previous antimicrobial studies of curcumin towards its application in the future studies as a natural antimicrobial agent.

  8. In vitro anti-viral activity of aqueous extracts of Kenyan Carissa ...

    African Journals Online (AJOL)

    kemrilib

    143. In vitro anti-viral activity of aqueous extracts of Kenyan Carissa edulis. Prunus africana and Melia azedarach against human cytomegalovirus. Festus M. Tolo1,7. *. , Geoffrey M.Rukunga 1,7, Faith W. Muli 4, John Ochora 6,7, Yoshito Eizuru2,5, Charles N. Muthaura1, Cecilia W. Kimani1, Geoffrey M Mungai3 and Mawuli ...

  9. Targeting APOBEC3A to the viral nucleoprotein complex confers antiviral activity

    Directory of Open Access Journals (Sweden)

    Strebel Klaus

    2007-08-01

    Full Text Available Abstract Background APOBEC3 (A3 proteins constitute a family of cytidine deaminases that provide intracellular resistance to retrovirus replication and to transposition of endogenous retroelements. A3A has significant homology to the C-terminus of A3G but has only a single cytidine deaminase active site (CDA, unlike A3G, which has a second N-terminal CDA previously found to be important for Vif sensitivity and virus encapsidation. A3A is packaged into HIV-1 virions but, unlike A3G, does not have antiviral properties. Here, we investigated the reason for the lack of A3A antiviral activity. Results Sequence alignment of A3G and A3A revealed significant homology of A3A to the C-terminal region of A3G. However, while A3G co-purified with detergent-resistant viral nucleoprotein complexes (NPC, virus-associated A3A was highly detergent-sensitive leading us to speculate that the ability to assemble into NPC may be a property conveyed by the A3G N-terminus. To test this model, we constructed an A3G-3A chimeric protein, in which the N-terminal half of A3G was fused to A3A. Interestingly, the A3G-3A chimera was packaged into HIV-1 particles and, unlike A3A, associated with the viral NPC. Furthermore, the A3G-3A chimera displayed strong antiviral activity against HIV-1 and was sensitive to inhibition by HIV-1 Vif. Conclusion Our results suggest that the A3G N-terminal domain carries determinants important for targeting the protein to viral NPCs. Transfer of this domain to A3A results in A3A targeting to viral NPCs and confers antiviral activity.

  10. Dufulin activates HrBP1 to produce antiviral responses in tobacco.

    Directory of Open Access Journals (Sweden)

    Zhuo Chen

    Full Text Available BACKGROUND: Dufulin is a new antiviral agent that is highly effective against plant viruses and acts by activating systemic acquired resistance (SAR in plants. In recent years, it has been used widely to prevent and control tobacco and rice viral diseases in China. However, its targets and mechanism of action are still poorly understood. METHODOLOGY/PRINCIPAL FINDINGS: Here, differential in-gel electrophoresis (DIGE and classical two-dimensional electrophoresis (2-DE techniques were combined with mass spectrometry (MS to identify the target of Dufulin. More than 40 proteins were found to be differentially expressed (≥1.5 fold or ≤1.5 fold upon Dufulin treatment in Nicotiana tabacum K(326. Based on annotations in the Gene Ontology (GO and the Kyoto Encyclopedia of Genes and Genomes (KEGG databases, these proteins were found to be related to disease resistance. Directed acyclic graph (DAG analysis of the various pathways demonstrated harpin binding protein-1 (HrBP1 as the target of action of Dufulin. Additionally, western blotting, semi-quantitative reverse transcription polymerase chain reaction (RT-PCR, and real time PCR analyses were also conducted to identify the specific mechanism of action of Dufulin. Our results show that activation of HrBP1 triggers the salicylic acid (SA signaling pathway and thereby produces antiviral responses in the plant host. A protective assay based on lesion counting further confirmed the antiviral activity of Dufulin. CONCLUSION: This study identified HrBP1 as a target protein of Dufulin and that Dufulin can activate the SA signaling pathway to induce host plants to generate antiviral responses.

  11. Dufulin activates HrBP1 to produce antiviral responses in tobacco.

    Science.gov (United States)

    Chen, Zhuo; Zeng, Mengjiao; Song, Baoan; Hou, Chengrui; Hu, Deyu; Li, Xiangyang; Wang, Zhenchao; Fan, Huitao; Bi, Liang; Liu, Jiaju; Yu, Dandan; Jin, Linhong; Yang, Song

    2012-01-01

    Dufulin is a new antiviral agent that is highly effective against plant viruses and acts by activating systemic acquired resistance (SAR) in plants. In recent years, it has been used widely to prevent and control tobacco and rice viral diseases in China. However, its targets and mechanism of action are still poorly understood. Here, differential in-gel electrophoresis (DIGE) and classical two-dimensional electrophoresis (2-DE) techniques were combined with mass spectrometry (MS) to identify the target of Dufulin. More than 40 proteins were found to be differentially expressed (≥1.5 fold or ≤1.5 fold) upon Dufulin treatment in Nicotiana tabacum K(326). Based on annotations in the Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) databases, these proteins were found to be related to disease resistance. Directed acyclic graph (DAG) analysis of the various pathways demonstrated harpin binding protein-1 (HrBP1) as the target of action of Dufulin. Additionally, western blotting, semi-quantitative reverse transcription polymerase chain reaction (RT-PCR), and real time PCR analyses were also conducted to identify the specific mechanism of action of Dufulin. Our results show that activation of HrBP1 triggers the salicylic acid (SA) signaling pathway and thereby produces antiviral responses in the plant host. A protective assay based on lesion counting further confirmed the antiviral activity of Dufulin. This study identified HrBP1 as a target protein of Dufulin and that Dufulin can activate the SA signaling pathway to induce host plants to generate antiviral responses.

  12. Antiviral activity of Ladania067, an extract from wild black currant leaves against influenza A virus in vitro and in vivo.

    Science.gov (United States)

    Haasbach, Emanuel; Hartmayer, Carmen; Hettler, Alice; Sarnecka, Alicja; Wulle, Ulrich; Ehrhardt, Christina; Ludwig, Stephan; Planz, Oliver

    2014-01-01

    Influenza, a respiratory disease caused by influenza viruses, still represents a major threat to humans and several animal species. Besides vaccination, only two classes of drugs are available for antiviral treatment against this pathogen. Thus, there is a strong need for new effective antivirals against influenza viruses. Here, we tested Ladania067, an extract from the leaves of the wild black currant (Ribes nigrum folium) for potential antiviral activity against influenza A virus in vitro and in vivo. In the range of 0-1 mg/ml the extract showed no cytotoxic effect on three cell lines and a CC50 of 0.5 ± 0.3 mg/ml, on peripheral blood mononuclear cells. Furthermore, the extract did not influence the proliferative status of human lymphocytes. In contrast, Ladania067 was highly effective (EC50 value: 49.3 ± 1.1 ng/ml) against the human pandemic influenza virus strain A/Regensburg/D6/09 (H1N1). The extract exhibited an antiviral effect when the virus was pre-incubated prior to infection or when added directly after infection. No antiviral effect was found when infected cells were treated 2, 4, or 8 h after infection, indicating that Ladania067 blocks a very early step in the virus infection cycle. In the mouse infection model we were able to demonstrate that an intranasal application of 500 μg Ladania067 inhibits progeny virus titers in the lung up to 85% after 24 h. We conclude that the extract from the leaves of the wild black currant may be a promising source for the identification of new molecules with antiviral functions against influenza virus.

  13. Determination of antioxidant activity, phenolic contents and antiviral ...

    African Journals Online (AJOL)

    Purpose: This study was aimed to evaluate the antioxidant activity of the methanol extract of Euphorbia spinidens Bornm (Euphorbiaceae) and its effect on Herpes simplex virus type-1 (HSV-1) replication. Methods: The methanol extract of aerial parts of E. spinidens collected from Khorasan State in North- Eastern part of Iran ...

  14. Antiviral and antifungal activity of some dermaseptin S4 analogues

    African Journals Online (AJOL)

    ajl yemi

    2011-10-26

    Oct 26, 2011 ... 14(40): 22-25. Brand GD, Leite JR, Silva LP, Albuquerque S, Prates MV, Azevedo RB,. Carregaro V, Silva JS, Sá VC, Brandão RA, Bloch CJr (2002). Dermaseptins from Phyllomedusa oreades and Phyllomedusa distincta. Anti-trypanosoma cruzi activity without cytotoxicity to mammalian cells. J. Biol. Chem.

  15. Antiviral activity and mechanism of action of arbidol against Hantaan ...

    African Journals Online (AJOL)

    The levels of iNOS and TNF-α were examined using enzyme-linked immunosorbent assay (ELISA). Results: Pre-treatment with arbidol, rather than simultaneous treatment or post-treatment, effectively inhibited up-regulation of cellular TLR4 expression (up to 40 ± 6.1 % inhibition) and activity of supernatant iNOS induced by ...

  16. Antiviral and Antioxidant Activities of Sulfated Galactomannans from Plants of Caatinga Biome

    Directory of Open Access Journals (Sweden)

    Márcia Maria Mendes Marques

    2015-01-01

    Full Text Available Dengue represents a serious social and economic public health problem; then trying to contribute to improve its control, the objective of this research was to develop phytoterapics for dengue treatment using natural resources from Caatinga biome. Galactomannans isolated from Adenanthera pavonina L., Caesalpinia ferrea Mart., and Dimorphandra gardneriana Tull were chemically sulfated in order to evaluate the antioxidant, and antiviral activities and the role in the inhibition of virus DENV-2 in Vero cells. A positive correlation between the degree of sulfation, antioxidant and antiviral activities was observed. The sulfated galactomannans showed binding to the virus surface, indicating that they interact with DENV-2. The sulfated galactomannans from C. ferrea showed 96% inhibition of replication of DENV-2 followed by D. gardneriana (94% and A. pavonina (77% at 25 µg/mL and all sulfated galactomannans also showed antioxidant activity. This work is the first report of the antioxidant and antiviral effects of sulfated galactomannans against DENV-2. The results are very promising and suggest that these sulfated galactomannans from plants of Caatinga biome act in the early step of viral infection. Thus, sulfated galactomannans may act as an entry inhibitor of DENV-2.

  17. Mechanism of TRIM25 Catalytic Activation in the Antiviral RIG-I Pathway

    Directory of Open Access Journals (Sweden)

    Jacint G. Sanchez

    2016-08-01

    Full Text Available Antiviral response pathways induce interferon by higher-order assembly of signaling complexes called signalosomes. Assembly of the RIG-I signalosome is regulated by K63-linked polyubiquitin chains, which are synthesized by the E3 ubiquitin ligase, TRIM25. We have previously shown that the TRIM25 coiled-coil domain is a stable, antiparallel dimer that positions two catalytic RING domains on opposite ends of an elongated rod. We now show that the RING domain is a separate self-association motif that engages ubiquitin-conjugated E2 enzymes as a dimer. RING dimerization is required for catalysis, TRIM25-mediated RIG-I ubiquitination, interferon induction, and antiviral activity. We also provide evidence that RING dimerization and E3 ligase activity are promoted by binding of the TRIM25 SPRY domain to the RIG-I effector domain. These results indicate that TRIM25 actively participates in higher-order assembly of the RIG-I signalosome and helps to fine-tune the efficiency of the RIG-I-mediated antiviral response.

  18. SUMO-interacting motifs of human TRIM5α are important for antiviral activity.

    Directory of Open Access Journals (Sweden)

    Gloria Arriagada

    2011-04-01

    Full Text Available Human TRIM5α potently restricts particular strains of murine leukemia viruses (the so-called N-tropic strains but not others (the B- or NB-tropic strains during early stages of infection. We show that overexpression of SUMO-1 in human 293T cells, but not in mouse MDTF cells, profoundly blocks N-MLV infection. This block is dependent on the tropism of the incoming virus, as neither B-, NB-, nor the mutant R110E of N-MLV CA (a B-tropic switch are affected by SUMO-1 overexpression. The block occurred prior to reverse transcription and could be abrogated by large amounts of restricted virus. Knockdown of TRIM5α in 293T SUMO-1-overexpressing cells resulted in ablation of the SUMO-1 antiviral effects, and this loss of restriction could be restored by expression of a human TRIM5α shRNA-resistant plasmid. Amino acid sequence analysis of human TRIM5α revealed a consensus SUMO conjugation site at the N-terminus and three putative SUMO interacting motifs (SIMs in the B30.2 domain. Mutations of the TRIM5α consensus SUMO conjugation site did not affect the antiviral activity of TRIM5α in any of the cell types tested. Mutation of the SIM consensus sequences, however, abolished TRIM5α antiviral activity against N-MLV. Mutation of lysines at a potential site of SUMOylation in the CA region of the Gag gene reduced the SUMO-1 block and the TRIM5α restriction of N-MLV. Our data suggest a novel aspect of TRIM5α-mediated restriction, in which the presence of intact SIMs in TRIM5α, and also the SUMO conjugation of CA, are required for restriction. We propose that at least a portion of the antiviral activity of TRIM5α is mediated through the binding of its SIMs to SUMO-conjugated CA.

  19. Antiviral Activity of Hederasaponin B from Hedera helix against Enterovirus 71 Subgenotypes C3 and C4a

    National Research Council Canada - National Science Library

    Song, Jaehyoung; Yeo, Sang-Gu; Hong, Eun-Hye; Lee, Bo-Ra; Kim, Jin-Won; Kim, Jeonghoon; Jeong, Hyeongun; Kwon, Yongsoo; Kim, Hyunpyo; Lee, Sangwon; Park, Jae-Hak; Ko, Hyun-Jeong

    2014-01-01

    Enterovirus 71 (EV71) is the predominant cause of hand, foot and mouth disease (HFMD). The antiviral activity of hederasaponin B from Hedera helix against EV71 subgenotypes C3 and C4a was evaluated in vero cells...

  20. Antiviral activities of extracts and phenolic components of two Spondias species against dengue virus

    Directory of Open Access Journals (Sweden)

    Ara Silva

    2011-01-01

    Full Text Available In recent years, the search for natural plant products to fight viral diseases has been increasing. In this work, two Spondias species, namely S. mombin and S. tuberosa, found in Ceará state (Brazil, and their main phenolic components were evaluated against dengue virus. In vitro antiviral tests were performed against type-2 dengue virus by the MTT method and standard cytopathic effect reduction assay in C6/36 cells. Cytotoxicity was also evaluated by MTT. The presence of phenolic compounds quercetin, rutin, and ellagic acid in plant extracts was characterized by HPLC analysis. Both Spondias species extracts and components were nontoxic to the cells whereas rutin and quercetin displayed relevant antiviral activity with IC50 of 362.68 µg/mL and 500 µg/mL, respectively.

  1. Antiviral Activity of HPMPC (Cidofovir) Against ORF Virus Infected Lambs

    Science.gov (United States)

    Scagliarini, A.; McInnes, C.J.; Gallina, L.; Dal, Pozzo F.; Scagliarini, L.; Snoeck, R.; Prosperi, S.; Sales, J.; Gilray, J.A.; Nettleton, P.F.

    2007-01-01

    (S)-9-[3-hydroxy-2-(phosphonomethoxy)propyl]-2,6-diaminopurine (HPMPC, cidofovir, CDV, Vistide®) is an acyclic nucleoside analogue with a potent and selective activity against a broad spectrum of DNA viruses including the poxviruses. In this study we present the results of different treatment regimens in lambs experimentally infected with orf virus with different cidofovir formulations prepared in Beeler basis and Unguentum M. Our results show that choice of excipient, concentration of cidofovir and treatment regimen were all important to the clinical outcome of the therapy. Whilst one particular regimen appeared to exacerbate the lesion, treatment with 1% w/v cidofovir cream, prepared in Beeler Basis, for 4 consecutive days did result in milder lesions that resolved more quickly than untreated lesions. Furthermore the scabs of the treated animals contained significantly lower amounts of viable virus meaning there should be less contamination of the environment with virus than would normally occur. PMID:17049627

  2. Antiviral activity of gliotoxin, gentian violet and brilliant green against Nipah and Hendra virus in vitro

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    Meyer Adam G

    2009-11-01

    Full Text Available Abstract Background Using a recently described monolayer assay amenable to high throughput screening format for the identification of potential Nipah virus and Hendra virus antivirals, we have partially screened a low molecular weight compound library (>8,000 compounds directly against live virus infection and identified twenty eight promising lead molecules. Initial single blind screens were conducted with 10 μM compound in triplicate with a minimum efficacy of 90% required for lead selection. Lead compounds were then further characterised to determine the median efficacy (IC50, cytotoxicity (CC50 and the in vitro therapeutic index in live virus and pseudotype assay formats. Results While a number of leads were identified, the current work describes three commercially available compounds: brilliant green, gentian violet and gliotoxin, identified as having potent antiviral activity against Nipah and Hendra virus. Similar efficacy was observed against pseudotyped Nipah and Hendra virus, vesicular stomatitis virus and human parainfluenza virus type 3 while only gliotoxin inhibited an influenza A virus suggesting a non-specific, broad spectrum activity for this compound. Conclusion All three of these compounds have been used previously for various aspects of anti-bacterial and anti-fungal therapy and the current results suggest that while unsuitable for internal administration, they may be amenable to topical antiviral applications, or as disinfectants and provide excellent positive controls for future studies.

  3. Nutritional and Chemical Composition and Antiviral Activity of Cultivated Seaweed Sargassum naozhouense Tseng et Lu

    Science.gov (United States)

    Peng, Yan; Xie, Enyi; Zheng, Kai; Fredimoses, Mangaladoss; Yang, Xianwen; Zhou, Xuefeng; Wang, Yifei; Yang, Bin; Lin, Xiuping; Liu, Juan; Liu, Yonghong

    2012-01-01

    Sargassum naozhouense is a brown seaweed used in folk medicine and applied for thousands of years in Zhanjiang, Guangdong province, China. This study is the first time to investigate its chemical composition and antiviral activity. On the dry weight basis, this seaweed was constituted of ca. 35.18% ash, 11.20% protein, 1.06% lipid and 47.73% total carbohydrate, and the main carbohydrate was water-soluble polysaccharide. The protein analysis indicated the presence of essential amino acids, which accounted for 36.35% of the protein. The most abundant fatty acids were C14:0, C16:0, C18:1 and C20:4. The ash fraction analysis indicated that essential minerals and trace elements, such as Fe, Zn and Cu, were present in the seaweed. IR analysis revealed that polysaccharides from cultivated S. naozhouense may be alginates and fucoidan. The polysaccharides possessed strong antiviral activity against HSV-1 in vitro with EC50 of 8.92 μg/mL. These results demonstrated cultivated S. naozhouense has a potential for its use in functional foods and antiviral new drugs. PMID:23271422

  4. Broad spectrum antiviral activity of favipiravir (T-705: protection from highly lethal inhalational Rift Valley Fever.

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    Amy L Caroline

    2014-04-01

    Full Text Available BACKGROUND: Development of antiviral drugs that have broad-spectrum activity against a number of viral infections would be of significant benefit. Due to the evolution of resistance to currently licensed antiviral drugs, development of novel anti-influenza drugs is in progress, including Favipiravir (T-705, which is currently in human clinical trials. T-705 displays broad-spectrum in vitro activity against a number of viruses, including Rift Valley Fever virus (RVFV. RVF is an important neglected tropical disease that causes human, agricultural, and economic losses in endemic regions. RVF has the capacity to emerge in new locations and also presents a potential bioterrorism threat. In the current study, the in vivo efficacy of T-705 was evaluated in Wistar-Furth rats infected with the virulent ZH501 strain of RVFV by the aerosol route. METHODOLOGY/PRINCIPAL FINDINGS: Wistar-Furth rats are highly susceptible to a rapidly lethal disease after parenteral or inhalational exposure to the pathogenic ZH501 strain of RVFV. In the current study, two experiments were performed: a dose-determination study and a delayed-treatment study. In both experiments, all untreated control rats succumbed to disease. Out of 72 total rats infected with RVFV and treated with T-705, only 6 succumbed to disease. The remaining 66 rats (92% survived lethal infection with no significant weight loss or fever. The 6 treated rats that succumbed survived significantly longer before succumbing to encephalitic disease. CONCLUSIONS/SIGNIFICANCE: Currently, there are no licensed antiviral drugs for treating RVF. Here, T-705 showed remarkable efficacy in a highly lethal rat model of Rift Valley Fever, even when given up to 48 hours post-infection. This is the first study to show protection of rats infected with the pathogenic ZH501 strain of RVFV. Our data suggest that T-705 has potential to be a broad-spectrum antiviral drug.

  5. beta-Cyclodextrin derivatives as carriers to enhance the antiviral activity of an antisense oligonucleotide directed toward a coronavirus intergenic consensus sequence.

    Science.gov (United States)

    Abdou, S; Collomb, J; Sallas, F; Marsura, A; Finance, C

    1997-01-01

    The ability of cyclodextrins to enhance the antiviral activity of a phosphodiester oligodeoxynucleotide has been investigated. A 18-mer oligodeoxynucleotide complementary to the initiation region of the mRNA coding for the spike protein and containing the intergenic consensus sequence of an enteric coronavirus has been tested for antiviral action against virus growth in human adenocarcinoma cells. The phosphodiester oligodeoxynucleotide only showed a limited effect on virus growth rate (from 12 to 34% viral inhibition in cells treated with 7.5 to 25 microM oligodeoxynucleotide, respectively, at a multiplicity of infection of 0.1 infectious particle per cell). In the same conditions, the phosphorothioate analogue exhibited stronger antiviral activity, the inhibition increased from 56 to 90%. The inhibitory effect of this analogue was antisense and sequence-specific. Northern blot analysis showed that the sequence-dependent mechanism of action appears to be the inhibition of mRNA transcription. We conclude that the coronavirus intergenic consensus sequence is a good target for an antisense oligonucleotide antiviral action. The properties of the phosphodiester oligonucleotide was improved after its complexation with cyclodextrins. The most important increase of the antiviral activity (90% inhibition) was obtained with only 7.5 microM oligonucleotide complexed to a cyclodextrin derivative, 6-deoxy-6-S-beta-D-galactopyranosyl-6-thio-cyclomalto-heptaose+ ++ in a molar ratio of 1:100. These studies suggest that the use of cyclodextrin derivatives as carrier for phosphodiester oligonucleotides delivery may be an effective method for increasing the therapeutic potential of these compounds in viral infections.

  6. The antiviral activity of arctigenin in traditional Chinese medicine on porcine circovirus type 2.

    Science.gov (United States)

    Chen, Jie; Li, Wentao; Jin, Erguang; He, Qigai; Yan, Weidong; Yang, Hanchun; Gong, Shiyu; Guo, Yi; Fu, Shulin; Chen, Xiabing; Ye, Shengqiang; Qian, Yunguo

    2016-06-01

    Arctigenin (ACT) is a phenylpropanoid dibenzylbutyrolactone lignan extracted from the traditional herb Arctium lappa L. (Compositae) with anti-viral and anti-inflammatory effects. Here, we investigated the antiviral activity of ACT found in traditional Chinese medicine on porcine circovirus type 2 (PCV2) in vitro and in vivo. Results showed that dosing of 15.6-62.5μg/mL ACT could significantly inhibit the PCV2 proliferation in PK-15 cells (P<0.01). Dosing of 62.5μg/mL ACT 0, 4 or 8h after challenge inoculation significantly inhibited the proliferation of 1MOI and 10MOI in PK-15 cells (P<0.01), and the inhibitory effect of ACT dosing 4h or 8h post-inoculation was greater than 0h after dosing (P<0.01). In vivo test with mice challenge against PCV2 infection demonstrated that intraperitoneal injection of 200μg/kg ACT significantly inhibited PCV2 proliferation in the lungs, spleens and inguinal lymph nodes, with an effect similar to ribavirin, demonstrating the effectiveness of ACT as an antiviral agent against PCV2 in vitro and in vivo. This compound, therefore, may have the potential to serve as a drug for protection of pigs against the infection of PCV2. Copyright © 2015 Elsevier Ltd. All rights reserved.

  7. The anti-obesity drug orlistat reveals anti-viral activity.

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    Ammer, Elisabeth; Nietzsche, Sandor; Rien, Christian; Kühnl, Alexander; Mader, Theresa; Heller, Regine; Sauerbrei, Andreas; Henke, Andreas

    2015-12-01

    The administration of drugs to inhibit metabolic pathways not only reduces the risk of obesity-induced diseases in humans but may also hamper the replication of different viral pathogens. In order to investigate the value of the US Food and Drug Administration-approved anti-obesity drug orlistat in view of its anti-viral activity against different human-pathogenic viruses, several anti-viral studies, electron microscopy analyses as well as fatty acid uptake experiments were performed. The results indicate that administrations of non-cytotoxic concentrations of orlistat reduced the replication of coxsackievirus B3 (CVB3) in different cell types significantly. Moreover, orlistat revealed cell protective effects and modified the formation of multi-layered structures in CVB3-infected cells, which are necessary for viral replication. Lowering fatty acid uptake from the extracellular environment by phloretin administrations had only marginal impact on CVB3 replication. Finally, orlistat reduced also the replication of varicella-zoster virus moderately but had no significant influence on the replication of influenza A viruses. The data support further experiments into the value of orlistat as an inhibitor of the fatty acid synthase to develop new anti-viral compounds, which are based on the modulation of cellular metabolic pathways.

  8. Cloning, expression and antiviral activity of IFNγ from the Australian fruit bat, Pteropus alecto.

    Science.gov (United States)

    Janardhana, Vijaya; Tachedjian, Mary; Crameri, Gary; Cowled, Chris; Wang, Lin-Fa; Baker, Michelle L

    2012-03-01

    Bats are natural reservoir hosts to a variety of viruses, many of which cause morbidity and mortality in other mammals. Currently there is a paucity of information regarding the nature of the immune response to viral infections in bats, partly due to a lack of appropriate bat specific reagents. IFNγ plays a key role in controlling viral replication and coordinating a response for long term control of viral infection. Here we describe the cloning and expression of IFNγ from the Australian flying fox, Pteropus alecto and the generation of mouse monoclonal and chicken egg yolk antibodies specific to bat IFNγ. Our results demonstrate that P. alecto IFNγ is conserved with IFNγ from other species and is induced in bat splenocytes following stimulation with T cell mitogens. P. alecto IFNγ has antiviral activity on Semliki forest virus in cell lines from P. alecto and the microbat, Tadarida brasiliensis. Additionally recombinant bat IFNγ was able to mitigate Hendra virus infection in P. alecto cells. These results provide the first evidence for an antiviral role for bat IFNγin vitro in addition to the application of important immunological reagents for further studies of bat antiviral immunity. Crown Copyright © 2011. Published by Elsevier Ltd. All rights reserved.

  9. In vitro antiviral activity of Ficus carica latex against caprine herpesvirus-1.

    Science.gov (United States)

    Camero, Michele; Marinaro, Mariarosaria; Lovero, Angela; Elia, Gabriella; Losurdo, Michele; Buonavoglia, Canio; Tempesta, Maria

    2014-01-01

    The latex of Ficus carica Linn. (Moraceae) has been shown to possess antiviral properties against some human viruses. To determine the ability of F. carica latex (F-latex) to interfere with the infection of caprine herpesvirus-1 (CpHV-1) in vitro, F-latex was resuspended in culture media containing 1% ethanol and was tested for potential antiviral effects against CpHV-1. Titration of CpHV-1 in the presence or in the absence of F-latex was performed on monolayers of Madin Darby Bovine Kidney (MDBK) cells. Simultaneous addition of F-latex and CpHV-1 to monolayers of MDBK cells resulted in a significant reduction of CpHV-1 titres 3 days post-infection and this effect was comparable to that induced by acyclovir. The study suggests that the F-latex is able to interfere with the replication of CpHV-1 in vitro on MDBK cells and future studies will determine the mechanisms responsible for the observed antiviral activity.

  10. [Experimental study of antiviral activity of spore-forming bacterium Bacillus pumilus "Pashkov"].

    Science.gov (United States)

    Mikhaĭlova, N A; Nagieva, F G; Grin'ko, O M; Zverev, V V

    2010-01-01

    To study antiviral activity of metabolites of spore-forming strain "Pashkov" of B. pumilus on the model of enterovirus infection in vitro. B. pumilus strain "Pashkov" isolated from environment and identified by common methods. Cell cultures: Vero-6, Vero-ECC, and Vero-E6. Enteroviruses: type 1 poliovirus, Coxsackie B virus (1-6), ECHO-3, and ECHO-6 viruses. Unfectious activity of viruses was evaluated according to their cytopathogenic effect on Vero- E6 cell line by method of serial dilutions. Cultural fluid (CF) for the study was obtained by centrifugation and sterilizing filtration of B. pumilus strain "Pashkov" biomass produced by cultivation during 72 hours on optimized nutrient medium. Cytotoxicity of CF (chronic and acute) and maximal tolerated dose were measured by effect on viability of Vero-E6 cells, which was assessed by trypan blue exclusion test of cell viability. For measurement of antiviral activity (AV-activity), two treatment schedules--therapeutic and prophylactic--were used. The most sensitive cell lines were Vero-ECC and Vero-E6. Assessment of AV-activity showed that protective effect was observed for all dilutions of CF and lasted for 7 days from time of infection by used doses of virus. CF does not have acute and chronic cytotoxicity. CF studied in vitro with Vero-E6 cells infected with 4 types of enteroviruses provided protection against viruses and had prophylactic effect. Degree of effect of CF depended from type of enterovirus, dose used and CF dilution. For the first time effective antiviral activity of CF, which have low cytotoxicity for Vero-E6 cell culture in vitro and is produced by strain "Pashkov" of B. pumilus, was demonstrated. Obtained data open perspectives for development of medications against enterovirus infections.

  11. A Study on in vitro antiviral activities of lyophilized extracts of Glycyrrhiza glabra on Hepatitis B Virus

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    Sangeetha Vani

    2016-06-01

    Full Text Available The present study is to determine the effect of lyophilized extracts of different solvents of Glycyrrhiza glabra on Hepatitis B. The lyophilized plant extracts were collected and studied for its cytotoxicity in HepG2 cell line and in vitro antiviral activity of these extracts was investigated by HBs Ag binding Inhibition Assay, Hepatitis B Virus DNA Polymerase Inhibition Assay using fluorescent probes. The results from Glycyrrhiza glabra were promising in acting as a potent antiviral agent.

  12. Rhodiola rosea Exerts Antiviral Activity in Athletes Following a Competitive Marathon Race.

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    Ahmed, Maryam; Henson, Dru A; Sanderson, Matthew C; Nieman, David C; Zubeldia, Jose M; Shanely, R Andrew

    2015-01-01

    Rhodiola rosea, a medicinal plant with demonstrated adaptogenic properties, has recently been reported to contain active compounds with antimicrobial activity. The goal of this study was to measure the antiviral and antibacterial properties of the bioactive metabolites of Rhodiola rosea in the serum of experienced marathon runners following supplementation. Marathon runners, randomly divided into two groups, ingested 600 mg/day of Rhodiola rosea (n = 24, 6 female, 18 male) or placebo (n = 24, 7 females, 17 males) for 30 days prior to, the day of, and 7 days post-marathon. Blood serum samples were collected the day before, 15 min post-, and 1.5 h post-marathon. Serum from Rhodiola rosea-supplemented runners collected after marathon running did not attenuate the marathon-induced susceptibility of HeLa cells to killing by vesicular stomatitis virus. However, the use of Rhodiola rosea induced antiviral activity at early times post-infection by delaying an exercise-dependent increase in virus replication (P = 0.013 compared to placebo). Serum from both groups collected 15 min post-marathon significantly promoted the growth of Escherichia coli in culture as compared to serum collected the day before the marathon (P = 0.003, all subjects). Furthermore, the serum from subjects ingesting Rhodiola rosea did not display antibacterial properties at any time point as indicated by a lack of group differences immediately (P = 0.785) or 1.5 h (P = 0.633) post-marathon. These results indicate that bioactive compounds in the serum of subjects ingesting Rhodiola rosea may exert protective effects against virus replication following intense and prolonged exercise by inducing antiviral activity.

  13. Rhodiola rosea exerts anti-viral activity in athletes following a competitive marathon race

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    Maryam eAhmed

    2015-07-01

    Full Text Available Rhodiola rosea, a medicinal plant with demonstrated adaptogenic properties, has recently been reported to contain active compounds with antimicrobial activity. The goal of this study was to measure the antiviral and antibacterial properties of the bioactive metabolites of Rhodiola rosea in the serum of experienced marathon runners following supplementation. Marathon runners, randomly divided into two group, ingested 600mg/day of Rhodiola rosea (n=24, 6 female, 18 male or placebo (n=24, 7 female, 17 male for 30 days prior to, the day of, and seven days post-marathon. Blood serum samples were collected the day before, 15 minutes post- and 1.5 hours post-marathon. Serum from Rhodiola rosea supplemented runners collected after marathon running did not attenuate the marathon-induced susceptibility of HeLa cells to killing by vesicular stomatitis virus (VSV. However, the use of Rhodiola rosea induced antiviral activity at early times post-infection by delaying an exercise-dependent increase in virus replication (P=0.013 compared to placebo. Serum from both groups collected 15 minutes post-marathon significantly promoted the growth of Escherichia coli in culture as compared to serum collected the day before the marathon (P=0.003, all subjects. Furthermore, the serum from subjects ingesting Rhodiola rosea did not display antibacterial properties at any time point as indicated by a lack of group differences immediately (P=0.785 or 1.5 hours (P=0.633 post-marathon. These results indicate that bioactive compounds in the serum of subjects ingesting Rhodiola rosea may exert protective effects against virus replication following intense and prolonged exercise by inducing antiviral activity.

  14. Antiviral activity of stachyflin on influenza A viruses of different hemagglutinin subtypes.

    Science.gov (United States)

    Motohashi, Yurie; Igarashi, Manabu; Okamatsu, Masatoshi; Noshi, Takeshi; Sakoda, Yoshihiro; Yamamoto, Naoki; Ito, Kimihito; Yoshida, Ryu; Kida, Hiroshi

    2013-04-16

    The hemagglutinin (HA) of influenza viruses is a possible target for antiviral drugs because of its key roles in the initiation of infection. Although it was found that a natural compound, Stachyflin, inhibited the growth of H1 and H2 but not H3 influenza viruses in MDCK cells, inhibitory activity of the compound has not been assessed against H4-H16 influenza viruses and the precise mechanism of inhibition has not been clarified. Inhibitory activity of Stachyflin against H4-H16 influenza viruses, as well as H1-H3 viruses was examined in MDCK cells. To identify factors responsible for the susceptibility of the viruses to this compound, Stachyflin-resistant viruses were selected in MDCK cells and used for computer docking simulation. It was found that in addition to antiviral activity of Stachyflin against influenza viruses of H1 and H2 subtypes, it inhibited replication of viruses of H5 and H6 subtypes, as well as A(H1N1)pdm09 virus in MDCK cells. Stachyflin also inhibited the virus growth in the lungs of mice infected with A/WSN/1933 (H1N1) and A/chicken/Ibaraki/1/2005 (H5N2). Substitution of amino acid residues was found on the HA2 subunit of Stachyflin-resistant viruses. Docking simulation indicated that D37, K51, T107, and K121 are responsible for construction of the cavity for the binding of the compound. In addition, 3-dimensional structure of the cavity of the HA of Stachyflin-susceptible virus strains was different from that of insusceptible virus strains. Antiviral activity of Stachyflin was found against A(H1N1)pdm09, H5, and H6 viruses, and identified a potential binding pocket for Stachyflin on the HA. The present results should provide us with useful information for the development of HA inhibitors with more effective and broader spectrum.

  15. Mixture toxicity of the antiviral drug Tamiflu (oseltamivir ethylester) and its active metabolite oseltamivir acid

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    Escher, Beate I., E-mail: b.escher@uq.edu.au [University of Queensland, National Research Centre for Environmental Toxicology (Entox), 39 Kessels Rd, Brisbane, Qld 4108 (Australia); Eawag, Swiss Federal Institute of Aquatic Science and Technology, 8600 Duebendorf (Switzerland); Bramaz, Nadine; Lienert, Judit; Neuwoehner, Judith [Eawag, Swiss Federal Institute of Aquatic Science and Technology, 8600 Duebendorf (Switzerland); Straub, Juerg Oliver [F.Hoffmann-La Roche Ltd, Corporate Safety, Health and Environmental Protection, 4070 Basel (Switzerland)

    2010-02-18

    Tamiflu (oseltamivir ethylester) is an antiviral agent for the treatment of influenza A and B. The pro-drug Tamiflu is converted in the human body to the pharmacologically active metabolite, oseltamivir acid, with a yield of 75%. Oseltamivir acid is indirectly photodegradable and slowly biodegradable in sewage works and sediment/water systems. A previous environmental risk assessment has concluded that there is no bioaccumulation potential of either of the compounds. However, little was known about the ecotoxicity of the metabolite. Ester hydrolysis typically reduces the hydrophobicity and thus the toxicity of a compound. In this case, a zwitterionic, but overall neutral species is formed from the charged parent compound. If the speciation and predicted partitioning into biological membranes is considered, the metabolite may have a relevant contribution to the overall toxicity. These theoretical considerations triggered a study to investigate the toxicity of oseltamivir acid (OA), alone and in binary mixtures with its parent compound oseltamivir ethylester (OE). OE and OA were found to be baseline toxicants in the bioluminescence inhibition test with Vibrio fischeri. Their mixture effect lay between predictions for concentration addition and independent action for the mixture ratio excreted in urine and nine additional mixture ratios of OE and OA. In contrast, OE was an order of magnitude more toxic than OA towards algae, with a more pronounced effect when the direct inhibition of photosystem II was used as toxicity endpoint opposed to the 24 h growth rate endpoint. The binary mixtures in this assay yielded experimental mixture effects that agreed with predictions for independent action. This is consistent with the finding that OE exhibits slightly enhanced toxicity, while OA acts as baseline toxicant. Therefore, with respect to mixture classification, the two compounds can be considered as acting according to different modes of toxic action, although there are

  16. Antiviral activity of extracts from Morinda citrifolia leaves and chlorophyll catabolites, pheophorbide a and pyropheophorbide a, against hepatitis C virus.

    Science.gov (United States)

    Ratnoglik, Suratno Lulut; Aoki, Chie; Sudarmono, Pratiwi; Komoto, Mari; Deng, Lin; Shoji, Ikuo; Fuchino, Hiroyuki; Kawahara, Nobuo; Hotta, Hak

    2014-03-01

    The development of complementary and/or alternative drugs for treatment of hepatitis C virus (HCV) infection is still needed. Antiviral compounds in medicinal plants are potentially good targets to study. Morinda citrifolia is a common plant distributed widely in Indo-Pacific region; its fruits and leaves are food sources and are also used as a treatment in traditional medicine. In this study, using a HCV cell culture system, it was demonstrated that a methanol extract, its n-hexane, and ethyl acetate fractions from M. citrifolia leaves possess anti-HCV activities with 50%-inhibitory concentrations (IC(50)) of 20.6, 6.1, and 6.6 μg/mL, respectively. Bioactivity-guided purification and structural analysis led to isolation and identification of pheophorbide a, the major catabolite of chlorophyll a, as an anti-HCV compound present in the extracts (IC(50) = 0.3 μg/mL). It was also found that pyropheophorbide a possesses anti-HCV activity (IC(50) = 0.2 μg/mL). The 50%-cytotoxic concentrations (CC(50)) of pheophorbide a and pyropheophorbide a were 10.0 and 7.2 μg/mL, respectively, their selectivity indexes being 33 and 36, respectively. On the other hand, chlorophyll a, sodium copper chlorophyllin, and pheophytin a barely, or only marginally, exhibited anti-HCV activities. Time-of-addition analysis revealed that pheophorbide a and pyropheophorbide a act at both entry and the post-entry steps. The present results suggest that pheophorbide a and its related compounds would be good candidates for seed compounds for developing antivirals against HCV. © 2014 The Societies and Wiley Publishing Asia Pty Ltd.

  17. Antiviral Protection via RdRP-Mediated Stable Activation of Innate Immunity.

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    Meghan M Painter

    2015-12-01

    Full Text Available For many emerging and re-emerging infectious diseases, definitive solutions via sterilizing adaptive immunity may require years or decades to develop, if they are even possible. The innate immune system offers alternative mechanisms that do not require antigen-specific recognition or a priori knowledge of the causative agent. However, it is unclear whether effective stable innate immune system activation can be achieved without triggering harmful autoimmunity or other chronic inflammatory sequelae. Here, we show that transgenic expression of a picornavirus RNA-dependent RNA polymerase (RdRP, in the absence of other viral proteins, can profoundly reconfigure mammalian innate antiviral immunity by exposing the normally membrane-sequestered RdRP activity to sustained innate immune detection. RdRP-transgenic mice have life-long, quantitatively dramatic upregulation of 80 interferon-stimulated genes (ISGs and show profound resistance to normally lethal viral challenge. Multiple crosses with defined knockout mice (Rag1, Mda5, Mavs, Ifnar1, Ifngr1, and Tlr3 established that the mechanism operates via MDA5 and MAVS and is fully independent of the adaptive immune system. Human cell models recapitulated the key features with striking fidelity, with the RdRP inducing an analogous ISG network and a strict block to HIV-1 infection. This RdRP-mediated antiviral mechanism does not depend on secondary structure within the RdRP mRNA but operates at the protein level and requires RdRP catalysis. Importantly, despite lifelong massive ISG elevations, RdRP mice are entirely healthy, with normal longevity. Our data reveal that a powerfully augmented MDA5-mediated activation state can be a well-tolerated mammalian innate immune system configuration. These results provide a foundation for augmenting innate immunity to achieve broad-spectrum antiviral protection.

  18. Antiviral Protection via RdRP-Mediated Stable Activation of Innate Immunity.

    Science.gov (United States)

    Painter, Meghan M; Morrison, James H; Zoecklein, Laurie J; Rinkoski, Tommy A; Watzlawik, Jens O; Papke, Louisa M; Warrington, Arthur E; Bieber, Allan J; Matchett, William E; Turkowski, Kari L; Poeschla, Eric M; Rodriguez, Moses

    2015-12-01

    For many emerging and re-emerging infectious diseases, definitive solutions via sterilizing adaptive immunity may require years or decades to develop, if they are even possible. The innate immune system offers alternative mechanisms that do not require antigen-specific recognition or a priori knowledge of the causative agent. However, it is unclear whether effective stable innate immune system activation can be achieved without triggering harmful autoimmunity or other chronic inflammatory sequelae. Here, we show that transgenic expression of a picornavirus RNA-dependent RNA polymerase (RdRP), in the absence of other viral proteins, can profoundly reconfigure mammalian innate antiviral immunity by exposing the normally membrane-sequestered RdRP activity to sustained innate immune detection. RdRP-transgenic mice have life-long, quantitatively dramatic upregulation of 80 interferon-stimulated genes (ISGs) and show profound resistance to normally lethal viral challenge. Multiple crosses with defined knockout mice (Rag1, Mda5, Mavs, Ifnar1, Ifngr1, and Tlr3) established that the mechanism operates via MDA5 and MAVS and is fully independent of the adaptive immune system. Human cell models recapitulated the key features with striking fidelity, with the RdRP inducing an analogous ISG network and a strict block to HIV-1 infection. This RdRP-mediated antiviral mechanism does not depend on secondary structure within the RdRP mRNA but operates at the protein level and requires RdRP catalysis. Importantly, despite lifelong massive ISG elevations, RdRP mice are entirely healthy, with normal longevity. Our data reveal that a powerfully augmented MDA5-mediated activation state can be a well-tolerated mammalian innate immune system configuration. These results provide a foundation for augmenting innate immunity to achieve broad-spectrum antiviral protection.

  19. Indole alkaloid sulfonic acids from an aqueous extract of Isatis indigotica roots and their antiviral activity

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    Lingjie Meng

    2017-05-01

    Full Text Available Six new indole alkaloid sulfonic acids (1–6, together with two analogues (7 and 8 that were previously reported as synthetic products, were isolated from an aqueous extract of the Isatis indigotica root. Their structures including the absolute configurations were determined by spectroscopic data analysis, combined with enzyme hydrolysis and comparison of experimental circular dichroism and calculated electronic circular dichroism spectra. In the preliminary assay, compounds 2 and 4 showed antiviral activity against Coxsackie virus B3 and influenza virus A/Hanfang/359/95 (H3N2, respectively.

  20. A Study of the Interferon Antiviral Mechanism: Apoptosis Activation by the 2–5A System

    Science.gov (United States)

    Castelli, JoAnn C.; Hassel, Bret A.; Wood, Katherine A.; Li, Xiao-Ling; Amemiya, Kei; Dalakas, Marinos C.; Torrence, Paul F.; Youle, Richard J.

    1997-01-01

    The 2–5A system contributes to the antiviral effect of interferons through the synthesis of 2–5A and its activation of the ribonuclease, RNase L. RNase L degrades viral and cellular RNA after activation by unique, 2′–5′ phosphodiester-linked, oligoadenylates [2–5A, (pp)p5′ A2′(P5′A2′)]n, n ⩾2. Because both the 2–5A system and apoptosis can serve as viral defense mechanisms and RNA degradation occurs during both processes, we investigated the potential role of RNase L in apoptosis. Overexpression of human RNase L by an inducible promoter in NIH3T3 fibroblasts decreased cell viability and triggered apoptosis. Activation of endogenous RNase L, specifically with 2–5A or with dsRNA, induced apoptosis. Inhibition of RNase L with a dominant negative mutant suppressed poly (I)·poly (C)–induced apoptosis in interferon-primed fibroblasts. Moreover, inhibition of RNase L suppressed apoptosis induced by poliovirus. Thus, increased RNase L levels induced apoptosis and inhibition of RNase L activity blocked viral-induced apoptosis. Apoptosis may be one of the antiviral mechanisms regulated by the 2–5A system. PMID:9294150

  1. Autophagy is involved in anti-viral activity of pentagalloylglucose (PGG) against Herpes simplex virus type 1 infection in vitro

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    Pei, Ying, E-mail: peiying-19802@163.com [Biomedicine Research and Development Center of Jinan University, Guangzhou, Guangdong 510632 (China); Chen, Zhen-Ping, E-mail: 530670663@qq.com [Biomedicine Research and Development Center of Jinan University, Guangzhou, Guangdong 510632 (China); Ju, Huai-Qiang, E-mail: 344464448@qq.com [Biomedicine Research and Development Center of Jinan University, Guangzhou, Guangdong 510632 (China); Komatsu, Masaaki, E-mail: komatsu-ms@igakuken.or.jp [Laboratory of Frontier Science, Tokyo Metropolitan Institute of Medical Science, Bunkyo-ku, Tokyo 113-8613 (Japan); Ji, Yu-hua, E-mail: tjyh@jnu.edu.cn [Institute of Tissue Transplantation and Immunology, College of Life Science and Technology, Jinan University, Guangzhou 510632 (China); Liu, Ge, E-mail: lggege_15@hotmail.com [Division of Molecular Pharmacology of Infectious agents, Department of Molecular Microbiology and Immunology, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki 852-8521 (Japan); Guo, Chao-wan, E-mail: chaovan_kwok@hotmail.com [Division of Molecular Pharmacology of Infectious agents, Department of Molecular Microbiology and Immunology, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki 852-8521 (Japan); Zhang, Ying-Jun, E-mail: zhangyj@mail.kib.ac.cn [Kunming Institute of Botany, the Chinese Academy of Sciences, Yunnan, Kunming 650204 (China); Yang, Chong-Ren, E-mail: cryang@mail.kib.ac.cn [Kunming Institute of Botany, the Chinese Academy of Sciences, Yunnan, Kunming 650204 (China); Wang, Yi-Fei, E-mail: twang-yf@163.com [Biomedicine Research and Development Center of Jinan University, Guangzhou, Guangdong 510632 (China); Kitazato, Kaio, E-mail: kkholi@msn.com [Division of Molecular Pharmacology of Infectious agents, Department of Molecular Microbiology and Immunology, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki 852-8521 (Japan)

    2011-02-11

    Research highlights: {yields} We showed PGG has anti-viral activity against Herpes simplex virus type 1 (HSV-1) and can induce autophgy. {yields} Autophagy may be a novel and important mechanism mediating PGG anti-viral activities. {yields} Inhibition of mTOR pathway is an important mechanism of induction of autophagy by PGG. -- Abstract: Pentagalloylglucose (PGG) is a natural polyphenolic compound with broad-spectrum anti-viral activity, however, the mechanisms underlying anti-viral activity remain undefined. In this study, we investigated the effects of PGG on anti-viral activity against Herpes simplex virus type 1 (HSV-1) associated with autophagy. We found that the PGG anti-HSV-1 activity was impaired significantly in MEF-atg7{sup -/-} cells (autophagy-defective cells) derived from an atg7{sup -/-} knockout mouse. Transmission electron microscopy revealed that PGG-induced autophagosomes engulfed HSV-1 virions. The mTOR signaling pathway, an essential pathway for the regulation of autophagy, was found to be suppressed following PGG treatment. Data presented in this report demonstrated for the first time that autophagy induced following PGG treatment contributed to its anti-HSV activity in vitro.

  2. Evaluation of antiviral activity of fractionated extracts of sage Salvia officinalis L. (Lamiaceae

    Directory of Open Access Journals (Sweden)

    Šmidling Dragana

    2008-01-01

    Full Text Available In the present study, we examined cytotoxicity and extracellular and intracellular antiviral activity of frac­tionated extracts of wild and cultivated sage Salvia officinalis L. (Lamiaceae in vitro using the WISH-VSV model system. Extracts were obtained by fractionating depigmented ethanol extracts of sage plants with supercritical CO2 at different pressures. Cytotoxicity was determined by examining cellular morphology in situ with the aid of a colorimetric micromethod and by cell staining with trypan blue. The fraction of distilled cultivated sage obtained at CO2 pressure of 300 bars and temperature of 60°C (149/3 was the most cytotoxic, with CTD10 44 μg/ml. That of non-distilled cultivated sage obtained at CO2 pressure of 500 bars and temperature of 100°C (144/5 was the least toxic (CTD10 199 μg/ml. Moreover, 144/5 had an antiviral effect at the intracellular level: when added 5 hours before VSV infection, it caused 100% reduction of CPE at concentrations of 99.5 and 199.0 μg/ml; when added after virus penetration had occurred, the same concentrations caused 35 and 60% reduction, respectively. The obtained results indicate that antiviral activity of 144/5 involves inhibition of the early steps of the virus infective cycle without a direct virucidal effect. Abbreviations: WISH - human amnion epithelial cells, VSV - vesicular stomatitis virus, HSV - herpes simplex virus, CPE - cytopathic effect, IS - selectivity index, TCID50 - tissue culture infective dose, CTD10 - 10% cytotoxic concentrations.

  3. Design, synthesis, antiviral activity and three-dimensional quantitative structure-activity relationship study of novel 1,4-pentadien-3-one derivatives containing the 1,3,4-oxadiazole moiety.

    Science.gov (United States)

    Gan, Xiuhai; Hu, Deyu; Li, Pei; Wu, Jian; Chen, Xuewen; Xue, Wei; Song, Baoan

    2016-03-01

    1,4-Pentadien-3-one and 1,3,4-oxadiazole derivatives possess good antiviral activities, and their substructure units are usually used in antiviral agent design. In order to discover novel molecules with high antiviral activities, a series of 1,4-pentadien-3-one derivatives containing the 1,3,4-oxadiazole moiety were designed and synthesised. Bioassays showed that most of the title compounds exhibited good inhibitory activities against tobacco mosaic virus (TMV) in vivo. The compound 8f possessing the best protective activity against TMV had an EC50 value of 135.56 mg L(-1) , which was superior to that of ribavirin (435.99 mg L(-1) ). Comparative molecular field analysis (CoMFA) and comparative molecular similarity index analysis (CoMSIA) techniques were used in three-dimensional quantitative structure-activity relationship (3D-QSAR) studies of protective activities, with values of q(2) and r(2) for the CoMFA and CoMSIA models of 0.751 and 0.775 and 0.936 and 0.925 respectively. Compound 8k with higher protective activity (EC50 = 123.53 mg L(-1) ) according to bioassay was designed and synthesised on the basis of the 3D-QSAR models. Some of the title compounds displayed good antiviral activities. 3D-QSAR models revealed that the appropriate compact electron-withdrawing and hydrophobic group at the benzene ring could enhance antiviral activity. These results could provide important structural insights for the design of highly active 1,4-pentadien-3-one derivatives. © 2015 Society of Chemical Industry.

  4. The antiviral drug ganciclovir does not inhibit microglial proliferation and activation.

    Science.gov (United States)

    Skripuletz, Thomas; Salinas Tejedor, Laura; Prajeeth, Chittappen K; Hansmann, Florian; Chhatbar, Chintan; Kucman, Valeria; Zhang, Ning; Raddatz, Barbara B; Detje, Claudia N; Sühs, Kurt-Wolfram; Pul, Refik; Gudi, Viktoria; Kalinke, Ulrich; Baumgärtner, Wolfgang; Stangel, Martin

    2015-10-08

    Ganciclovir is effective in the treatment of human infections with viruses of the Herpesviridae family. Beside antiviral properties, recently ganciclovir was described to inhibit microglial proliferation and disease severity of experimental autoimmune encephalomyelitis, an inflammatory model of multiple sclerosis. Microglial activation and proliferation are main characteristics of neuroinflammatory CNS diseases and inhibition of microglial functions might be beneficial in autoimmune diseases, or detrimental in infectious diseases. The objective of this study was to determine potential inhibitory effects of ganciclovir in three different murine animal models of CNS neuroinflammation in which microglia play an important role: Theiler´s murine encephalomyelitis, the cuprizone model of de- and remyelination, and the vesicular stomatitis virus encephalitis model. In addition, in vitro experiments with microglial cultures were performed to test the hypothesis that ganciclovir inhibits microglial proliferation. In all three animal models, neither microglial proliferation or recruitment nor disease activity was changed by ganciclovir. In vitro experiments confirmed that microglial proliferation was not affected by ganciclovir. In conclusion, our results show that the antiviral drug ganciclovir does not inhibit microglial activation and proliferation in the murine CNS.

  5. Potent in vitro antiviral activity of Cistus incanus extract against HIV and Filoviruses targets viral envelope proteins

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    Rebensburg, Stephanie; Helfer, Markus; Schneider, Martha; Koppensteiner, Herwig; Eberle, Josef; Schindler, Michael; Gürtler, Lutz; Brack-Werner, Ruth

    2016-01-01

    Novel therapeutic options are urgently needed to improve global treatment of virus infections. Herbal products with confirmed clinical safety features are attractive starting material for the identification of new antiviral activities. Here we demonstrate that Cistus incanus (Ci) herbal products inhibit human immunodeficiency virus (HIV) infections in vitro. Ci extract inhibited clinical HIV-1 and HIV-2 isolates, and, importantly, a virus isolate with multiple drug resistances, confirming broad anti-HIV activity. Antiviral activity was highly selective for virus particles, preventing primary attachment of the virus to the cell surface and viral envelope proteins from binding to heparin. Bioassay-guided fractionation indicated that Ci extract contains numerous antiviral compounds and therefore has favorably low propensity to induce virus resistance. Indeed, no resistant viruses emerged during 24 weeks of continuous propagation of the virus in the presence of Ci extracts. Finally, Ci extracts also inhibited infection by virus particles pseudotyped with Ebola and Marburg virus envelope proteins, indicating that antiviral activity of Ci extract extends to emerging viral pathogens. These results demonstrate that Ci extracts show potent and broad in vitro antiviral activity against viruses that cause life-threatening diseases in humans and are promising sources of agents that target virus particles. PMID:26833261

  6. Innate immunity in the vagina (Part II): Anti-HIV activity and antiviral content of human vaginal secretions.

    Science.gov (United States)

    Patel, Mickey V; Ghosh, Mimi; Fahey, John V; Ochsenbauer, Christina; Rossoll, Richard M; Wira, Charles R

    2014-07-01

    Whether the concentrations of antiviral proteins, and anti-HIV activity, within human vaginal secretions change across the menstrual cycle is unknown. Using a menstrual cup, vaginal secretions from pre-menopausal women were recovered at the proliferative (d6-8), mid-cycle (d13-15), and secretory (d21-23) stages of the menstrual cycle. Antiviral protein concentration was determined by ELISA, and anti-HIV activity assessed using the TZM-bl reporter cell line. CCL20, RANTES, elafin, HBD2, SDF-1α, and IL-8 levels were detectable in the secretions. Vaginal secretions had anti-HIV activity against specific clade B strains of HIV, with significant inhibition of IIIB and increased infectivity of transmitted/founder CH077.t. No significant differences in either antiviral protein concentration or anti-HIV activity with respect to menstrual cycle stage were measured, but marked differences were observed in both parameters over the course of the cycle between different women and in consecutive cycles from the same woman. The vagina contains a complement of antiviral proteins. The variation in anti-HIV activity demonstrates that immune protection in the vagina is not constant. Intra- and interindividual variations suggest that factors in addition to sex hormones influence antiviral protection. Lastly, the menstrual cup is a new model for recovering undiluted vaginal secretions from women throughout their reproductive life. © 2014 John Wiley & Sons Ltd.

  7. Immunity in the Vagina (Part II): Anti-HIV Activity and Antiviral Content of Human Vaginal Secretions

    Science.gov (United States)

    Patel, Mickey V.; Ghosh, Mimi; Fahey, John V.; Ochsenbauer, Christina; Rossoll, Richard M.; Wira, Charles R.

    2015-01-01

    Problem Whether the concentrations of antiviral proteins, and anti-HIV activity, within human vaginal secretions changes across the menstrual cycle is unknown. Method of Study Using a menstrual cup, vaginal secretions from premenopausal women were recovered at the proliferative (d6–8), mid-cycle (d13–15) and secretory (d21–23) stages of the menstrual cycle. Antiviral protein concentration was determined by ELISA, and anti-HIV activity assessed using the TZM-bl reporter cell line. Results CCL20, RANTES, elafin, HBD2, SDF-1α and IL-8 levels were detectable in the secretions. Vaginal secretions had anti-HIV activity against specific clade B strains of HIV, with significant inhibition of IIIB and increased infectivity of transmitted/founder CH077.t. No significant differences in either antiviral protein concentration or anti-HIV activity with respect to menstrual cycle stage were measured, but marked differences were observed in both parameters over the course of the cycle between different women, and in consecutive cycles from the same woman. Conclusion The vagina contains a complement of antiviral proteins. The variation in anti-HIV activity demonstrates that immune protection in the vagina is not constant. Intra- and inter-individual variations suggest that factors in addition to sex hormones influence antiviral protection. Lastly, the menstrual cup is a new model for recovering undiluted vaginal secretions from women throughout their reproductive life. PMID:24806967

  8. A Lipopeptide HIV-1/2 Fusion Inhibitor with Highly Potent In Vitro, Ex Vivo, and In Vivo Antiviral Activity.

    Science.gov (United States)

    Chong, Huihui; Xue, Jing; Xiong, Shengwen; Cong, Zhe; Ding, Xiaohui; Zhu, Yuanmei; Liu, Zixuan; Chen, Ting; Feng, Yifan; He, Lei; Guo, Yan; Wei, Qiang; Zhou, Yusen; Qin, Chuan; He, Yuxian

    2017-06-01

    Peptides derived from the C-terminal heptad repeat (CHR) region of the human immunodeficiency virus type 1 (HIV-1) fusogenic protein gp41 are potent viral entry inhibitors, and currently, enfuvirtide (T-20) is the only one approved for clinical use; however, emerging drug resistance largely limits its efficacy. In this study, we generated a novel lipopeptide inhibitor, named LP-19, by integrating multiple design strategies, including an N-terminal M-T hook structure, an HIV-2 sequence, intrahelical salt bridges, and a membrane-anchoring lipid tail. LP-19 showed stable binding affinity and highly potent, broad, and long-lasting antiviral activity. In in vitro studies, LP-19 efficiently inhibited HIV-1-, HIV-2-, and simian immunodeficiency virus (SIV)-mediated cell fusion, viral entry, and infection, and it was highly active against diverse subtypes of primary HIV-1 isolates and inhibitor-resistant mutants. Ex vivo studies demonstrated that LP-19 exhibited dramatically increased anti-HIV activity and an extended half-life in rhesus macaques. In short-term monotherapy, LP-19 reduced viral loads to undetectable levels in acutely and chronically simian-human immunodeficiency virus (SHIV)-infected monkeys. Therefore, this study offers an ideal HIV-1/2 fusion inhibitor for clinical development and emphasizes the importance of the viral fusion step as a drug target.IMPORTANCE The peptide drug T-20 is the only viral fusion inhibitor in the clinic, which is used for combination therapy of HIV-1 infection; however, it requires a high dosage and easily induces drug resistance, calling for a new drug with significantly improved pharmaceutical profiles. Here, we have developed a short-lipopeptide-based fusion inhibitor, termed LP-19, which mainly targets the conserved gp41 pocket site and shows highly potent inhibitory activity against HIV-1, HIV-2, and even SIV isolates. LP-19 exhibits dramatically increased antiviral activity and an extended half-life in rhesus macaques, and

  9. Enhancement of antiviral activity of collectin trimers through cross-linking and mutagenesis of the carbohydrate recognition domain

    DEFF Research Database (Denmark)

    White, Mitchell R; Boland, Patrick; Tecle, Tesfaldet

    2010-01-01

    Surfactant protein D (SP-D) plays important roles in innate defense against respiratory viruses [including influenza A viruses (IAVs)]. Truncated trimers composed of its neck and carbohydrate recognition domains (NCRDs) bind various ligands; however, they have minimal inhibitory activity for IAV...... protein binding site. Herein, we show that a multivalent S protein complex caused cross-linking and also increased the antiviral activity of NCRDs. NCRDs of conglutinin and CL43 had greater intrinsic antiviral activity than those of SP-D or mannose-binding lectin. Based on motifs found in these serum...

  10. Ophthalmic antiviral chemotherapy : An overview

    Directory of Open Access Journals (Sweden)

    Athmanathan Sreedharan

    1997-01-01

    Full Text Available Antiviral drug development has been slow due to many factors. One such factor is the difficulty to block the viral replication in the cell without adversely affecting the host cell metabolic activity. Most of the antiviral compounds are analogs of purines and pyramidines. Currently available antiviral drugs mainly inhibit viral nucleic acid synthesis, hence act only on actively replicating viruses. This article presents an overview of some of the commonly used antiviral agents in clinical ophthalmology.

  11. Clevudine demonstrates potent antiviral activity in naïve chronic hepatitis B patients.

    Science.gov (United States)

    Lee, June Sung; Park, Eun Taek; Kang, Seung Sik; Gu, Eun Sil; Kim, Jong Sun; Jang, Dong Seob; Lee, Kyoung Seog; Lee, Jae-Su; Park, Nung Hwa; Bae, Chang Hwang; Baik, Soon Koo; Yu, Byeong Jeon; Lee, Soon Hyung; Lee, Eun Jong; Park, Sung Il; Bae, Myoung; Shin, Jung Woo; Choi, Jae Hong; Gu, Chul; Moon, Sin Kil; Chun, Gab Jin; Kim, Ju Hyun; Kim, Hong Soo; Choi, Sung-Kyu

    2010-01-01

    Clevudine has demonstrated antiviral potency in the treatment of naïve chronic hepatitis B patients in pivotal studies. The objectives of this study were to evaluate the safety and efficacy of a 1-year treatment with clevudine in chronic hepatitis B patients. This is a post-marketing surveillance using case report forms which were submitted to the health authorities. Analysis of individual data showed that hepatitis B virus (HBV) DNA after a 1-year treatment was viral suppression up to week 48. The proportion of patients who showed normal alanine aminotransferase at week 48 was 86% in HBeAg-positive patients and 87% in HBeAg-negative patients. The rates of HBeAg-loss were 21%. Two patients showed viral breakthrough during treatment. Clevudine monotherapy demonstrates potent antiviral activity as well as biochemical and serological response with a 0.7% rate of viral breakthrough in naïve chronic hepatitis B patients. Copyright 2009 S. Karger AG, Basel.

  12. Endophytic Fungi Isolated from Coleus amboinicus Lour Exhibited Antimicrobial Activity

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    Puji Astuti

    2014-12-01

    Full Text Available Purpose: Coleus amboinicus is a medicinal plant traditionally used to treat various diseases such as throat infection, cough and fever, diarrhea, nasal congestion and digestive problems. The plant was explored for endophytic fungi producing antimicrobial agents. Methods: Screening for endophytic fungi producing antimicrobial agents was conducted using agar plug method and antimicrobial activity of promising ethyl acetate extracts was determined by disc diffusion assay. Thin layer chromatography (TLC - bioautography was performed to localize the bioactive components within the extract. TLC visualization detection reagents were used to preliminary analyze phytochemical groups of the bioactive compounds. Results: Three endophytic fungi were obtained, two of them showed promising potential. Agar diffusion method showed that endophytic fungi CAL-2 exhibited antimicrobial activity against P. aeruginosa, B. subtilis, S. aureus and S. thypi, whilst CAS-1 inhibited the growth of B. subtilis. TLC bioautography of ethyl acetate extract of CAL-2 revealed at least three bands exhibited antimicrobial activity and at least two bands showed inhibition of B. subtilis growth. Preliminary analysis of the crude extracts suggests that bioactive compounds within CAL-2 extract are terpenoids, phenolics and phenyl propanoid compounds whilst the antimicrobial agents within CAS-1 extract are terpenoids, propylpropanoids, alkaloids or heterocyclic nitrogen compounds. Conclusion: These data suggest the potential of endophytic fungi of C. amboinicus as source for antimicrobial agents.

  13. Endophytic Fungi Isolated from Coleus amboinicus Lour Exhibited Antimicrobial Activity.

    Science.gov (United States)

    Astuti, Puji; Sudarsono, Sudarsono; Nisak, Khoirun; Nugroho, Giri Wisnu

    2014-12-01

    Coleus amboinicus is a medicinal plant traditionally used to treat various diseases such as throat infection, cough and fever, diarrhea, nasal congestion and digestive problems. The plant was explored for endophytic fungi producing antimicrobial agents. Screening for endophytic fungi producing antimicrobial agents was conducted using agar plug method and antimicrobial activity of promising ethyl acetate extracts was determined by disc diffusion assay. Thin layer chromatography (TLC) - bioautography was performed to localize the bioactive components within the extract. TLC visualization detection reagents were used to preliminary analyze phytochemical groups of the bioactive compounds. Three endophytic fungi were obtained, two of them showed promising potential. Agar diffusion method showed that endophytic fungi CAL-2 exhibited antimicrobial activity against P. aeruginosa, B. subtilis, S. aureus and S. thypi, whilst CAS-1 inhibited the growth of B. subtilis. TLC bioautography of ethyl acetate extract of CAL-2 revealed at least three bands exhibited antimicrobial activity and at least two bands showed inhibition of B. subtilis growth. Preliminary analysis of the crude extracts suggests that bioactive compounds within CAL-2 extract are terpenoids, phenolics and phenyl propanoid compounds whilst the antimicrobial agents within CAS-1 extract are terpenoids, propylpropanoids, alkaloids or heterocyclic nitrogen compounds. These data suggest the potential of endophytic fungi of C. amboinicus as source for antimicrobial agents.

  14. In Vitro Antiviral Activity and Resistance Profile Characterization of the Hepatitis C Virus NS5A Inhibitor Ledipasvir

    Science.gov (United States)

    Tian, Yang; Doehle, Brian; Peng, Betty; Corsa, Amoreena; Lee, Yu-Jen; Gong, Ruoyu; Yu, Mei; Han, Bin; Xu, Simin; Dvory-Sobol, Hadas; Perron, Michel; Xu, Yili; Mo, Hongmei; Pagratis, Nikos; Link, John O.; Delaney, William

    2016-01-01

    Ledipasvir (LDV; GS-5885), a component of Harvoni (a fixed-dose combination of LDV with sofosbuvir [SOF]), is approved to treat chronic hepatitis C virus (HCV) infection. Here, we report key preclinical antiviral properties of LDV, including in vitro potency, in vitro resistance profile, and activity in combination with other anti-HCV agents. LDV has picomolar antiviral activity against genotype 1a and genotype 1b replicons with 50% effective concentration (EC50) values of 0.031 nM and 0.004 nM, respectively. LDV is also active against HCV genotypes 4a, 4d, 5a, and 6a with EC50 values of 0.11 to 1.1 nM. LDV has relatively less in vitro antiviral activity against genotypes 2a, 2b, 3a, and 6e, with EC50 values of 16 to 530 nM. In vitro resistance selection with LDV identified the single Y93H and Q30E resistance-associated variants (RAVs) in the NS5A gene; these RAVs were also observed in patients after a 3-day monotherapy treatment. In vitro antiviral combination studies indicate that LDV has additive to moderately synergistic antiviral activity when combined with other classes of HCV direct-acting antiviral (DAA) agents, including NS3/4A protease inhibitors and the nucleotide NS5B polymerase inhibitor SOF. Furthermore, LDV is active against known NS3 protease and NS5B polymerase inhibitor RAVs with EC50 values equivalent to those for the wild type. PMID:26824950

  15. Antiviral Activity of Dual-acting Hydrocarbon-stapled Peptides against HIV-1 Predominantly Circulating in China.

    Science.gov (United States)

    Wang, Yan; Curreli, Francesca; Xu, Wei Si; Li, Zhen Peng; Kong, De Sheng; Ren, Li; Hong, Kun Xue; Jiang, Shi Bo; Shao, Yi Ming; Debnath, Asim K; Ma, Li Ying

    2017-06-01

    New rationally designed i,i+7-hydrocarbon-stapled peptides that target both HIV-1 assembly and entry have been shown to have antiviral activity against HIV-1 subtypes circulating in Europe and North America. Here, we aimed to evaluate the antiviral activity of these peptides against HIV-1 subtypes predominantly circulating in China. The antiviral activity of three i,i+7-hydrocarbon-stapled peptides, NYAD-36, NYAD-67, and NYAD-66, against primary HIV-1 CRF07_BC and CRF01_AE isolates was evaluated in peripheral blood mononuclear cells (PBMCs). The activity against the CRF07_BC and CRF01_AE Env-pseudotyped viruses was analyzed in TZM-bl cells. We found that all the stapled peptides were effective in inhibiting infection by all the primary HIV-1 isolates tested, with 50% inhibitory concentration toward viral replication (IC50) in the low micromolar range. NYAD-36 and NYAD-67 showed better antiviral activity than NYAD-66 did. We further evaluated the sensitivity of CRF01_AE and CRF07_BC Env-pseudotyped viruses to these stapled peptides in a single-cycle virus infectivity assay. As observed with the primary isolates, the IC50s were in the low micromolar range, and NYAD-66 was less effective than NYAD-36 and NYAD-67. Hydrocarbon-stapled peptides appear to have broad antiviral activity against the predominant HIV-1 viruses in China. This finding may provide the impetus to the rational design of peptides for future antiviral therapy. Copyright © 2017 The Editorial Board of Biomedical and Environmental Sciences. Published by China CDC. All rights reserved.

  16. Synthesis, antimicrobial, and antiviral activities of some new 5-sulphonamido-8-hydroxyquinoline derivatives.

    Science.gov (United States)

    Kassem, Emad M; El-Sawy, Eslam R; Abd-Alla, Howaida I; Mandour, Adel H; Abdel-Mogeed, Dina; El-Safty, Mounir M

    2012-06-01

    A series of fused pyranopyrazole and pyranoimidazole, namely 5-(3,6-diamino-4-aryl-5-carbonitrile-pyrano(2,3-c)pyrazol-2-yl)sulphonyl-8-hydroxyquinolines (5a-e), 5-(6-amino-4-aryl-5-carbonitrile-pyrano(2,3-c)pyrazol-3-yl)sulphonamido-8-hydroxyquinolines (6a-e), 5-(2-thioxo-4-aryl-5-carbonitrile-6-amino-pyrano(2,3-d)imidazol-2-yl)sulphonyl-8-hydroxyquinolines (10a-e), and 5-(2-oxo-4-aryl-5-carbonitrile-6-amino-pyrano(2,3-d)imidazol-2-yl) sulphonyl-8-hydroxyquinolines (11a-e), have been prepared via condensation of some arylidine malononitriles with 5-sulphonamido-8-hydroxyquinoline derivatives 3, 4, 8 and 9. All the synthesized compounds were screened for their antimicrobial activities, and most of the tested compounds showed potent inhibition growth activity towards Escherichia coli, Pseudomonas aeruginosa (Gramnegative bacteria). Furthermore, six selected compounds were tested for their antiviral activity against avian paramyxovirus type1 (APMV-1) and laryngotracheitis virus (LTV), and the results showed that a concentration range of 3-4 μg per mL of compounds 2, 3, and 4 showed marked viral inhibitory activity for APMV-1 of 5000 tissue culture infected dose fifty (TCID(50)) and LTV of 500 TCID(50) in Vero cell cultures based on their cytopathic effect. Chicken embryo experiments show that compounds 2, 3, and 4 possess high antiviral activity in vitro with an inhibitory concentration fifty (IC(50)) range of 3-4 μg per egg against avian APMV-1 and LTV and their toxic concentration fifty (CC(50)) of 200-300 μg per egg.

  17. Cloning, expression, and antiviral activity of interferon β from the Chinese microbat, Myotis davidii.

    Science.gov (United States)

    Liang, Ying-Zi; Wu, Li-Jun; Zhang, Qian; Zhou, Peng; Wang, Mei-Niang; Yang, Xing-Lou; Ge, Xing-Yi; Wang, Lin-Fa; Shi, Zheng-Li

    2015-12-01

    Bats are natural reservoir hosts for many viruses that produce no clinical symptoms in bats. Therefore, bats may have evolved effective mechanisms to control viral replication. However, little information is available on bat immune responses to viral infection. Type I interferon (IFN) plays a key role in controlling viral infections. In this study, we report the cloning, expression, and biological activity of interferon β (IFNβ) from the Chinese microbat species, Myotis davidii. We demonstrated the upregulation of IFNB and IFN-stimulated genes in a kidney cell line derived from M. davidii after treatment with polyI:C or infection with Sendai virus. Furthermore, the recombinant IFNβ inhibited vesicular stomatitis virus and bat adenovirus replication in cell lines from two bat species, M. davidii and Rhinolophus sinicus. We provide the first in vitro evidence of IFNβ antiviral activity in microbats, which has important implications for virus interactions with these hosts.

  18. Benzophenone C-glucosides and gallotannins from mango tree stem bark with broad-spectrum anti-viral activity.

    Science.gov (United States)

    Abdel-Mageed, Wael M; Bayoumi, Soad A H; Chen, Caixia; Vavricka, Christopher J; Li, Li; Malik, Ajamaluddin; Dai, Huanqin; Song, Fuhang; Wang, Luoqiang; Zhang, Jingyu; Gao, George F; Lv, Yali; Liu, Lihong; Liu, Xueting; Sayed, Hanaa M; Zhang, Lixin

    2014-04-01

    The high mutation rate of RNA viruses has resulted in limitation of vaccine effectiveness and increased emergence of drug-resistant viruses. New effective antivirals are therefore needed to control of the highly mutative RNA viruses. The n-butanol fraction of the stem bark of Mangifera indica exhibited inhibitory activity against influenza neuraminidase (NA) and coxsackie virus 3C protease. Bioassay guided phytochemical study of M. indica stem bark afforded two new compounds including one benzophenone C-glycoside (4) and one xanthone dimer (7), together with eleven known compounds. The structures of these isolated compounds were elucidated on the basis of spectroscopic evidences and correlated with known compounds. Anti-influenza and anti-coxsackie virus activities were evaluated by determining the inhibition of anti-influenza neuraminidase (NA) from pandemic A/RI/5+/1957 H2N2 influenza A virus and inhibition of coxsackie B3 virus 3C protease, respectively. The highest anti-influenza activity was observed for compounds 8 and 9 with IC50 values of 11.9 and 9.2μM, respectively. Compounds 8 and 9 were even more potent against coxsackie B3 virus 3C protease, with IC50 values of 1.1 and 2.0μM, respectively. Compounds 8 and 9 showed weak cytotoxic effect against human hepatocellular carcinoma and human epithelial carcinoma cell lines through MTT assay. Copyright © 2014 Elsevier Ltd. All rights reserved.

  19. A few atoms make the difference: synthetic, CD, NMR and computational studies on antiviral and antibacterial activities of glycopeptide antibiotic aglycon derivatives.

    Science.gov (United States)

    Bereczki, Ilona; Mándi, Attila; Rőth, Erzsébet; Borbás, Anikó; Fizil, Ádám; Komáromi, István; Sipos, Attila; Kurtán, Tibor; Batta, Gyula; Ostorházi, Eszter; Rozgonyi, Ferenc; Vanderlinden, Evelien; Naesens, Lieve; Sztaricskai, Ferenc; Herczegh, Pál

    2015-04-13

    Despite the close structural similarity between the heptapeptide cores of the glycopeptide antibiotics teicoplanin and ristocetin, synthetically modified derivatives of their aglycons show significantly different antibacterial and antiviral properties. The teicoplanin aglycon derivatives with one exception proved to be potent antibacterials but they did not exhibit anti-influenza virus activity. In contrast, the aglycoristocetin derivatives generally showed high anti-influenza virus activity and possessed moderate antibacterial activity. A systematic structure-activity relationship study has been carried out on ristocetin and teicoplanin aglycon derivatives, to explore which structural differences are responsible for these markedly different biological activities. According to electronic circular dichroism and in silico conformational studies, it was found that the differences in anti-influenza virus activity are mainly determined by the conformation of the heptapeptide core of the antibiotics controlled by the presence or absence of chloro substituents. Knowledge of the bioactive conformation will help to design new analogs with improved anti-influenza virus activity. For the teicoplanin derivatives, it was shown that derivatization to improve the antiviral efficacy was accompanied by a significant decrease in antibacterial activity. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

  20. Antiviral activity of a small molecule deubiquitinase inhibitor occurs via induction of the unfolded protein response.

    Directory of Open Access Journals (Sweden)

    Jeffrey W Perry

    Full Text Available Ubiquitin (Ub is a vital regulatory component in various cellular processes, including cellular responses to viral infection. As obligate intracellular pathogens, viruses have the capacity to manipulate the ubiquitin (Ub cycle to their advantage by encoding Ub-modifying proteins including deubiquitinases (DUBs. However, how cellular DUBs modulate specific viral infections, such as norovirus, is poorly understood. To examine the role of DUBs during norovirus infection, we used WP1130, a small molecule inhibitor of a subset of cellular DUBs. Replication of murine norovirus in murine macrophages and the human norovirus Norwalk virus in a replicon system were significantly inhibited by WP1130. Chemical proteomics identified the cellular DUB USP14 as a target of WP1130 in murine macrophages, and pharmacologic inhibition or siRNA-mediated knockdown of USP14 inhibited murine norovirus infection. USP14 is a proteasome-associated DUB that also binds to inositol-requiring enzyme 1 (IRE1, a critical mediator of the unfolded protein response (UPR. WP1130 treatment of murine macrophages did not alter proteasome activity but activated the X-box binding protein-1 (XBP-1 through an IRE1-dependent mechanism. In addition, WP1130 treatment or induction of the UPR also reduced infection of other RNA viruses including encephalomyocarditis virus, Sindbis virus, and La Crosse virus but not vesicular stomatitis virus. Pharmacologic inhibition of the IRE1 endonuclease activity partially rescued the antiviral effect of WP1130. Taken together, our studies support a model whereby induction of the UPR through cellular DUB inhibition blocks specific viral infections, and suggest that cellular DUBs and the UPR represent novel targets for future development of broad spectrum antiviral therapies.

  1. Early gene activation initiates neuroinflammation prior to VSV neuroinvasion: Impact on antiviral responses and sleep.

    Science.gov (United States)

    Ciavarra, Richard P; Lundberg, Patric; Machida, Mayumi; Ambrozewicz, Marta A; Wellman, Laurie L; Breving, Kimberly; Steel, Christina; Sanford, Larry D

    2017-02-15

    Rapid eye movement (REM) sleep is rapidly and persistently suppressed during vesicular stomatitis virus (VSV) encephalitis in C57Bl/6J (B6) mice. REM sleep suppression was associated with a complex global brain chemokine/cytokine response with bimodal kinetics although regionally distinct cytokine profiles were readily identified. Cytokine mRNA was translated either immediately or suppressed until the pathogen was cleared from the CNS. Innate signaling pathway (TLRs, RIG-I) activation occurred rapidly and sequentially prior to VSV neuroinvasion suggesting that antiviral states are quickly established in the CNS in advance of viral pathogen penetration. Il1β suppressed REM sleep mimicking aspects of VSV-induced sleep alterations whereas some robustly induced chemokines may be protective of REM. Thus, multiple brain chemokines may mediate sleep across VSV encephalitis via differential somnogenic effects. Copyright © 2016 Elsevier B.V. All rights reserved.

  2. Structures and antiviral activities of butyrolactone derivatives isolated from Aspergillus terreus MXH-23

    Science.gov (United States)

    Ma, Xinhua; Zhu, Tianjiao; Gu, Qianqun; Xi, Rui; Wang, Wei; Li, Dehai

    2014-12-01

    A new butyrolactone derivative, namely butyrolactone VIII ( 1), and six known butyrolactones ( 2-7) were separated from the ethyl acetate (EtOAc) extract of the fermentation broth of a fungus, Aspergillus terreus MXH-23. The chemical structures of these metabolites were identified by analyzing their nuclear magnetic resonance (NMR) and mass spectrometry (MS). Known butyrolactone derivatives contain an α, β-unsaturated γ-lactone ring with α-hydroxyl and γ-benzyl, and butyrolactone VIII ( 1) was the first butyrolactones contains α-benzyl and γ-hydroxyl on α, β-unsaturated lactone ring. All of the butyrolactone derivatives were tested for their anti-influenza (H1N1) effects. Derivatives 4 and 7 showed moderate antiviral activities while the newly-identified, derivative 1, did not.

  3. Bougainvillea spectabilis Exhibits Antihyperglycemic and Antioxidant Activities in Experimental Diabetes.

    Science.gov (United States)

    Chauhan, Pratibha; Mahajan, Sunil; Kulshrestha, Archana; Shrivastava, Sadhana; Sharma, Bechan; Goswamy, H M; Prasad, G B K S

    2016-07-01

    The study investigates the effects of aqueous extract of Bougainvillea spectabilis leaves on blood glucose, glycosylated hemoglobin, lipid profile, oxidative stress, and on DNA damage, if any, as well as on liver and kidney functions in streptozotocin-induced diabetes in Wistar rats. Daily administration of the aqueous extract of B spectabilis leaves for 28 days resulted in significant reduction in hyperglycemia and hyperlipidemia as evident from restoration of relevant biochemical markers following extract administration. The extract also exhibited significant antioxidant activity as evidenced from the enzymatic and nonenzymatic responses and DNA damage markers. The extract restored kidney and liver functions to normal and proved to be nontoxic. A marked improvement in the histological changes of tissues was also observed. The present study documented antihyperglycemic, antihyperlipidemic, and antioxidative potentials of the aqueous extract of B spectabilis leaves without any toxicity in streptozotocin-treated Wistar rats. © The Author(s) 2015.

  4. Design and evaluation of novel interferon lambda analogs with enhanced antiviral activity and improved drug attributes

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    Yu D

    2016-01-01

    Full Text Available Debin Yu,1 Mingzhi Zhao,2 Liwei Dong,1 Lu Zhao,1 Mingwei Zou,3 Hetong Sun,4 Mengying Zhang,4 Hongyu Liu,4 Zhihua Zou1 1National Engineering Laboratory for AIDS Vaccine, Key Laboratory for Molecular Enzymology and Engineering of the Ministry of Education, School of Life Sciences, Jilin University, Changchun, 2State Key Laboratory of Proteomics, National Engineering Research Center for Protein Drugs, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, Beijing, People’s Republic of China; 3Department of Psychology, College of Liberal Arts and Social Sciences, University of Houston, Houston, TX, USA; 4Prosit Sole Biotechnology, Co., Ltd., Beijing, People’s Republic of China Abstract: Type III interferons (IFNs (also called IFN-λ: IFN-λ1, IFN-λ2, IFN-λ3, and IFN-λ4 are critical players in the defense against viral infection of mucosal epithelial cells, where the activity of type I IFNs is weak, and unlike type I IFNs that are associated with severe and diverse side effects, type III IFNs cause minimal side effects due to the highly restricted expression of their receptors, and thus appear to be promising agents for the treatment and prevention of respiratory and gastrointestinal viral infection. However, the antiviral potency of natural type III IFNs is weak compared to type I and, although IFN-λ3 possesses the highest bioactivity among the type III IFNs, IFN-λ1, instead of IFN-λ3, is being developed as a therapeutic drug due to the difficulty to express IFN-λ3 in the prokaryotic expression system. Here, to develop optimal IFN-λ molecules with improved drug attributes, we designed a series of IFN-λ analogs by replacing critical amino acids of IFN-λ1 with the IFN-λ3 counterparts, and vice versa. Four of the designed analogs were successfully expressed in Escherichia coli with high yield and were easily purified from inclusion bodies. Interestingly, all four analogs showed potent activity in inducing the

  5. Coxsackievirus cloverleaf RNA containing a 5' triphosphate triggers an antiviral response via RIG-I activation

    NARCIS (Netherlands)

    Feng, Qian; Langereis, Martijn A; Olagnier, David; Chiang, Cindy; van de Winkel, Roel; van Essen, Peter; Zoll, Jan; Hiscott, John; van Kuppeveld, Frank J M

    2014-01-01

    Upon viral infections, pattern recognition receptors (PRRs) recognize pathogen-associated molecular patterns (PAMPs) and stimulate an antiviral state associated with the production of type I interferons (IFNs) and inflammatory markers. Type I IFNs play crucial roles in innate antiviral responses by

  6. Antiviral activity of extracts from Brazilian seaweeds against herpes simplex virus

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    Angélica Ribeiro Soares

    2012-08-01

    Full Text Available Organic extracts of 36 species of marine algae (sixteen species of Rhodophyta, eight species of Ochrophyta and twelve species of Chlorophyta from seven locations on the Brazilian coast were evaluated for their anti-HSV-1 and anti-HSV-2 activity resistant to Acyclovir (ACV. Activity tests in crude extracts, followed by the identification of the major compounds present, were performed for all species. The chemical profiles of all crude extracts were obtained by ¹H-NMR and 13C-NMR spectroscopy. The percentage of extracts with antiviral activity was higher for HSV-1 (86.1% than for HSV-2 (55.5%. The green algae Ulva fasciata and Codium decorticatum both showed the highest activity (99.9% against HSV-1, with triacylglycerols and fatty acids as the major components. The red alga Laurencia dendroidea showed good activity against HSV-1 (97.5% and the halogenated sesquiterpenes obtusol and (--elatol were identified as the major components in the extract. Against HSV-2, the green alga Penicillus capitatus (Chlorophyta and Stypopodium zonale (Ochrophyta were the most active (96.0 and 95.8%. Atomaric acid, a meroditerpene, was identified as the major secondary metabolite in the S. zonale extract. These results reinforce the role of seaweeds as important sources of compounds with the potential to enter into the pipeline for development of new drugs against herpes simplex.

  7. Antiviral and Cytotoxic Activities of Extracts from the Cell Cultures and Respective Parts of Some Turkish Medicinal Plants

    OpenAIRE

    SÖKMEN, ATALAY

    2001-01-01

    Extracts from respective parts and cell cultures of some Turkish medicinal plants have been assessed for their antiviral and cytotoxic properties. None of the extracts tested showed notable activity against herpes simplex viruses (HSV-I and II), but a slight antiretroviral activity against HIV-I was determined in an extract from Hypericum capitatum cell cultures. On the other hand, according to cytotoxic activity test results against brine shrimp (Artemia salina), an activity level of LD50 a...

  8. Antimicrobial, Anthelmintic, and Antiviral Activity of Plants Traditionally Used for Treating Infectious Disease in the Similipal Biosphere Reserve, Odisha, India

    Science.gov (United States)

    Panda, Sujogya K.; Padhi, Laxmipriya; Leyssen, Pieter; Liu, Maoxuan; Neyts, Johan; Luyten, Walter

    2017-01-01

    In the present study, we tested in vitro different parts of 35 plants used by tribals of the Similipal Biosphere Reserve (SBR, Mayurbhanj district, India) for the management of infections. From each plant, three extracts were prepared with different solvents (water, ethanol, and acetone) and tested for antimicrobial (E. coli, S. aureus, C. albicans); anthelmintic (C. elegans); and antiviral (enterovirus 71) bioactivity. In total, 35 plant species belonging to 21 families were recorded from tribes of the SBR and periphery. Of the 35 plants, eight plants (23%) showed broad-spectrum in vitro antimicrobial activity (inhibiting all three test strains), while 12 (34%) exhibited narrow spectrum activity against individual pathogens (seven as anti-staphylococcal and five as anti-candidal). Plants such as Alangium salviifolium, Antidesma bunius, Bauhinia racemosa, Careya arborea, Caseria graveolens, Cleistanthus patulus, Colebrookea oppositifolia, Crotalaria pallida, Croton roxburghii, Holarrhena pubescens, Hypericum gaitii, Macaranga peltata, Protium serratum, Rubus ellipticus, and Suregada multiflora showed strong antibacterial effects, whilst Alstonia scholaris, Butea monosperma, C. arborea, C. pallida, Diospyros malbarica, Gmelina arborea, H. pubescens, M. peltata, P. serratum, Pterospermum acerifolium, R. ellipticus, and S. multiflora demonstrated strong antifungal activity. Plants such as A. salviifolium, A. bunius, Aporosa octandra, Barringtonia acutangula, C. graveolens, C. pallida, C. patulus, G. arborea, H. pubescens, H. gaitii, Lannea coromandelica, M. peltata, Melastoma malabathricum, Millettia extensa, Nyctanthes arbor-tristis, P. serratum, P. acerifolium, R. ellipticus, S. multiflora, Symplocos cochinchinensis, Ventilago maderaspatana, and Wrightia arborea inhibit survival of C. elegans and could be a potential source for anthelmintic activity. Additionally, plants such as A. bunius, C. graveolens, C. patulus, C. oppositifolia, H. gaitii, M. extensa, P

  9. Antiviral activity of α-helical stapled peptides designed from the HIV-1 capsid dimerization domain

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    Cowburn David

    2011-05-01

    Full Text Available Abstract Background The C-terminal domain (CTD of HIV-1 capsid (CA, like full-length CA, forms dimers in solution and CTD dimerization is a major driving force in Gag assembly and maturation. Mutations of the residues at the CTD dimer interface impair virus assembly and render the virus non-infectious. Therefore, the CTD represents a potential target for designing anti-HIV-1 drugs. Results Due to the pivotal role of the dimer interface, we reasoned that peptides from the α-helical region of the dimer interface might be effective as decoys to prevent CTD dimer formation. However, these small peptides do not have any structure in solution and they do not penetrate cells. Therefore, we used the hydrocarbon stapling technique to stabilize the α-helical structure and confirmed by confocal microscopy that this modification also made these peptides cell-penetrating. We also confirmed by using isothermal titration calorimetry (ITC, sedimentation equilibrium and NMR that these peptides indeed disrupt dimer formation. In in vitro assembly assays, the peptides inhibited mature-like virus particle formation and specifically inhibited HIV-1 production in cell-based assays. These peptides also showed potent antiviral activity against a large panel of laboratory-adapted and primary isolates, including viral strains resistant to inhibitors of reverse transcriptase and protease. Conclusions These preliminary data serve as the foundation for designing small, stable, α-helical peptides and small-molecule inhibitors targeted against the CTD dimer interface. The observation that relatively weak CA binders, such as NYAD-201 and NYAD-202, showed specificity and are able to disrupt the CTD dimer is encouraging for further exploration of a much broader class of antiviral compounds targeting CA. We cannot exclude the possibility that the CA-based peptides described here could elicit additional effects on virus replication not directly linked to their ability to bind

  10. Chemical composition of 8 eucalyptus species' essential oils and the evaluation of their antibacterial, antifungal and antiviral activities

    Science.gov (United States)

    2012-01-01

    Background In 1957, Tunisia introduced 117 species of Eucalyptus; they have been used as fire wood, for the production of mine wood and to fight erosion. Actually, Eucalyptus essential oil is traditionally used to treat respiratory tract disorders such as pharyngitis, bronchitis, and sinusitis. A few investigations were reported on the biological activities of Eucalyptus oils worldwide. In Tunisia, our previous works conducted in 2010 and 2011 had been the first reports to study the antibacterial activities against reference strains. At that time it was not possible to evaluate their antimicrobial activities against clinical bacterial strains and other pathogens such as virus and fungi. Methods The essential oils of eight Eucalyptus species harvested from the Jbel Abderrahman, Korbous (North East Tunisia) and Souinet arboreta (North of Tunisia) were evaluated for their antimicrobial activities by disc diffusion and microbroth dilution methods against seven bacterial isolates: Haemophilus influenzae, Klebsiella pneumoniae, Pseudomonas aeruginosa, Staphylococcus aureus, Streptococcus agalactiae, Streptococcus pneumoniae and Streptococcus pyogenes. In addition, the bactericidal, fungicidal and the antiviral activities of the tested oils were carried out. Results Twenty five components were identified by GC/FID and GC/MS. These components were used to correlate with the biological activities of the tested oils. The chemical principal component analysis identified three groups, each of them constituted a chemotype. According to the values of zone diameter and percentage of the inhibition (zdi, % I, respectively), four groups and subgroups of bacterial strains and three groups of fungal strains were characterized by their sensitivity levels to Eucalyptus oils. The cytotoxic effect and the antiviral activity varied significantly within Eucalyptus species oils. Conclusions E. odorata showed the strongest activity against S. aureus, H. influenzae, S. agalactiae, S. pyogenes

  11. Chemical composition of 8 eucalyptus species' essential oils and the evaluation of their antibacterial, antifungal and antiviral activities

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    Elaissi Ameur

    2012-06-01

    Full Text Available Abstract Background In 1957, Tunisia introduced 117 species of Eucalyptus; they have been used as fire wood, for the production of mine wood and to fight erosion. Actually, Eucalyptus essential oil is traditionally used to treat respiratory tract disorders such as pharyngitis, bronchitis, and sinusitis. A few investigations were reported on the biological activities of Eucalyptus oils worldwide. In Tunisia, our previous works conducted in 2010 and 2011 had been the first reports to study the antibacterial activities against reference strains. At that time it was not possible to evaluate their antimicrobial activities against clinical bacterial strains and other pathogens such as virus and fungi. Methods The essential oils of eight Eucalyptus species harvested from the Jbel Abderrahman, Korbous (North East Tunisia and Souinet arboreta (North of Tunisia were evaluated for their antimicrobial activities by disc diffusion and microbroth dilution methods against seven bacterial isolates: Haemophilus influenzae, Klebsiella pneumoniae, Pseudomonas aeruginosa, Staphylococcus aureus, Streptococcus agalactiae, Streptococcus pneumoniae and Streptococcus pyogenes. In addition, the bactericidal, fungicidal and the antiviral activities of the tested oils were carried out. Results Twenty five components were identified by GC/FID and GC/MS. These components were used to correlate with the biological activities of the tested oils. The chemical principal component analysis identified three groups, each of them constituted a chemotype. According to the values of zone diameter and percentage of the inhibition (zdi, % I, respectively, four groups and subgroups of bacterial strains and three groups of fungal strains were characterized by their sensitivity levels to Eucalyptus oils. The cytotoxic effect and the antiviral activity varied significantly within Eucalyptus species oils. Conclusions E. odorata showed the strongest activity against S. aureus, H. influenzae

  12. Isolation, characterization, molecular cloning and modeling of a new lipid transfer protein with antiviral and antiproliferative activities from Narcissus tazetta.

    Science.gov (United States)

    Ooi, Linda S M; Tian, Li; Su, Miaoxian; Ho, Wing-Shan; Sun, Samuel S M; Chung, Hau-Yin; Wong, Henry N C; Ooi, Vincent E C

    2008-12-01

    A fetuin-binding peptide with a molecular mass of about 9kDa (designated NTP) was isolated and purified from the bulbs of Chinese daffodil, Narcissus tazetta var. chinensis L., by gel filtration and high-performance liquid chromatography, after removing the mannose-binding proteins by mannose-agarose column. Molecular cloning revealed that NTP contained an open reading frame of 354bp encoding a polypeptide of 118 amino acids which included a 26-amino-acid signal peptide. An analysis of the deduced amino acid sequence of NTP shows considerable sequence homology to the non-specific lipid transfer proteins (nsLTPs) of certain plants. Model of the three-dimensional (3D) structure of NTP exhibits an internal hydrophobic cavity which can bind lipid-like molecules and transfer a wide range of ligands. As a member of the putative non-specific lipid transfer protein of N. tazetta, NTP did not possess hemagglutinating activity toward rabbit erythrocytes. In a cell-free system, it could arrest the protein synthesis of rabbit reticulocytes. Using the in vitro antiviral assays, NTP could significantly inhibit the plaque formation by respiratory syncytial virus (RSV) and the cytopathic effect induced by influenza A (H1N1) virus, as well as the proliferation of human acute promyelocytic leukemia cells (HL-60).

  13. Antibody complementarity-determining regions (CDRs can display differential antimicrobial, antiviral and antitumor activities.

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    Luciano Polonelli

    Full Text Available BACKGROUND: Complementarity-determining regions (CDRs are immunoglobulin (Ig hypervariable domains that determine specific antibody (Ab binding. We have shown that synthetic CDR-related peptides and many decapeptides spanning the variable region of a recombinant yeast killer toxin-like antiidiotypic Ab are candidacidal in vitro. An alanine-substituted decapeptide from the variable region of this Ab displayed increased cytotoxicity in vitro and/or therapeutic effects in vivo against various bacteria, fungi, protozoa and viruses. The possibility that isolated CDRs, represented by short synthetic peptides, may display antimicrobial, antiviral and antitumor activities irrespective of Ab specificity for a given antigen is addressed here. METHODOLOGY/PRINCIPAL FINDINGS: CDR-based synthetic peptides of murine and human monoclonal Abs directed to: a a protein epitope of Candida albicans cell wall stress mannoprotein; b a synthetic peptide containing well-characterized B-cell and T-cell epitopes; c a carbohydrate blood group A substance, showed differential inhibitory activities in vitro, ex vivo and/or in vivo against C. albicans, HIV-1 and B16F10-Nex2 melanoma cells, conceivably involving different mechanisms of action. Antitumor activities involved peptide-induced caspase-dependent apoptosis. Engineered peptides, obtained by alanine substitution of Ig CDR sequences, and used as surrogates of natural point mutations, showed further differential increased/unaltered/decreased antimicrobial, antiviral and/or antitumor activities. The inhibitory effects observed were largely independent of the specificity of the native Ab and involved chiefly germline encoded CDR1 and CDR2 of light and heavy chains. CONCLUSIONS/SIGNIFICANCE: The high frequency of bioactive peptides based on CDRs suggests that Ig molecules are sources of an unlimited number of sequences potentially active against infectious agents and tumor cells. The easy production and low cost of small

  14. Comparative Analysis of the Antiviral Activity of Camel, Bovine, and Human Lactoperoxidases Against Herpes Simplex Virus Type 1.

    Science.gov (United States)

    El-Fakharany, Esmail M; Uversky, Vladimir N; Redwan, Elrashdy M

    2017-05-01

    Lactoperoxidase is a milk hemoprotein that acts as a non-immunoglobulin protective protein and shows strong antimicrobial activity. Bovine milk contains about 15 and 7 times higher levels of lactoperoxidase than human colustrum and camel milk, respectively. Human, bovine, and camel lactoperoxidases (hLPO, bLPO, and cLPO, respectively) were purified as homogeneous samples with specific activities of 4.2, 61.3, and 8.7 u/mg, respectively. The optimal working pH was 7.5 (hLPO and bLPO) and 6.5 (cLPO), whereas the optimal working temperature for these proteins was 40 °C. The K m of hLPO, cLPO, and bLPO were 17, 16, and 19 mM, and their corresponding V max values were 2, 1.7, and 2.7 μmol/min ml. However, in the presence of H2O2, the K m values were 11 mM for hLPO and cLPO and 20 mM for bLPO, while the corresponding V max values were 1.17 for hLPO and 1.4 μmol/min ml for cLPO and bLPO. All three proteins were able to inhibit the herpes simplex virus type 1 (HSV-1) in Vero cell line model. The relative antiviral activities were proportional to the protein concentrations. The highest anti-HSV-1 activity was exhibited by bLPO that inhibited the HSV particles at a concentration of 0.5 mg/ml with the relative activity of 100%.

  15. Infection of goats with goatpox virus triggers host antiviral defense through activation of innate immune signaling.

    Science.gov (United States)

    Zeng, Xiancheng; Wang, Song; Chi, Xiaojuan; Chen, Shi-long; Huang, Shile; Lin, Qunqun; Xie, Baogui; Chen, Ji-Long

    2016-02-01

    Goatpox, caused by goatpox virus (GTPV), is one of the most serious infectious diseases associated with high morbidity and mortality in goats. However, little is known about involvement of host innate immunity during the GTPV infection. For this, goats were experimentally infected with GTPV. The results showed that GTPV infection significantly induced mRNA expression of type I interferon (IFN)-α and IFN-β in peripheral blood lymphocytes, spleen and lung. In addition, GTPV infection enhanced expression of several inflammatory cytokines, including interleukin (IL)-1β, IL-6, IL-18; and tumor necrosis factor-α (TNF-α). Strikingly, infection with GTPV activated signal transducers and activators of transcription 3 (STAT3), a critical cytokine signaling molecule. Interestingly, the virus infection induced expression of suppressor of cytokine signaling (SOCS)-1. Importantly, the infection resulted in an increased expression of some critical interferon-stimulated genes, such as interferon-induced transmembrane protein (IFITM) 1, IFITM3, interferon stimulated gene (ISG) 15 and ISG20. Furthermore, we found that infection with GTPV up-regulated expression of Toll-like receptor (TLR) 2 and TLR9. These results revealed that GTPV infection activated host innate immune signaling and thereby triggered antiviral innate immunity. The findings provide novel insights into complex mechanisms underlying GTPV-host interaction and pathogenesis of GTPV. Copyright © 2015 Elsevier Ltd. All rights reserved.

  16. Antiviral activity of Aloe hijazensis against some haemagglutinating viruses infection and its phytoconstituents.

    Science.gov (United States)

    Abd-Alla, Howaida I; Abu-Gabal, Nagat S; Hassan, Amal Z; El-Safty, Mounir M; Shalaby, Nagwa M M

    2012-08-01

    Evaluation of the antiviral activities of flowers, flower-peduncles, leaves, and roots of Aloe hijazensis against haemagglutinating viruses of avian paramyxovirus type-1 (APMV-1), avian influenza virus type A (AI-H5N1), Newcastle disease virus (NDV), and egg-drop syndrome virus (EDSV) in specific pathogen free (SPF) chicken embryos were carried out. Extract of the flowers and leaves showed relatively higher activity than the extracts of other plant parts. Thirteen compounds were isolated from both the flowers and flower-peduncles of A. hijazensis. The isolated compounds were classified into: five anthraquinones; ziganein, ziganein-5-methyl ether, aloesaponarin I, chrysophanol, aloe-emodin, one dihydroisocoumarin; feralolide, four flavonoids; homoplantaginin, isoorientin, luteolin 7-glucuronopyranoside, isovitexin, one phenolic acid; p-coumaric acid, the anthrone; barbaloin together with aloenin. Eleven compounds were attributed to the flowers and seven to the flower-peduncles. Homoplantaginin and luteolin 7-glucuronopyranoside are reported here for the first time from Aloe spp. To the best of our knowledge, this is the first report on the chemical composition and biological activity of those plant parts.

  17. Antiviral Activity of Crude Hydroethanolic Extract from Schinus terebinthifolia against Herpes simplex Virus Type 1.

    Science.gov (United States)

    Nocchi, Samara Requena; Companhoni, Mychelle Vianna Pereira; de Mello, João Carlos Palazzo; Dias Filho, Benedito Prado; Nakamura, Celso Vataru; Carollo, Carlos Alexandre; Silva, Denise Brentan; Ueda-Nakamura, Tânia

    2017-04-01

    Herpes simplex virus infections persist throughout the lifetime of the host and affect more than 80 % of the humans worldwide. The intensive use of available therapeutic drugs has led to undesirable effects, such as drug-resistant strains, prompting the search for new antiherpetic agents. Although diverse bioactivities have been identified in Schinus terebinthifolia, its antiviral activity has not attracted much attention. The present study evaluated the antiherpetic effects of a crude hydroethanolic extract from the stem bark of S. terebinthifolia against Herpes simplex virus type 1 in vitro and in vivo as well as its genotoxicity in bone marrow in mammals and established the chemical composition of the crude hydroethanolic extract based on liquid chromatography-diode array detector-mass spectrometry and MS/MS. The crude hydroethanolic extract inhibited all of the tested Herpes simplex virus type 1 strains in vitro and was effective in the attachment and penetration stages, and showed virucidal activity, which was confirmed by transmission electron microscopy. The micronucleus test showed that the crude hydroethanolic extract had no genotoxic effect at the concentrations tested. The crude hydroethanolic extract afforded protection against lesions that were caused by Herpes simplex virus type 1 in vivo. Liquid chromatography-diode array detector-mass spectrometry and MS/MS identified 25 substances, which are condensed tannins mainly produced by a B-type linkage and prodelphinidin and procyanidin units. Georg Thieme Verlag KG Stuttgart · New York.

  18. Antiviral Activity of Fridericia formosa (Bureau L. G. Lohmann (Bignoniaceae Extracts and Constituents

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    Geraldo Célio Brandão

    2017-01-01

    Full Text Available A phytochemical study of Fridericia formosa (Bignoniaceae ethanol extracts of leaves, stems, and fruits was guided by in vitro assays against vaccinia virus Western Reserve (VACV-WR, human herpes virus 1 (HSV-1, murine encephalomyocarditis virus (EMCV, and dengue virus type 2 (DENV-2 by the MTT method. All the ethanol extracts were active against DENV-2, HSV-1, and VACV-WR with best results for the fruits extract against DENV-2 (SI > 38.2. For VACV-WR and HSV-1, EC50 values > 200 μg mL−1 were determined, while no inhibition of the cytopathic effect was observed with EMCV. Five compounds were isolated and identified as the C-glucosylxanthones mangiferin (1, 2′-O-trans-caffeoylmangiferin (2, 2′-O-trans-coumaroylmangiferin (3, 2′-O-trans-cinnamoylmangiferin (5, and the flavonoid chrysin (4. The most active compound was 2′-O-trans-coumaroylmangiferin (3 with SI > 121.9 against DENV-2 and 108.7 for HSV-1. These results indicate that mangiferin cinnamoyl esters might be potential antiviral drugs.

  19. Study of the Biological Activity of Novel Synthetic Compounds with Antiviral Properties against Human Rhinoviruses

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    Raffaello Pompei

    2011-04-01

    Full Text Available Picornaviridae represent a very large family of small RNA viruses, some of which are the cause of important human and animal diseases. Since no specific therapy against any of these viruses currently exists, palliative symptomatic treatments are employed. The early steps of the picornavirus replicative cycle seem to be privileged targets for some antiviral compounds like disoxaril and pirodavir. Pirodavir’s main weakness is its cytotoxicity on cell cultures at relatively low doses. In this work some original synthetic compounds were tested, in order to find less toxic compounds with an improved protection index (PI on infected cells. Using an amino group to substitute the oxygen atom in the central chain, such as that in the control molecule pirodavir, resulted in decreased activity against Rhinoviruses and Polioviruses. The presence of an -ethoxy-propoxy- group in the central chain (as in compound I-6602 resulted in decreased cell toxicity and in improved anti-Rhinovirus activity. This compound actually showed a PI >700 on HRV14, while pirodavir had a PI of 250. These results demonstrate that modification of pirodavir’s central hydrocarbon chain can lead to the production of novel derivatives with low cytotoxicity and improved PI against some strains of Rhinoviruses.

  20. Mx Is Not Responsible for the Antiviral Activity of Interferon-α against Japanese Encephalitis Virus

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    Jing Zhou

    2017-01-01

    Full Text Available Mx proteins are interferon (IFN-induced dynamin-like GTPases that are present in all vertebrates and inhibit the replication of myriad viruses. However, the role Mx proteins play in IFN-mediated suppression of Japanese encephalitis virus (JEV infection is unknown. In this study, we set out to investigate the effects of Mx1 and Mx2 expression on the interferon-α (IFNα restriction of JEV replication. To evaluate whether the inhibitory activity of IFNα on JEV is dependent on Mx1 or Mx2, we knocked down Mx1 or Mx2 with siRNA in IFNα-treated PK-15 cells and BHK-21 cells, then challenged them with JEV; the production of progeny virus was assessed by plaque assay, RT-qPCR, and Western blotting. Our results demonstrated that depletion of Mx1 or Mx2 did not affect JEV restriction imposed by IFNα, although these two proteins were knocked down 66% and 79%, respectively. Accordingly, expression of exogenous Mx1 or Mx2 did not change the inhibitory activity of IFNα to JEV. In addition, even though virus-induced membranes were damaged by Brefeldin A (BFA, overexpressing porcine Mx1 or Mx2 did not inhibit JEV proliferation. We found that BFA inhibited JEV replication, not maturation, suggesting that BFA could be developed into a novel antiviral reagent. Collectively, our findings demonstrate that IFNα inhibits JEV infection by Mx-independent pathways.

  1. Evaluation of In vitro Antiviral Activity of Datura metel Linn. Against Rabies Virus

    Science.gov (United States)

    Roy, Soumen; Mukherjee, Sandeepan; Pawar, Sandip; Chowdhary, Abhay

    2016-01-01

    Objective: The soxhlet and cold extracts of Datura metel Linn. were evaluated for in vitro antirabies activity. Materials and Methods: Soxhlet and cold extraction method were used to extract Datura (fruit and seed) extracts. In vitro cytotoxicity assay was performed by 3-(4,5-dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide assay. Based on the CC50 range, the in vitro antirabies activity of the extracts was screened by rapid fluorescent focus inhibition test and molecular method. Results: The Datura (fruit and seed) extracts were not cytotoxic below 5 mg/ml (CC50). Titer of 10−4 rabies virus challenge virus standard (RV CVS) (1 50% tissue culture infective dose [1 TCID50]) was obtained by RFFT method and the challenge dose of 10 TCID50 was used for antirabies assay. Datura fruit and seed (soxhlet and cold) extracts showed 50% inhibition of RV CVS at 2.5 mg/ml and 1.25 mg/ml (inhibitory concentration 50% [IC50]), respectively. The tested extracts showed selectivity index (CC50/IC50) ranging from 2 to 4. The viral RNA was extracted and real-time reverse transcription-polymerase chain reaction was performed which also revealed a 2-fold reduction of viral load at 1.25 mg/ml of the Datura seed (soxhlet methanolic and cold aqueous) extracts. Conclusion: To the best of our knowledge, this is the first study of in vitro antiviral activity of D. metel Linn. against rabies virus. Datura seed extracts have a potential in vitro antirabies activity and, in future, can be further screened for in vivo activity against rabies virus in murine model. SUMMARY In the present study, Datura metel. Linn showed and in-vitro anti rabies activity in Vero cell line which was determined by RFFIT method and PCR method PMID:27695266

  2. In Vitro Antiviral Activity of Clove and Ginger Aqueous Extracts against Feline Calicivirus, a Surrogate for Human Norovirus.

    Science.gov (United States)

    Aboubakr, Hamada A; Nauertz, Andrew; Luong, Nhungoc T; Agrawal, Shivani; El-Sohaimy, Sobhy A A; Youssef, Mohammed M; Goyal, Sagar M

    2016-06-01

    Foodborne viruses, particularly human norovirus, are a concern for public health, especially in fresh vegetables and other minimally processed foods that may not undergo sufficient decontamination. It is necessary to explore novel nonthermal techniques for preventing foodborne viral contamination. In this study, aqueous extracts of six raw food materials (flower buds of clove, fenugreek seeds, garlic and onion bulbs, ginger rhizomes, and jalapeño peppers) were tested for antiviral activity against feline calicivirus (FCV) as a surrogate for human norovirus. The antiviral assay was performed using dilutions of the extracts below the maximum nontoxic concentrations of the extracts to the host cells of FCV, Crandell-Reese feline kidney (CRFK) cells. No antiviral effect was seen when the host cells were pretreated with any of the extracts. However, pretreatment of FCV with nondiluted clove and ginger extracts inactivated 6.0 and 2.7 log of the initial titer of the virus, respectively. Also, significant dosedependent inactivation of FCV was seen when host cells were treated with clove and ginger extracts at the time of infection or postinfection at concentrations equal to or lower than the maximum nontoxic concentrations. By comprehensive two-dimensional gas chromatography-mass spectrometry analysis, eugenol (29.5%) and R-(-)-1,2-propanediol (10.7%) were identified as the major components of clove and ginger extracts, respectively. The antiviral effect of the pure eugenol itself was tested; it showed antiviral activity similar to that of clove extract, albeit at a lower level, which indicates that some other clove extract constituents, along with eugenol, are responsible for inactivation of FCV. These results showed that the aqueous extracts of clove and ginger hold promise for prevention of foodborne viral contamination.

  3. TRIM11 negatively regulates IFNβ production and antiviral activity by targeting TBK1.

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    Younglang Lee

    Full Text Available The innate immune response is a host defense mechanism against infection by viruses and bacteria. Type I interferons (IFNα/β play a crucial role in innate immunity. If not tightly regulated under normal conditions and during immune responses, IFN production can become aberrant, leading to inflammatory and autoimmune diseases. In this study, we identified TRIM11 (tripartite motif containing 11 as a novel negative regulator of IFNβ production. Ectopic expression of TRIM11 decreased IFNβ promoter activity induced by poly (I:C stimulation or overexpression of RIG-I (retinoic acid-inducible gene-I signaling cascade components RIG-IN (constitutively active form of RIG-I, MAVS (mitochondrial antiviral signaling protein, or TBK1 (TANK-binding kinase-1. Conversely, TRIM11 knockdown enhanced IFNβ promoter activity induced by these stimuli. Moreover, TRIM11 overexpression inhibited the phosphorylation and dimerization of IRF3 and expression of IFNβ mRNA. By contrast, TRIM11 knockdown increased the IRF3 phosphorylation and IFNβ mRNA expression. We also found that TRIM11 and TBK1, a key kinase that phosphorylates IRF3 in the RIG-I pathway, interacted with each other through CC and CC2 domain, respectively. This interaction was enhanced in the presence of the TBK1 adaptor proteins, NAP1 (NF-κB activating kinase-associated protein-1, SINTBAD (similar to NAP1 TBK1 adaptor or TANK (TRAF family member-associated NF-κB activator. Consistent with its inhibitory role in RIG-I-mediated IFNβ signaling, TRIM11 overexpression enhanced viral infectivity, whereas TRIM11 knockdown produced the opposite effect. Collectively, our results suggest that TRIM11 inhibits RIG-I-mediated IFNβ production by targeting the TBK1 signaling complex.

  4. Antiviral CD8+ T Cells Restricted by Human Leukocyte Antigen Class II Exist during Natural HIV Infection and Exhibit Clonal Expansion.

    Science.gov (United States)

    Ranasinghe, Srinika; Lamothe, Pedro A; Soghoian, Damien Z; Kazer, Samuel W; Cole, Michael B; Shalek, Alex K; Yosef, Nir; Jones, R Brad; Donaghey, Faith; Nwonu, Chioma; Jani, Priya; Clayton, Gina M; Crawford, Frances; White, Janice; Montoya, Alana; Power, Karen; Allen, Todd M; Streeck, Hendrik; Kaufmann, Daniel E; Picker, Louis J; Kappler, John W; Walker, Bruce D

    2016-10-18

    CD8+ T cell recognition of virus-infected cells is characteristically restricted by major histocompatibility complex (MHC) class I, although rare examples of MHC class II restriction have been reported in Cd4-deficient mice and a macaque SIV vaccine trial using a recombinant cytomegalovirus vector. Here, we demonstrate the presence of human leukocyte antigen (HLA) class II-restricted CD8+ T cell responses with antiviral properties in a small subset of HIV-infected individuals. In these individuals, T cell receptor β (TCRβ) analysis revealed that class II-restricted CD8+ T cells underwent clonal expansion and mediated killing of HIV-infected cells. In one case, these cells comprised 12% of circulating CD8+ T cells, and TCRα analysis revealed two distinct co-expressed TCRα chains, with only one contributing to binding of the class II HLA-peptide complex. These data indicate that class II-restricted CD8+ T cell responses can exist in a chronic human viral infection, and may contribute to immune control. Copyright © 2016 The Author(s). Published by Elsevier Inc. All rights reserved.

  5. Antiviral, Antifungal and Antibacterial Activities of a BODIPY-Based Photosensitizer

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    Bradley L. Carpenter

    2015-06-01

    Full Text Available Antimicrobial photodynamic inactivation (aPDI employing the BODIPY-based photosensitizer 2,6-diiodo-1,3,5,7-tetramethyl-8-(N-methyl-4-pyridyl-4,4′-difluoro-boradiazaindacene (DIMPy-BODIPY was explored in an in vitro assay against six species of bacteria (eight total strains, three species of yeast, and three viruses as a complementary approach to their current drug-based or non-existent treatments. Our best results achieved a noteworthy 5–6 log unit reduction in CFU at 0.1 μM for Staphylococcus aureus (ATCC-2913, methicillin-resistant S. aureus (ATCC-44, and vancomycin-resistant Enterococcus faecium (ATCC-2320, a 4–5 log unit reduction for Acinetobacter baumannii ATCC-19606 (0.25 μM, multidrug resistant A. baumannii ATCC-1605 (0.1 μM, Pseudomonas aeruginosa ATCC-97 (0.5 μM, and Klebsiella pneumoniae ATCC-2146 (1 μM, and a 3 log unit reduction for Mycobacterium smegmatis mc2155 (ATCC-700084. A 5 log unit reduction in CFU was observed for Candida albicans ATCC-90028 (1 μM and Cryptococcus neoformans ATCC-64538 (0.5 μM, and a 3 log unit reduction was noted for Candida glabrata ATCC-15545 (1 μM. Infectivity was reduced by 6 log units in dengue 1 (0.1 μM, by 5 log units (0.5 μM in vesicular stomatitis virus, and by 2 log units (5 μM in human adenovirus-5. Overall, the results demonstrate that DIMPy-BODIPY exhibits antiviral, antibacterial and antifungal photodynamic inactivation at nanomolar concentrations and short illumination times.

  6. A new resin glycoside from Calystegia soldanella and its antiviral activity towards herpes.

    Science.gov (United States)

    Ono, Masateru; Kanemaru, Yukiyo; Yasuda, Shin; Okawa, Masafumi; Kinjo, Junei; Miyashita, Hiroyuki; Yokomizo, Kazumi; Yoshimitsu, Hitoshi; Nohara, Toshihiro

    2017-11-01

    A new resin glycoside, named calysolin XVIII (1), was isolated from the leaves, stems and roots of Calystegia soldanella Roem. et Schult. (Convolvulaceae). The structure of 1 was defined as 11S-jalapinolic acid 11-O-β-d-glucopyranosyl-(1 → 3)-O-(2-O-2S-methylbutyryl,4-O-3-hydroxy-2-methylenebutyryl)-α-l-rhamnopyranosyl-(1 → 2)-[O-β-d-glucopyranosyl-(1 → 6)-O-(34-di-O-2S-methylbutyryl)-β-d-glucopyranosyl-(1 → 3)]-O-β-d-glucopyranosyl-(1 → 2)-β-d-quinovopyranoside, intramolecular 1,2″'″'-ester on the basis of spectroscopic data. Compound 1 is the first known resin glycoside to feature 3-hydroxy-2-methylenebutyric acid as a component organic acid. In addition, 1 demonstrated an antiviral activity against herpes simplex virus type 1, with an IC 50 value 2.3 μM.

  7. Synthesis and evaluation of antiviral activities of novel sonochemical silver nanorods against HIV and HSV viruses

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    Mazyar Etemadzade

    2016-11-01

    Full Text Available Objective: To evaluate the effect of novel sonochemical silver nanorods on HIV and herpes simplex virus type 1 (HSV-1 viruses in human cervical cancer HeLa cells. Methods: The formation of silver nanorods conjugated with sodium 2-mercaptoethane sulfonate (Ag-MES was characterized by scanning electron microscopy, Fourier transform infrared spectroscopy and thermal gravimetric analysis. The antiviral activity of this Ag-MES was examined against HIV and HSV-1 virus replication. Results: The characterizations of Ag-MES and physiochemical structure were determined by scanning electron microscopy, Fourier transform infrared spectroscopy and thermal gravimetric analysis. Approximately entire viral replication was inhibited by Ag-MES at 10 µmol/mL concentration. About 90% of HSV virions failed to replicate in the present of this concentration of nanorods. However, HIV showed more sensitivity to Ag-MES than HSV-1. Conclusions: According to the obtained data, the synthesized sonochemical silver nanorod in this study is a promising candidate for further drug discovery investigation.

  8. [Antiviral activity of Ingavirin on an animal model for experimental disseminated adenovirus infection].

    Science.gov (United States)

    Zarubaev, V V; Slita, A V; Beliaevskaia, S V; Nebol'sin, V E; Kiselev, O I; Reĭkhart, D V

    2011-01-01

    Adenoviruses constitute a clinically important family of human pathogens. Due to their wide tissue tropism, adenoviruses are able to induce different diseases from moderate respiratory disorders to fatal outcomes in patients with immunodeficiencies. The authors present the results of a trial of the antiviral activity of the new drug Ingavirin [2-(imidazole-4-yl-ethanamide) pentandioic-1,5 acid] against human adenovirus type 5 on an animal model. Ingavirin is shown to decrease an adenoviral infectious titer in the liver and lung of neonatal Syrian hamsters (by approximately 1 log10 TCID50 as compared to the control) and to reduce the sizes of liver inflammation foci by 2-fold. Furthermore, it also decreases the count of virus-infected cells detectable by morphological analysis. Hepatocytes from Ingavirin-treated animals appear intact unlike strongly vacuolized cells from the animals given placebo. The findings make it possible to regard Ingavirin as a promising agent of the combination therapy of human adenovirus disease.

  9. Antiviral Activity of a Nanoemulsion of Polyprenols from Ginkgo Leaves against Influenza A H3N2 and Hepatitis B Virus in Vitro

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    Cheng-Zhang Wang

    2015-03-01

    Full Text Available In order to improve the bioavailability levels of polyprenols (derived from ginkgo leaves (GBP in the human body, a GBP nanoemulsion was prepared, and its antiviral activity was evaluated against influenza A H3N2 and hepatitis B virus in vitro. Methods: A GBP nanoemulsion was prepared by inversed-phase emulsification (IPE. Next, we investigated the antiviral activity of the GBP nanoemulsion on influenza A H3N2 and hepatitis B virus in vitro by the MTT (3-(4,5-dimethylthiazol-2-yl-2,5-diphenlytetrezolium bromide method. ELISA and the fluorescent quantitative PCR method were used to measure the content of HBsAg, HBeAg and DNA virus in human samples. Results: The GBP nanoemulsion exhibited uniformity at an average particle size 97 nm with a hydrophilic-lipophilic balance (HLB of 9.5. GBP is non-toxic to normal cells, hepatitis B virus DNA, hepatitis B virus antigen and HepG2215. Furthermore, GBP could reach a 70% virucidal activity and a 74.9% protection rate (*** p < 0.001 on MDCK cells infected with H3N2 virus at a high concentration of 100 μg/mL. GBP had a good inhibition rate on HBsAg (52.11%, ** p < 0.01 at 50 μg/mL and Day 9 of incubation, and a 67.32% inhibition effect on HBeAg at a high concentration of 100 μg/mL and Day 9. GBP had good inhibition on HBV DNA with CT 18.6 and lower copies (** p < 0.01 at a middle concentration of 12.5 to 25 μg/mL. Conclusions: The GBP nanoemulsion was very stable and non-toxic and had very strong antiviral activity against influenza A H3N2 and hepatitis B virus in vitro. The inhibitory effects and reactive mechanisms were similar to the drug, 3TC; by lengthening the incubation time and increasing the drug concentration, GBP has promising potential as an antiviral drug.

  10. Atividade antiviral de extratos de plantas medicinais disponíveis comercialmente frente aos herpesvírus suíno e bovino Antiviral activity of commercially available medicinal plants on suid and bovine herpesviruses

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    V.M. Kaziyama

    2012-01-01

    Full Text Available O presente trabalho teve como objetivo pesquisar a atividade antiviral in vitro de plantas medicinais disponíveis comercialmente sobre herpesvírus suíno (SuHV-1 e bovino (BoHV-1. As espécies adquiridas foram Mikania glomerata, Cymbopogon citratus, Equisetum arvense, Peumus boldus, Solanum paniculatum, Malva sylvestris, Piper umbellatun e Solidago microglossa. A citotoxicidade dos extratos foi avaliada na linhagem celular MDBK pelas alterações morfológicas das células e obtenção da concentração máxima não citotóxica (CMNC de cada planta. A atividade antiviral foi realizada com os extratos em suas respectivas CMNC e avaliada com base na redução do título viral e expressos em porcentagem de inibição. Os extratos aquosos de Peumus boldus e Solanum paniculatum apresentaram atividade antiviral sobre o SuHV-1 com 98% de inibição viral enquanto o de Peumus boldus inibiu apenas o BoHV-1 em 99%.This paper aims to find commercially available medicinal plants showing antiviral activity in vitro on suid and bovine herpesviruses. The following species were tested: Mikania glomerata, Cymbopogon citratus, Equisetum arvense, Peumus boldus, Solanum paniculatum, Malva sylvestris, Piper umbellatun and Solidago microglossa. The cytotoxicity was evaluated by morphological changes in cells determining the maximum not cytotoxic concentration (MNCC. The antiviral activity was evaluated by viral title reduction. The extracts from Peumus boldus and Solanum paniculatum showed antiviral activity against SuHV-1 with 98% of inhibition. The extract of Peumus boldus also showed activity against BoHV-1 with 99% of inhibition.

  11. Biliverdin inhibits hepatitis C virus nonstructural 3/4A protease activity: mechanism for the antiviral effects of heme oxygenase?

    Science.gov (United States)

    Zhu, Zhaowen; Wilson, Anne T; Luxon, Bruce A; Brown, Kyle E; Mathahs, M Meleah; Bandyopadhyay, Sarmistha; McCaffrey, Anton P; Schmidt, Warren N

    2010-12-01

    Induction of heme oxygenase-1 (HO-1) inhibits hepatitis C virus (HCV) replication. Of the products of the reaction catalyzed by HO-1, iron has been shown to inhibit HCV ribonucleic acid (RNA) polymerase, but little is known about the antiviral activity of biliverdin (BV). Herein, we report that BV inhibits viral replication and viral protein expression in a dose-dependent manner in replicons and cells harboring the infectious J6/JFH construct. Using the SensoLyte 620 HCV Protease Assay with a wide wavelength excitation/emission (591 nm/622 nm) fluorescence energy transfer peptide, we found that both recombinant and endogenous nonstructural 3/4A (NS3/4A) protease from replicon microsomes are potently inhibited by BV. Of the tetrapyrroles tested, BV was the strongest inhibitor of NS3/4A activity, with a median inhibitory concentration (IC(50)) of 9 μM, similar to that of the commercial inhibitor, AnaSpec (Fremont, CA) #25346 (IC(50) 5 μM). Lineweaver-Burk plots indicated mixed competitive and noncompetitive inhibition of the protease by BV. In contrast, the effects of bilirubin (BR) on HCV replication and NS3/4A were much less potent. Because BV is rapidly converted to BR by biliverdin reductase (BVR) intracellularly, the effect of BVR knockdown on BV antiviral activity was assessed. After greater than 80% silencing of BVR, inhibition of viral replication by BV was enhanced. BV also increased the antiviral activity of α-interferon in replicons. BV is a potent inhibitor of HCV NS3/4A protease, which likely contributes to the antiviral activity of HO-1. These findings suggest that BV or its derivatives may be useful in future drug therapies targeting the NS3/4A protease. Copyright © 2010 American Association for the Study of Liver Diseases.

  12. Biliverdin Inhibits Hepatitis C Virus NS3/4A Protease Activity: Mechanism for the Antiviral Effects of Heme Oxygenase?

    Science.gov (United States)

    Zhu, Zhaowen; Wilson, Anne T.; Luxon, Bruce A.; Brown, Kyle E.; Mathahs, M. Meleah; Bandyopadhyay, Sarmistha; McCaffrey, Anton P.; Schmidt, Warren N.

    2010-01-01

    Induction of heme oxygenase -1 (HO-1) inhibits hepatitis C virus (HCV) replication. Of the products of the reaction catalyzed by HO-1 iron has been shown to inhibit HCV RNA polymerase, but little is known about the antiviral activity of biliverdin (BV). Herein, we report that BV inhibits viral replication and viral protein expression in a dose-dependent manner in replicons and cells harboring the infectious J6/JFH construct. Using the SensoLyte 620 HCV Protease Assay with a wide wavelength excitation/emission (591nm/622nm) fluorescence energy transfer peptide, we found that both recombinant and endogenous NS3/4A protease from replicon microsomes are potently inhibited by BV. Of the tetrapyrroles tested, BV was the strongest inhibitor of NS3/4A activity with an IC50 of 9 uM, similar to that of the commercial inhibitor, AnaSpec #25346 (IC50 5 uM). Lineweaver-Burk plots indicated mixed competitive and non-competitive inhibition of the protease by BV. In contrast, the effects of bilirubin (BR) on HCV replication and NS3/4A were much less potent. Because BV is rapidly converted to BR by biliverdin reductase (BVR) intracellularly, the effect of BVR knockdown on BV antiviral activity was assessed. After >80% silencing of BVR, inhibition of viral replication by BV was enhanced. BV also increased the antiviral activity of α-interferon in replicons. Conclusion BV is a potent inhibitor of HCV NS3/4A protease, which likely contributes to the antiviral activity of HO-1. These findings suggest that BV or its derivatives may be useful future drug therapies targeting the NS3/4A protease. PMID:21105106

  13. Antiviral activities of plants occurring in the state of Minas Gerais, Brazil: Part 2. Screening Bignoniaceae species

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    Geraldo Célio Brandão

    2010-11-01

    Full Text Available Ethanol extracts of eighteen Bignoniaceae species have been evaluated by the MTT assay for cytotoxicity in Vero cells and for antiviral activity against Human herpes virus type 1, Vaccinia virus and murine Encephalomyocarditis virus. Among such species, seven are reported to be of traditional medicinal use No cytotoxicity was observed for most of the extracts up to the concentration of 500 μg/mL. Fourteen (50% of the 28 extracts assayed have disclosed antiviral activity with EC50 values in the range of 4.6+0.3 to 377.2+17.7 μg/mL. Only two species, Arrabidaea samydoides and Callichlamys latifolia, have shown activity against all the three viruses. The extracts were chemically characterized by their TLC and HPLC-DAD profiles. Mangiferin is the major constituent of A. samydoides but the isolated compound has been less active than the crude extract. This is the first report on the antiviral evaluation of the eighteen Bignoniaceae species assayed.

  14. Evaluation of antiviral activity of South American plant extracts against herpes simplex virus type 1 and rabies virus.

    Science.gov (United States)

    Müller, Vanessa; Chávez, Juliana H; Reginatto, Flávio H; Zucolotto, Silvana M; Niero, Rivaldo; Navarro, Dionezine; Yunes, Rosendo A; Schenkel, Eloir P; Barardi, Célia R M; Zanetti, Carlos R; Simões, Cláudia M O

    2007-10-01

    This paper describes the screening of different South American plant extracts and fractions. Aqueous and organic extracts were prepared and tested for antiherpetic (HSV-1, KOS and 29R strains) and antirabies (PV strain) activities. The evaluation of the potential antiviral activity of these extracts was performed by using an MTT assay for HSV-1, and by a viral cytopathic effect (CPE) inhibitory method for rabies virus (RV). The results were expressed as 50% cytotoxicity (CC(50)) for MTT assay and 50% effective (EC(50)) concentrations for CPE, and with them it was possible to calculate the selectivity indices (SI = CC(50)/EC(50)) of each tested material. From the 18 extracts/fractions tested, six extracts and four fractions showed antiviral action. Ilex paraguariensis, Lafoensia pacari, Passiflora edulis, Rubus imperialis and Slonea guianensis showed values of SI > 7 against HSV-1 KOS and 29-R strains and Alamanda schottii showed a SI of 5.6 against RV, PV strain.

  15. Anti-viral and anti-bacterial activities of an extract of blackcurrants (Ribes nigrum L.).

    Science.gov (United States)

    Ikuta, Kazufumi; Hashimoto, Koichi; Kaneko, Hisatoshi; Mori, Shuichi; Ohashi, Kazutaka; Suzutani, Tatsuo

    2012-12-01

    The inhibitory effects of an extract of the blackcurrant (Ribes nigrum L.) against pathogens associated with oral, nasopharyngeal and upper respiratory infectious diseases; namely respiratory syncytial virus (RSV), influenza virus A and B (IFV-A and IFV-B), adenovirus (AdV), herpes simplex virus type 1, Haemophilus influenzae type B, Streptococcus pneumoniae and Streptococcus mutans, were investigated. Less than 1% concentration of extract of blackcurrant inhibited replication of RSV, IFV-A and -B and HSV-1 by over 50% and a 10% extract inhibited adsorption of these viruses onto the cell surface by over 95%. The effects on AdV were much less pronounced; the half minimal inhibitory concentration of AdV replication was 2.54 ± 0.26, and a 10% concentration of the extract inhibited AdV adsorption on the cell surface by 72.9 ± 3.4%. The antibacterial activities of the blackcurrant were evaluated based on its efficacy as a disinfectant. A 10% extract disinfected 99.8% of H. Influenzae type B and 78.9% of S. pneumoniae in 10 min, but had no demonstrable effect against S. mutans. The blackcurrant extract still showed antiviral and antibacterial activities after the pH had been made neutral with sodium hydroxide, suggesting that these activities are not the result of acidic reactions or of components precipitated at a neutral pH. These findings demonstrate the potential of blackcurrant extract as a functional food for oral care. © 2012 The Societies and Wiley Publishing Asia Pty Ltd.

  16. Stereoselective Synthesis and Antiviral Activity of Novel 4'(α)-Hydroxymethyl and 6'(α)-Methyl Dually Branched Carbocyclic Nucleosides

    Energy Technology Data Exchange (ETDEWEB)

    Jin Woo Kim, Joon Hee Hong [Chosun University, Gwangju (Korea, Republic of); Choi, Bo Gil [Chonnam National University, Gwangju (Korea, Republic of)

    2004-12-15

    The stereoselective synthesis 4',6'-dually branched carbocyclic nucleosides was accomplished in this study. The introduction of a methyl group in the 6'(α)-position was accomplished by Felkin-Anh controlled alkylation. The construction of the required 4'(α)-quaternary carbon was carried out using a [3,3]-sigmatropic rearrangement. Bis-vinyl 6 was successfully cyclized using a Grubbs' catalyst II. The natural bases (adenine, cytosine) were efficiently coupled using a Pd(0) catalyst. When the synthesized compounds were examined for their activity against several viruses such as the HIV-1, HSV-1, HSV-2 and HCMV, the cytosine analogue 13 exhibited good antiviral activity against the HCMV.

  17. Antiviral Activity of Marine Actinobacteria against Bovine Viral Diarrhea Virus, a Surrogate Model of the Hepatitis C Virus

    OpenAIRE

    Juliana Cristina Santiago Bastos; Cláudia Beatriz Afonso de Menezes; Fabiana Fantinatti-Garboggini; Marina Aiello Padilla; Clarice Weis Arns; Luciana Konecny Kohn

    2015-01-01

    The Hepatitis C virus (Flaviviridae family, Hepacivirus genus) represents a major public health problem worldwide and it is responsible for chronic infections in humans, which can develop to liver cirrhosis and hepatocellular carcinoma. As this virus does not replicate efficiently in cell culture and in animals, bovine viral diarrhea virus (BVDV) is used as a surrogate model for screening assays of antiviral activity, and mechanism of action assays. From marine invertebrates and their microor...

  18. Antiviral activity of punicalagin toward human enterovirus 71 in vitro and in vivo.

    Science.gov (United States)

    Yang, Yajun; Xiu, Jinghui; Zhang, Lianfeng; Qin, Chuan; Liu, Jiangning

    2012-12-15

    Human enterovirus 71 is one of the major causative agents of hand, foot and mouth disease in children and has caused mortalities in large-scale outbreaks in the Asia-Pacific region in recent years. No vaccine or antiviral therapy is available currently in the clinic. In this work, we investigated the antiviral effect of punicalagin on enterovirus 71 both in vitro and in vivo. The results showed that punicalagin reduced the viral cytopathic effect on rhabdomyosarcoma cells with an IC₅₀) value of 15 μg/ml. Moreover, punicalagin treatment of mice challenged with a lethal dose of enterovirus 71 resulted in a reduction of mortality and relieved clinical symptoms by inhibiting viral replication. Our work suggested that punicalagin have the potential for further development as antiviral agents against enterovirus 71. Copyright © 2012 Elsevier GmbH. All rights reserved.

  19. Circulating Metabolites of the Human Immunodeficiency Virus Protease Inhibitor Nelfinavir in Humans: Structural Identification, Levels in Plasma, and Antiviral Activities

    Science.gov (United States)

    Zhang, Kanyin E.; Wu, Ellen; Patick, Amy K.; Kerr, Bradley; Zorbas, Mark; Lankford, Angela; Kobayashi, Takuo; Maeda, Yuki; Shetty, Bhasker; Webber, Stephanie

    2001-01-01

    Nelfinavir mesylate (Viracept, formally AG1343) is a potent and orally bioavailable human immunodeficiency virus (HIV) type 1 (HIV-1) protease inhibitor (Ki = 2 nM) and is being widely prescribed in combination with HIV reverse transcriptase inhibitors for the treatment of HIV infection. The current studies evaluated the presence of metabolites circulating in plasma following the oral administration of nelfinavir to healthy volunteers and HIV-infected patients, as well as the levels in plasma and antiviral activities of these metabolites. The results showed that the parent drug was the major circulating chemical species, followed in decreasing abundance by its hydroxy-t-butylamide metabolite (M8) and 3′-methoxy-4′-hydroxynelfinavir (M1). Antiviral assays with HIV-1 strain RF-infected CEM-SS cells showed that the 50% effective concentrations (EC50) of nelfinavir, M8, and M1 were 30, 34, and 151 nM, respectively, and that the corresponding EC50 against another HIV-1 strain, IIIB, in MT-2 cells were 60, 86, and 653 nM. Therefore, apparently similar in vitro antiviral activities were demonstrated for nelfinavir and M8, whereas an approximately 5- to 11-fold-lower level of antiviral activity was observed for M1. The active metabolite, M8, showed a degree of binding to human plasma proteins similar to that of nelfinavir (ca. 98%). Concentrations in plasma of nelfinavir and its metabolites in 10 HIV-positive patients receiving nelfinavir therapy (750 mg three times per day) were determined by a liquid chromatography tandem mass spectrometry assay. At steady state (day 28), the mean plasma nelfinavir concentrations ranged from 1.73 to 4.96 μM and the M8 concentrations ranged from 0.55 to 1.96 μM, whereas the M1 concentrations were low and ranged from 0.09 to 0.19 μM. In conclusion, the findings from the current studies suggest that, in humans, nelfinavir forms an active metabolite circulating at appreciable levels in plasma. The active metabolite M8 may account for

  20. Comparison of antiviral activity between IgA and IgG specific to influenza virus hemagglutinin: increased potential of IgA for heterosubtypic immunity

    National Research Council Canada - National Science Library

    Muramatsu, Mieko; Yoshida, Reiko; Yokoyama, Ayaka; Miyamoto, Hiroko; Kajihara, Masahiro; Maruyama, Junki; Nao, Naganori; Manzoor, Rashid; Takada, Ayato

    2014-01-01

    .... Although IgA antibodies are believed to have unique advantages in mucosal immunity, information on direct comparisons of the in vitro antiviral activities of IgA and IgG antibodies recognizing...

  1. TLR9-dependent recognition of MCMV by IPC and DC generates coordinated cytokine responses that activate antiviral NK cell function.

    Science.gov (United States)

    Krug, Anne; French, Anthony R; Barchet, Winfried; Fischer, Jens A A; Dzionek, Andrzej; Pingel, Jeanette T; Orihuela, Michael M; Akira, Shizuo; Yokoyama, Wayne M; Colonna, Marco

    2004-07-01

    Natural interferon-producing cells (IPC) respond to viruses by secreting type I interferon (IFN) and interleukin-12 (IL-12). Toll-like receptor (TLR) 9 mediates IPC recognition of some of these viruses in vitro. However, whether TLR9-induced activation of IPC is necessary for an effective antiviral response in vivo is not clear. Here, we demonstrate that IPC and dendritic cells (DC) recognize murine cytomegalovirus (MCMV) through TLR9. TLR9-mediated cytokine secretion promotes viral clearance by NK cells that express the MCMV-specific receptor Ly49H. Although depletion of IPC leads to a drastic reduction of the IFN-alpha response, this allows other cell types to secrete IL-12, ensuring normal IFN-gamma and NK cell responses to MCMV. We conclude that the TLR9/MyD88 pathway mediates antiviral cytokine responses by IPC, DC, and possibly other cell types, which are coordinated to promote effective NK cell function and MCMV clearance.

  2. Free fatty acids induce ER stress and block antiviral activity of interferon alpha against hepatitis C virus in cell culture

    Directory of Open Access Journals (Sweden)

    Gunduz Feyza

    2012-08-01

    Full Text Available Abstract Background Hepatic steatosis is recognized as a major risk factor for liver disease progression and impaired response to interferon based therapy in chronic hepatitis C (CHC patients. The mechanism of response to interferon-alpha (IFN-α therapy under the condition of hepatic steatosis is unexplored. We investigated the effect of hepatocellular steatosis on hepatitis C virus (HCV replication and IFN-α antiviral response in a cell culture model. Methods Sub-genomic replicon (S3-GFP and HCV infected Huh-7.5 cells were cultured with a mixture of saturated (palmitate and unsaturated (oleate long-chain free fatty acids (FFA. Intracytoplasmic fat accumulation in these cells was visualized by Nile red staining and electron microscopy then quantified by microfluorometry. The effect of FFA treatment on HCV replication and IFN-α antiviral response was measured by flow cytometric analysis, Renilla luciferase activity, and real-time RT-PCR. Results FFA treatment induced dose dependent hepatocellular steatosis and lipid droplet accumulation in the HCV replicon cells was confirmed by Nile red staining, microfluorometry, and by electron microscopy. Intracellular fat accumulation supports replication more in the persistently HCV infected culture than in the sub-genomic replicon (S3-GFP cell line. FFA treatment also partially blocked IFN-α response and viral clearance by reducing the phosphorylation of Stat1 and Stat2 dependent IFN-β promoter activation. We show that FFA treatment induces endoplasmic reticulum (ER stress response and down regulates the IFNAR1 chain of the type I IFN receptor leading to defective Jak-Stat signaling and impaired antiviral response. Conclusion These results suggest that intracellular fat accumulation in HCV cell culture induces ER stress, defective Jak-Stat signaling, and attenuates the antiviral response, thus providing an explanation to the clinical observation regarding how hepatocellular steatosis influences IFN

  3. Antiviral activity of crude extracts from Commiphora swynnertonii against Newcastle disease virus in ovo.

    Science.gov (United States)

    Bakari, Gaymary George; Max, Robert A; Mdegela, Robinson H; Phiri, Elliot C J; Mtambo, Mkumbukwa M A

    2012-10-01

    Studies were carried out to investigate the effect of crude extracts from resin, leaves, stem barks and root barks of Commiphora swynnertonii against Newcastle disease virus (NDV) using an in ovo assay. Nine-day-old embryonated chicken eggs were divided into seven groups (n = 6) and received various treatments. Six groups were inoculated with velogenic NDV strain; five groups out of these were treated with different concentrations of the four extracts or a diluent, dimethylsulphoxide. The uninoculated and inoculated groups were left as negative and positive controls, respectively. Embryo survival was observed daily and embryo weights were measured day 5 post-inoculation; a few eggs from selected groups were left to hatch. Allantoic fluid from treated eggs and serum from hatched chicks were collected for hemagglutination and hemagglutination inhibition (HI) tests to detect NDV in the eggs and antibodies against NDV in the hatched chicks respectively. Results showed that embryo survival and mean embryo weight were significantly higher (p < 0.001) in those groups which were treated with the crude extracts from C. swynnertonii than the positive control group. Also the extracts significantly (p < 0.001) reduced virus titres, whereas no viruses were detected in the allantoic fluids of the resin-treated group at the highest concentration of 500 μg/mL. Furthermore, the HI test results showed very low levels of antibodies against NDV in chicks hatched from resin and root bark extract-treated eggs suggesting that these plant materials were capable of destroying the NDV before stimulating the developing chick's immunity. The current findings have clearly demonstrated that crude extracts especially that of resin from C. swynnertonii have strong antiviral activity against NDV in ovo. In vivo trials are needed to validate the use of resin from the tree in controlling Newcastle disease in chickens.

  4. Charge modification of plasma and milk proteins results in antiviral active compounds

    NARCIS (Netherlands)

    Swart, P J; Harmsen, M C; Kuipers, M E; Van Dijk, A A; Van Der Strate, B W; Van Berkel, P H; Nuijens, J H; Smit, C; Witvrouw, M; De Clercq, E; de Béthune, M P; Pauwels, R; Meijer, D K

    1999-01-01

    Previous studies have shown that acylated plasma and milk proteins with increased negative charge, derived from various animal and human sources, are potent anti-HIV compounds. The antiviral effects seemed to correlate positively with the number of negative charges introduced into the various

  5. Piper betle extracts exhibit antitumor activity by augmenting antioxidant potential

    OpenAIRE

    ALAM, BADRUL; MAJUMDER, RAJIB; AKTER, SHAHINA; LEE, SANG-HAN

    2014-01-01

    The present study was conducted to evaluate the methanolic extract of Piper betle leaves (MPBL) and its organic fractions with regard to antitumor activity against Ehrlich ascites carcinoma (EAC) in Swiss albino mice and to confirm their antioxidant activities. At 24 h post-intraperitoneal inoculation of tumor cells into mice, extracts were administered at 25, 50 and 100 mg/kg body weight for nine consecutive days. The antitumor effects of the extracts were then assessed according to tumor vo...

  6. Pomegranate extract exhibits in vitro activity against Clostridium difficile.

    Science.gov (United States)

    Finegold, Sydney M; Summanen, Paula H; Corbett, Karen; Downes, Julia; Henning, Susanne M; Li, Zhaoping

    2014-10-01

    To determine the possible utility of pomegranate extract in the management or prevention of Clostridium difficile infections or colonization. The activity of pomegranate was tested against 29 clinical C. difficile isolates using the Clinical and Laboratory Standards Institute-approved agar dilution technique. Total phenolics content of the pomegranate extract was determined by Folin-Ciocalteau colorimetric method and final concentrations of 6.25 to 400 μg/mL gallic acid equivalent were achieved in the agar. All strains had MICs at 12.5 to 25 mg/mL gallic acid equivalent range. Our results suggest antimicrobial in vitro activity for pomegranate extract against toxigenic C. difficile. Pomegranate extract may be a useful contributor to the management and prevention of C. difficile disease or colonization. Copyright © 2014 Elsevier Inc. All rights reserved.

  7. [The structure of the skin of the external auditory canal and the antiviral activity of the cerumen in carnivorous mammals].

    Science.gov (United States)

    Sokolov, V E; Ushakova, N A; Chernova, O F; Alimbarova, L M; Barinskiĭ, I F

    1996-01-01

    The structure of the meatus acusticus externus skin was studied in the sable, mink, and European polecat with a parallel estimation of antiherpetic activity of the cerumen. Morphologically, these species differ in the degree of fat cellulose development, vascularization, and association with the lymphoid tissue. Lymphocytes are present both in the tissue and along the skin gland ducts and hair follicles up to the external surface only in the sable. The cerumen samples have antiviral activity also in the sable alone. The relationship between physiological properties of the mammalian cerumen and morphogenetic features is discussed.

  8. Imidazole Alkaloids from the South China Sea Sponge Pericharax heteroraphis and Their Cytotoxic and Antiviral Activities

    Directory of Open Access Journals (Sweden)

    Kai-Kai Gong

    2016-01-01

    Full Text Available Marine sponges continue to serve as a rich source of alkaloids possessing interesting biological activities and often exhibiting unique structural frameworks. In the current study, chemical investigation on the marine sponge Pericharax heteroraphis collected from the South China Sea yielded one new imidazole alkaloid named naamidine J (1 along with four known ones (2–5. Their structures were established by extensive spectroscopic methods and comparison of their data with those of the related known compounds. All the isolates possessed a central 2-aminoimidazole ring, substituted by one or two functionalized benzyl groups in some combination of the C4 and C5 positions. The cytotoxicities against selected HL-60, HeLa, A549 and K562 tumor cell lines and anti-H1N1 (Influenza a virus (IAV activity for the isolates were evaluated. Compounds 1 and 2 exhibited cytotoxicities against the K562 cell line with IC50 values of 11.3 and 9.4 μM, respectively. Compound 5 exhibited weak anti-H1N1 (influenza a virus, IAV activity with an inhibition ratio of 33%.

  9. Eupafolin and Ethyl Acetate Fraction of Kalanchoe gracilis Stem Extract Show Potent Antiviral Activities against Enterovirus 71 and Coxsackievirus A16

    Directory of Open Access Journals (Sweden)

    Ching-Ying Wang

    2013-01-01

    Full Text Available Enterovirus 71 (EV71 and coxsackievirus A16 (CoxA16 are main pathogens of hand-foot-and-mouth disease, occasionally causing aseptic meningitis and encephalitis in tropical and subtropical regions. Kalanchoe gracilis, Da-Huan-Hun, is a Chinese folk medicine for treating pain and inflammation, exhibiting antioxidant and anti-inflammatory activities. Our prior report (2012 cited K. gracilis leaf extract as moderately active against EV71 and CoxA16. This study further rates antienteroviral potential of K. gracilis stem (KGS extract to identify potent antiviral fractions and components. The extract moderately inhibits viral cytopathicity and virus yield, as well as in vitro replication of EV71 (IC50 = 75.18 μg/mL and CoxA16 (IC50 = 81.41 μg/mL. Ethyl acetate (EA fraction of KGS extract showed greater antiviral activity than that of n-butanol or aqueous fraction: IC50 values of 4.21 μg/mL against EV71 and 9.08 μg/mL against CoxA16. HPLC analysis, UV-Vis absorption spectroscopy, and plaque reduction assay indicate that eupafolin is a vital component of EA fraction showing potent activity against EV71 (IC50 = 1.39 μM and CoxA16 (IC50 = 5.24 μM. Eupafolin specifically lessened virus-induced upregulation of IL-6 and RANTES by inhibiting virus-induced ERK1/2, AP-1, and STAT3 signals. Anti-enteroviral potency of KGS EA fraction and eupafolin shows the clinical potential against EV71 and CoxA16 infection.

  10. Antiviral activity of plant extract from Tanacetum vulgare against Cucumber Mosaic Virus and Potato Virus Y

    Directory of Open Access Journals (Sweden)

    Nikolay Petrov

    2016-09-01

    Full Text Available Cucumber mosaic virus (CMV and Potato virus Y (PVY have been described among the top five important viruses infecting vegetable species worldwide. They cause severe damages in fruits and cultivated plants. There is currently no available effective pesticide to control these viral diseases. Higher plants contain a wide spectrum of secondary metabolites such as phenolics, flavonoids, quinones, tannins, essential oils, alkaloids, saponins, sterols and others. Extracts prepared from different plants have been reported to have a variety of properties including antifungal, antiviral and antibacterial properties against pathogens. Tanacetum vulgare (Tansy is native to Europe, Asia, and North Africa. It has many horticultural and pharmacological qualities. T. vulgare is principally used in traditional Asian and North African medicine as an antihelminthic, antispasmodic, stimulant to abdominal viscera, tonic, antidiabetic and diuretic, and it is antihypertensive. In our research we established antiviral effect of methanol extract from T. vulgare against CMV and PVY in tomato plants.

  11. Catalase-peroxidases (KatG) exhibit NADH oxidase activity.

    Science.gov (United States)

    Singh, Rahul; Wiseman, Ben; Deemagarn, Taweewat; Donald, Lynda J; Duckworth, Harry W; Carpena, Xavi; Fita, Ignacio; Loewen, Peter C

    2004-10-08

    Catalase-peroxidases (KatG) produced by Burkholderia pseudomallei, Escherichia coli, and Mycobacterium tuberculosis catalyze the oxidation of NADH to form NAD+ and either H2O2 or superoxide radical depending on pH. The NADH oxidase reaction requires molecular oxygen, does not require hydrogen peroxide, is not inhibited by superoxide dismutase or catalase, and has a pH optimum of 8.75, clearly differentiating it from the peroxidase and catalase reactions with pH optima of 5.5 and 6.5, respectively, and from the NADH peroxidase-oxidase reaction of horseradish peroxidase. B. pseudomallei KatG has a relatively high affinity for NADH (Km=12 microm), but the oxidase reaction is slow (kcat=0.54 min(-1)) compared with the peroxidase and catalase reactions. The catalase-peroxidases also catalyze the hydrazinolysis of isonicotinic acid hydrazide (INH) in an oxygen- and H2O2-independent reaction, and KatG-dependent radical generation from a mixture of NADH and INH is two to three times faster than the combined rates of separate reactions with NADH and INH alone. The major products from the coupled reaction, identified by high pressure liquid chromatography fractionation and mass spectrometry, are NAD+ and isonicotinoyl-NAD, the activated form of isoniazid that inhibits mycolic acid synthesis in M. tuberculosis. Isonicotinoyl-NAD synthesis from a mixture of NAD+ and INH is KatG-dependent and is activated by manganese ion. M. tuberculosis KatG catalyzes isonicotinoyl-NAD formation from NAD+ and INH more efficiently than B. pseudomallei KatG.

  12. Antiviral activity of recombinant ankyrin targeted to the capsid domain of HIV-1 Gag polyprotein

    OpenAIRE

    Nangola Sawitree; Urvoas Agathe; Valerio-Lepiniec Marie; Khamaikawin Wannisa; Sakkhachornphop Supachai; Hong Saw-See; Boulanger Pierre; Minard Philippe; Tayapiwatana Chatchai

    2012-01-01

    Abstract Background Ankyrins are cellular mediators of a number of essential protein-protein interactions. Unlike intrabodies, ankyrins are composed of highly structured repeat modules characterized by disulfide bridge-independent folding. Artificial ankyrin molecules, designed to target viral components, might act as intracellular antiviral agents and contribute to the cellular immunity against viral pathogens such as HIV-1. Results A phage-displayed library of artificial ankyrins was constr...

  13. Partial antiviral activities detection of chicken Mx jointing with neuraminidase gene (NA against Newcastle disease virus.

    Directory of Open Access Journals (Sweden)

    Yani Zhang

    Full Text Available As an attempt to increase the resistance to Newcastle Disease Virus (NDV and so further reduction of its risk on the poultry industry. This work aimed to build the eukaryotic gene co-expression plasmid of neuraminidase (NA gene and myxo-virus resistance (Mx and detect the gene expression in transfected mouse fibroblasts (NIH-3T3 cells, it is most important to investigate the influence of the recombinant plasmid on the chicken embryonic fibroblasts (CEF cells. cDNA fragment of NA and mutant Mx gene were derived from pcDNA3.0-NA and pcDNA3.0-Mx plasmid via PCR, respectively, then NA and Mx cDNA fragment were inserted into the multiple cloning sites of pVITRO2 to generate the eukaryotic co-expression plasmid pVITRO2-Mx-NA. The recombinant plasmid was confirmed by restriction endonuclease treatment and sequencing, and it was transfected into the mouse fibroblasts (NIH-3T3 cells. The expression of genes in pVITRO2-Mx-NA were measured by RT-PCR and indirect immunofluorescence assay (IFA. The recombinant plasmid was transfected into CEF cells then RT-PCR and the micro-cell inhibition tests were used to test the antiviral activity for NDV. Our results showed that co-expression vector pVITRO2-Mx-NA was constructed successfully; the expression of Mx and NA could be detected in both NIH-3T3 and CEF cells. The recombinant proteins of Mx and NA protect CEF cells from NDV infection until after 72 h of incubation but the individually mutagenic Mx protein or NA protein protects CEF cells from NDV infection till 48 h post-infection, and co-transfection group decreased significantly NDV infection compared with single-gene transfection group (P<0. 05, indicating that Mx-NA jointing contributed to delaying the infection of NDV in single-cell level and the co-transfection of the jointed genes was more powerful than single one due to their synergistic effects.

  14. Studies of Antiviral Activity and Cytotoxicity of Wrightia tinctoria and Morinda citrifolia

    Science.gov (United States)

    Selvam, P.; Murugesh, N.; Witvrouw, M.; Keyaerts, E.; Neyts, J.

    2009-01-01

    Different extracts of leaf parts of Wrightia tinctoria and fruit powder of Morinda citrifolia have been studied against replication of HIV-1(IIIB) in MT-4 cells and HCV in Huh 5.2 cells. Chloroform extract of Wrightia tinctoria exhibited a maximum protection of 48% against the cytopathic effect of HIV-1(IIIB) in MT-4 cells. Fruit juice of Morinda citrifolia exhibited a displayed marked cytotoxic activity in lymphocyte (MT-4) cells (CC50: 0.19 mg/ml). The 50% effective concentration for inhibition of HCV subgenomic replicon replication in Huh 5-2 cells by Morinda citrifolia was 0.98 μg/ml and by chloroform extract of Wrightia tinctoria was 10 μg/ml. The concentration that reduced the growth of exponentially proliferating Huh 5-2 cells by 50% was greater than 50 μg/ml. PMID:20376221

  15. CD40 ligand exhibits a direct antiviral effect on Herpes Simplex Virus type-1 infection via a PI3K-dependent, autophagy-independent mechanism.

    Science.gov (United States)

    Vlahava, Virginia-Maria; Eliopoulos, Aristides G; Sourvinos, George

    2015-06-01

    The interaction between CD40 and its ligand, CD40L/CD154, is crucial for the efficient initiation and regulation of immune responses against viruses. Herpes Simplex Virus type-1 (HSV-1) is a neurotropic virus capable of manipulating host responses and exploiting host proteins to establish productive infection. Herein we have examined the impact of CD40L-mediated CD40 activation on HSV-1 replication in U2OS cells stably expressing the CD40 receptor. Treatment of these cells with CD40L significantly reduced the HSV-1 progeny virus compared to non-treated cells. The activation of CD40 signaling did not affect the binding of HSV-1 virions on the cell surface but rather delayed the translocation of VP16 to the nucleus, affecting all stages of viral life cycle. Using pharmacological inhibitors and RNAi we show that inhibition of PI3 kinase but not autophagy reverses the effects of CD40L on HSV-1 replication. Collectively, these data demonstrate that CD40 activation exerts a direct inhibitory effect on HSV-1, initiating from the very early stages of the infection by exploiting PI3 kinase-dependent but autophagy-independent mechanisms. Copyright © 2015 Elsevier Inc. All rights reserved.

  16. Antiviral activity of triazine analogues of 1- (S)-[3-hydroxy-2-(phosphonomethoxy)propyl]cytosine (Cidofovir) and related compounds

    Czech Academy of Sciences Publication Activity Database

    Krečmerová, Marcela; Holý, Antonín; Pískala, Alois; Masojídková, Milena; Andrei, G.; Naesens, L.; Neyts, J.; Balzarini, J.; De Clercq, E.; Snoeck, R.

    2007-01-01

    Roč. 50, č. 5 (2007), s. 1069-1077 ISSN 0022-2623 R&D Projects: GA AV ČR 1QS400550501; GA MŠk 1M0508 Grant - others:NIH(US) 1UC1 AI062540-01; René Descartes Prize-2001(XE) HPAV-2002-100096 Institutional research plan: CEZ:AV0Z40550506 Keywords : acyclic nucleoside phosphonate * cidofovir * antiviral activity Subject RIV: CC - Organic Chemistry Impact factor: 4.895, year: 2007

  17. Proteolytic activation of the SARS-coronavirus spike protein: cutting enzymes at the cutting edge of antiviral research.

    Science.gov (United States)

    Simmons, Graham; Zmora, Pawel; Gierer, Stefanie; Heurich, Adeline; Pöhlmann, Stefan

    2013-12-01

    The severe acute respiratory syndrome (SARS) pandemic revealed that zoonotic transmission of animal coronaviruses (CoV) to humans poses a significant threat to public health and warrants surveillance and the development of countermeasures. The activity of host cell proteases, which cleave and activate the SARS-CoV spike (S) protein, is essential for viral infectivity and constitutes a target for intervention. However, the identities of the proteases involved have been unclear. Pioneer studies identified cathepsins and type II transmembrane serine proteases as cellular activators of SARS-CoV and demonstrated that several emerging viruses might exploit these enzymes to promote their spread. Here, we will review the proteolytic systems hijacked by SARS-CoV for S protein activation, we will discuss their contribution to viral spread in the host and we will outline antiviral strategies targeting these enzymes. This paper forms part of a series of invited articles in Antiviral Research on "From SARS to MERS: 10years of research on highly pathogenic human coronaviruses.'' Copyright © 2013 Elsevier B.V. All rights reserved.

  18. Proteolytic activation of the SARS-coronavirus spike protein: Cutting enzymes at the cutting edge of antiviral research

    Science.gov (United States)

    Simmons, Graham; Zmora, Pawel; Gierer, Stefanie; Heurich, Adeline; Pöhlmann, Stefan

    2013-01-01

    The severe acute respiratory syndrome (SARS) pandemic revealed that zoonotic transmission of animal coronaviruses (CoV) to humans poses a significant threat to public health and warrants surveillance and the development of countermeasures. The activity of host cell proteases, which cleave and activate the SARS-CoV spike (S) protein, is essential for viral infectivity and constitutes a target for intervention. However, the identities of the proteases involved have been unclear. Pioneer studies identified cathepsins and type II transmembrane serine proteases as cellular activators of SARS-CoV and demonstrated that several emerging viruses might exploit these enzymes to promote their spread. Here, we will review the proteolytic systems hijacked by SARS-CoV for S protein activation, we will discuss their contribution to viral spread in the host and we will outline antiviral strategies targeting these enzymes. This paper forms part of a series of invited articles in Antiviral Research on “From SARS to MERS: 10 years of research on highly pathogenic human coronaviruses.” PMID:24121034

  19. Antiviral activity in vitro of Urtica dioica L., Parietaria diffusa M. et K. and Sambucus nigra L.

    Science.gov (United States)

    Uncini Manganelli, R E; Zaccaro, L; Tomei, P E

    2005-04-26

    Parietaria diffusa M. et K., Urtica dioica L. (Urticaceae) and Sambucus nigra L. (Caprifoliaceae) are plants usually used in popular medicine of central Italy for treating numerous diseases, first of all Herpes zoster. Several plant products have been described as potential antiviral agents, with special attention being devoted to those having retroviruses as etiological agents, including acquired immunodeficiency syndrome (AIDS), in which a retrovirus, the designated human immunodeficiency virus HIV, has been clearly identified as the primary cause of this disease. The present study proposes a preliminary screening of the antiviral activity of Parietaria diffusa, Sambucus nigra and Urtica dioica preparation against the feline immunodeficiency virus (FIV) infection. The feline immunodeficiency virus is a widespread lentivirus of domestic cats sharing numerous biological and pathogenic features with the human immunodeficiency virus (HIV). FIV infection in cats has therefore been proposed as an animal model for AIDS studies with respect to pathogenesis, chemotherapy, and vaccine development [Pedersen, N.C., 1993. Feline immunodeficiency virus infection. In: Levy, J.A. (Ed.), The Retroviridae. Plenum Press, New York; Bendinelli, M., Pistello, M., Lombardi, S., Poli, A., Garzelli, C., Matteucci, D., Ceccherini-Nelli, L., Malvaldi, G., Tozzini, F., 1995. Feline immunodeficiency virus: an interesting model for AIDS studies and an important cat pathogen. Clinical Microbiology Revue 8, 87-112; North, T.W., LaCasse, R.A., 1995. Testing anti-HIV drugs in the FIV model. Nature Medicine 1, 410-411; Matteucci, D., Pistello, M., Mazzetti, P., Giannechini, S., Isola, P., Merico, A., Zaccaro, L., Rizzati, A., Bendinelli, M., 2000. AIDS vaccination studies using feline immunodeficiency virus as a model: immunisation with inactivated whole virus suppresses viraemia levels following intravaginal challenge with infected cells but non-following intravenous challenge with cell

  20. Recombinant myxoma virus lacking all poxvirus ankyrin-repeat proteins stimulates multiple cellular anti-viral pathways and exhibits a severe decrease in virulence.

    Science.gov (United States)

    Lamb, Stephanie A; Rahman, Masmudur M; McFadden, Grant

    2014-09-01

    Although the production of single gene knockout viruses is a useful strategy to study viral gene functions, the redundancy of many host interactive genes within a complex viral genome can obscure their collective functions. In this study, a rabbit-specific poxvirus, myxoma virus (MYXV), was genetically altered to disrupt multiple members of the poxviral ankyrin-repeat (ANK-R) protein superfamily, M-T5, M148, M149 and M150. A particularly robust activation of the NF-κB pathway was observed in A549 cells following infection with the complete ANK-R knockout (vMyx-ANKsKO). Also, an increased release of IL-6 was only observed upon infection with vMyx-ANKsKO. In virus-infected rabbit studies, vMyx-ANKsKO was the most extensively attenuated and produced the smallest primary lesion of all ANK-R mutant constructs. This study provides the first insights into the shared functions of the poxviral ANK-R protein superfamily in vitro and in vivo. Copyright © 2014 Elsevier Inc. All rights reserved.

  1. Antiviral activity of an aqueous extract derived from Aloe arborescens Mill. against a broad panel of viruses causing infections of the upper respiratory tract.

    Science.gov (United States)

    Glatthaar-Saalmüller, B; Fal, A M; Schönknecht, K; Conrad, F; Sievers, H; Saalmüller, A

    2015-09-15

    A number of antiviral therapies have evolved that may be effectively administered to treat respiratory viral diseases. But these therapies are very often of limited efficacy or have severe side effects. Therefore there is great interest in developing new efficacious and safe antiviral compounds e.g. based on the identification of compounds of herbal origin. Since an aqueous extract of Aloe arborescens Mill. shows antiviral activity against viruses causing infections of the upper respiratory tract in vitro we hypothesised that a product containing it such as Biaron C(®) could have an antiviral activity too. Antiviral activity of Bioaron C(®), an herbal medicinal product consisting of an aqueous extract of Aloe arborescens Mill., Vitamin C, and Aronia melanocarpa Elliot. succus, added as an excipient, was tested in vitro against a broad panel of viruses involved in upper respiratory tract infections. These studies included human adenovirus and several RNA viruses and were performed either with plaque reduction assays or with tests for the detection of a virus-caused cytopathic effect. Our studies demonstrated an impressive activity of Bioaron C(®) against members of the orthomyxoviridae - influenza A and influenza B viruses. Replication of both analysed influenza A virus strains - H1N1 and H3N2 - as well as replication of two analysed influenza B viruses - strains Yamagatal and Beiying - was significantly reduced after addition of Bioaron C(®) to the infected cell cultures. In contrast antiviral activity of Bioaron C(®) against other RNA viruses showed a heterogeneous pattern. Bioaron C(®) inhibited the replication of human rhinovirus and coxsackievirus, both viruses belonging to the family of picornaviridae and both representing non-enveloped RNA viruses. In vitro infections with respiratory syncytial virus and parainfluenza virus, both belonging to the paramyxoviridae, were only poorly blocked by the test substance. No antiviral activity of Bioaron C(®) was

  2. Staining characteristics and antiviral activity of sulforhodamine B and lissamine green B.

    Science.gov (United States)

    Chodosh, J; Dix, R D; Howell, R C; Stroop, W G; Tseng, S C

    1994-03-01

    Fluorescein and rose bengal are dyes used routinely in the examination of the ocular surface. As part of an ongoing search for a superior ophthalmic dye with optimal specificity and sensitivity and a lack of interference with subsequent viral cultures, and as part of studies that use chemical dyes to understand better the pathophysiology of ocular surface disorders, the staining characteristics and antiviral activity of sulforhodamine B and lissamine green B were investigated. Staining of rabbit corneal epithelial cell cultures by sulforhodamine B and lissamine green B was compared to that of fluorescein and rose bengal. Diffusion of each dye through a collagen gel was measured. Uptake of lissamine green B by herpes simplex virus type 1 (HSV-1)-infected Vero cell cultures was compared at several times postinfection. The effect of sulforhodamine B and lissamine green B on HSV-1 plaque formation in Vero cells was determined. The cellular toxicity of sulforhodamine B and lissamine green B in vitro was examined by a quantitative 14C-amino acid uptake assay and by a qualitative cell viability assay. Finally, the effect of sulforhodamine B and lissamine green B on viral replication was compared in vivo with that of rose bengal in a rabbit model of herpetic epithelial keratitis. Rose bengal vividly stained cell monolayers of explant cultures of rabbit corneal epithelium. By light microscopy, sulforhodamine B and lissamine green B, like fluorescein, did not stain the epithelial cells, but did stain the corneal explant stroma. Pretreatment of epithelial cells with 0.25% trypsin for 5 minutes failed to induce dye uptake; however, pretreatment with 0.5% Triton X-100 for 5 minutes resulted in nuclear staining by lissamine green B, but not sulforhodamine B. When added to a collagen gel, the relative diffusion rate was fluorescein > lissamine green B > sulforhodamine B > rose bengal. By spectrophotometric analysis, HSV-1-infected and uninfected Vero cells bound equivalent

  3. Expression of recombinant human interferon-γ with antiviral activity in the bi-cistronic baculovirus-insect/larval system.

    Science.gov (United States)

    Chen, Wen-Shuo; Villaflores, Oliver B; Jinn, Tzyy-Rong; Chan, Ming-Tsair; Chang, Yen-Chung; Wu, Tzong-Yuan

    2011-01-01

    A bi-cistronic baculovirus-insect/larval system containing a polyhedron promoter, an internal ribosome entry site (IRES), and an egfp gene was developed as a cost-effective platform for the production of recombinant human interferon gamma (rhIFN-γ). There was no significant difference between the amounts of rhIFN-γ produced in the baculovirus-infected Spodoptera frugiferda 21 cells grown in serum-free medium and the serum-supplemented medium, while the Trichoplusia ni (T. ni) and Spodoptera exigua (S. exigua) larvae afforded rhIFN-γ amounting to 1.08±0.04 and 9.74±0.35 µg/mg protein respectively. The presence of non-glycosylated and glycosylated rhIFN-γ was confirmed by immunoblot and lectin blot. The immunological activity of purified rhIFN-γ, with 96% purity by Nickel (II)-nitrilotriacetic acid (Ni-NTA) affinity chromatography, was similar to that commercially available. Moreover, the rhIFN-γ protein from T. ni had more potent antiviral activity. These findings suggest that this IRES-based expression system is a simple and inexpensive alternative for large-scale protein production in anti-viral research.

  4. In Vitro Antiviral Activity of Cinnamomum cassia and Its Nanoparticles Against H7N3 Influenza A Virus.

    Science.gov (United States)

    Fatima, Munazza; Zaidi, Najam-Us-Sahar Sadaf; Amraiz, Deeba; Afzal, Farhan

    2016-01-01

    Nanoparticles have wide-scale applications in various areas, including medicine, chemistry, electronics, and energy generation. Several physical, biological, and chemical methods have been used for synthesis of silver nanoparticles. Green synthesis of silver nanoparticles using plants provide advantages over other methods as it is easy, efficient, and eco-friendly. Nanoparticles have been extensively studied as potential antimicrobials to target pathogenic and multidrug-resistant microorganisms. Their applications recently extended to development of antivirals to inhibit viral infections. In this study, we synthesized silver nanoparticles using Cinnamomum cassia (Cinnamon) and evaluated their activity against highly pathogenic avian influenza virus subtype H7N3. The synthesized nanoparticles were characterized using UVVis absorption spectroscopy, scanning electron microscopy, and Fourier transform infrared spectroscopy. Cinnamon bark extract and its nanoparticles were tested against H7N3 influenza A virus in Vero cells and the viability of cells was determined by tetrazolium dye (MTT) assay. The silver nanoparticles derived from Cinnamon extract enhanced the antiviral activity and were found to be effective in both treatments, when incubated with the virus prior to infection and introduced to cells after infection. In order to establish the safety profile, Cinnamon and its corresponding nanoparticles were tested for their cytotoxic effects in Vero cells. The tested concentrations of extract and nanoparticles (up to 500 μg/ml) were found non-toxic to Vero cells. The biosynthesized nanoparticles may, hence, be a promising approach to provide treatment against influenza virus infections.

  5. Antiviral activity produced by an IPNV-carrier EPC cell culture confers resistance to VHSV infection.

    Science.gov (United States)

    Jurado, María Teresa; García-Valtanen, Pablo; Estepa, Amparo; Perez, Luis

    2013-10-25

    Infectious pancreatic necrosis virus (IPNV), a fish birnavirus, can establish a persistent infection on epithelioma papulosum cyprinid (EPC) cells producing a carrier state where a small fraction of IPNV-infected cells is maintained in the culture after continuous subculture. The EPC(IPNV) cells are resistant to challenge with IPNV as well as to challenge with viral hemorrhagic septicemia virus (VHSV), a rhabdovirus. In this work, the antiviral effect of the IPNV carrier culture conditioned medium (EPC(IPNV)-CM) was tested and analyzed in detail. EPC cells treated with the carrier culture supernatant become protected against VHSV challenge. Size-fractionation by filtration and acid and heat treatment showed that the IPNV persistently infected cells release an acid-resistant soluble factor in the molecular weight fraction bellow 50 kDa. The capacity of the EPC(IPNV)-CM to induce cytokine genes in EPC cells was also determined by real-time RT-PCR. We found that there is a positive correlation between up-regulation of mx gene expression in EPC cells treated with EPC(IPNV)-CM and protection against VHSV challenge. Our findings indicate that the control of IPNV multiplication in the carrier culture as well as the interference with rhabdovirus replication are connected to the production and release of an antiviral (interferon-like) factor to the medium. Copyright © 2013 Elsevier B.V. All rights reserved.

  6. Hypoxia impairs anti-viral activity of natural killer (NK) cells but has little effect on anti-fibrotic NK cell functions in hepatitis C virus infection.

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    Wolter, Franziska; Glässner, Andreas; Krämer, Benjamin; Kokordelis, Pavlos; Finnemann, Claudia; Kaczmarek, Dominik J; Goeser, Felix; Lutz, Philipp; Nischalke, Hans Dieter; Strassburg, Christian P; Spengler, Ulrich; Nattermann, Jacob

    2015-12-01

    Natural killer (NK) cells have been shown to exert anti-viral as well as anti-fibrotic functions in hepatitis C virus (HCV) infection. Previous studies, however, analyzed NK cell functions exclusively under atmospheric oxygen conditions despite the fact that the liver microenvironment is hypoxic. Here, we analyzed the effects of low oxygen tension on anti-viral and anti-fibrotic NK cell activity. Peripheral (n=34) and intrahepatic (n=15) NK cells from HCV(+) patients as well as circulating NK cells from healthy donors (n=20) were studied with respect to anti-viral and anti-fibrotic activity via co-culture experiments with HuH7 replicon cells and hepatic stellate cells, respectively. Anti-viral activity of resting NK cells from healthy controls was not affected by hypoxia. However, hypoxia significantly reduced the response of healthy NK cells to cytokine stimulation. In contrast to healthy controls, we observed resting and cytokine activated peripheral NK cells from HCV patients to display a significantly decreased anti-viral activity when cultured at 5% or 1% oxygen, suggesting HCV NK cells to be very sensitive to hypoxia. These findings could be confirmed when intrahepatic NK cells were tested. Finally, we show that anti-fibrotic NK cell activity was not affected by low oxygen tension. Our results show that anti-viral function of NK cells from HCV(+) patients is critically affected by a hypoxic microenvironment and, therefore, indicate that in order to obtain an accurate understanding of intrahepatic NK cell anti-HCV activity, the laboratory modelling should take into account the liver specific levels of oxygen. Copyright © 2015 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

  7. Short communication: antiviral activity of subcritical water extract of Brassica juncea against influenza virus A/H1N1 in nonfat milk.

    Science.gov (United States)

    Lee, N-K; Lee, J-H; Lim, S-M; Lee, K A; Kim, Y B; Chang, P-S; Paik, H-D

    2014-09-01

    Subcritical water extract (SWE) of Brassica juncea was studied for antiviral effects against influenza virus A/H1N1 and for the possibility of application as a nonfat milk supplement for use as an "antiviral food." At maximum nontoxic concentrations, SWE had higher antiviral activity against influenza virus A/H1N1 than n-hexane, ethanol, or hot water (80°C) extracts. Addition of 0.5mg/mL of B. juncea SWE to culture medium led to 50.35% cell viability (% antiviral activity) for Madin-Darby canine kidney cells infected with influenza virus A/H1N1. Nonfat milk supplemented with 0.28mg/mL of B. juncea SWE showed 39.62% antiviral activity against influenza virus A/H1N1. Thus, the use of B. juncea SWE as a food supplement might aid in protection from influenza viral infection. Copyright © 2014 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

  8. In vitro schistosomicidal and antiviral activities of Arctium lappa L. (Asteraceae) against Schistosoma mansoni and Herpes simplex virus-1.

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    Dias, Mirna Meana; Zuza, Ohana; Riani, Lorena R; de Faria Pinto, Priscila; Pinto, Pedro Luiz Silva; Silva, Marcos P; de Moraes, Josué; Ataíde, Ana Caroline Z; de Oliveira Silva, Fernanda; Cecílio, Alzira Batista; Da Silva Filho, Ademar A

    2017-10-01

    Schistosomiasis and herpes diseases represent serious issues to the healthcare systems, infecting a large number of people worldwide, mainly in developing countries. Arctium lappa L. (Asteraceae), known as "bardana" and "burdock", is a medicinal plant popularly used for several purposes, including as antiseptic. In this study, we evaluated the in vitro schistosomicidal and antiherpes activities of the crude extract of A. lappa, which have not yet been described. Fruits of A. lappa L. were extracted by maceration with ethanol: H 2 O (96:4 v/v) in order to obtain the hydroalcoholic extract of A. lappa (AL). In vitro schistosomicidal assays were assessed against adult worms of Schistosoma mansoni, while the in vitro antiviral activity of AL was evaluated on replication of Herpes simplex virus type-1 (HSV-1). Cell viability was measured by MTT assay, using Vero cells and chemical composition of AL was determined by qualitative UPLC-ESI-QTOF-MS analysis. UPLC-ESI-QTOF-MS analysis of AL revealed the presence of dibenzylbutyrolactone lignans, such as arctiin and arctigenin. Results showed that AL was not cytotoxic to Vero cells even when tested at 400μg/mL. qPCR results indicated a significant viral load decreased for all tested concentrations of AL (400, 50, and 3.125μg/mL), which showed similar antiviral effect to acyclovir (50μg/mL) when tested at 400μg/mL. Also, AL (400, 200, and 100μg/mL) caused 100% mortality and significantly reduction on motor activity of all adult worms of S. mansoni. Confocal laser scanning microscopy showed tegumental morphological alterations and changes on the numbers of tubercles of S. mansoni worms in a dose-dependent manner after treatment with AL. This report provides the first evidence for the in vitro schistosomicidal and antiherpes activities of AL, opening the route to further schistosomicidal and antiviral studies with AL and their compounds, especially lignans. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  9. Receptor Activator of NF-κB Orchestrates Activation of Antiviral Memory CD8 T Cells in the Spleen Marginal Zone

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    Mohamed Habbeddine

    2017-11-01

    Full Text Available The spleen plays an important role in protective immunity to bloodborne pathogens. Macrophages and dendritic cells (DCs in the spleen marginal zone capture microbial antigens to trigger adaptive immune responses. Marginal zone macrophages (MZMs can also act as a replicative niche for intracellular pathogens, providing a platform for mounting the immune response. Here, we describe a role for RANK in the coordinated function of antigen-presenting cells in the spleen marginal zone and triggering anti-viral immunity. Targeted deletion of RANK results in the selective loss of CD169+ MZMs, which provide a niche for viral replication, while RANK signaling in DCs promotes the recruitment and activation of anti-viral memory CD8 T cells. These studies reveal a role for the RANKL/RANK signaling axis in the orchestration of protective immune responses in the spleen marginal zone that has important implications for the host response to viral infection and induction of acquired immunity.

  10. Antiviral Activity of a Cloned Peptide RC28 Isolated from the Higher Basidiomycetes Mushroom Rozites caperata in a Mouse Model of HSV-1 Keratitis.

    Science.gov (United States)

    Yan, Naihong; He, Fen; Piraino, Frank F; Xiang, Haotian; Chen, Jun; Wang, Yun; Liu, Xuyang

    2015-01-01

    An Escherichia coli-expressed peptide with a molecular weight of 28.26, derived from the complementary DNA of antiviral protein RC28 isolated from the mushroom Rozites caperata (=Cortinarius caperatus), demonstrated potent antiviral activity against herpes simplex virus-1 in Vero cells and in a herpes simplex virus-1 mouse keratitis model. Plaque assays in Vero cells showed that the peptide reduced viral yields by at least 1.2 logs; in the animal model the cloned peptide delayed the occurrence of stromal keratitis and alleviated the severity of the disease. We believe this is the first report of a cloned mushroom peptide with antiviral activity for the prevention and treatment of a viral disease.

  11. Novel halogenated 3-deazapurine, 7-deazapurine and alkylated 9-deazapurine derivatives of L-ascorbic or imino-L-ascorbic acid: Synthesis, antitumour and antiviral activity evaluations.

    Science.gov (United States)

    Stipković Babić, Maja; Makuc, Damjan; Plavec, Janez; Martinović, Tamara; Kraljević Pavelić, Sandra; Pavelić, Krešimir; Snoeck, Robert; Andrei, Graciela; Schols, Dominique; Wittine, Karlo; Mintas, Mladen

    2015-09-18

    Keeping the potential synergy of biological activity of synthetic anomalous derivatives of deazapurines and l-ascorbic acid (l-AA) in mind, we have synthesized new 3-, 7- and 9-deazapurine derivatives of l-ascorbic (1-4, 8-10, 13-15) and imino-l-ascorbic acid (5-7, 11, 12, 16-19). These novel compounds were evaluated for their cytostatic and antiviral activity in vitro against a panel of human malignant tumour cell lines and normal murine fibroblasts (3T3). Among all evaluated compounds, the 9-deazapurine derivative of l-AA (13) exerted the most potent inhibitory activity on the growth of CEM/0 cells (IC50 = 4.1 ± 1.8 μM) and strong antiproliferative effect against L1210/0 (IC50 = 4.7 ± 0.1 μM) while the 9-deazahypoxanthine derivative of l-AA (15) showed the best effect against HeLa cells (IC50 = 5.6 ± 1.3 μM) and prominent effect on L1210/0 (IC50 = 4.5 ± 0.5 μM). Furthermore, the 9-deazapurine derivative disubstituted with two imino-l-AA moieties (18) showed the best activity against L1210/0 tumour cells (IC50 = 4.4 ± 0.3 μM) and the most pronounced antiproliferative effects against MiaPaCa-2 cells (IC50 = 5.7 ± 0.2 μM). All these compounds showed selective cytostatic effect on tumour cell lines in comparison with embryonal murine fibroblasts (3T3). When evaluating their antiviral activity, the 3-deazapurine derivative of l-AA (3) exhibited the highest activity against both laboratory-adapted strains of human cytomegalovirus (HCMV) (AD-169 and Davis) with EC50 values comparable to those of the well-known anti-HCMV drug ganciclovir and without cytotoxic effects on normal human embryonal lung (HEL) cells. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

  12. The mitochondrial anti-viral protein MAVS associates with NLRP3 and regulates its inflammasome activity1

    Science.gov (United States)

    Park, Sangjun; Juliana, Christine; Hong, Sujeong; Datta, Pinaki; Hwang, Inhwa; Fernandes-Alnemri, Teresa; Yu, Je-Wook; Alnemri, Emad S.

    2013-01-01

    NLRP3 assembles an inflammasome complex that activates caspase-1 upon sensing various danger signals derived from pathogenic infection, tissue damage and environmental toxins. How NLRP3 senses these various stimuli is still poorly understood, but mitochondria and mitochondrial reactive oxygen species (mtROS) have been proposed to play a critical role in NLRP3 activation. Here, we provide evidence that the mitochondrial anti-viral signaling protein MAVS associates with NLRP3 and facilitates its oligomerization leading to caspase-1 activation. In reconstituted 293T cells, full length MAVS promoted NLRP3-dependent caspase-1 activation, while a C-terminal transmembrane domain-truncated mutant of MAVS (MAVS-ΔTM) did not. MAVS, but not MAVS-ΔTM, interacted with NLRP3 and triggered the oligomerization of NLRP3, suggesting that mitochondrial localization of MAVS and intact MAVS signaling are essential for activating the NLRP3 inflammasome. Supporting this, activation of MAVS signaling by Sendai virus infection promoted NLRP3-dependent caspase-1 activation, whereas, knocking down MAVS expression clearly attenuated the activation of NLRP3 inflammasome by Sendai virus in THP-1 and mouse macrophages. Taken together, our results suggest that MAVS facilitates the recruitment of NLRP3 to the mitochondria and may enhance its oligomerization and activation by bringing it in close proximity to mtROS. PMID:24048902

  13. N-terminal amino acids of bovine alpha interferons are relevant for the neutralization of their antiviral activity

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    J.B. Barreto Filho

    2001-05-01

    Full Text Available The structure-function relationship of interferons (IFNs has been studied by epitope mapping. Epitopes of bovine IFNs, however, are practically unknown, despite their importance in virus infections and in the maternal recognition of pregnancy. It has been shown that recombinant bovine (rBoIFN-alphaC and rBoIFN-alpha1 differ only in 12 amino acids and that the F12 monoclonal antibody (mAb binds to a linear sequence of residues 10 to 34. We show here that the antiviral activities of these two IFNs were neutralized by the F12 mAb to different extents using two tests. In residual activity tests the antiviral activity dropped by more than 99% with rBoIFN-alphaC and by 84% with rBoIFN-alpha1. In checkerboard antibody titrations, the F12 mAb titer was 12,000 with rBoIFN-alphaC and only 600 with rBoIFN-alpha1. Since these IFNs differ in their amino acid sequence at positions 11, 16 and 19 of the amino terminus, only these amino acids could account for the different neutralization titers, and they should participate in antibody binding. According to the three-dimensional structure described for human and murine IFNs, these amino acids are located in the alpha helix A; amino acids 16 and 19 of the bovine IFNs would be expected to be exposed and could bind to the antibody directly. The amino acid at position 11 forms a hydrogen bond in human IFNs-alpha and it is possible that, in bovine IFNs-alpha, the F12 mAb, binding near position 11, would disturb this hydrogen bond, resulting in the difference in the extent of neutralization observed.

  14. Antiviral activity of the green marine alga Ulva fasciata on the replication of human metapneumovirus Atividade antiviral da alga verde marinha Ulva fasciata na replicação do metapneumovírus humano

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    Gabriella da Silva Mendes

    2010-02-01

    Full Text Available We evaluated the antiviral activity of the marine alga, Ulva fasciata, collected from Rasa beach and Forno beach, Búzios, Rio de Janeiro, Brazil on the replication of human metapneumovirus (HMPV. The algae extracts were prepared using three different methodologies to compare the activity of different groups of chemical composites obtained through these different methodologies. Four out of the six extracts inhibited nearly 100% of viral replication. The results demonstrated that the majority of the extracts (five out of six possess virucidal activity and therefore have the ability to interact with the extracellular viral particles and prevent the infection. On the other hand, only two extracts (from Forno beach, obtained by maceration and maceration of the decoction were able to interact with cell receptors, hindering the viral entry. Finally, only the extract of algae collected at Forno beach, obtained by maceration presented intracellular activity. To our knowledge, this is a pioneer study on antiviral activity of marine algae against HMPV. It is also the first on antiviral activity against HMPV ever done in Brazil. The study also shows the effect of different environment factors and different chemical procedures used to obtain the extract on its biological properties.Neste artigo, foi avaliada a atividade antiviral da alga marinha Ulva fasciata, coletada nas Praias do Forno e Rasa, em Búzios, Rio de Janeiro, Brasil, sobre a replicação do metapneumovírus humano (HMPV. Os extratos desta alga foram preparados utilizando três diferentes metodologias, visando a comparação da atividade de diferentes grupos de compostos químicos que são obtidos dependendo da metodologia empregada. Quatro, do total de seis extratos foram capazes de inibir praticamente 100% da replicação viral. Os resultados demonstram também que a maioria dos extratos (cinco, dos seis, possui atividade virucida e, portanto, possuem a habilidade de interagir com a part

  15. Application of "Hydrogen-Bonding Interaction" in Drug Design. Part 2: Design, Synthesis, and Structure-Activity Relationships of Thiophosphoramide Derivatives as Novel Antiviral and Antifungal Agents.

    Science.gov (United States)

    Lu, Aidang; Ma, Yuanyuan; Wang, Ziwen; Zhou, Zhenghong; Wang, Qingmin

    2015-11-04

    On the basis of the structure of natural product harmine, lead compound 18, and the structure of compounds in part 1, a series of thiophosphoramide derivatives 1-17 were designed and synthesized from various amines in one step. Their antiviral and antifungal activities were evaluated. Most of the compounds showed significantly higher antiviral activity against tobacco mosaic virus (TMV) than commercial virucide ribavirin. Compound (R,R)-17 showed the best anti-TMV activity in vitro (70%/500 μg/mL and 33%/100 μg/mL) and in vivo (inactivation effect, 68%/500 μg/mL and 30%/100 μg/mL; curative effect, 64%/500 μg/mL and 31%/100 μg/mL; protection effect, 66%/500 μg/mL and 31%/100 μg/mL), which is higher than that of ningnanmycin and lead compound 18. The antiviral activity of (R,R)-17·HCl is about similar to that of (R,R)-17. However, the antifungal activity of (R,R)-17·HCl against Puccinia sorghi is slightly lower than that of (R,R)-17. The systematic study provides compelling evidence that these simple thiophosphoramide compounds could become efficient antiviral and antifungal agents.

  16. Evaluation of the cytotoxic effect and antibacterial, antifungal, and antiviral activities of Hypericum triquetrifolium Turra essential oils from Tunisia

    Science.gov (United States)

    2013-01-01

    Background A number of bio-active secondary metabolites have been identified and reported for several Hypericum species. Many studies have reported the potential use of the plant extracts against several pathogens. However, Hypericum triquetrifolium is one of the least studied species for its antimicrobial activity. The aim of the present study was to evaluate the cytotoxic effect of the essential oils of Hypericum triquetrifolium as well as their antimicrobial potential against coxsakievirus B3 and a range of bacterial and fungal strains. Methods The essential oils of Hypericum triquetrifolium harvested from five different Tunisian localities (Fondouk DJedid, Bou Arada, Bahra, Fernana and Dhrea Ben Jouder) were evaluated for their antimicrobial activities by micro-broth dilution methods against bacterial and fungal strains. In addition, the cytotoxic effect and the antiviral activity of these oils were carried out using Vero cell lines and coxsakievirus B3. Results The results showed a good antibacterial activities against a wide range of bacterial strains, MIC values ranging between 0.39-12.50 mg/ml and MBC values between 1.56-25.0 mg/ml. In addition, the essential oils showed promising antifungal activity with MIC values ranging between 0.39 μg/mL and 12.50 μg/mL; MFC values ranged between 3.12 μg/mL and 25.00 μg/mL; a significant anticandidal activity was noted (MIC values comprised between 0.39 μg/mL and 12.50 μg/mL). Although their low cytotoxic effect (CC50 ranged between 0.58 mg/mL and 12.00 mg/mL), the essential oils did not show antiviral activity against coxsakievirus B3. Conclusion The essential oils obtained from Hypericum triquetrifolium can be used as antimicrobial agents and could be safe at non cytotoxic doses. As shown for the tested essential oils, comparative analysis need to be undertaken to better characterize also the antimicrobial activities of Hypericum triquetrifolium extracts with different solvents as well as their

  17. Broad-spectrum antiviral activity including human immunodeficiency and hepatitis C viruses mediated by a novel retinoid thiosemicarbazone derivative.

    Science.gov (United States)

    Kesel, Andreas J

    2011-05-01

    Aromatic aldehyde-derived thiosemicarbazones 4-6, the S-substituted modified thiosemicarbazones 7/8, and a vitamin A-derived (retinoid) thiosemicarbazone derivative 12 were investigated as inhibitors of human hepatitis C virus (HCV) subgenomic RNA replicon Huh7 ET (luc-ubi-neo/ET) replication. Compounds 4-6 and 12 were found to be potent suppressors of HCV RNA replicon replication. The trifluoromethoxy-substituted thiosemicarbazone 6 and the retinoid thiosemicarbazone derivative 12 were even superior in selectivity to the included reference agent recombinant human alpha-interferon-2b, showing potencies in the nanomolar range of concentration. In addition, compounds 5, 6, 8 and 12 were tested as inhibitors of cytopathic effect (CPE) induced by human varicella-zoster virus (VZV) and/or human cytomegalovirus (HCMV). Compounds 4-6, 8 and 12 were additionally examined as inhibitors of CPE induced by cowpox virus and vaccinia virus. Thiosemicarbazone 4 was inhibitory on cowpox and vaccinia virus replication comparable in potency and selectivity to the reference agent cidofovir. Retinoid thiosemicarbazone derivative 12 was active as micromolar inhibitor of VZV, HCMV, and, in addition, human immunodeficiency virus type 1 (HIV-1) replication. These results indicate that thiosemicarbazone derivatives are appropriate lead structures to be evaluated in targeted antiviral therapies for hepatitis C (STAT-C), and that the vitamin A-related thiosemicarbazone derivative 12 emerges as a broad-spectrum antiviral agent, co-suppressing the multiplication of important RNA and DNA viruses. Copyright © 2011 Elsevier Masson SAS. All rights reserved.

  18. Assorted Processing of Synthetic Trans-Acting siRNAs and Its Activity in Antiviral Resistance.

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    Mingmin Zhao

    Full Text Available The use of syn-tasiRNAs has been proposed as an RNA interference technique alternative to those previously described: hairpin based, virus induced gene silencing or artificial miRNAs. In this study we engineered the TAS1c locus to impair Plum pox virus (PPV infection by replacing the five native siRNAs with two 210-bp fragments from the CP and the 3´NCR regions of the PPV genome. Deep sequencing analysis of the small RNA species produced by both constructs in planta has shown that phased processing of the syn-tasiRNAs is construct-specific. While in syn-tasiR-CP construct the processing was as predicted 21-nt phased in register with miR173-guided cleavage, the processing of syn-tasiR-3NCR is far from what was expected. A 22-nt species from the miR173-guided cleavage was a guide of two series of phased small RNAs, one of them in an exact 21-nt register, and the other one in a mixed of 21-/22-nt frame. In addition, both constructs produced abundant PPV-derived small RNAs in the absence of miR173 as a consequence of a strong sense post-transcriptional gene silencing induction. The antiviral effect of both constructs was also evaluated in the presence or absence of miR173 and showed that the impairment of PPV infection was not significantly higher when miR173 was present. The results show that syn-tasiRNAs processing depends on construct-specific factors that should be further studied before the so-called MIGS (miRNA-induced gene silencing technology can be used reliably.

  19. Assorted Processing of Synthetic Trans-Acting siRNAs and Its Activity in Antiviral Resistance.

    Science.gov (United States)

    Zhao, Mingmin; San León, David; Mesel, Frida; García, Juan Antonio; Simón-Mateo, Carmen

    2015-01-01

    The use of syn-tasiRNAs has been proposed as an RNA interference technique alternative to those previously described: hairpin based, virus induced gene silencing or artificial miRNAs. In this study we engineered the TAS1c locus to impair Plum pox virus (PPV) infection by replacing the five native siRNAs with two 210-bp fragments from the CP and the 3´NCR regions of the PPV genome. Deep sequencing analysis of the small RNA species produced by both constructs in planta has shown that phased processing of the syn-tasiRNAs is construct-specific. While in syn-tasiR-CP construct the processing was as predicted 21-nt phased in register with miR173-guided cleavage, the processing of syn-tasiR-3NCR is far from what was expected. A 22-nt species from the miR173-guided cleavage was a guide of two series of phased small RNAs, one of them in an exact 21-nt register, and the other one in a mixed of 21-/22-nt frame. In addition, both constructs produced abundant PPV-derived small RNAs in the absence of miR173 as a consequence of a strong sense post-transcriptional gene silencing induction. The antiviral effect of both constructs was also evaluated in the presence or absence of miR173 and showed that the impairment of PPV infection was not significantly higher when miR173 was present. The results show that syn-tasiRNAs processing depends on construct-specific factors that should be further studied before the so-called MIGS (miRNA-induced gene silencing) technology can be used reliably.

  20. Detection of the antiviral activity of epicatechin isolated from Salacia crassifolia (Celastraceae) against Mayaro virus based on protein C homology modelling and virtual screening.

    Science.gov (United States)

    Ferreira, P G; Ferraz, A C; Figueiredo, J E; Lima, C F; Rodrigues, V G; Taranto, A G; Ferreira, J M S; Brandão, G C; Vieira-Filho, S A; Duarte, L P; de Brito Magalhães, C L; de Magalhães, J C

    2018-02-24

    Mayaro fever, caused by Mayaro virus (MAYV) is a sub-lethal disease with symptoms that are easily confused with those of dengue fever, except for polyarthralgia, which may culminate in physical incapacitation. Recently, outbreaks of MAYV have been documented in metropolitan areas, and to date, there is no therapy or vaccine available. Moreover, there is no information regarding the three-dimensional structure of the viral proteins of MAYV, which is important in the search for antivirals. In this work, we constructed a three-dimensional model of protein C of MAYV by homology modelling, and this was employed in a manner similar to that of receptors in virtual screening studies to evaluate 590 molecules as prospective antiviral agents. In vitro bioassays were utilized to confirm the potential antiviral activity of the flavonoid epicatechin isolated from Salacia crassifolia (Celastraceae). The virtual screening showed that six flavonoids were promising ligands for protein C. The bioassays showed potent antiviral action of epicatechin, which protected the cells from almost all of the effects of viral infection. An effective concentration (EC 50 ) of 0.247 μmol/mL was observed with a selectivity index (SI) of 7. The cytotoxicity assay showed that epicatechin has low toxicity, with a 50% cytotoxic concentration (CC 50 ) greater than 1.723 µmol/mL. Epicatechin was found to be twice as potent as the reference antiviral ribavirin. Furthermore, a replication kinetics assay showed a strong inhibitory effect of epicatechin on MAYV growth, with a reduction of at least four logs in virus production. Our results indicate that epicatechin is a promising candidate for further testing as an antiviral agent against Mayaro virus and other alphaviruses.

  1. Putative phage-display epitopes of the porcine epidemic diarrhea virus S1 protein and their anti-viral activity.

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    Cao, Liyan; Ge, Xuying; Gao, Yu; Zarlenga, Dante S; Wang, Kexiong; Li, Xunliang; Qin, Zhaoheng; Yin, Xiangping; Liu, Jisheng; Ren, Xiaofeng; Li, Guangxin

    2015-10-01

    Porcine epidemic diarrhea virus (PEDV) is a pathogen of swine that causes severe diarrhea and dehydration resulting in substantial morbidity and mortality in newborn piglets. Phage display is a technique with wide application, in particular, the identification of key antigen epitopes for the development of therapeutic and diagnostic reagents and vaccines. To identify antigen epitopes with specificity for PEDV, a monoclonal antibody (MAb-5E12) against the immunodominant region of the PEDV Spike protein (S1) was used as the target for biopanning a 12-mer phage display, random peptide library. After multiple rounds of biopanning and stringent washing, three phage-displayed peptides, designated L, W and H, were identified that recognize MAb-5E12. Sequence analysis showed that the one or more of the peptides exhibited partial sequence similarity to the native S1 sequence 'MQYVYTPTYYML' (designated peptide M) at position 201-212. In combination with software analysis for the prediction of B cell epitopes, aa 201-212 exhibited characteristics of a linear epitope on the PEDV S1 protein. In contrast to peptide M, a consensus motif 'PxxY' was identified on both peptides L and W, and on the S1 protein, but not on peptide H. Peptide M and the MAb-5E12-recognizing peptides L and W significantly inhibited the adsorption of PEDV on the cell surface as monitored through plaque-reduction assays. Furthermore, data from real-time PCR and indirect immunofluorescence assays were consistent with the ability of peptides M, L and W to block viral protein expression and thereby function as antiviral agents for PEDV.

  2. The effect of antiviral activity of a green seaweed from the Persian Gulf, Caulerpa sertularioides on Herpes Simplex Virus Type 1

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    Keyvan Zandi

    2006-09-01

    Full Text Available Background: By considering the daily increase in drug resistance of various viruses, novel antiviral compounds extracted from natural resources – due to their fewer side effects, had always been important to researchers. In the present study, we investigated antiviral activity of the hot water extract of a green seaweed, Caulerpa sertularioides, collected from coastal water of Bushehr in the Persian Gulf, against Herpes Simplex Virus Type 1 (HSV-1. Methods: The hot water extract of a green seaweed, Caulerpa sertularioides was sterilized by autoclave and filtration methods. After determining its cytotoxic concentration 50 (CC50 value, the effect of the extract on the inhibition of HSV-1 replication was examined in Vero cell culture. Results: The extract showed antiviral activity against HSV-1 in both attachment and entry of virus to the Vero cells and also on post attachment stages of virus replication. Inhibitory concentration 50 (IC50 values of the autoclaved extract were 81µg/ml and 126 µg/ml for attachment and post attachment stages, respectively. IC50 values of the filtered extract were 73 µg/ml and 104 µg/ml for attachment and post attachment stages, respectively. CC50 values for autoclaved and filtered extracts were 3140 µg/ml and 3095 µg/ml, respectively. Conclusion: The hot water extract of Caulerpa sertularioides of the Persian Gulf had antiviral effect against HSV-1.

  3. Which Plant Proteins Are Involved in Antiviral Defense? Review on In Vivo and In Vitro Activities of Selected Plant Proteins against Viruses.

    Science.gov (United States)

    Musidlak, Oskar; Nawrot, Robert; Goździcka-Józefiak, Anna

    2017-11-01

    Plants have evolved a variety of defense mechanisms to tackle virus attack. Endogenous plant proteins can function as virus suppressors. Different types of proteins mediate defense responses against plant viruses. Pathogenesis-related (PR) proteins are activated upon pathogen infections or in different stress situations and their production is one of many components in plant defense. Ribosome-inactivating proteins (RIPs) suppress translation by enzymatically damaging ribosomes and they have been found to have antiviral activity. RNA-binding proteins (RBPs) bind to target RNAs via specialized RNA-binding domain and can directly or indirectly function in plant defense system against RNA viruses. Proteins involved in silencing machinery, namely Dicer-like (DCL) proteins, Argonaute (AGO) proteins, and RNA-dependent RNA polymerases (RDRs) confer innate antiviral defense in plants as they are able to degrade foreign RNA of viral origin. This review aims to provide a comprehensive and up-to-date picture of plant proteins participating in antiviral defense. As a result we discuss proteins conferring plant antiviral resistance and their potential future applications in different fields of life including agriculture and medicine.

  4. Which Plant Proteins Are Involved in Antiviral Defense? Review on In Vivo and In Vitro Activities of Selected Plant Proteins against Viruses

    Directory of Open Access Journals (Sweden)

    Oskar Musidlak

    2017-11-01

    Full Text Available Plants have evolved a variety of defense mechanisms to tackle virus attack. Endogenous plant proteins can function as virus suppressors. Different types of proteins mediate defense responses against plant viruses. Pathogenesis-related (PR proteins are activated upon pathogen infections or in different stress situations and their production is one of many components in plant defense. Ribosome-inactivating proteins (RIPs suppress translation by enzymatically damaging ribosomes and they have been found to have antiviral activity. RNA-binding proteins (RBPs bind to target RNAs via specialized RNA-binding domain and can directly or indirectly function in plant defense system against RNA viruses. Proteins involved in silencing machinery, namely Dicer-like (DCL proteins, Argonaute (AGO proteins, and RNA-dependent RNA polymerases (RDRs confer innate antiviral defense in plants as they are able to degrade foreign RNA of viral origin. This review aims to provide a comprehensive and up-to-date picture of plant proteins participating in antiviral defense. As a result we discuss proteins conferring plant antiviral resistance and their potential future applications in different fields of life including agriculture and medicine.

  5. Mitochondrial localization of the antiviral signaling adaptor IPS-1 is important for its induction of caspase activation.

    Science.gov (United States)

    Okazaki, Tomohiko; Higuchi, Maiko; Gotoh, Yukiko

    2013-06-01

    The RIG-I-like receptor (RLR) family of intracellular receptors detects viral nucleic acids and transmits an antiviral signal through the adaptor IPS-1. IPS-1 activation triggers host defense mechanisms, including rapid production of type I interferon (IFN), such as IFN-β, and induction of apoptosis. IPS-1 is mainly localized to mitochondria, and this localization has been proposed to be essential for inducing production of type I IFN and IFN-stimulated genes (ISGs). However, the importance of this mitochondrial localization of IPS-1 in executing apoptosis has remained unclear. Here, using IPS-1 mutants that were directed to specific subcellular locations such as cytoplasm, plasma membrane and mitochondria, we found that IPS-1's localization to mitochondria is important to activate caspase, but not to signal for IFN-β gene induction. We also found that IPS-1 possesses a BH3-like motif, which is commonly found among members of the Bcl-2 family. Mutations within this motif promoted IPS-1-induced caspase activation, suggesting that this domain acts as an intrinsic inhibitor domain of apoptosis induction. These results establish that the mitochondrial location of IPS-1 is essential to its ability to induce apoptosis. © 2013 The Authors Genes to Cells © 2013 by the Molecular Biology Society of Japan and Wiley Publishing Asia Pty Ltd.

  6. Biomedical potential of actinobacterially synthesized selenium nanoparticles with special reference to anti-biofilm, anti-oxidant, wound healing, cytotoxic and anti-viral activities.

    Science.gov (United States)

    Ramya, Suseenthar; Shanmugasundaram, Thangavel; Balagurunathan, Ramasamy

    2015-10-01

    Currently, there is an ever-increasing need to develop environmentally benign processes in place of synthetic protocols. As a result, researchers in the field of nanoparticle synthesis are focusing their attention on microbes from rare biological ecosystems. One potential actinobacterium, Streptomyces minutiscleroticus M10A62 isolated from a magnesite mine had the ability to synthesize selenium nanoparticles (SeNPs), extracellularly. Actinobacteria mediated SeNP synthesis were characterized by UV-visible, Fourier transform infrared (FT-IR), X-ray diffraction (XRD), energy dispersive X-ray spectroscopy (EDX) and high resolution transmission electron microscopy (HR-TEM) analysis. The UV-spectral analysis of SeNPs indicated the maximum absorption at 510nm, FT-IR spectral analysis confirms the presence of capping protein, peptide, amine and amide groups. The selenium signals confirm the presence of SeNPs. All the diffraction peaks in the XRD pattern and HR-TEM confirm the size of SeNPs in the range of 10-250nm. Further, the anti-biofilm and antioxidant activity of the SeNPs increased proportionally with rise in concentration, and the test strains reduced to 75% at concentration of 3.2μg. Selenium showed significant anti-proliferative activity against HeLa and HepG2 cell lines. The wound healing activity of SeNPs reveals that 5% selenium oinment heals the excision wound of Wistar rats up to 85% within 18 days compared to the standard ointment. The biosynthesized SeNPs exhibited good antiviral activity against Dengue virus. The present study concludes that extremophilic actinobacterial strain was a novel source for SeNPs with versatile biomedical applications and larger studies are needed to quantify these observed effects of SeNPs. Copyright © 2015 Elsevier GmbH. All rights reserved.

  7. Cross-Species Antiviral Activity of Goose Interferons against Duck Plague Virus Is Related to Its Positive Self-Feedback Regulation and Subsequent Interferon Stimulated Genes Induction

    Directory of Open Access Journals (Sweden)

    Hao Zhou

    2016-07-01

    Full Text Available Interferons are a group of antiviral cytokines acting as the first line of defense in the antiviral immunity. Here, we describe the antiviral activity of goose type I interferon (IFNα and type II interferon (IFNγ against duck plague virus (DPV. Recombinant goose IFNα and IFNγ proteins of approximately 20 kDa and 18 kDa, respectively, were expressed. Following DPV-enhanced green fluorescent protein (EGFP infection of duck embryo fibroblast cells (DEFs with IFNα and IFNγ pre-treatment, the number of viral gene copies decreased more than 100-fold, with viral titers dropping approximately 100-fold. Compared to the control, DPV-EGFP cell positivity was decreased by goose IFNα and IFNγ at 36 hpi (3.89%; 0.79% and 48 hpi (17.05%; 5.58%. In accordance with interferon-stimulated genes being the “workhorse” of IFN activity, the expression of duck myxovirus resistance (Mx and oligoadenylate synthetases-like (OASL was significantly upregulated (p < 0.001 by IFN treatment for 24 h. Interestingly, duck cells and goose cells showed a similar trend of increased ISG expression after goose IFNα and IFNγ pretreatment. Another interesting observation is that the positive feedback regulation of type I IFN and type II IFN by goose IFNα and IFNγ was confirmed in waterfowl for the first time. These results suggest that the antiviral activities of goose IFNα and IFNγ can likely be attributed to the potency with which downstream genes are induced by interferon. These findings will contribute to our understanding of the functional significance of the interferon antiviral system in aquatic birds and to the development of interferon-based prophylactic and therapeutic approaches against viral disease.

  8. Antiviral Activity of Bacillus sp. Isolated from the Marine Sponge Petromica citrina against Bovine Viral Diarrhea Virus, a Surrogate Model of the Hepatitis C Virus

    Science.gov (United States)

    Bastos, Juliana Cristina Santiago; Kohn, Luciana Konecny; Fantinatti-Garboggini, Fabiana; Padilla, Marina Aiello; Flores, Eduardo Furtado; da Silva, Bárbara Pereira; de Menezes, Cláudia Beatriz Afonso; Arns, Clarice Weis

    2013-01-01

    The Hepatitis C virus causes chronic infections in humans, which can develop to liver cirrhosis and hepatocellular carcinoma. The Bovine viral diarrhea virus is used as a surrogate model for antiviral assays for the HCV. From marine invertebrates and microorganisms isolated from them, extracts were prepared for assessment of their possible antiviral activity. Of the 128 tested, 2 were considered active and 1 was considered promising. The best result was obtained from the extracts produced from the Bacillus sp. isolated from the sponge Petromica citrina. The extracts 555 (500 µg/mL, SI>18) and 584 (150 µg/mL, SI 27) showed a percentage of protection of 98% against BVDV, and the extract 616, 90% of protection. All of them showed activity during the viral adsorption. Thus, various substances are active on these studied organisms and may lead to the development of drugs which ensure an alternative therapy for the treatment of hepatitis C. PMID:23628828

  9. Antiviral activity of Bacillus sp. isolated from the marine sponge Petromica citrina against bovine viral diarrhea virus, a surrogate model of the hepatitis C virus.

    Science.gov (United States)

    Bastos, Juliana Cristina Santiago; Kohn, Luciana Konecny; Fantinatti-Garboggini, Fabiana; Padilla, Marina Aiello; Flores, Eduardo Furtado; da Silva, Bárbara Pereira; de Menezes, Cláudia Beatriz Afonso; Arns, Clarice Weis

    2013-04-29

    The Hepatitis C virus causes chronic infections in humans, which can develop to liver cirrhosis and hepatocellular carcinoma. The Bovine viral diarrhea virus is used as a surrogate model for antiviral assays for the HCV. From marine invertebrates and microorganisms isolated from them, extracts were prepared for assessment of their possible antiviral activity. Of the 128 tested, 2 were considered active and 1 was considered promising. The best result was obtained from the extracts produced from the Bacillus sp. isolated from the sponge Petromica citrina. The extracts 555 (500 µg/mL, SI>18) and 584 (150 µg/mL, SI 27) showed a percentage of protection of 98% against BVDV, and the extract 616, 90% of protection. All of them showed activity during the viral adsorption. Thus, various substances are active on these studied organisms and may lead to the development of drugs which ensure an alternative therapy for the treatment of hepatitis C.

  10. Alkaloids from Piper nigrum Exhibit Antiinflammatory Activity via Activating the Nrf2/HO-1 Pathway.

    Science.gov (United States)

    Ngo, Quynh Mai Thi; Tran, Phuong Thao; Tran, Manh Hung; Kim, Jeong Ah; Rho, Seong Soo; Lim, Chi-Hwan; Kim, Jin-Cheol; Woo, Mi Hee; Choi, Jae Sui; Lee, Jeong-Hyung; Min, Byung Sun

    2017-04-01

    In the present study, ten alkaloids, namely chabamide (1), pellitorine (2), retrofractamide A (3), pyrroperine (4), isopiperolein B (5), piperamide C9:1 (8E) (6), 6,7-dehydrobrachyamide B (7), 4,5-dihydropiperine (8), dehydropipernonaline (9), and piperine (10), were isolated from the fruits of Piper nigrum. Among these, chabamide (1), pellitorine (2), retrofractamide A (3), isopiperolein B (5), and 6,7-dehydrobrachyamide B (7) exhibited significant inhibitory activity on lipopolysaccharide-induced nitric oxide (NO) production in RAW264.7 cells, with IC50 values of 6.8, 14.5, 30.2, 23.7, and 38.5 μM, respectively. Furthermore, compound 1 inhibited lipopolysaccharide-induced NO production in bone marrow-derived macrophages with IC50 value of 9.5 μM. Consistent with NO inhibition, treatment of RAW264.7 cells with chabamide (1), pellitorine (2), and 6,7-dehydrobrachyamide B (7) suppressed expression of inducible NO synthase and cyclooxygenase-2. Chabamide (1), pellitorine (2), and 6,7-dehydrobrachyamide B (7) induced heme-oxygenase-1 expression at the transcriptional level. In addition, compound 1 induced the nuclear translocation of nuclear factor-E2-related factor 2 (Nrf2) and upregulated the expression of Nrf2 target genes, NAD(P)H:quinone oxidoreductase 1 and γ-glutamyl cysteine synthetase catalytic subunit, in a concentration-dependent manner in RAW264.7 cells. These findings suggest that chabamide (1) from P. nigrum exert antiinflammatory effects via the activation of the Nrf2/heme-oxygenase-1 pathway; hence, it might be a promising candidate for the treatment of inflammatory diseases. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

  11. Multiple interferon stimulated genes synergize with the zinc finger antiviral protein to mediate anti-alphavirus activity.

    Directory of Open Access Journals (Sweden)

    Sophiya Karki

    Full Text Available The zinc finger antiviral protein (ZAP is a host factor that mediates inhibition of viruses in the Filoviridae, Retroviridae and Togaviridae families. We previously demonstrated that ZAP blocks replication of Sindbis virus (SINV, the prototype Alphavirus in the Togaviridae family at an early step prior to translation of the incoming genome and that synergy between ZAP and one or more interferon stimulated genes (ISGs resulted in maximal inhibitory activity. The present study aimed to identify those ISGs that synergize with ZAP to mediate Alphavirus inhibition. Using a library of lentiviruses individually expressing more than 350 ISGs, we screened for inhibitory activity in interferon defective cells with or without ZAP overexpression. Confirmatory tests of the 23 ISGs demonstrating the largest infection reduction in combination with ZAP revealed that 16 were synergistic. Confirmatory tests of all potentially synergistic ISGs revealed 15 additional ISGs with a statistically significant synergistic effect in combination with ZAP. These 31 ISGs are candidates for further mechanistic studies. The number and diversity of the identified ZAP-synergistic ISGs lead us to speculate that ZAP may play an important role in priming the cell for optimal ISG function.

  12. In vitro antiviral activity of Chamaecrista nictitans (Fabaceae against herpes simplex virus: Biological characterization of mechanisms of action

    Directory of Open Access Journals (Sweden)

    Libia Herrero Uribe

    2004-09-01

    Full Text Available We have previously identified a crude extract of the plant Chamaecrista nictitans (Fabaceaewith antiviral activity against herpes simplex virus.The main objectives of this research were to identify the step of the replication cycle of herpes simplex inhibited by the extract,and to attempt to characterize the chemical characteristics of this extract.The crude extract from Chamaecrista nictitans (Fabaceaewas extracted with a mixture of diclorometane/methanol,and further fractionated following a bioassay-guided protocol using a combination of preparative thin layer and column chromatography.Toxicity and bioassay experiments were carried out in monolayers of Vero cells.The antiviral activity of the extract was assessed by total inhibition of cytopathic effect after three-day incubation.The highest concentration of the extract which was not toxic to the cells was 200 mu g/ml. Western blot and immunofluorescence techniques were used to elucidate the antiviral mechanism of the extract by infecting Vero cells with the virus at different times and monitoring the synthesis of viral proteins.A 60 kDa protein was detected at 2 hr and 8 hr post-infection but no additional proteins were synthesized at later time intervals,and cytopathic effect was not observed after 24 hr.This result indicates that the extract acts at the intracellular level in order to inhibit late transcription.However,it does not inhibit transcription/translation of early viral proteins.These results were confirmed by immunofluorescence experiments.A strong fluorescent signal was observed in control cell monolayers at 24 hr post infection,accompanied with a clear cytopathic effect.In contrast,in the presence of acyclovir or the extract,cells showed very discrete immunofluorescence,characterized by a punctuated pattern, and no cytopathic effect was observed.Neutralization assays were performed using pre-incubation of virus with either specific herpes simplex-1 antiserum,200 mu g/ml of the

  13. Synthesis of benzopolycyclic cage amines: NMDA receptor antagonist, trypanocidal and antiviral activities.

    Science.gov (United States)

    Torres, Eva; Duque, María D; López-Querol, Marta; Taylor, Martin C; Naesens, Lieve; Ma, Chunlong; Pinto, Lawrence H; Sureda, Francesc X; Kelly, John M; Vázquez, Santiago

    2012-01-15

    The synthesis of several 6,7,8,9,10,11-hexahydro-9-methyl-5,7:9,11-dimethano-5H-benzocyclononen-7-amines is reported. Several of them display low micromolar NMDA receptor antagonist and/or trypanocidal activities. Two compounds are endowed with micromolar anti vesicular stomatitis virus activity, while only one compound shows micromolar anti-influenza activity. The anti-influenza activity of this compound does not seem to be mediated by blocking of the M2 protein. Copyright © 2011 Elsevier Ltd. All rights reserved.

  14. Synthesis of benzopolycyclic cage amines: NMDA receptor antagonist, trypanocidal and antiviral activities

    Science.gov (United States)

    Torres, Eva; Duque, María D.; López-Querol, Marta; Taylor, Martin C.; Naesens, Lieve; Ma, Chunlong; Pinto, Lawrence H.; Sureda, Francesc X.; Kelly, John M.; Vázquez, Santiago

    2012-01-01

    The synthesis of several 6,7,8,9,10,11-hexahydro-9-methyl-5,7:9,11-dimethano-5H-benzocyclononen-7-amines is reported. Several of them display low micromolar NMDA receptor antagonist and/or trypanocidal activities. Two compounds are endowed with micromolar anti vesicular stomatitis virus activity, while only one compound shows micromolar anti-influenza activity. The anti-influenza activity of this compound does not seem to be mediated by blocking of the M2 protein. PMID:22178660

  15. Characterization of Catalase from Psychrotolerant Psychrobacter piscatorii T-3 Exhibiting High Catalase Activity

    OpenAIRE

    Hidetoshi Matsuyma; Isao Yumoto; Hideyuki Kimoto; Kazuaki Yoshimune

    2012-01-01

    A psychrotolerant bacterium, strain T-3 (identified as Psychrobacter piscatorii), that exhibited an extraordinarily high catalase activity was isolated from the drain pool of a plant that uses H2O2 as a bleaching agent. Its cell extract exhibited a catalase activity (19,700 U·mg protein−1) that was higher than that of Micrococcus luteus used for industrial catalase production. Catalase was approximately 10% of the total proteins in the cell extract of the strain. The catalase (PktA) was purif...

  16. Metabolic variations, antioxidant potential, and antiviral activity of different extracts of Eugenia singampattiana (an endangered medicinal plant used by Kani tribals, Tamil Nadu, India) leaf.

    Science.gov (United States)

    John, K M Maria; Ayyanar, Muniappan; Jeeva, Subbiah; Suresh, Murugesan; Enkhtaivan, Gansukh; Kim, Doo Hwan

    2014-01-01

    Eugenia singampattiana is an endangered medicinal plant used by the Kani tribals of South India. The plant had been studied for its antioxidant, antitumor, antihyperlipidemic, and antidiabetic activity. But its primary and secondary metabolites profile and its antiviral properties were unknown, and so this study sought to identify this aspect in Eugenia singampattiana plant through different extraction methods along with their activities against porcine reproductive and respiratory syndrome virus (PRRSV). The GC-MS analysis revealed that 11 primary metabolites showed significant variations among the extracts. Except for fructose all other metabolites were high with water extract. Among 12 secondary metabolites showing variations, the levels of 4-hydroxy benzoic acid, caffeic acid, rutin, ferulic acid, coumaric acid, epigallocatechin gallate, quercetin, myricetin, and kaempferol were high with methanol extract. Since the flavonoid content of methanol extracts was high, the antioxidant potential, such as ABTS, and phosphomolybdenum activity increased. The plants antiviral activity against PRRSV was for the first time confirmed and the results revealed that methanol 25 µg and 75 to 100 µg in case of water extracts revealed antiviral activity.

  17. Thiosemicarbazones and Phthalyl-Thiazoles compounds exert antiviral activity against yellow fever virus and Saint Louis encephalitis virus.

    Science.gov (United States)

    Pacca, Carolina Colombelli; Marques, Rafael Elias; Espindola, José Wanderlan P; Filho, Gevânio B O Oliveira; Leite, Ana Cristina Lima; Teixeira, Mauro Martins; Nogueira, Mauricio L

    2017-03-01

    Arboviruses, arthropod-borneviruses, are frequency associated to human outbreak and represent a serious health problem. The genus Flavivirus, such as Yellow Fever Virus (YFV) and Saint Louis Encephalitis Virus (SLEV), are important pathogens with high morbidity and mortality worldwide. In Brazil, YFV is maintained in sylvatic cycle, but many cases are notified annually, despite the efficiency of vaccine. SLEV causes an acute encephalitis and is widely distributed in the Americas. There is no specific antiviral drugs for these viruses, only supporting treatment that can alleviate symptoms and prevent complications. Here, we evaluated the potential anti-YFV and SLEV activity of a series of thiosemicarbazones and phthalyl-thiazoles. Plaque reduction assay, flow cytometry, immunofluorescence and cellular viability were used to test the compounds in vitro. Treated cells showed efficient inhibition of the viral replication at concentrations that presented minimal toxicity to cells. The assays showed that phthalyl-thiazole and phenoxymethyl-thiosemicarbazone reduced 60% of YFV replication and 75% of SLEV replication. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  18. Screening of Dengue virus antiviral activity of marine seaweeds by an in situ enzyme-linked immunosorbent assay.

    Directory of Open Access Journals (Sweden)

    Andrea Cristine Koishi

    Full Text Available Dengue is a significant public health problem worldwide. Despite the important social and clinical impact, there is no vaccine or specific antiviral therapy for prevention and treatment of dengue virus (DENV infection. Considering the above, drug discovery research for dengue is of utmost importance; in addition natural marine products provide diverse and novel chemical structures with potent biological activities that must be evaluated. In this study we propose a target-free approach for dengue drug discovery based on a novel, rapid, and economic in situ enzyme-linked immunosorbent assay and the screening of a panel of marine seaweed extracts. The in situ ELISA was standardized and validated for Huh7.5 cell line infected with all four serotypes of DENV, among them clinical isolates and a laboratory strain. Statistical analysis showed an average S/B of 7.2 and Z-factor of 0.62, demonstrating assay consistency and reliability. A panel of fifteen seaweed extracts was then screened at the maximum non-toxic dose previously determined by the MTT and Neutral Red cytotoxic assays. Eight seaweed extracts were able to reduce DENV infection of at least one serotype tested. Four extracts (Phaeophyta: Canistrocarpus cervicornis, Padina gymnospora; Rhodophyta: Palisada perforate; Chlorophyta: Caulerpa racemosa were chosen for further evaluation, and time of addition studies point that they might act at an early stage of the viral infection cycle, such as binding or internalization.

  19. Screening of Dengue Virus Antiviral Activity of Marine Seaweeds by an In Situ Enzyme-Linked Immunosorbent Assay

    Science.gov (United States)

    Koishi, Andrea Cristine; Zanello, Paula Rodrigues; Bianco, Éverson Miguel; Bordignon, Juliano; Nunes Duarte dos Santos, Claudia

    2012-01-01

    Dengue is a significant public health problem worldwide. Despite the important social and clinical impact, there is no vaccine or specific antiviral therapy for prevention and treatment of dengue virus (DENV) infection. Considering the above, drug discovery research for dengue is of utmost importance; in addition natural marine products provide diverse and novel chemical structures with potent biological activities that must be evaluated. In this study we propose a target-free approach for dengue drug discovery based on a novel, rapid, and economic in situ enzyme-linked immunosorbent assay and the screening of a panel of marine seaweed extracts. The in situ ELISA was standardized and validated for Huh7.5 cell line infected with all four serotypes of DENV, among them clinical isolates and a laboratory strain. Statistical analysis showed an average S/B of 7.2 and Z-factor of 0.62, demonstrating assay consistency and reliability. A panel of fifteen seaweed extracts was then screened at the maximum non-toxic dose previously determined by the MTT and Neutral Red cytotoxic assays. Eight seaweed extracts were able to reduce DENV infection of at least one serotype tested. Four extracts (Phaeophyta: Canistrocarpus cervicornis, Padina gymnospora; Rhodophyta: Palisada perforate; Chlorophyta: Caulerpa racemosa) were chosen for further evaluation, and time of addition studies point that they might act at an early stage of the viral infection cycle, such as binding or internalization. PMID:23227238

  20. Efficacious early antiviral activity of HIV Gag- and Pol-specific HLA-B 2705-restricted CD8+ T cells

    DEFF Research Database (Denmark)

    Payne, Rebecca P; Kløverpris, Henrik; Sacha, Jonah B

    2010-01-01

    The association between HLA-B 2705 and the immune control of human immunodeficiency virus type 1 (HIV-1) has previously been linked to the targeting of the HLA-B 2705-restricted Gag epitope KRWIILGLNK (KK10) by CD8(+) T cells. In order to better define the mechanisms of the HLA-B 2705 immune...... control of HIV, we first characterized the CD8(+) T-cell responses of nine highly active antiretroviral therapy (HAART)-naïve B 2705-positive subjects. Unexpectedly, we observed a strong response to an HLA-B 2705-restricted Pol epitope, KRKGGIGGY (KY9), in 8/9 subjects. The magnitude of the KY9 response...... by the respective CD8(+) T-cell response. By comparing inhibitions of viral replication by CD8(+) T cells specific for the Gag KK10, Pol KY9, and Vpr VL9 HLA-B 2705-restricted epitopes, we observed a consistent hierarchy of antiviral efficacy (Gag KK10 > Pol KY9 > Vpr VL9). This hierarchy was associated with early...

  1. Antiviral Activity of Gold/Copper Sulfide Core/Shell Nanoparticles against Human Norovirus Virus-Like Particles.

    Directory of Open Access Journals (Sweden)

    Jessica Jenkins Broglie

    Full Text Available Human norovirus is a leading cause of acute gastroenteritis worldwide in a plethora of residential and commercial settings, including restaurants, schools, and hospitals. Methods for easily detecting the virus and for treating and preventing infection are critical to stopping norovirus outbreaks, and inactivation via nanoparticles (NPs is a more universal and attractive alternative to other physical and chemical approaches. Using norovirus GI.1 (Norwalk virus-like particles (VLPs as a model viral system, this study characterized the antiviral activity of Au/CuS core/shell nanoparticles (NPs against GI.1 VLPs for the rapid inactivation of HuNoV. Inactivation of VLPs (GI.1 by Au/CuS NPs evaluated using an absorbance-based ELISA indicated that treatment with 0.083 μM NPs for 10 min inactivated ~50% VLPs in a 0.37 μg/ml VLP solution and 0.83 μM NPs for 10 min completely inactivated the VLPs. Increasing nanoparticle concentration and/or VLP-NP contact time significantly increased the virucidal efficacy of Au/CuS NPs. Changes to the VLP particle morphology, size, and capsid protein were characterized using dynamic light scattering, transmission electron microscopy, and Western blot analysis. The strategy reported here provides the first reported proof-of-concept Au/CuS NPs-based virucide for rapidly inactivating human norovirus.

  2. Computer-aided identification, design and synthesis of a novel series of compounds with selective antiviral activity against chikungunya virus.

    Science.gov (United States)

    Bassetto, Marcella; De Burghgraeve, Tine; Delang, Leen; Massarotti, Alberto; Coluccia, Antonio; Zonta, Nicola; Gatti, Valerio; Colombano, Giampiero; Sorba, Giovanni; Silvestri, Romano; Tron, Gian Cesare; Neyts, Johan; Leyssen, Pieter; Brancale, Andrea

    2013-04-01

    Chikungunya virus (CHIKV) is an Arbovirus that is transmitted to humans primarily by the mosquito species Aedes aegypti. Infection with this pathogen is often associated with fever, rash and arthralgia. Neither a vaccine nor an antiviral drug is available for the prevention or treatment of this disease. Albeit considered a tropical pathogen, adaptation of the virus to the mosquito species Aedes albopictus, which is also very common in temperate zones, has resulted in recent outbreaks in Europe and the US. In the present study, we report on the discovery of a novel series of compounds that inhibit CHIKV replication in the low μM range. In particular, we initially performed a virtual screening simulation of ∼5 million compounds on the CHIKV nsP2, the viral protease, after which we investigated and explored the Structure-Activity Relationships of the hit identified in silico. Overall, a series of 26 compounds, including the original hit, was evaluated in a virus-cell-based CPE reduction assay. The study of such selective inhibitors will contribute to a better understanding of the CHIKV replication cycle and may represents a first step towards the development of a clinical candidate drug for the treatment of this disease. Copyright © 2013 Elsevier B.V. All rights reserved.

  3. MEK/ERK activation plays a decisive role in yellow fever virus replication: implication as an antiviral therapeutic target.

    Science.gov (United States)

    Albarnaz, Jonas D; De Oliveira, Leonardo C; Torres, Alice A; Palhares, Rafael M; Casteluber, Marisa C; Rodrigues, Claudiney M; Cardozo, Pablo L; De Souza, Aryádina M R; Pacca, Carolina C; Ferreira, Paulo C P; Kroon, Erna G; Nogueira, Maurício L; Bonjardim, Cláudio A

    2014-11-01

    Exploiting the inhibition of host signaling pathways aiming for discovery of potential antiflaviviral compounds is clearly a beneficial strategy for the control of life-threatening diseases caused by flaviviruses. Here we describe the antiviral activity of the MEK1/2 inhibitor U0126 against Yellow fever virus 17D vaccine strain (YFV-17D). Infection of VERO cells with YFV-17D stimulates ERK1/2 phosphorylation early during infection. Pharmacological inhibition of MEK1/2 through U0126 treatment of VERO cells blockades not only the YFV-stimulated ERK1/2 phosphorylation, but also inhibits YFV replication by ∼99%. U0126 was also effective against dengue virus (DENV-2 and -3) and Saint-Louis encephalitis virus (SLEV). Levels of NS4AB, as detected by immunofluorescence, are diminished upon treatment with the inhibitor, as well as the characteristic endoplasmic reticulum membrane invagination stimulated during the infection. Though not protective, treatment of YFV-infected, adult BALB/c mice with U0126 resulted in significant reduction of virus titers in brains. Collectively, our data suggest the potential targeting of the MEK1/2 kinase as a therapeutic tool against diseases caused by flaviviruses such as yellow fever, adverse events associated with yellow fever vaccination and dengue. Copyright © 2014 Elsevier B.V. All rights reserved.

  4. Screening of Dengue virus antiviral activity of marine seaweeds by an in situ enzyme-linked immunosorbent assay.

    Science.gov (United States)

    Koishi, Andrea Cristine; Zanello, Paula Rodrigues; Bianco, Éverson Miguel; Bordignon, Juliano; Nunes Duarte dos Santos, Claudia

    2012-01-01

    Dengue is a significant public health problem worldwide. Despite the important social and clinical impact, there is no vaccine or specific antiviral therapy for prevention and treatment of dengue virus (DENV) infection. Considering the above, drug discovery research for dengue is of utmost importance; in addition natural marine products provide diverse and novel chemical structures with potent biological activities that must be evaluated. In this study we propose a target-free approach for dengue drug discovery based on a novel, rapid, and economic in situ enzyme-linked immunosorbent assay and the screening of a panel of marine seaweed extracts. The in situ ELISA was standardized and validated for Huh7.5 cell line infected with all four serotypes of DENV, among them clinical isolates and a laboratory strain. Statistical analysis showed an average S/B of 7.2 and Z-factor of 0.62, demonstrating assay consistency and reliability. A panel of fifteen seaweed extracts was then screened at the maximum non-toxic dose previously determined by the MTT and Neutral Red cytotoxic assays. Eight seaweed extracts were able to reduce DENV infection of at least one serotype tested. Four extracts (Phaeophyta: Canistrocarpus cervicornis, Padina gymnospora; Rhodophyta: Palisada perforate; Chlorophyta: Caulerpa racemosa) were chosen for further evaluation, and time of addition studies point that they might act at an early stage of the viral infection cycle, such as binding or internalization.

  5. Activation of cGAS-dependent antiviral responses by DNA intercalating agents

    OpenAIRE

    P?pin, Genevi?ve; Nejad, Charlotte; Thomas, Belinda J.; Ferrand, Jonathan; McArthur, Kate; Bardin, Philip G.; Williams, Bryan R.G.; Gantier, Michael P.

    2016-01-01

    Acridine dyes, including proflavine and acriflavine, were commonly used as antiseptics before the advent of penicillins in the mid-1940s. While their mode of action on pathogens was originally attributed to their DNA intercalating activity, work in the early 1970s suggested involvement of the host immune responses, characterized by induction of interferon (IFN)-like activities through an unknown mechanism. We demonstrate here that sub-toxic concentrations of a mixture of acriflavine and profl...

  6. CD40 activation rescues antiviral CD8⁺ T cells from PD-1-mediated exhaustion.

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    Masanori Isogawa

    Full Text Available The intrahepatic immune environment is normally biased towards tolerance. Nonetheless, effective antiviral immune responses can be induced against hepatotropic pathogens. To examine the immunological basis of this paradox we studied the ability of hepatocellularly expressed hepatitis B virus (HBV to activate immunologically naïve HBV-specific CD8⁺ T cell receptor (TCR transgenic T cells after adoptive transfer to HBV transgenic mice. Intrahepatic priming triggered vigorous in situ T cell proliferation but failed to induce interferon gamma production or cytolytic effector function. In contrast, the same T cells differentiated into cytolytic effector T cells in HBV transgenic mice if Programmed Death 1 (PD-1 expression was genetically ablated, suggesting that intrahepatic antigen presentation per se triggers negative regulatory signals that prevent the functional differentiation of naïve CD8⁺ T cells. Surprisingly, coadministration of an agonistic anti-CD40 antibody (αCD40 inhibited PD-1 induction and restored T cell effector function, thereby inhibiting viral gene expression and causing a necroinflammatory liver disease. Importantly, the depletion of myeloid dendritic cells (mDCs strongly diminished the αCD40 mediated functional differentiation of HBV-specific CD8⁺ T cells, suggesting that activation of mDCs was responsible for the functional differentiation of HBV-specific CD8⁺ T cells in αCD40 treated animals. These results demonstrate that antigen-specific, PD-1-mediated CD8⁺ T cell exhaustion can be rescued by CD40-mediated mDC-activation.

  7. Critical role for cross-linking of trimeric lectin domains of surfactant protein D in antiviral activity against influenza A virus

    DEFF Research Database (Denmark)

    Tecle, Tesfaldet; White, Mitchell R; Sørensen, Grith Lykke

    2008-01-01

    binding activity for some ligands and mediate some functional activities. The lung collectin SP-D (surfactant protein D) has strong neutralizing activity for IAVs (influenza A viruses) in vitro and in vivo, however, the NCRD derived from SP-D has weak viral-binding ability and lacks neutralizing activity...... and antiviral activity of NCRDs as assessed by haemagglutination and neuraminidase inhibition and by viral neutralization. mAb-mediated cross-linking also enabled NCRDs to induce viral aggregation and to increase viral uptake by neutrophils and virus-induced respiratory burst responses by these cells...

  8. Semisynthesis, cytotoxicity, antiviral activity, and drug interaction liability of 7-O-methylated analogues of flavonolignans from milk thistle.

    Science.gov (United States)

    Althagafy, Hanan S; Graf, Tyler N; Sy-Cordero, Arlene A; Gufford, Brandon T; Paine, Mary F; Wagoner, Jessica; Polyak, Stephen J; Croatt, Mitchell P; Oberlies, Nicholas H

    2013-07-01

    Silymarin, an extract of the seeds of milk thistle (Silybum marianum), is used as an herbal remedy, particularly for hepatoprotection. The main chemical constituents in silymarin are seven flavonolignans. Recent studies explored the non-selective methylation of one flavonolignan, silybin B, and then tested those analogues for cytotoxicity and inhibition of both cytochrome P450 (CYP) 2C9 activity in human liver microsomes and hepatitis C virus infection in a human hepatoma (Huh7.5.1) cell line. In general, enhanced bioactivity was observed with the analogues. To further probe the biological consequences of methylation of the seven major flavonolignans, a series of 7-O-methylflavonolignans were generated. Optimization of the reaction conditions permitted selective methylation at the phenol in the 7-position in the presence of each metabolite's 4-5 other phenolic and/or alcoholic positions without the use of protecting groups. These 7-O-methylated analogues, in parallel with the corresponding parent compounds, were evaluated for cytotoxicity against Huh7.5.1 cells; in all cases the monomethylated analogues were more cytotoxic than the parent compounds. Moreover, parent compounds that were relatively non-toxic and inactive or weak inhibitors of hepatitis C virus infection had enhanced cytotoxicity and anti-HCV activity upon 7-O-methylation. Also, the compounds were tested for inhibition of major drug metabolizing enzymes (CYP2C9, CYP3A4/5, UDP-glucuronsyltransferases) in pooled human liver or intestinal microsomes. Methylation of flavonolignans differentially modified inhibitory potency, with compounds demonstrating both increased and decreased potency depending upon the compound tested and the enzyme system investigated. In total, these data indicated that monomethylation modulates the cytotoxic, antiviral, and drug interaction potential of silymarin flavonolignans. Copyright © 2013 Elsevier Ltd. All rights reserved.

  9. Synthesis and Antiviral Activity of N-Phenylbenzamide Derivatives, a Novel Class of Enterovirus 71 Inhibitors

    Directory of Open Access Journals (Sweden)

    Zhuo-Rong Li

    2013-03-01

    Full Text Available A series of novel N-phenylbenzamide derivatives were synthesized and their anti-EV 71 activities were assayed in vitro. Among the compounds tested, 3-amino-N-(4-bromophenyl-4-methoxybenzamide (1e was active against the EV 71 strains tested at low micromolar concentrations, with IC50 values ranging from 5.7 ± 0.8–12 ± 1.2 μM, and its cytotoxicity to Vero cells (TC50 = 620 ± 0.0 μM was far lower than that of pirodavir (TC50 = 31 ± 2.2 μM. Based on these results, compound 1e is a promising lead compound for the development of anti-EV 71 drugs.

  10. DENV up-regulates the HMG-CoA reductase activity through the impairment of AMPK phosphorylation: A potential antiviral target.

    Directory of Open Access Journals (Sweden)

    Rubén Soto-Acosta

    2017-04-01

    Full Text Available Dengue is the most common mosquito-borne viral disease in humans. Changes of lipid-related metabolites in endoplasmic reticulum of dengue virus (DENV infected cells have been associated with replicative complexes formation. Previously, we reported that DENV infection inhibits HMGCR phosphorylation generating a cholesterol-enriched cellular environment in order to favor viral replication. In this work, using enzymatic assays, ELISA, and WB we found a significant higher activity of HMGCR in DENV infected cells, associated with the inactivation of AMPK. AMPK activation by metformin declined the HMGCR activity suggesting that AMPK inactivation mediates the enhanced activity of HMGCR. A reduction on AMPK phosphorylation activity was observed in DENV infected cells at 12 and 24 hpi. HMGCR and cholesterol co-localized with viral proteins NS3, NS4A and E, suggesting a role for HMGCR and AMPK activity in the formation of DENV replicative complexes. Furthermore, metformin and lovastatin (HMGCR inhibitor altered this co-localization as well as replicative complexes formation supporting that active HMGCR is required for replicative complexes formation. In agreement, metformin prompted a significant dose-dependent antiviral effect in DENV infected cells, while compound C (AMPK inhibitor augmented the viral genome copies and the percentage of infected cells. The PP2A activity, the main modulating phosphatase of HMGCR, was not affected by DENV infection. These data demonstrate that the elevated activity of HMGCR observed in DENV infected cells is mediated through AMPK inhibition and not by increase in PP2A activity. Interestingly, the inhibition of this phosphatase showed an antiviral effect in an HMGCR-independent manner. These results suggest that DENV infection increases HMGCR activity through AMPK inactivation leading to higher cholesterol levels in endoplasmic reticulum necessary for replicative complexes formation. This work provides new information

  11. Virucidal activity presence in Trichilia glabra leaves Presencia de actividad antiviral en hojas de Trichilia glabra

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    M. Cella

    2004-09-01

    Full Text Available Different immunomodulatory activities present in Trichilia glabra (TG leaf extracts have already been described. Particularly, chloroform-methanol extracts were responsible for an in-vivo anti-inflammatory effect. The effect of such extracts on the infectivity of enveloped and naked viruses were investigated. Methanolic fraction extracts were active against herpes simplex virus type 1 (HSV-1 and vesicular stomatitis virus (VSV, while no activity against poliovirus type 3 was observed. VSV was slightly more affected than HSV-1: 2.8 log10 reduction in VSV titer against 2.4 log10reduction in HSV-1 titer when 0.25 mg/ml F2 fraction was tested and a reduction of 2.7 log10in VSV virus titer and of 1.5 log10in HSV-1 virus titer was observed when 0.25 mg/ml F3 fraction was tested. Results obtained in this work suggest a potential pharmaceutical use of TG extract components.Previamente se han descripto distintas actividades inmunomoduladoras, presentes en extractos de hojas de Trichilia glabra (TG. En particular, se ha demostrado una actividad antiinflamatoria presente en extractos metanólicos. En este trabajo se investigó la actividad virucida de dichos extractos sobre virus envueltos y desnudos. Distintos extractos metanólicos han inactivado en forma moderada los virus herpes simplex tipo 1 (HSV-1 y el virus de la estomatitis vesicular (VSV, mientras no evidenciaron actividad sobre poliovirus tipo 3. VSV resultó algo mas afectado que HSV-1: se observó una reducción en el título viral de 2,8 log10para VSV y de 2,4 log10para HSV-1 cuando se uso una concentración de 0,25 mg/ml de la fracción F2 y una reducción de 2,7 log10para VSV y de 1,5 log 10para HSV-1 cuando se usó una concentración de 0,25 mg/ml de la fracción F3. Los resultados obtenidos en este trabajo, sugieren un potencial uso farmacéutico de los componentes presentes en los extractos de TG.

  12. Low cost antiviral activity of Plodia interpunctella haemolymph in vivo demonstrated by dose dependent infection.

    Science.gov (United States)

    Saejeng, A; Siva-Jothy, M T; Boots, M

    2011-02-01

    Given the ubiquity of infectious disease it is important to understand the way in which hosts defend themselves and any costs that they may pay for this defence. Despite this, we know relatively little about insect immune responses to viruses when compared to their well-characterized responses to other pathogens. In particular it is unclear whether there is significant haemocoelic response to viral infection. Here we directly examine this question by examining whether there is a dose-dependency in infection risk when a DNA virus is injected directly into the haemocoel. Infection from direct injection into the haemocoel showed a clear dose dependency that is indicative of an active intrahaemocoelic immune response to DNA viruses in insects. In contrast to the natural oral infection route, we found no measurable sublethal effects in the survivors from direct injection. This suggests that the immune responses in the haemocoel are less costly than those that occur earlier. Copyright © 2010 . Published by Elsevier Ltd.

  13. Activated CD56(+) lymphocytes (NK+NKT) mediate immunomodulatory and anti-viral effects during Japanese encephalitis virus infection of dendritic cells in-vitro.

    Science.gov (United States)

    Sooryanarain, Harini; Ayachit, Vijay; Gore, Milind

    2012-10-25

    Japanese encephalitis virus (JEV) remains one of the major causative agents of pediatric encephalitis. Interaction of dendritic cells (DCs) with innate lymphocytes (NK and NKT) represents a crucial event during anti-viral innate immune response. In the current study, we have tried to understand the interaction between JEV, human monocyte derived DCs (MDDCs), and CD56(+) cells (NK+NKT) in-vitro. We have used two JEV strains (i) JE057434 (neurovirulent, wild-type) and (ii) SA14-14-2 (non-neurovirulent, live-attenuated vaccine) to investigate the effect of viral virulence on the functional status of primary human MDDCs. Our preliminary results indicate that replicating JEV induces MDDCs maturation via PI3K and p38 pathways. We also show that the presence of IL2-activated CD56(+) cells impart both immunomodulatory and anti-viral effects on DCs infected with JEV. Mechanistic studies illustrate that, IL2-activated CD56(+) lymphocytes mediated immunomodulation occurs through direct cell-to-cell contact and TNFα, while the anti-viral effect is dependent on direct cell-to-cell contact. Copyright © 2012 Elsevier Inc. All rights reserved.

  14. Safety and antiviral activity of albinterferon alfa-2b in prior interferon nonresponders with chronic hepatitis C.

    Science.gov (United States)

    Nelson, David R; Rustgi, Vinod; Balan, Vijayan; Sulkowski, Mark S; Davis, Gary L; Muir, Andrew J; Lambiase, Louis R; Dickson, Rolland C; Weisner, Russell H; Fiscella, Michele; Cronin, Patrick W; Pulkstenis, Erik; McHutchison, John G; Subramanian, G Mani

    2009-02-01

    Pegylated interferon alfa-2a/2b is used in combination with ribavirin to treat patients with chronic hepatitis C (CHC), although many do not achieve a sustained virologic response (SVR). Albinterferon alfa-2b, a recombinant protein consisting of interferon alfa-2b fused to human albumin, may increase drug exposure. This phase 2 study evaluated the safety/efficacy of albinterferon in CHC patients who had not responded to interferon-based regimens. A total of 115 patients were assigned to 5 groups given 1200 microg albinterferon every 4 weeks or 900, 1200, 1500, or 1800 microg every 2 weeks, plus oral ribavirin, for 48 weeks. The primary efficacy end point was achievement of an SVR after 24 weeks. Treatment was extended to 72 weeks for 6 slow responders who were negative for hepatitis C virus RNA after 24 weeks. The types of adverse events were similar across groups; the overall discontinuation rate as a result of adverse events was 10.4%. Reductions in absolute neutrophil counts were less frequent in the every 4 weeks group and comparable among the every 2 weeks groups. The overall SVR rate was 17% (11% for previous nonresponders to pegylated interferon-alfa/ribavirin with genotype 1 infection). An SVR occurred in 3 of 6 slow responders by 72 weeks. The greatest reductions in hepatitis C virus RNA in nonresponders to pegylated interferon-alfa/ribavirin with genotype 1 infection were observed in the 1800-microg group. In patients with CHC who did not respond to interferon-based regimens, higher doses of albinterferon had significant early antiviral activity and a low incidence of adverse events, with the types of adverse events similar to those observed with interferon.

  15. Characterization of Catalase from Psychrotolerant Psychrobacter piscatorii T-3 Exhibiting High Catalase Activity

    Science.gov (United States)

    Kimoto, Hideyuki; Yoshimune, Kazuaki; Matsuyma, Hidetoshi; Yumoto, Isao

    2012-01-01

    A psychrotolerant bacterium, strain T-3 (identified as Psychrobacter piscatorii), that exhibited an extraordinarily high catalase activity was isolated from the drain pool of a plant that uses H2O2 as a bleaching agent. Its cell extract exhibited a catalase activity (19,700 U·mg protein−1) that was higher than that of Micrococcus luteus used for industrial catalase production. Catalase was approximately 10% of the total proteins in the cell extract of the strain. The catalase (PktA) was purified homogeneously by only two purification steps, anion exchange and hydrophobic chromatographies. The purified catalase exhibited higher catalytic efficiency and higher sensitivity of activity at high temperatures than M. luteus catalase. The deduced amino acid sequence showed the highest homology with catalase of Psycrobacter cryohalolentis, a psychrotolelant bacterium obtained from Siberian permafrost. These findings suggest that the characteristics of the PktA molecule reflected the taxonomic relationship of the isolate as well as the environmental conditions (low temperatures and high concentrations of H2O2) under which the bacterium survives. Strain T-3 efficiently produces a catalase (PktA) at a higher rate than Exiguobacterium oxidotolerans, which produces a very strong activity of catalase (EktA) at a moderate rate, in order to adapt to high concentration of H2O2. PMID:22408420

  16. Characterization of Catalase from Psychrotolerant Psychrobacter piscatorii T-3 Exhibiting High Catalase Activity

    Directory of Open Access Journals (Sweden)

    Hidetoshi Matsuyma

    2012-02-01

    Full Text Available A psychrotolerant bacterium, strain T-3 (identified as Psychrobacter piscatorii, that exhibited an extraordinarily high catalase activity was isolated from the drain pool of a plant that uses H2O2 as a bleaching agent. Its cell extract exhibited a catalase activity (19,700 U·mg protein−1 that was higher than that of Micrococcus luteus used for industrial catalase production. Catalase was approximately 10% of the total proteins in the cell extract of the strain. The catalase (PktA was purified homogeneously by only two purification steps, anion exchange and hydrophobic chromatographies. The purified catalase exhibited higher catalytic efficiency and higher sensitivity of activity at high temperatures than M. luteus catalase. The deduced amino acid sequence showed the highest homology with catalase of Psycrobacter cryohalolentis, a psychrotolelant bacterium obtained from Siberian permafrost. These findings suggest that the characteristics of the PktA molecule reflected the taxonomic relationship of the isolate as well as the environmental conditions (low temperatures and high concentrations of H2O2 under which the bacterium survives. Strain T-3 efficiently produces a catalase (PktA at a higher rate than Exiguobacterium oxidotolerans, which produces a very strong activity of catalase (EktA at a moderate rate, in order to adapt to high concentration of H2O2.

  17. Antiviral and Virucidal Activities of N-Cocoyl-L-Arginine Ethyl Ester

    Directory of Open Access Journals (Sweden)

    Hisashi Yamasaki

    2011-01-01

    Full Text Available Various amino acid-derived compounds, for example, Nα-Cocoyl-L-arginine ethyl ester (CAE, alkyloxyhydroxylpropylarginine, arginine cocoate, and cocoyl glycine potassium salt (Amilite, were examined for their virucidal activities against herpes simplex virus type 1 and 2 (HSV-1 and HSV-2, influenza A virus (IAV, and poliovirus type 1 (PV-1 in comparison to benzalkonium chloride (BKC and sodium dodecylsulfate (SDS as a cationic and anionic control detergent and also to other commercially available disinfectants. While these amino acid-derived compounds were all effective against HSV-1 and HSV-2, CAE and Amilite were the most effective. These two compounds were, however, not as effective against IAV, another enveloped virus, as against HSV. Cytotoxicity of CAE was weak; at 0.012%, only 5% of the cells were killed under the conditions, in which 100% cells were killed by either SDS or BKC. In addition to these direct virucidal effects, CAE inhibited the virus growth in the HSV-1- or PV-1-infected cells even at 0.01%. These results suggest a potential application of CAE as a therapeutic or preventive medicine against HSV superficial infection at body surface.

  18. Conformational adaptation of Asian macaque TRIMCyp directs lineage specific antiviral activity.

    Directory of Open Access Journals (Sweden)

    Laura M J Ylinen

    2010-08-01

    Full Text Available TRIMCyps are anti-retroviral proteins that have arisen independently in New World and Old World primates. All TRIMCyps comprise a CypA domain fused to the tripartite domains of TRIM5alpha but they have distinct lentiviral specificities, conferring HIV-1 restriction in New World owl monkeys and HIV-2 restriction in Old World rhesus macaques. Here we provide evidence that Asian macaque TRIMCyps have acquired changes that switch restriction specificity between different lentiviral lineages, resulting in species-specific alleles that target different viruses. Structural, thermodynamic and viral restriction analysis suggests that a single mutation in the Cyp domain, R69H, occurred early in macaque TRIMCyp evolution, expanding restriction specificity to the lentiviral lineages found in African green monkeys, sooty mangabeys and chimpanzees. Subsequent mutations have enhanced restriction to particular viruses but at the cost of broad specificity. We reveal how specificity is altered by a scaffold mutation, E143K, that modifies surface electrostatics and propagates conformational changes into the active site. Our results suggest that lentiviruses may have been important pathogens in Asian macaques despite the fact that there are no reported lentiviral infections in current macaque populations.

  19. Mytilus galloprovincialis myticin C: a chemotactic molecule with antiviral activity and immunoregulatory properties.

    Directory of Open Access Journals (Sweden)

    Pablo Balseiro

    Full Text Available Previous research has shown that an antimicrobial peptide (AMP of the myticin class C (Myt C is the most abundantly expressed gene in cDNA and suppressive subtractive hybridization (SSH libraries after immune stimulation of mussel Mytilus galloprovincialis. However, to date, the expression pattern, the antimicrobial activities and the immunomodulatory properties of the Myt C peptide have not been determined. In contrast, it is known that Myt C mRNA presents an unusual and high level of polymorphism of unidentified biological significance. Therefore, to provide a better understanding of the features of this interesting molecule, we have investigated its function using four different cloned and expressed variants of Myt C cDNA and polyclonal anti-Myt C sera. The in vivo results suggest that this AMP, mainly present in hemocytes, could be acting as an immune system modulator molecule because its overexpression was able to alter the expression of mussel immune-related genes (as the antimicrobial peptides Myticin B and Mytilin B, the C1q domain-containing protein MgC1q, and lysozyme. Moreover, the in vitro results indicate that Myt C peptides have antimicrobial and chemotactic properties. Their recombinant expression in a fish cell line conferred protection against two different fish viruses (enveloped and non-enveloped. Cell extracts from Myt C expressing fish cells were also able to attract hemocytes. All together, these results suggest that Myt C should be considered not only as an AMP but also as the first chemokine/cytokine-like molecule identified in bivalves and one of the few examples in all of the invertebrates.

  20. CHARACTERIZATION OF A NARROW SPECTRUM ANTIMICROBIAL THAT EXHIBITS SPECIFIC ACTIVITY AGAINST UROPATHOGENIC BACTERIA

    Science.gov (United States)

    2017-08-28

    NARROW-SPECTRUM ANTIMICROBIAL THAT EXHIBITS SPECIFIC ACTIVITY AGAINST UROPATHOGENIC BACTERIA by Caitlin M. Barrows Courtney M. Cowell Jennifer...AGAINST UROPATHOGENIC BACTERIA 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) Caitlin M. Barrows, Courtney M...antimicrobials which have been implicated as a critical cause of the rise of drug resistant bacteria . Additionally, the presence of females in the field

  1. Identification of an anti-lipopolysacchride factor possessing both antiviral and antibacterial activity from the red claw crayfish Cherax quadricarinatus.

    Science.gov (United States)

    Lin, Feng-Yu; Gao, Yan; Wang, Hao; Zhang, Qiu-Xia; Zeng, Chang-Lin; Liu, Hai-Peng

    2016-10-01

    It is well-known that anti-lipopolysacchride factors (ALFs) are involved in the recognition and elimination of invading pathogens. In this study, the full-length ALF cDNA sequence of the red claw crayfish Cherax quadricarinatus (termed CqALF) was cloned from a suppression subtractive hybridization library constructed using red claw crayfish hematopoietic tissue cell (Hpt cell) cultures following challenge with white spot syndrome virus (WSSV). The full-length cDNA sequence of CqALF was 863 bp, and the open reading frame encoded 123 amino acids with a signal peptide in the N-terminus and a conserved LPS-binding domain. Unlike most ALFs, which are highly expressed in haemocytes, high expression levels of CqALF were detected in epithelium, the stomach and eyestalks, while lower expression was detected in Hpt, nerves, the heart, muscle tissue, gonads, haemocytes, intestines, gills and the hepatopancreas. To further explore the biological activities of CqALF, mature recombinant CqALF protein (rCqALF) was expressed and purified using a eukaryotic expression system, and an antimicrobial activity test was carried out. rCqALF clearly exerted antiviral activity, as evidenced by the severe disruption of the envelope of intact WSSV virions following co-incubation of virions with rCqALF. Additionally, pre-incubation of WSSV with rCqALF resulted in both a significant reduction in WSSV replication in red claw crayfish Hpt cell cultures and an increased survival rate among animals. Furthermore, rCqALF was effective against both Gram-negative bacteria and Gram-positive bacteria, particularly Shigella flexneri and Staphylococcus aureus. A membrane integrity assay suggested that rCqALF was unlikely to disrupt bacterial membrane integrity compared to cecropin P1. Taken together, these data suggest that CqALF may play an important role in immune defence in the crustacean C. quadricarinatus. Copyright © 2016 Elsevier Ltd. All rights reserved.

  2. Pharmacodynamics, Pharmacokinetics, and Antiviral Activity of BAY 81-8781, a Novel NF-κB Inhibiting Anti-influenza Drug

    Directory of Open Access Journals (Sweden)

    Karoline Droebner

    2017-11-01

    Full Text Available Influenza is a respiratory disease that causes annual epidemics. Antiviral treatment options targeting the virus exist, but their efficiency is limited and influenza virus strains easily develop resistance. Thus, new treatment strategies are urgently needed. In the present study, we investigated the anti-influenza virus properties of D,L-lysine acetylsalicylate ⋅ glycine (BAY 81-8781; LASAG that is approved as Aspirin i.v. for intravenous application. Instead of targeting the virus directly BAY 81-8781 inhibits the activation of the NF-κB pathway, which is required for efficient influenza virus propagation. Using highly pathogenic avian influenza virus strains we could demonstrate that BAY 81-8781 was able to control influenza virus infection in vitro. In the mouse infection model, inhalation of BAY 81-8781 resulted in reduced lung virus titers and protection of mice from lethal infection. Pharmacological studies demonstrated that the oral route of administration was not suitable to reach the sufficient concentrations of BAY 81-8781 for a successful antiviral effect in the lung. BAY 81-8781 treatment of mice infected with influenza virus started as late as 48 h after infection was still effective in protecting 50% of the animals from death. In summary, the data represent a successful proof of the novel innovative antiviral concept of targeting a host cell signaling pathway that is required for viral propagation instead of viral structures.

  3. Small changes result in large differences: discovery of (-)-incrustoporin derivatives as novel antiviral and antifungal agents.

    Science.gov (United States)

    Lu, Aidang; Wang, Jinjin; Liu, Tengjiao; Han, Jian; Li, Yinhui; Su, Min; Chen, Jianxin; Zhang, Hui; Wang, Lizhong; Wang, Qingmin

    2014-09-03

    On the basis of the structure of natural product (-)-incrustoporin (1), a series of lactone compounds 4a-i and 5a-i were designed and synthesized from nitroolefin. The antiviral and antifungal activities of these compounds were evaluated in vitro and in vivo. The small changes between 4 and 5 at the 3,4-position result in large differences in bioactivities. Compounds 4 exhibited significantly higher antiviral activity against tobacco mosaic virus (TMV) than dehydro compounds 5. However, the antifungal activity of 4 is relatively lower than that of 5. Compounds 4a, 4c, and 4i with excellent in vivo anti-TMV activity emerged as new antiviral lead compounds. Compounds 5d-g showed superiority over the commercial fungicides chlorothalonil and carbendazim against Cercospora arachidicola Hor at 50 mg kg(-1). The present study provides fundamental support for the development and optimization of (-)-incrustoporin derivatives as potential inhibitors of plant virus and pathogenic fungi.

  4. Antiviral activities of lactoferrin

    NARCIS (Netherlands)

    van der Strate, BWA; Beljaars, L; Molema, G; Harmsen, MC; Meijer, DKF

    2001-01-01

    Lactoferrin (LF) is an iron binding glycoprotein that is present in several mucosal secretions. Many biological functions have been ascribed to LF. One of the functions of LF is the transport of metals, but LF is also an important component of the non-specific immune system, since LF has

  5. Antiviral activity and possible mechanism of action of constituents identified in Paeonia lactiflora root toward human rhinoviruses.

    Directory of Open Access Journals (Sweden)

    Luong Thi My Ngan

    Full Text Available Human rhinoviruses (HRVs are responsible for more than half of all cases of the common cold and cost billions of USD annually in medical visits and missed school and work. An assessment was made of the antiviral activities and mechanisms of action of paeonol (PA and 1,2,3,4,6-penta-O-galloyl-β-D-glucopyranose (PGG from Paeonia lactiflora root toward HRV-2 and HRV-4 in MRC5 cells using a tetrazolium method and real-time quantitative reverse transcription polymerase chain reaction and enzyme-linked immunosorbent assay. Results were compared with those of a reference control ribavirin. Based on 50% inhibitory concentration values, PGG was 13.4 and 18.0 times more active toward HRV-2 (17.89 μM and HRV-4 (17.33 μM in MRC5 cells, respectively, than ribavirin. The constituents had relatively high selective index values (3.3->8.5. The 100 μg/mL PA and 20 μg/mL PGG did not interact with the HRV-4 particles. These constituents inhibited HRV-4 infection only when they were added during the virus inoculation (0 h, the adsorption period of HRVs, but not after 1 h or later. Moreover, the RNA replication levels of HRVs were remarkably reduced in the MRC5 cultures treated with these constituents. These findings suggest that PGG and PA may block or reduce the entry of the viruses into the cells to protect the cells from the virus destruction and abate virus replication, which may play an important role in interfering with expressions of rhinovirus receptors (intercellular adhesion molecule-1 and low-density lipoprotein receptor, inflammatory cytokines (interleukin (IL-6, IL-8, tumor necrosis factor, interferon beta, and IL-1β, and Toll-like receptor, which resulted in diminishing symptoms induced by HRV. Global efforts to reduce the level of synthetic drugs justify further studies on P. lactiflora root-derived materials as potential anti-HRV products or lead molecules for the prevention or treatment of HRV.

  6. Antiviral activity and possible mechanism of action of constituents identified in Paeonia lactiflora root toward human rhinoviruses.

    Science.gov (United States)

    Ngan, Luong Thi My; Jang, Myeong Jin; Kwon, Min Jung; Ahn, Young Joon

    2015-01-01

    Human rhinoviruses (HRVs) are responsible for more than half of all cases of the common cold and cost billions of USD annually in medical visits and missed school and work. An assessment was made of the antiviral activities and mechanisms of action of paeonol (PA) and 1,2,3,4,6-penta-O-galloyl-β-D-glucopyranose (PGG) from Paeonia lactiflora root toward HRV-2 and HRV-4 in MRC5 cells using a tetrazolium method and real-time quantitative reverse transcription polymerase chain reaction and enzyme-linked immunosorbent assay. Results were compared with those of a reference control ribavirin. Based on 50% inhibitory concentration values, PGG was 13.4 and 18.0 times more active toward HRV-2 (17.89 μM) and HRV-4 (17.33 μM) in MRC5 cells, respectively, than ribavirin. The constituents had relatively high selective index values (3.3->8.5). The 100 μg/mL PA and 20 μg/mL PGG did not interact with the HRV-4 particles. These constituents inhibited HRV-4 infection only when they were added during the virus inoculation (0 h), the adsorption period of HRVs, but not after 1 h or later. Moreover, the RNA replication levels of HRVs were remarkably reduced in the MRC5 cultures treated with these constituents. These findings suggest that PGG and PA may block or reduce the entry of the viruses into the cells to protect the cells from the virus destruction and abate virus replication, which may play an important role in interfering with expressions of rhinovirus receptors (intercellular adhesion molecule-1 and low-density lipoprotein receptor), inflammatory cytokines (interleukin (IL)-6, IL-8, tumor necrosis factor, interferon beta, and IL-1β), and Toll-like receptor, which resulted in diminishing symptoms induced by HRV. Global efforts to reduce the level of synthetic drugs justify further studies on P. lactiflora root-derived materials as potential anti-HRV products or lead molecules for the prevention or treatment of HRV.

  7. Highly Active Ruthenium Metathesis Catalysts Exhibiting Unprecedented Activity and Z-Selectivity

    Science.gov (United States)

    Rosebrugh, Lauren E.; Herbert, Myles B.; Marx, Vanessa M.; Keitz, Benjamin K.; Grubbs, Robert H.

    2013-01-01

    A novel chelated ruthenium-based metathesis catalyst bearing an N-2,6-diisopropylphenyl group is reported and displays near-perfect selectivity for the Z-olefin (>95%), as well as unparalleled TONs of up to 7400, in a variety of homodimerization and industrially relevant metathesis reactions. This derivative and other new catalytically-active species were synthesized using an improved method employing sodium carboxylates to induce the salt metathesis and C-H activation of these chelated complexes. All of these new ruthenium-based catalysts are highly Z-selective in the homodimerization of terminal olefins. PMID:23317178

  8. Do microRNAs induced by Viral Hemorrhagic Septicemia virus in rainbow trout (Oncorhynchus mykiss) possess anti-viral activity?

    DEFF Research Database (Denmark)

    Bela-Ong, Dennis; Schyth, Brian Dall; Lorenzen, Niels

    2013-01-01

    RNAs were also up regulated in the liver and muscle (vaccination site) of fish vaccinated with a DNA vaccine expressing the VHSV glycoprotein gene. Recent studies further indicate that the expression of these miRNAs is induced by interferons. In order to analyze if miRNA-462 and miRNA-731 have any anti-viral...... processes. Some miRNAs have been shown to have direct anti-viral effects. We have previously observed and validated that the fish-specific miRNAs, miR-462 and miR-731, were among the most highly expressed miRNAs in rainbow trout liver following Viral hemorrhagic septicemia virus (VHSV) infection. These mi...

  9. A viral ubiquitin ligase has substrate preferential SUMO targeted ubiquitin ligase activity that counteracts intrinsic antiviral defence.

    Directory of Open Access Journals (Sweden)

    Chris Boutell

    2011-09-01

    Full Text Available Intrinsic antiviral resistance represents the first line of intracellular defence against virus infection. During herpes simplex virus type-1 (HSV-1 infection this response can lead to the repression of viral gene expression but is counteracted by the viral ubiquitin ligase ICP0. Here we address the mechanisms by which ICP0 overcomes this antiviral response. We report that ICP0 induces the widespread proteasome-dependent degradation of SUMO-conjugated proteins during infection and has properties related to those of cellular SUMO-targeted ubiquitin ligases (STUbLs. Mutation of putative SUMO interaction motifs within ICP0 not only affects its ability to degrade SUMO conjugates, but also its capacity to stimulate HSV-1 lytic infection and reactivation from quiescence. We demonstrate that in the absence of this viral countermeasure the SUMO conjugation pathway plays an important role in mediating intrinsic antiviral resistance and the repression of HSV-1 infection. Using PML as a model substrate, we found that whilst ICP0 preferentially targets SUMO-modified isoforms of PML for degradation, it also induces the degradation of PML isoform I in a SUMO modification-independent manner. PML was degraded by ICP0 more rapidly than the bulk of SUMO-modified proteins in general, implying that the identity of a SUMO-modified protein, as well as the presence of SUMO modification, is involved in ICP0 targeting. We conclude that ICP0 has dual targeting mechanisms involving both SUMO- and substrate-dependent targeting specificities in order to counteract intrinsic antiviral resistance to HSV-1 infection.

  10. Antiviral cationic peptides as a strategy for innovation in global health therapeutics for dengue virus: high yield production of the biologically active recombinant plectasin peptide.

    Science.gov (United States)

    Rothan, Hussin A; Mohamed, Zulqarnain; Suhaeb, Abdulrazzaq M; Rahman, Noorsaadah Abd; Yusof, Rohana

    2013-11-01

    Dengue virus infects millions of people worldwide, and there is no vaccine or anti-dengue therapeutic available. Antimicrobial peptides have been shown to possess effective antiviral activity against various viruses. One of the main limitations of developing these peptides as potent antiviral drugs is the high cost of production. In this study, high yield production of biologically active plectasin peptide was inexpensively achieved by producing tandem plectasin peptides as inclusion bodies in E. coli. Antiviral activity of the recombinant peptide towards dengue serotype-2 NS2B-NS3 protease (DENV2 NS2B-NS3pro) was assessed as a target to inhibit dengue virus replication in Vero cells. Single units of recombinant plectasin were collected after applying consecutive steps of refolding, cleaving by Factor Xa, and nickel column purification to obtain recombinant proteins of high purity. The maximal nontoxic dose (MNTD) of the recombinant peptide against Vero cells was 20 μM (100 μg/mL). The reaction velocity of DENV2 NS2B-NS3pro decreased significantly after increasing concentrations of recombinant plectasin were applied to the reaction mixture. Plectasin peptide noncompetitively inhibited DENV2 NS2B-NS3pro at Ki value of 5.03 ± 0.98 μM. The percentage of viral inhibition was more than 80% at the MNTD value of plectasin. In this study, biologically active recombinant plectasin which was able to inhibit dengue protease and viral replication in Vero cells was successfully produced in E. coli in a time- and cost- effective method. These findings are potentially important in the development of potent therapeutics against dengue infection.

  11. Comparison of antiviral activity between IgA and IgG specific to influenza virus hemagglutinin: increased potential of IgA for heterosubtypic immunity.

    Directory of Open Access Journals (Sweden)

    Mieko Muramatsu

    Full Text Available Both IgA and IgG antibodies are known to play important roles in protection against influenza virus infection. While IgG is the major isotype induced systemically, IgA is predominant in mucosal tissues, including the upper respiratory tract. Although IgA antibodies are believed to have unique advantages in mucosal immunity, information on direct comparisons of the in vitro antiviral activities of IgA and IgG antibodies recognizing the same epitope is limited. In this study, we demonstrate differences in antiviral activities between these isotypes using monoclonal IgA and IgG antibodies obtained from hybridomas of the same origin. Polymeric IgA-producing hybridoma cells were successfully subcloned from those originally producing monoclonal antibody S139/1, a hemaggulutinin (HA-specific IgG that was generated against an influenza A virus strain of the H3 subtype but had cross-neutralizing activities against the H1, H2, H13, and H16 subtypes. These monoclonal S139/1 IgA and IgG antibodies were assumed to recognize the same epitope and thus used to compare their antiviral activities. We found that both S139/1 IgA and IgG antibodies strongly bound to the homologous H3 virus in an enzyme-linked immunosorbent assay, and there were no significant differences in their hemagglutination-inhibiting and neutralizing activities against the H3 virus. In contrast, S139/1 IgA showed remarkably higher cross-binding to and antiviral activities against H1, H2, and H13 viruses than S139/1 IgG. It was also noted that S139/1 IgA, but not IgG, drastically suppressed the extracellular release of the viruses from infected cells. Electron microscopy revealed that S139/1 IgA deposited newly produced viral particles on the cell surface, most likely by tethering the particles. These results suggest that anti-HA IgA has greater potential to prevent influenza A virus infection than IgG antibodies, likely due to increased avidity conferred by its multivalency, and that this

  12. Comparison of antiviral activity between IgA and IgG specific to influenza virus hemagglutinin: increased potential of IgA for heterosubtypic immunity.

    Science.gov (United States)

    Muramatsu, Mieko; Yoshida, Reiko; Yokoyama, Ayaka; Miyamoto, Hiroko; Kajihara, Masahiro; Maruyama, Junki; Nao, Naganori; Manzoor, Rashid; Takada, Ayato

    2014-01-01

    Both IgA and IgG antibodies are known to play important roles in protection against influenza virus infection. While IgG is the major isotype induced systemically, IgA is predominant in mucosal tissues, including the upper respiratory tract. Although IgA antibodies are believed to have unique advantages in mucosal immunity, information on direct comparisons of the in vitro antiviral activities of IgA and IgG antibodies recognizing the same epitope is limited. In this study, we demonstrate differences in antiviral activities between these isotypes using monoclonal IgA and IgG antibodies obtained from hybridomas of the same origin. Polymeric IgA-producing hybridoma cells were successfully subcloned from those originally producing monoclonal antibody S139/1, a hemaggulutinin (HA)-specific IgG that was generated against an influenza A virus strain of the H3 subtype but had cross-neutralizing activities against the H1, H2, H13, and H16 subtypes. These monoclonal S139/1 IgA and IgG antibodies were assumed to recognize the same epitope and thus used to compare their antiviral activities. We found that both S139/1 IgA and IgG antibodies strongly bound to the homologous H3 virus in an enzyme-linked immunosorbent assay, and there were no significant differences in their hemagglutination-inhibiting and neutralizing activities against the H3 virus. In contrast, S139/1 IgA showed remarkably higher cross-binding to and antiviral activities against H1, H2, and H13 viruses than S139/1 IgG. It was also noted that S139/1 IgA, but not IgG, drastically suppressed the extracellular release of the viruses from infected cells. Electron microscopy revealed that S139/1 IgA deposited newly produced viral particles on the cell surface, most likely by tethering the particles. These results suggest that anti-HA IgA has greater potential to prevent influenza A virus infection than IgG antibodies, likely due to increased avidity conferred by its multivalency, and that this advantage may be

  13. Synthesis of 1,2,3-triazole hydrazide derivatives exhibiting anti-phytopathogenic activity.

    Science.gov (United States)

    Wang, Xing; Dai, Zhi-Cheng; Chen, Yong-Fei; Cao, Ling-Ling; Yan, Wei; Li, Sheng-Kun; Wang, Jian-Xin; Zhang, Zheng-Guang; Ye, Yong-Hao

    2017-01-27

    A series of new 1,2,3-triazole derivatives have been prepared and screened for their antifungal activity against phytopathogenic fungi using the mycelium growth inhibition method in vitro. The results indicated that the 1,2,3-triazole hydrazide scaffold displayed significant antifungal activity. Compound 6ad exhibited the most potent anti-phytopathogenic activity, with EC50 values of 0.18, 0.35, 0.37 and 2.25 μg mL-1 against Rhizoctonia solani, Sclerotinia sclerotiorum, Fusarium graminearum, and Magnaporthe oryzae, respectively. In vivo testing demonstrated that 6ad was effective for the control of rice sheath blight, rape sclerotinia rot, fusarium head blight and rice blast caused by the aforementioned phytopathogens. This work suggests that the combination of 1,2,3-triazole and hydrazide moiety could be a promising fungicide scaffold in the future. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  14. Antiviral Terpenoid Constituents of Ganoderma pfeifferi.

    Science.gov (United States)

    Niedermeyer, Timo H J; Lindequist, Ulrike; Mentel, Renate; Gördes, Dirk; Schmidt, Enrico; Thurow, Kerstin; Lalk, Michael

    2005-12-01

    Four sterols and 10 triterpenes were isolated from the fruiting bodies of Ganoderma pfeifferi, including the three new triterpenes 3,7,11-trioxo-5alpha-lanosta-8,24-diene-26-al (lucialdehyde D, 1), 5alpha-lanosta-8,24-diene-26-hydroxy-3,7-dione (ganoderone A, 2), and 5alpha-lanosta-8-ene-24,25-epoxy-26-hydroxy-3,7-dione (ganoderone C, 3). The structures of 1-3 were determined on the basis of spectroscopic evidence. Antibacterial, antifungal, and antiviral activity were studied for some of the isolated compounds. Ganoderone A (2), lucialdehyde B (4), and ergosta-7,22-dien-3beta-ol (7) were found to exhibit potent inhibitory activity against herpes simplex virus.

  15. Atividade antiviral do extrato de própolis contra o calicivírus felino, adenovírus canino 2 e vírus da diarréia viral bovina Antiviral activity of propolis extracts against feline calicivirus, canine adenovirus 2, and bovine viral diarrhea virus

    Directory of Open Access Journals (Sweden)

    Ana Paula Cueto

    2011-10-01

    Full Text Available Dentre as propriedades biológicas da própolis, a atividade antimicrobiana tem merecido destacada atenção. Neste artigo, descreve-se a atividade antiviral de dois extratos etanólicos de própolis (EP1 e EP2 frente aos vírus: calicivírus felino (FCV, adenovírus canino tipo 2 (CAV-2 e vírus da diarréia viral bovina (BVDV. Um dos extratos (EP1 foi obtido por extração etanólica de própolis obtida da região central do Estado do Rio Grande do Sul e o segundo (EP2, obtido comercialmente de uma empresa de Minas Gerais. A análise dos extratos de própolis através da cromatografia líquida de alta eficiência (CLAE identificou a presença de flavonóides como: rutina, quercetina e ácido gálico. A atividade antiviral bem como a citotoxicidade dos extratos aos cultivos celulares foram avaliadas através do MTT [3- (4,5 dimetiltiazol-2yl-2-5-difenil-2H tetrazolato de bromo]. Ambos os extratos evidenciaram atividade antiviral frente ao BVDV e CAV-2 quando acrescidos ao cultivo celular anteriormente à inoculação viral. Os extratos foram menos efetivos contra o FCV em comparação aos resultados obtidos com os outros vírus, e a atividade antiviral neste caso foi observada apenas quando a própolis estava presente após a inoculação viral. O extrato obtido no laboratório (EP1 apresentou valores mais altos de índice de seletividade (IS=CC50/ CE50, quando comparado à outra amostra (EP2. Em resumo, a própolis apresentou atividade antiviral frente a três diferentes vírus, o que a torna alvo para o desenvolvimento de novos compostos naturais com atividade antiviral.Propolis is a resinous substance produced by bees for which several biological activities have been attributed. In this article, the antiviral activity of two propolis extracts was tested against bovine viral diarrhea virus (BVDV, canine adenovirus type 2 (CAV-2, and feline calicivirus (FCV. One of the extracts was obtained by ethanolic extraction of propolis from the Santa

  16. Extracts from Fermented Black Soybean Milk Exhibit Antioxidant and Cytotoxic Activities

    Directory of Open Access Journals (Sweden)

    Kuan-Chen Cheng

    2011-01-01

    Full Text Available In this study, ethanol extracts from 2-day fermented black soybean milk (FBE by immobilized Rhizopus oligosporus NTU5 have been evaluated for both antioxidant and cytotoxic activities. The results reveal that a 2-day FBE had strong 2,2-diphenyl-1-picrylhydrazyl (DPPH scavenging effect (76 %. The extracts were further fractionated by silica gel column chromatography and an unknown compound, FBE5-A, was obtained, which exhibited strong antioxidant activity. IC50 of the DPPH scavenging effect of FBE5-A was 7.5 μg/mL, which is stronger than a commonly used antioxidant, vitamin E (α-tocopherol; 17.4 μg/mL, and similar to vitamin C (ascorbic acid; 7.6 μg/mL. The cytotoxic test demonstrated that extracts of 2-day fermented broth exhibited selective cytotoxic activity towards human carcinoma cells, Hep 3B (IC50=150.2 μg/mL, and did not affect normal human lung fibroblasts, MRC-5 (p<0.05. The results indicate the potential applications of fermented black soybean milk as functional food, pharmaceutical or cancer therapy formula.

  17. Antifouling activity exhibited by secondary metabolites of the marine sponge, Haliclona exigua (Kirkpatrick)

    Digital Repository Service at National Institute of Oceanography (India)

    LimnaMol, V.P.; Raveendran, T.V.; Parameswaran, P.S.

    stream_size 29406 stream_content_type text/plain stream_name Int_Biodeterior_Biodegrad_63_67.pdf.txt stream_source_info Int_Biodeterior_Biodegrad_63_67.pdf.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8... 1    Author version: Int. Biodeterior. Biodegrad.: 63(1); 2009; 67-72 Antifouling activity exhibited by secondary metabolites of the marine sponge, Haliclona exigua (Kirkpatrick) VP LIMNA MOL a , TV RAVEENDRAN a, * & PS PARAMESWARAN b a...

  18. Macrolactone Nuiapolide, Isolated from a Hawaiian Marine Cyanobacterium, Exhibits Anti-Chemotactic Activity

    Science.gov (United States)

    Mori, Shogo; Williams, Howard; Cagle, Davey; Karanovich, Kristopher; Horgen, F. David; Smith, Roger; Watanabe, Coran M. H.

    2015-01-01

    A new bioactive macrolactone, nuiapolide (1) was identified from a marine cyanobacterium collected off the coast of Niihau, near Lehua Rock. The natural product exhibits anti-chemotactic activity at concentrations as low as 1.3 μM against Jurkat cells, cancerous T lymphocytes, and induces a G2/M phase cell cycle shift. Structural characterization of the natural product revealed the compound to be a 40-membered macrolactone with nine hydroxyl functional groups and a rare tert-butyl carbinol residue. PMID:26473885

  19. Polyhydroxylated Steroids from the South China Sea Soft Coral Sarcophyton sp. and Their Cytotoxic and Antiviral Activities

    Directory of Open Access Journals (Sweden)

    Kai-Kai Gong

    2013-12-01

    Full Text Available Chemical investigation on the soft coral Sarcophyton sp. collected from the South China Sea yielded three new polyhydroxylated steroids, compounds (1–3, together with seven known ones (4–10. Their structures were established by extensive spectroscopic methods and comparison of their data with those of the related known compounds. All the isolates possessed the 3β,5α,6β-trihydroxylated steroidal nucleus. The cytotoxicities against selected HL-60, HeLa and K562 tumor cell lines and anti-H1N1 (Influenza A virus (IAV activities for the isolates were evaluated. Compounds 2, 3 and 5–8 exhibited potent activities against K562 cell lines with IC50 values ranging from 6.4 to 10.3 μM. Compounds 1, 6–8 potently inhibited the growth of HL-60 tumor cell lines, and 6 also showed cytotoxicity towards HeLa cell lines. In addition, preliminary structure-activity relationships for the isolates are discussed. The OAc group at C-11 is proposed to be an important pharmacophore for their cytotoxicities in the 3β,5α,6β-triol steroids. Compounds 4 and 9 exhibited significant anti-H1N1 IAV activity with IC50 values of 19.6 and 36.7 μg/mL, respectively.

  20. Short communication: antiviral activity of subcritical water extract of Brassica juncea against influenza virus A/H1N1 in nonfat milk

    National Research Council Canada - National Science Library

    Lee, N-K; Lee, J-H; Lim, S-M; Lee, K A; Kim, Y B; Chang, P-S; Paik, H-D

    2014-01-01

    Subcritical water extract (SWE) of Brassica juncea was studied for antiviral effects against influenza virus A/H1N1 and for the possibility of application as a nonfat milk supplement for use as an "antiviral food...

  1. Tulbaghia violacea and Allium ursinum Extracts Exhibit Anti-Parasitic and Antimicrobial Activities

    Directory of Open Access Journals (Sweden)

    Sonja Krstin

    2018-02-01

    Full Text Available Garlic has played an important role in culinary arts and remedies in the traditional medicine throughout human history. Parasitic infections represent a burden in the society of especially poor countries, causing more than 1 billion infections every year and leading to around one million deaths. In this study, we investigated the mode of anti-parasitic activity of “wild garlics” Tulbaghia violacea and Allium ursinum dichloromethane extracts against parasites Trypanosoma brucei brucei and Leishmania tarentolae with regard to their already known antimicrobial activity. We also evaluated their cytotoxic potential against human cells. Both extracts showed a relevant trypanocidal and leishmanicidal activity, although L. tarentolae was less sensitive. We determined that the probable mode of action of both extracts is the irreversible inhibition of the activity of Trypanosoma brucei trypanothione reductase enzyme. The extracts showed a mild cytotoxic activity against human keratinocytes. They also exhibited weak—in most cases comparable—antibacterial and antifungal activity. HPLC-MS/MS analysis showed that both extracts are abundant in sulfur compounds. Thus, for the first time, the ability of Allium ursinum and Tulbaghia violacea to kill Trypanosoma sp. and Leishmania sp. parasites, probably by binding to and inactivating sulfur-containing compounds essential for the survival of the parasite, is shown.

  2. Tulbaghia violacea and Allium ursinum Extracts Exhibit Anti-Parasitic and Antimicrobial Activities.

    Science.gov (United States)

    Krstin, Sonja; Sobeh, Mansour; Braun, Markus Santhosh; Wink, Michael

    2018-02-02

    Garlic has played an important role in culinary arts and remedies in the traditional medicine throughout human history. Parasitic infections represent a burden in the society of especially poor countries, causing more than 1 billion infections every year and leading to around one million deaths. In this study, we investigated the mode of anti-parasitic activity of "wild garlics" Tulbaghia violacea and Allium ursinum dichloromethane extracts against parasites Trypanosoma brucei brucei and Leishmania tarentolae with regard to their already known antimicrobial activity. We also evaluated their cytotoxic potential against human cells. Both extracts showed a relevant trypanocidal and leishmanicidal activity, although L. tarentolae was less sensitive. We determined that the probable mode of action of both extracts is the irreversible inhibition of the activity of Trypanosoma brucei trypanothione reductase enzyme. The extracts showed a mild cytotoxic activity against human keratinocytes. They also exhibited weak-in most cases comparable-antibacterial and antifungal activity. HPLC-MS/MS analysis showed that both extracts are abundant in sulfur compounds. Thus, for the first time, the ability of Allium ursinum and Tulbaghia violacea to kill Trypanosoma sp. and Leishmania sp. parasites, probably by binding to and inactivating sulfur-containing compounds essential for the survival of the parasite, is shown.

  3. Bauhinia variegata leaf extracts exhibit considerable antibacterial, antioxidant, and anticancer activities.

    Science.gov (United States)

    Mishra, Amita; Sharma, Amit Kumar; Kumar, Shashank; Saxena, Ajit K; Pandey, Abhay K

    2013-01-01

    The present study reports the phytochemical profiling, antimicrobial, antioxidant, and anticancer activities of Bauhinia variegata leaf extracts. The reducing sugar, anthraquinone, and saponins were observed in polar extracts, while terpenoids and alkaloids were present in nonpolar and ethanol extracts. Total flavonoid contents in various extracts were found in the range of 11-222.67 mg QE/g. In disc diffusion assays, petroleum ether and chloroform fractions exhibited considerable inhibition against Klebsiella pneumoniae. Several other extracts also showed antibacterial activity against pathogenic strains of E. coli, Proteus spp. and Pseudomonas spp. Minimum bactericidal concentration (MBC) values of potential extracts were found between 3.5 and 28.40 mg/mL. The lowest MBC (3.5 mg/mL) was recorded for ethanol extract against Pseudomonas spp. The antioxidant activity of the extracts was compared with standard antioxidants. Dose dependent response was observed in reducing power of extracts. Polar extracts demonstrated appreciable metal ion chelating activity at lower concentrations (10-40 μg/mL). Many extracts showed significant antioxidant response in beta carotene bleaching assay. AQ fraction of B. variegata showed pronounced cytotoxic effect against DU-145, HOP-62, IGR-OV-1, MCF-7, and THP-1 human cancer cell lines with 90-99% cell growth inhibitory activity. Ethyl acetate fraction also produced considerable cytotoxicity against MCF-7 and THP-1 cell lines. The study demonstrates notable antibacterial, antioxidant, and anticancer activities in B. variegata leaf extracts.

  4. Bauhinia variegata Leaf Extracts Exhibit Considerable Antibacterial, Antioxidant, and Anticancer Activities

    Directory of Open Access Journals (Sweden)

    Amita Mishra

    2013-01-01

    Full Text Available The present study reports the phytochemical profiling, antimicrobial, antioxidant, and anticancer activities of Bauhinia variegata leaf extracts. The reducing sugar, anthraquinone, and saponins were observed in polar extracts, while terpenoids and alkaloids were present in nonpolar and ethanol extracts. Total flavonoid contents in various extracts were found in the range of 11–222.67 mg QE/g. In disc diffusion assays, petroleum ether and chloroform fractions exhibited considerable inhibition against Klebsiella pneumoniae. Several other extracts also showed antibacterial activity against pathogenic strains of E. coli, Proteus spp. and Pseudomonas spp. Minimum bactericidal concentration (MBC values of potential extracts were found between 3.5 and 28.40 mg/mL. The lowest MBC (3.5 mg/mL was recorded for ethanol extract against Pseudomonas spp. The antioxidant activity of the extracts was compared with standard antioxidants. Dose dependent response was observed in reducing power of extracts. Polar extracts demonstrated appreciable metal ion chelating activity at lower concentrations (10–40 μg/mL. Many extracts showed significant antioxidant response in beta carotene bleaching assay. AQ fraction of B. variegata showed pronounced cytotoxic effect against DU-145, HOP-62, IGR-OV-1, MCF-7, and THP-1 human cancer cell lines with 90–99% cell growth inhibitory activity. Ethyl acetate fraction also produced considerable cytotoxicity against MCF-7 and THP-1 cell lines. The study demonstrates notable antibacterial, antioxidant, and anticancer activities in B. variegata leaf extracts.

  5. [Antimycoplasmic Activity of Fermentation Broth of Trichoderma harzianum Rifai F-180, an Organism Producing L-Lysine-α-Oxidase, an Antitumor and Antiviral Enzyme].

    Science.gov (United States)

    Smirnova, I P; Rakovskaya, I V

    2014-01-01

    A concentrate of the fermentation broth of Trichoderma harzianum Rifai F-180, an organism producing L-lysine-α-oxidase, an antitumor and antiviral enzyme, with the activity in the fermentation broth of 0.54-0.56 U/mI was recovered. The effect of the concentrate on the mycoplasmas growth was investigated for the first time. Two representatives of Mycoplasmafaceae, i.e. Mycoplasma hominis and Mycoplasma fermentans and one representative of Aholeplasmataceae. i. e. Aholeplasma laidlawii were used. It was shown that the fermentation broth inhibited the growth of Mycoplasma hominis after the preliminary exposure. The inhibition rate depended on the mycoplasma inoculation dose and the fermentation broth concentration.

  6. Antiviral, Immunomodulatory, and Free Radical Scavenging Activities of a Protein-Enriched Fraction from the Larvae of the Housefly, Musca domestica

    Science.gov (United States)

    Ai, Hui; Wang, Furong; Zhang, Na; Zhang, Lingyao; Lei, Chaoliang

    2013-01-01

    In our previous study, protein-enriched fraction (PEF) that was isolated from the larvae of the housefly, Musca domestica L. (Diptera: Muscidae), showed excellent hepatoprotective activity as well as the potential for clinical application in therapy for liver diseases. In this study, antiviral, immunomodulatory, and free radical scavenging activities of PEF were evaluated. The antiviral results demonstrated that PEF inhibited the infection of avian influenza virus H9N2 and had a virucidal effect against the multicapsid nucleopolyhedrovirus of the alfalfa looper, Autographa californica Speyer (Lepidoptera: Noctuidae) in vitro. The mortality of silkworm larve in a PEF treatment group decreased significantly compared with a negative control. PEF showed excellent scavenging activity for 1,1-diphenyl-2-picrylhydrazyl and superoxide anion radicals, which were similar to those of ascorbic acid. The imunomodulatory results suggested that PEF could effectively improve immune function in experimental mice. Our results indicated that PEF could possibly be used for the prophylaxis and treatment of diseases caused by avian influenza virus infection. In addition, PEF with virucidal activity against insect viruses might provide useful for the development of antimicrobial breeding technology for economically important insects. As a natural product from insects, PEF could be a potential source for the discovery of potent antioxidant and immunomodulatory agents. PMID:24735244

  7. Cucurbitacin IIb exhibits anti-inflammatory activity through modulating multiple cellular behaviors of mouse lymphocytes.

    Directory of Open Access Journals (Sweden)

    Yao Wang

    Full Text Available Cucurbitacin IIb (CuIIb is one of the major active compounds in Hemsleyadine tablets which have been used for clinical treatment of bacillary dysentery, enteritis and acute tonsilitis. However, its action mechanism has not been completely understood. This study aimed to explore the anti-inflammatory activity of CuIIb and its underlying mechanism in mitogen-activated lymphocytes isolated from mouse mesenteric lymph nodes. The results showed that CuIIb inhibited the proliferation of concanavalin A (Con A-activated lymphocytes in a time- and dose-dependent manner. CuIIb treatment arrested their cell cycle in S and G2/M phases probably due to the disruption of the actin cytoskeleton and the modulation of p27(Kip1 and cyclin levels. Moreover, the surface expression of activation markers CD69 and CD25 on Con A-activated CD3(+ T lymphocytes was suppressed by CuIIb treatment. Both Con A- and phorbol ester plus ionomycin-induced expression of TNF-α, IFN-γ and IL-6 proteins was attenuated upon exposure to CuIIb. Mechanistically, CuIIb treatment suppressed the phosphorylation of JNK and Erk1/2 but not p38 in Con A-activated lymphocytes. Although CuIIb unexpectedly enhanced the phosphorylation of IκB and NF-κB (p65, it blocked the nuclear translocation of NF-κB (p65. In support of this, CuIIb significantly decreased the mRNA levels of IκBα and TNF-α, two target genes of NF-κB, in Con A-activated lymphocytes. In addition, CuIIb downregulated Con A-induced STAT3 phosphorylation and increased cell apoptosis. Collectively, these results suggest that CuIIb exhibits its anti-inflammatory activity through modulating multiple cellular behaviors and signaling pathways, leading to the suppression of the adaptive immune response.

  8. Cucurbitacin IIb exhibits anti-inflammatory activity through modulating multiple cellular behaviors of mouse lymphocytes.

    Science.gov (United States)

    Wang, Yao; Zhao, Gao-Xiang; Xu, Li-Hui; Liu, Kun-Peng; Pan, Hao; He, Jian; Cai, Ji-Ye; Ouyang, Dong-Yun; He, Xian-Hui

    2014-01-01

    Cucurbitacin IIb (CuIIb) is one of the major active compounds in Hemsleyadine tablets which have been used for clinical treatment of bacillary dysentery, enteritis and acute tonsilitis. However, its action mechanism has not been completely understood. This study aimed to explore the anti-inflammatory activity of CuIIb and its underlying mechanism in mitogen-activated lymphocytes isolated from mouse mesenteric lymph nodes. The results showed that CuIIb inhibited the proliferation of concanavalin A (Con A)-activated lymphocytes in a time- and dose-dependent manner. CuIIb treatment arrested their cell cycle in S and G2/M phases probably due to the disruption of the actin cytoskeleton and the modulation of p27(Kip1) and cyclin levels. Moreover, the surface expression of activation markers CD69 and CD25 on Con A-activated CD3(+) T lymphocytes was suppressed by CuIIb treatment. Both Con A- and phorbol ester plus ionomycin-induced expression of TNF-α, IFN-γ and IL-6 proteins was attenuated upon exposure to CuIIb. Mechanistically, CuIIb treatment suppressed the phosphorylation of JNK and Erk1/2 but not p38 in Con A-activated lymphocytes. Although CuIIb unexpectedly enhanced the phosphorylation of IκB and NF-κB (p65), it blocked the nuclear translocation of NF-κB (p65). In support of this, CuIIb significantly decreased the mRNA levels of IκBα and TNF-α, two target genes of NF-κB, in Con A-activated lymphocytes. In addition, CuIIb downregulated Con A-induced STAT3 phosphorylation and increased cell apoptosis. Collectively, these results suggest that CuIIb exhibits its anti-inflammatory activity through modulating multiple cellular behaviors and signaling pathways, leading to the suppression of the adaptive immune response.

  9. Isolation of a homodimeric lectin with antifungal and antiviral activities from red kidney bean (Phaseolus vulgaris) seeds.

    Science.gov (United States)

    Ye, X Y; Ng, T B; Tsang, P W; Wang, J

    2001-07-01

    A homodimeric lectin adsorbed on Affi-gel blue gel and CM-Sepharose and possessing a molecular weight of 67 kDa was isolated from red kidney beans. The hemagglutinating activity of this lectin was inhibited by glycoproteins but not by simple sugars. The lectin manifested inhibitory activity on human immunodeficiency virus-1 reverse transcriptase and alpha-glucosidase. The N-terminal sequence of the lectin exhibited some differences from previously reported lectins from Phaseolus vulgaris but showed some similarity to chitinases. It exerted a suppressive effect on growth of the fungal species Fusarium oxysporum, Coprinus comatus, and Rhizoctonia solani. The lectin had low ribonuclease and negligible translation-inhibitory activities.

  10. Cysteine proteases from the Asclepiadaceae plants latex exhibited thrombin and plasmin like activities.

    Science.gov (United States)

    Shivaprasad, H V; Riyaz, M; Venkatesh Kumar, R; Dharmappa, K K; Tarannum, Shaista; Siddesha, J M; Rajesh, R; Vishwanath, B S

    2009-10-01

    In the present study we evaluated the presence of cysteine protease from the latex of four plants Asclepias curassavica L., Calotropis gigantea R.Br., Pergularia extensa R.Br. and Cynanchum puciflorum R.Br. belongs to the family Asclepiadaceae. Cysteine proteases from these plants latex exhibited both thrombin and plasmin like activities. Latex enzyme fraction in a concentration dependent manner induced the formation of clot in citrated blood plasma. Direct incubation of fibrinogen with latex enzyme fraction resulted in the formation of fibrin clot similar to thrombin enzyme. However prolonged incubation resulted in degradation of the formed fibrin clot suggesting plasmin like activity. Latex enzyme fraction preferentially hydrolyzed Aalpha and Bbeta chains of fibrinogen to form fibrin clot. Latex enzyme fraction also hydrolyzed the subunits of fully cross linked fibrin efficiently, the order of hydrolysis was alpha-polymer > alpha-chains > beta-chain and gamma-gamma dimer. Cysteine proteases from all the four Asclepiadaceae plants latex exhibited similar action on fibrinogen and fibrin. This study scientifically validate the use of plant latex in stop bleeding and wound healing by traditional healers all over the world.

  11. Anterior medial prefrontal cortex exhibits activation during task preparation but deactivation during task execution.

    Directory of Open Access Journals (Sweden)

    Hideya Koshino

    Full Text Available BACKGROUND: The anterior prefrontal cortex (PFC exhibits activation during some cognitive tasks, including episodic memory, reasoning, attention, multitasking, task sets, decision making, mentalizing, and processing of self-referenced information. However, the medial part of anterior PFC is part of the default mode network (DMN, which shows deactivation during various goal-directed cognitive tasks compared to a resting baseline. One possible factor for this pattern is that activity in the anterior medial PFC (MPFC is affected by dynamic allocation of attentional resources depending on task demands. We investigated this possibility using an event related fMRI with a face working memory task. METHODOLOGY/PRINCIPAL FINDINGS: Sixteen students participated in a single fMRI session. They were asked to form a task set to remember the faces (Face memory condition or to ignore them (No face memory condition, then they were given 6 seconds of preparation period before the onset of the face stimuli. During this 6-second period, four single digits were presented one at a time at the center of the display, and participants were asked to add them and to remember the final answer. When participants formed a task set to remember faces, the anterior MPFC exhibited activation during a task preparation period but deactivation during a task execution period within a single trial. CONCLUSIONS/SIGNIFICANCE: The results suggest that the anterior MPFC plays a role in task set formation but is not involved in execution of the face working memory task. Therefore, when attentional resources are allocated to other brain regions during task execution, the anterior MPFC shows deactivation. The results suggest that activation and deactivation in the anterior MPFC are affected by dynamic allocation of processing resources across different phases of processing.

  12. Streptovirudins, new antibiotics with antibacterial and antiviral activity. I. Culture taxonomy, fermentation and production of streptovirudin complex.

    Science.gov (United States)

    Thrum, H; Eckardt, K; Bradler, G; Fügner, R; Tonew, E; Tonew, M

    1975-07-01

    A new antibiotic complex has been isolated from cultures of Streptomyces strain No. JA 10124. On the basis of taxonomic studies, the producing microorganism is described as Streptomyces griseoflavus (Krainsky, 1914) Waksman et Henrici, 1948, subsp. thuringiensis subsp. nov., type strain JA 10124. The antibiotic complex, designated as streptovirudin, was isolated from extracts of both mycelium and culture filtrate. It is a white amorphous material which consists of ten closely related components including streptovirudins A, B, C, D and E. The streptovirudin complex exhibits antibiotic activity against Gram-positive bacteria, mycobacteria, and various DNA- and RNA-viruses.

  13. 76 FR 4929 - Agency Information Collection Activities: Entry of Articles for Exhibition.

    Science.gov (United States)

    2011-01-27

    ... Exhibition. AGENCY: U.S. Customs and Border Protection (CBP), Department of Homeland Security. ACTION: 60-Day... Entry of Articles for Exhibition (19 CFR 147.11(c)). This request for comment is being made pursuant to... for Exhibition. OMB Number: 1651-0037. Form Number: None. Abstract: Goods entered for exhibit at fairs...

  14. Green tea polyphenol, epigallocatechin-3-gallate, possesses the antiviral activity necessary to fight against the hepatitis B virus replication in vitro.

    Science.gov (United States)

    Pang, Jing-yao; Zhao, Kui-jun; Wang, Jia-bo; Ma, Zhi-jie; Xiao, Xiao-he

    2014-06-01

    Although several antiviral drugs and vaccines are available for use against hepatitis B virus (HBV), hepatitis caused by HBV remains a major public health problem worldwide, which has not yet been resolved, and new anti-HBV drugs are in great demand. The present study was performed to investigate the anti-HBV activity of epigallocatechin-3-gallate (EGCG), a natural-origin compound, in HepG2 2.2.15 cells. The antiviral activity of EGCG was examined by detecting the levels of HBsAg and HBeAg in the supernatant and extracellular HBV DNA. EGCG effectively suppressed the secretion of HBsAg and HBeAg from HepG2 2.2.15 cells in a dose- and time-dependent manner, and it showed stronger effects at the level of 0.11-0.44 μmol/ml (50-200 μg/ml) than lamivudine (3TC) at 0.87 μmol/ml (200 μg/ml). EGCG also suppressed the amount of extracellular HBV DNA. The data indicated that EGCG possessed anti-HBV activity and suggested the potential of EGCG as an effective anti-HBV agent with low toxicity.

  15. Increased activity of indoleamine 2,3-dioxygenase in serum from acutely infected dengue patients linked to gamma interferon antiviral function

    Science.gov (United States)

    Becerra, Aniuska; Warke, Rajas V.; Xhaja, Kris; Evans, Barbara; Evans, James; Martin, Katherine; de Bosch, Norma; Rothman, Alan L.; Bosch, Irene

    2009-01-01

    The depletion of l-tryptophan (L-Trp) has been associated with the inhibition of growth of micro-organisms and also has profound effects on T cell proliferation and immune tolerance. The enzyme indoleamine 2,3-dioxygenase (IDO) catalyses the rate-limiting step in the catabolic pathway of L-Trp. Gene expression analysis has shown upregulation of genes involved in L-Trp catabolism in in vitro models of dengue virus (DENV) infection. To understand the role of IDO during DENV infection, we measured IDO activity in sera from control and DENV-infected patients. We found increased IDO activity, lower levels of L-Trp and higher levels of l-kynurenine in sera from DENV-infected patients during the febrile days of the disease compared with patients with other febrile illnesses and healthy donors. Furthermore, we confirmed upregulation of IDO mRNA expression in response to DENV infection in vitro, using a dendritic cell (DC) model of DENV infection. We found that the antiviral effect of gamma interferon (IFN-γ) in DENV-infected DCs in vitro was partially dependent on IDO activity. Our results demonstrate that IDO plays an important role in the antiviral effect of IFN-γ against DENV infection in vitro and suggest that it has a role in the immune response to DENV infections in vivo. PMID:19264674

  16. Ester prodrugs of cyclic 1-(S)-[3-hydroxy-2-(phosphonomethoxy)propyl]-5-azacytosine: Synthesis and antiviral activity

    Czech Academy of Sciences Publication Activity Database

    Krečmerová, Marcela; Holý, Antonín; Pohl, Radek; Masojídková, Milena; Andrei, G.; Naesens, L.; Neyts, J.; Balzarini, J.; De Clercq, E.; Snoeck, R.

    2007-01-01

    Roč. 50, č. 23 (2007), s. 5765-5772 ISSN 0022-2623 R&D Projects: GA MŠk 1M0508; GA AV ČR 1QS400550501 Grant - others:NIH(US) 1UC1AI062540-01; René Descartes Prize-2001(XE) HPAW-2002-100096 Institutional research plan: CEZ:AV0Z40550506 Keywords : acyclic nucleoside phosphonates * antivirals * HPMP-5-azacytosine * alkoxyalkyl ester * hexadecyloxyethyl ester Subject RIV: CC - Organic Chemistry Impact factor: 4.895, year: 2007

  17. Protective Effect of Panax notoginseng Root Water Extract against Influenza A Virus Infection by Enhancing Antiviral Interferon-Mediated Immune Responses and Natural Killer Cell Activity

    Directory of Open Access Journals (Sweden)

    Jang-Gi Choi

    2017-11-01

    Full Text Available Influenza is an acute respiratory illness caused by the influenza A virus, which causes economic losses and social disruption mainly by increasing hospitalization and mortality rates among the elderly and people with chronic diseases. Influenza vaccines are the most effective means of preventing seasonal influenza, but can be completely ineffective if there is an antigenic mismatch between the seasonal vaccine virus and the virus circulating in the community. In addition, influenza viruses resistant to antiviral drugs are emerging worldwide. Thus, there is an urgent need to develop new vaccines and antiviral drugs against these viruses. In this study, we conducted in vitro and in vivo analyses of the antiviral effect of Panax notoginseng root (PNR, which is used as an herbal medicine and nutritional supplement in Korea and China. We confirmed that PNR significantly prevented influenza virus infection in a concentration-dependent manner in mouse macrophages. In addition, PNR pretreatment inhibited viral protein (PB1, PB2, HA, NA, M1, PA, M2, and NP and viral mRNA (NS1, HA, PB2, PA, NP, M1, and M2 expression. PNR pretreatment also increased the secretion of pro-inflammatory cytokines [tumor necrosis factor alpha and interleukin 6] and interferon (IFN-beta and the phosphorylation of type-I IFN-related proteins (TANK-binding kinase 1, STAT1, and IRF3 in vitro. In mice exposed to the influenza A H1N1 virus, PNR treatment decreased mortality by 90% and prevented weight loss (by approximately 10% compared with the findings in untreated animals. In addition, splenocytes from PNR-administered mice displayed significantly enhanced natural killer (NK cell activity against YAC-1 cells. Taking these findings together, PNR stimulates an antiviral response in murine macrophages and mice that protects against viral infection, which may be attributable to its ability to stimulate NK cell activity. Further investigations are needed to reveal the molecular

  18. Antiviral Activity and Resistance Analysis of NS3/4A Protease Inhibitor Grazoprevir and NS5A Inhibitor Elbasvir in Hepatitis C Virus GT4 Replicons.

    Science.gov (United States)

    Asante-Appiah, Ernest; Curry, Stephanie; McMonagle, Patricia; Ingravallo, Paul; Chase, Robert; Nickle, David; Qiu, Ping; Howe, Anita; Lahser, Frederick C

    2017-07-01

    Although genotype 4 (GT4)-infected patients represent a minor overall percentage of the global hepatitis C virus (HCV)-infected population, the high prevalence of the genotype in specific geographic regions coupled with substantial sequence diversity makes it an important genotype to study for antiviral drug discovery and development. We evaluated two direct-acting antiviral agents-grazoprevir, an HCV NS3/4A protease inhibitor, and elbasvir, an HCV NS5A inhibitor-in GT4 replicons prior to clinical studies in this genotype. Following a bioinformatics analysis of available GT4 sequences, a set of replicons bearing representative GT4 clinical isolates was generated. For grazoprevir, the 50% effective concentration (EC50) against the replicon bearing the reference GT4a (ED43) NS3 protease and NS4A was 0.7 nM. The median EC50 for grazoprevir against chimeric replicons encoding NS3/4A sequences from GT4 clinical isolates was 0.2 nM (range, 0.11 to 0.33 nM; n = 5). The difficulty in establishing replicons bearing NS3/4A resistance-associated substitutions was substantially overcome with the identification of a G162R adaptive substitution in NS3. Single NS3 substitutions D168A/V identified from de novo resistance selection studies reduced grazoprevir antiviral activity by 137- and 47-fold, respectively, in the background of the G162R replicon. For elbasvir, the EC50 against the replicon bearing the reference full-length GT4a (ED43) NS5A gene was 0.0002 nM. The median EC50 for elbasvir against chimeric replicons bearing clinical isolates from GT4 was 0.0007 nM (range, 0.0002 to 34 nM; n = 14). De novo resistance selection studies in GT4 demonstrated a high propensity to suppress the emergence of amino acid substitutions that confer high-potency reductions to elbasvir. Phenotypic characterization of the NS5A amino acid substitutions identified (L30F, L30S, M31V, and Y93H) indicated that they conferred 15-, 4-, 2.5-, and 7.5-fold potency losses, respectively, to elbasvir. The

  19. Potentiated virucidal activity of pomegranate rind extract (PRE) and punicalagin against Herpes simplex virus (HSV) when co-administered with zinc (II) ions, and antiviral activity of PRE against HSV and aciclovir-resistant HSV.

    Science.gov (United States)

    Houston, David M J; Bugert, Joachim J; Denyer, Stephen P; Heard, Charles M

    2017-01-01

    There is a clinical need for new therapeutic products against Herpes simplex virus (HSV). The pomegranate, fruit of the tree Punica granatum L, has since ancient times been linked to activity against infection. This work probed the activity of pomegranate rind extract (PRE) and co-administered zinc (II) ions. PRE was used in conjunction with zinc (II) salts to challenge HSV-1 and aciclovir-resistant HSV in terms of virucidal plaque assay reduction and antiviral activities in epithelial Vero host cells. Cytotoxicity was determined by the MTS assay using a commercial kit. Zinc sulphate, zinc citrate, zinc stearate and zinc gluconate demonstrated similar potentiated virucidal activity with PRE against HSV-1 by up to 4-fold. A generally parabolic relationship was observed when HSV-1 was challenged with PRE and varying concentrations of ZnSO4, with a maximum potentiation factor of 5.5. Punicalagin had 8-fold greater virucidal activity than an equivalent mass of PRE. However, antiviral data showed that punicalagin had significantly lower antiviral activity compared to the activity of PRE (EC50 = 0.56 μg mL-1) a value comparable to aciclovir (EC50 = 0.18 μg mL-1); however, PRE also demonstrated potency against aciclovir-resistant HSV (EC50 = 0.02 μg mL-1), whereas aciclovir showed no activity. Antiviral action of PRE was not influenced by ZnSO4. No cytotoxicity was detected with any test solution. The potentiated virucidal activity of PRE by coadministered zinc (II) has potential as a multi-action novel topical therapeutic agent against HSV infections, such as coldsores.

  20. Potentiated virucidal activity of pomegranate rind extract (PRE and punicalagin against Herpes simplex virus (HSV when co-administered with zinc (II ions, and antiviral activity of PRE against HSV and aciclovir-resistant HSV.

    Directory of Open Access Journals (Sweden)

    David M J Houston

    Full Text Available There is a clinical need for new therapeutic products against Herpes simplex virus (HSV. The pomegranate, fruit of the tree Punica granatum L, has since ancient times been linked to activity against infection. This work probed the activity of pomegranate rind extract (PRE and co-administered zinc (II ions.PRE was used in conjunction with zinc (II salts to challenge HSV-1 and aciclovir-resistant HSV in terms of virucidal plaque assay reduction and antiviral activities in epithelial Vero host cells. Cytotoxicity was determined by the MTS assay using a commercial kit.Zinc sulphate, zinc citrate, zinc stearate and zinc gluconate demonstrated similar potentiated virucidal activity with PRE against HSV-1 by up to 4-fold. A generally parabolic relationship was observed when HSV-1 was challenged with PRE and varying concentrations of ZnSO4, with a maximum potentiation factor of 5.5. Punicalagin had 8-fold greater virucidal activity than an equivalent mass of PRE. However, antiviral data showed that punicalagin had significantly lower antiviral activity compared to the activity of PRE (EC50 = 0.56 μg mL-1 a value comparable to aciclovir (EC50 = 0.18 μg mL-1; however, PRE also demonstrated potency against aciclovir-resistant HSV (EC50 = 0.02 μg mL-1, whereas aciclovir showed no activity. Antiviral action of PRE was not influenced by ZnSO4. No cytotoxicity was detected with any test solution.The potentiated virucidal activity of PRE by coadministered zinc (II has potential as a multi-action novel topical therapeutic agent against HSV infections, such as coldsores.

  1. pH-induced quaternary assembly of Vitreoscilla hemoglobin: the monomer exhibits better peroxidase activity.

    Science.gov (United States)

    Li, Wei; Zhang, Yubin; Xu, Haoran; Wu, Lei; Cao, Yufeng; Zhao, Haifeng; Li, Zhengqiang

    2013-10-01

    pH-dependent (pH6.0-8.0) quaternary structural changes of ferric Vitreoscilla hemoglobin (VHb) have been investigated using dynamic light scattering. The VHb exhibits a monomeric state under neutral conditions at pH7.0, while the protein forms distinct homodimeric species at pH6.0 and 8.0, respectively. The dissociation constant obtained using the Bio-Layer Interferometry technology indicates that, at pH7.0, the monomer-monomer dissociation of VHb is about 6-fold or 5-fold higher (KD=6.34μM) compared with that at slightly acidic pH (KD=1.05μM) or slightly alkaline pH (KD=1.22μM). The pH-dependent absorption spectra demonstrate that the heme microenvironment of VHb is sensitive to the changes of pH value. The maximum absorption band of heme group of VHb shifts from 402nm to 407nm when pH changes from 6.0 to 8.0. In addition, the fluorescence emission spectra of VHb, taken at excitation wavelength of 295nm, suggest that the single Trp122 fluorescence quantum yields in VHb are decreased due to the formation of the homodimeric species. However, the circular dichroism spectra data display that the secondary structures of VHb are little affected by pH transitions. The pH-dependent peroxidase activity of VHb was also investigated in this study. The optimum pH for VHb using 2,2'-azino-bis-(3-ethylbenzothiazoline-6-sulfonic acid) as substrate is 7.0, which implies that the monomer state of VHb would exhibit better peroxidase activity than the homodimeric species of VHb at pH6.0 and 8.0. © 2013.

  2. Volatile compounds of Lamiaceae exhibit a synergistic antibacterial activity with streptomycin

    Directory of Open Access Journals (Sweden)

    Sthéfane G. Araújo

    2014-12-01

    Full Text Available Bacterial infections cause thousands of deaths in the world every year. In most cases, infections are more serious because the patient is already weakened, and often, the bacteria are already resistant to the antibiotics used. Counterparting this negative scenario, the interest in medicinal plants as an alternative to the synthetic antimicrobial drugs is blossoming worldwide. In the present work, we identified the volatile compounds of ethanol extracts of Melissa officinalis, Mentha sp., Ocimum basilicum, Plectranthus barbatus, and Rosmarinus officinalis by gas chromatography/mass spectrometry (GC/MS. Also was evaluated antimicrobial activity of ethanol extracts against 6 bacteria of clinical interest, and was tested the interaction of these extracts with a commercial antibiotic streptomycin. Phytol was a compound identified in all extracts by GC/MS, being majoritary component in Plectranthus barbatus and Rosmarinus officinalis. The Gram-positive bacteria were more sensitive to ethanol extracts, and Plectranthus barbatus and Rosmarinus officinalis were the most active extracts. Ethanol extracts exhibited a synergetic effect with streptomycin. These results encourage additional studies, in order to evaluate the possibilities of using ethanol extracts of Lamiaceae family as natural source for antibacterial activity.

  3. Volatile compounds of Lamiaceae exhibit a synergistic antibacterial activity with streptomycin.

    Science.gov (United States)

    Araújo, Sthéfane G; Alves, Lucas F; Pinto, Maria Eduarda A; Oliveira, Graziela T; Siqueira, Ezequias P; Ribeiro, Rosy I M A; Ferreira, Jaqueline M S; Lima, Luciana A R S

    2014-01-01

    Bacterial infections cause thousands of deaths in the world every year. In most cases, infections are more serious because the patient is already weakened, and often, the bacteria are already resistant to the antibiotics used. Counterparting this negative scenario, the interest in medicinal plants as an alternative to the synthetic antimicrobial drugs is blossoming worldwide. In the present work, we identified the volatile compounds of ethanol extracts of Melissa officinalis, Mentha sp., Ocimum basilicum, Plectranthus barbatus, and Rosmarinus officinalis by gas chromatography/mass spectrometry (GC/MS). Also was evaluated antimicrobial activity of ethanol extracts against 6 bacteria of clinical interest, and was tested the interaction of these extracts with a commercial antibiotic streptomycin. Phytol was a compound identified in all extracts by GC/MS, being majoritary component in Plectranthus barbatus and Rosmarinus officinalis. The Gram-positive bacteria were more sensitive to ethanol extracts, and Plectranthus barbatus and Rosmarinus officinalis were the most active extracts. Ethanol extracts exhibited a synergetic effect with streptomycin. These results encourage additional studies, in order to evaluate the possibilities of using ethanol extracts of Lamiaceae family as natural source for antibacterial activity.

  4. Bulbispermine: A Crinine-Type Amaryllidaceae Alkaloid Exhibiting Cytostatic Activity towards Apoptosis-Resistant Glioma Cells

    Science.gov (United States)

    Luchetti, Giovanni; Johnston, Robert; Mathieu, Véronique; Lefranc, Florence; Hayden, Kathryn; Andolfi, Anna; Lamoral-Theys, Delphine; Reisenauer, Mary R.; Champion, Cody; Pelly, Stephen C.; van Otterlo, Willem A. L.; Magedov, Igor V.; Kiss, Robert; Evidente, Antonio; Rogelj, Snezna; Kornienko, Alexander

    2012-01-01

    The Amaryllidaceae alkaloid bulbispermine was derivatized to produce a small group of synthetic analogues. These, together with bulbispermine’s natural crinine-type congeners, were evaluated in vitro against a panel of cancer cell lines with various levels of resistance to proapoptotic stimuli. Bulbispermine, haemanthamine and haemanthidine showed the most potent antiproliferative activities as determined by the MTT colorimetric assay. Among the synthetic bulbispermine analogues, only the C1,C2-dicarbamate derivative exhibited noteworthy growth inhibitory properties. All active compounds were found not to discriminate between the cancer cell lines based on the apoptosis sensitivity criterion and displayed comparable potencies in both cell types, indicating that apoptosis induction is not the primary mechanism responsible for antiproliferative activity in this series of compounds. It was also found that bulbispermine inhibits the proliferation of glioblastoma cells through cytostatic effects, possibly arising from the rigidification of the actin cytoskeleton. These findings lead us to argue that crinine-type alkaloids are potentially useful drug leads for the treatment of apoptosis resistant cancers and glioblastoma in particular. PMID:22389235

  5. In Vitro Antiviral Activity of Circular Triple Helix Forming Oligonucleotide RNA towards Feline Infectious Peritonitis Virus Replication

    Directory of Open Access Journals (Sweden)

    Oi Kuan Choong

    2014-01-01

    Full Text Available Feline Infectious Peritonitis (FIP is a severe fatal immune-augmented disease in cat population. It is caused by FIP virus (FIPV, a virulent mutant strain of Feline Enteric Coronavirus (FECV. Current treatments and prophylactics are not effective. The in vitro antiviral properties of five circular Triple-Helix Forming Oligonucleotide (TFO RNAs (TFO1 to TFO5, which target the different regions of virulent feline coronavirus (FCoV strain FIPV WSU 79-1146 genome, were tested in FIPV-infected Crandell-Rees Feline Kidney (CRFK cells. RT-qPCR results showed that the circular TFO RNAs, except TFO2, inhibit FIPV replication, where the viral genome copy numbers decreased significantly by 5-fold log10 from 1014 in the virus-inoculated cells to 109 in the circular TFO RNAs-transfected cells. Furthermore, the binding of the circular TFO RNA with the targeted viral genome segment was also confirmed using electrophoretic mobility shift assay. The strength of binding kinetics between the TFO RNAs and their target regions was demonstrated by NanoITC assay. In conclusion, the circular TFOs have the potential to be further developed as antiviral agents against FIPV infection.

  6. Interferon-induced genes of the expanded IFIT family show conserved antiviral activities in non-mammalian species.

    Directory of Open Access Journals (Sweden)

    Mónica Varela

    Full Text Available Interferon-induced proteins with tetratricopeptide repeats (IFITs are involved in the protective response to viral infection, although the precise mechanism of IFITs for reducing viral proliferation is currently unknown. The interaction with the translation initiation factor eIF-3 or viral proteins and the sequestering of viral RNA have been proposed as potential antiviral functions for these proteins. In humans, four members of this family have been characterized. Nevertheless, information about these proteins in fish is almost non-existent. Exploiting the conservation of synteny between human and zebrafish genomes, we have identified ten members of the IFIT family located on four different chromosomes. The induction of these genes was examined both in vitro and in vivo after interferon (IFN administration and rhabdovirus challenge. Whereas an induction of IFIT genes was observed after interferon treatments (IFNΦ1, IFNΦ2 and IFNΦ3, the viral infection did not affect these IFN-induced genes in vitro, and even reduced the IFN-induced expression of these genes. The response was largely different in vivo, with a broad up-regulation of IFIT genes after viral challenge. In addition, three selected IFITs were cloned in an expression vector and microinjected into zebrafish larvae to examine the protective effect of IFITs upon viral infection. Reduction in the mortality rate was observed confirming a conserved antiviral function in non-mammalian species.

  7. Broad-spectrum antiviral activity of chebulagic acid and punicalagin against viruses that use glycosaminoglycans for entry.

    Science.gov (United States)

    Lin, Liang-Tzung; Chen, Ting-Ying; Lin, Song-Chow; Chung, Chueh-Yao; Lin, Ta-Chen; Wang, Guey-Horng; Anderson, Robert; Lin, Chun-Ching; Richardson, Christopher D

    2013-08-07

    We previously identified two hydrolyzable tannins, chebulagic acid (CHLA) and punicalagin (PUG) that blocked herpes simplex virus type 1 (HSV-1) entry and spread. These compounds inhibited viral glycoprotein interactions with cell surface glycosaminoglycans (GAGs). Based on this property, we evaluated their antiviral efficacy against several different viruses known to employ GAGs for host cell entry. Extensive analysis of the tannins' mechanism of action was performed on a panel of viruses during the attachment and entry steps of infection. Virus-specific binding assays and the analysis of viral spread during treatment with these compounds were also conducted. CHLA and PUG were effective in abrogating infection by human cytomegalovirus (HCMV), hepatitis C virus (HCV), dengue virus (DENV), measles virus (MV), and respiratory syncytial virus (RSV), at μM concentrations and in dose-dependent manners without significant cytotoxicity. Moreover, the natural compounds inhibited viral attachment, penetration, and spread, to different degrees for each virus. Specifically, the tannins blocked all these steps of infection for HCMV, HCV, and MV, but had little effect on the post-fusion spread of DENV and RSV, which could suggest intriguing differences in the roles of GAG-interactions for these viruses. CHLA and PUG may be of value as broad-spectrum antivirals for limiting emerging/recurring viruses known to engage host cell GAGs for entry. Further studies testing the efficacy of these tannins in vivo against certain viruses are justified.

  8. Zinc Acetate/Carrageenan Gels Exhibit Potent Activity In Vivo against High-Dose Herpes Simplex Virus 2 Vaginal and Rectal Challenge

    Science.gov (United States)

    Fernández-Romero, José A.; Abraham, Ciby J.; Rodriguez, Aixa; Kizima, Larisa; Jean-Pierre, Ninochka; Menon, Radhika; Begay, Othell; Seidor, Samantha; Ford, Brian E.; Gil, Pedro I.; Peters, Jennifer; Katz, David; Robbiani, Melissa

    2012-01-01

    Topical microbicides that block the sexual transmission of HIV and herpes simplex virus 2 (HSV-2) are desperately needed to reduce the incidence of HIV infections worldwide. Previously we completed phase 3 testing of the carrageenan-based gel Carraguard. Although the trial did not show that Carraguard is effective in preventing HIV transmission during vaginal sex, it did show that Carraguard is safe when used weekly for up to 2 years. Moreover, Carraguard has in vitro activity against human papillomavirus (HPV) and HSV-2 and favorable physical and rheological properties, which makes it a useful vehicle to deliver antiviral agents such as zinc acetate. To that end, we previously reported that a prototype zinc acetate carrageenan gel protects macaques against vaginal challenge with combined simian-human immunodeficiency virus reverse transcriptase (SHIV-RT). Herein, we report the safety and efficacy of a series of zinc acetate and/or carrageenan gels. The gels protected mice (75 to 85% survival; P gels were found to be effective spreading gels, exhibited limited toxicity in vitro, caused minimal damage to the architecture of the cervicovaginal and rectal mucosae in vivo, and induced no increased susceptibility to HSV-2 infection in a mouse model. Our results provide a strong rationale to further optimize and evaluate the zinc acetate/carrageenan gels for their ability to block the sexual transmission of HIV and HSV-2. PMID:22064530

  9. SP-303, an antiviral oligomeric proanthocyanidin from the latex of Croton lechleri (Sangre de Drago).

    Science.gov (United States)

    Ubillas, R; Jolad, S D; Bruening, R C; Kernan, M R; King, S R; Sesin, D F; Barrett, M; Stoddart, C A; Flaster, T; Kuo, J; Ayala, F; Meza, E; Castañel, M; McMeekin, D; Rozhon, E; Tempesta, M S; Barnard, D; Huffman, J; Smee, D; Sidwell, R; Soike, K; Brazier, A; Safrin, S; Orlando, R; Kenny, P T; Berova, N; Nakanishi, K

    1994-09-01

    SP-303, a large proanthocyanidin oligomer isolated from the latex of the plant species Croton lechleri (Eupborbiaceae) has demonstrated broad activity against a variety of DNA and RNA viruses. In cell culture, SP-303 exhibits potent activity against isolates and laboratory strains of respiratory syncytial virus (RSV), influenza A virus (FLU-A) and parainfluenza virus (PIV). Parallel assays of SP-303 and ribavirin showed comparable activity against these viruses. SP-303 also exhibits significant inhibitory activity against herpesvirus (HSV) types 1 and 2, including herpesviruses resistant to acyclovir and foscarnet. Inhibition was also observed against hepatitis A and B viruses. The antiviral mechanism of SP-303 seems to derive from its direct binding to components of the viral envelope, resulting in inhibition of viral attachment and penetration of the plasma membrane. Antiviral effects of SP-303 were measured by three distinct methods: CPE, MTT and precursor uptake/incorporation. Cytotoxicity endpoints were markedly greater than the respective antiviral endpoints. SP-303 exhibited activity in RSV-infected cotton rats and African green monkeys, PIV-3-infected cotton rats, HSV-2 infected mice and guinea pigs and FLU-A-infected mice. The most successful routes of SP-303 administration for producing efficacy were: topical application to HSV-2- genital lesions in mice and guinea pigs, aerosol inhalation to FLU-A-infected mice and PIV-3-infected cotton rats, and oral dosage to RSV-infected cotton rats. A variety of toxicological evaluations demonstrated the safety of SP-303, particularly orally, which was predictable, since condensed tannins are a common dietary component. It is notable that the larger proanthocyanidins as a class have high antiviral activity, whereas most of the monomers are inactive. Clinical trials are ongoing to evaluate SP-303 as a therapeutic antiviral agent. Copyright © 1994 Gustav Fischer Verlag, Stuttgart · Jena · New York. Published by

  10. 76 FR 17425 - Agency Information Collection Activities: Entry of Articles for Exhibition

    Science.gov (United States)

    2011-03-29

    ... Exhibition AGENCY: U.S. Customs and Border Protection, Department of Homeland Security. ACTION: 30-Day notice... approval in accordance with the Paperwork ] Reduction Act: Entry of Articles for Exhibition (19 CFR 147.11.... Title: Entry of Articles for Exhibition. OMB Number: 1651-0037. Form Number: None. Abstract: Goods...

  11. Inhibition of enterovirus 71 (EV-71 infections by a novel antiviral peptide derived from EV-71 capsid protein VP1.

    Directory of Open Access Journals (Sweden)

    Chee Wah Tan

    Full Text Available Enterovirus 71 (EV-71 is the main causative agent of hand, foot and mouth disease (HFMD. In recent years, EV-71 infections were reported to cause high fatalities and severe neurological complications in Asia. Currently, no effective antiviral or vaccine is available to treat or prevent EV-71 infection. In this study, we have discovered a synthetic peptide which could be developed as a potential antiviral for inhibition of EV-71. Ninety five synthetic peptides (15-mers overlapping the entire EV-71 capsid protein, VP1, were chemically synthesized and tested for antiviral properties against EV-71 in human Rhabdomyosarcoma (RD cells. One peptide, SP40, was found to significantly reduce cytopathic effects of all representative EV-71 strains from genotypes A, B and C tested, with IC(50 values ranging from 6-9.3 µM in RD cells. The in vitro inhibitory effect of SP40 exhibited a dose dependent concentration corresponding to a decrease in infectious viral particles, total viral RNA and the levels of VP1 protein. The antiviral activity of SP40 peptide was not restricted to a specific cell line as inhibition of EV-71 was observed in RD, HeLa, HT-29 and Vero cells. Besides inhibition of EV-71, it also had antiviral activities against CV-A16 and poliovirus type 1 in cell culture. Mechanism of action studies suggested that the SP40 peptide was not virucidal but was able to block viral attachment to the RD cells. Substitutions of arginine and lysine residues with alanine in the SP40 peptide at positions R3A, R4A, K5A and R13A were found to significantly decrease antiviral activities, implying the importance of positively charged amino acids for the antiviral activities. The data demonstrated the potential and feasibility of SP40 as a broad spectrum antiviral agent against EV-71.

  12. Inhibition of Enterovirus 71 (EV-71) Infections by a Novel Antiviral Peptide Derived from EV-71 Capsid Protein VP1

    Science.gov (United States)

    Tan, Chee Wah; Chan, Yoke Fun; Sim, Kooi Mow; Tan, Eng Lee; Poh, Chit Laa

    2012-01-01

    Enterovirus 71 (EV-71) is the main causative agent of hand, foot and mouth disease (HFMD). In recent years, EV-71 infections were reported to cause high fatalities and severe neurological complications in Asia. Currently, no effective antiviral or vaccine is available to treat or prevent EV-71 infection. In this study, we have discovered a synthetic peptide which could be developed as a potential antiviral for inhibition of EV-71. Ninety five synthetic peptides (15-mers) overlapping the entire EV-71 capsid protein, VP1, were chemically synthesized and tested for antiviral properties against EV-71 in human Rhabdomyosarcoma (RD) cells. One peptide, SP40, was found to significantly reduce cytopathic effects of all representative EV-71 strains from genotypes A, B and C tested, with IC50 values ranging from 6–9.3 µM in RD cells. The in vitro inhibitory effect of SP40 exhibited a dose dependent concentration corresponding to a decrease in infectious viral particles, total viral RNA and the levels of VP1 protein. The antiviral activity of SP40 peptide was not restricted to a specific cell line as inhibition of EV-71 was observed in RD, HeLa, HT-29 and Vero cells. Besides inhibition of EV-71, it also had antiviral activities against CV-A16 and poliovirus type 1 in cell culture. Mechanism of action studies suggested that the SP40 peptide was not virucidal but was able to block viral attachment to the RD cells. Substitutions of arginine and lysine residues with alanine in the SP40 peptide at positions R3A, R4A, K5A and R13A were found to significantly decrease antiviral activities, implying the importance of positively charged amino acids for the antiviral activities. The data demonstrated the potential and feasibility of SP40 as a broad spectrum antiviral agent against EV-71. PMID:22563456

  13. Methanol leaves extract Hibiscus micranthus Linn exhibited antibacterial and wound healing activities.

    Science.gov (United States)

    Begashaw, Berhan; Mishra, Bharat; Tsegaw, Asegedech; Shewamene, Zewdneh

    2017-06-26

    Infectious diseases are the most common causes of morbidity and mortality in developing countries. Wound and wound infections are also major health problem. Nowadays, medicinal plants play a major role in treatment of infectious diseases and wound healing and they are easily available and more affordable as compared to synthetic compounds. The aim of this study is therefore, to investigate the antibacterial and wound healing activities of 80% methanol extract of Hibiscus micranthus leaves using disc diffusion methods and rat excision model respectively. In vitro antibacterial screening was carried out against S. aureus, S.pneumoniae, S. pyogenes, E. coli, P. aeruginosa, K. pneumoniae and P. mirabilis bacterial strains using disc-well diffusion assay. Would healing activity was done in rats divided into four groups each consisting of six animals. Group I was served as a negative control (ointment base), Group II served as a positive control Nitrofurazone (NFZ 0.2% ointment), Groups III and IV was treated 5 and 10% extracts respectively. The acute oral toxicity test and skin sensitivity test were also performed before conducting the actual study. The extract was analyzed for secondary metabolites using standard methods. Preliminary phytochemical screening have revealed the presence of alkaloids, flavonoids, saponins, tannins, steroids, phenols, diterpines, anthraquinones and the absence of glycosides, terpinoides and triterpines. Based on acute oral toxicity test the extract was found to be safe up to a dose of 2 g/kg. In addition, acute dermal toxicity test indicated no sign of skin irritation. The leaves extract exhibited varying degrees of sensitivity with zones of inhibition ranging from 14.00 ± 0.333 (S.pyogenes) to 22.67 ± 1.202 mm (S.aureus). It was found that S. aureus and S. pneumonia (p healing study, the 5 and 10% w/w extract exhibited significant wound contraction rate of 99.30% and 99.13% as compared to NFZ ointment and simple ointment base

  14. Black cobra (Naja naja karachiensis) lysates exhibit broad-spectrum antimicrobial activities.

    Science.gov (United States)

    Sagheer, Mehwish; Siddiqui, Ruqaiyyah; Iqbal, Junaid; Khan, Naveed Ahmed

    2014-04-01

    It is hypothesized that animals living in polluted environments possess antimicrobials to counter pathogenic microbes. The fact that snakes feed on germ-infested rodents suggests that they encounter pathogenic microbes and likely possess antimicrobials. The venom is used only to paralyze the rodent, but the ability of snakes to counter potential infections in the gut due to disease-ridden rodents requires robust action of the immune system against a broad range of pathogens. To test this hypothesis, crude lysates of different organs of Naja naja karachiensis (black cobra) were tested for antimicrobial properties. The antimicrobial activities of extracts were tested against selected bacterial pathogens (neuropathogenic Escherichia coli K1, methicillin-resistant Staphylococcus aureus (MRSA), Pseudomonas aeruginosa, and Streptococcus pneumonia), protist (Acanthamoeba castellanii), and filamentous fungus (Fusarium solani). The findings revealed that plasma and various organ extracts of N. n. karachiensis exhibited antimicrobial activity against E. coli K1, MRSA, P. aeruginosa, S. pneumoniae, A. castellanii, and F. solani in a concentration-dependent manner. The results of this study are promising for the development of new antimicrobials.

  15. Alarm Odor Compounds of the Brown Marmorated Stink Bug Exhibit Antibacterial Activity.

    Science.gov (United States)

    Sagun, Steven; Collins, Elliot; Martin, Caleb; Nolan, E Joseph; Horzempa, Joseph

    2016-08-01

    Some insects release scented compounds as a defense against predators that also exhibit antimicrobial activity. Trans-2-octenal and trans-2-decenal are the major alarm aldehydes responsible for the scent of Halyomorpha halys, the brown marmorated stink bug. Previous research has shown these aldehydes are antifungal and produce an antipredatory effect, but have never been tested for antibacterial activity. We hypothesized that these compounds functioned similarly to the analogous multifunctional action of earwig compounds, so we tested whether these aldehydes could inhibit the growth of bacteria. Disk diffusion assays indicated that these aldehydes significantly inhibited the growth of Methicillin-resistant Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa, in vitro. Moreover, mealworm beetles (Tenebrio molitor) coated in stink bug aldehydes showed a substantial reduction in bacterial colonization compared to vehicle-treated insects. These results suggest that brown marmorated stinkbug aldehydes are indeed antibacterial agents and serve a multifunctional role for this insect. Therefore, stinkbug aldehydes may have potential for use as chemical antimicrobials.

  16. New Derivatives of Pyridoxine Exhibit High Antibacterial Activity against Biofilm-Embedded Staphylococcus Cells

    Directory of Open Access Journals (Sweden)

    Airat R. Kayumov

    2015-01-01

    Full Text Available Opportunistic bacteria Staphylococcus aureus and Staphylococcus epidermidis often form rigid biofilms on tissues and inorganic surfaces. In the biofilm bacterial cells are embedded in a self-produced polysaccharide matrix and thereby are inaccessible to biocides, antibiotics, or host immune system. Here we show the antibacterial activity of newly synthesized cationic biocides, the quaternary ammonium, and bisphosphonium salts of pyridoxine (vitamin B6 against biofilm-embedded Staphylococci. The derivatives of 6-hydroxymethylpyridoxine were ineffective against biofilm-embedded S. aureus and S. epidermidis at concentrations up to 64 μg/mL, although all compounds tested exhibited low MICs (2 μg/mL against planktonic cells. In contrast, the quaternary ammonium salt of pyridoxine (N,N-dimethyl-N-((2,2,8-trimethyl-4H-[1,3]dioxino[4,5-c]pyridin-5-ylmethyloctadecan-1-aminium chloride (3 demonstrated high biocidal activity against both planktonic and biofilm-embedded bacteria. Thus, the complete death of biofilm-embedded S. aureus and S. epidermidis cells was obtained at concentrations of 64 and 16 μg/mL, respectively. We suggest that the quaternary ammonium salts of pyridoxine are perspective to design new synthetic antibiotics and disinfectants for external application against biofilm-embedded cells.

  17. Specific antiviral activity of a poly(L-lysine)-conjugated oligodeoxyribonucleotide sequence complementary to vesicular stomatitis virus N protein mRNA initiation site

    Energy Technology Data Exchange (ETDEWEB)

    Lemaitre, M.; Bayard, B.; Lebleu, B.

    1987-02-01

    Antisense oligonucleotides represent an interesting tool for selective inhibition of gene expression, but their efficient introduction within intact cells provide to be difficult to realize. As a step toward this goal, small (13- or 15-mer) synthetic (/sup 14/C)-oligodeoxyribonucleotides have been coupled at their 3' ends to epsilon-amino groups of lysine residues of poly(L-lysine) (M/sub r/, 14,000). A 15-mer oligonucleotide-poly(L-Lysine) conjugate complementary to the initiation region of vesicular stomatitis virus (VSV) N-protein mRNA specifically inhibits the synthesis of VSV proteins and exerts an antiviral activity against the VSV when added in the cell culture medium at doses as low as 100 nM. Neither synthesis of cellular proteins nor multiplication of encephalomyocarditis virus was affected significantly by this oligonucleotide conjugate. The data suggest that oligonucleotide-poly(L-lysine) conjugates might become effective for studies on gene expression regulation and for antiviral chemotherapy.

  18. In vitro antiviral activity of SCH446211 (SCH6), a novel inhibitor of the hepatitis C virus NS3 serine protease.

    Science.gov (United States)

    Liu, Rong; Abid, Karim; Pichardo, John; Pazienza, Valerio; Ingravallo, Paul; Kong, Rong; Agrawal, Sony; Bogen, Stephane; Saksena, Anil; Cheng, Kuo-Chi; Prongay, Andrew; Njoroge, F George; Baroudy, Bahige M; Negro, Francesco

    2007-01-01

    Current hepatitis C virus (HCV) therapies may cure approximately 60% of infections. They are often contraindicated or poorly tolerated, underscoring the need for safer and more effective drugs. A novel, alpha-ketoamide-derived, substrate-based inhibitor of the HCV serine protease (SCH446211) was developed. Compared with earlier reported inhibitors of similar chemical class, it has a P1'-P2' extension which provides extended interaction with the protease active site. The aim of this study was to evaluate the in vitro antiviral activity of SCH446211. Binding constant of SCH446211 to HCV NS3 protease was measured with the chromogenic substrate in vitro cleavage assay. Cell-based activity of SCH446211 was evaluated in replicon cells, which are Huh-7 hepatoma cells stably transfected with a subgenomic HCV RNA as reported previously. After 72 h of incubation with SCH446211, viral transcription and protein expression were measured by real-time RT-PCR (TaqMan), quantitative in situ hybridization, immunoblot and indirect immunofluorescence. The binding constant of SCH446211 to HCV NS3 protease was 3.8 +/- 0.4 nM. HCV replication and protein expression were inhibited by SCH446211 in replicon cells as consistently shown by four techniques. In particular, based on quantitative real-time RT-PCR measurements, the IC50 and IC90 of SCH446211 were estimated to be 40 +/- 20 and 100 +/- 20 nM (n = 17), respectively. Long-term culture of replicon cells with SCH446211 reduced replicon RNA to <0.1 copy per cell. SCH446211 did not show cellular toxicity at concentrations up to 50 microM. SCH446211 is a potent inhibitor of HCV protease in vitro. Its extended interaction with the HCV NS3 protease active site is associated with potent in vitro antiviral activity. This observation is potentially a useful guide for development of future potent inhibitors against HCV NS3 protease.

  19. A peptide derived from phage display library exhibits antibacterial activity against E. coli and Pseudomonas aeruginosa.

    Directory of Open Access Journals (Sweden)

    Shilpakala Sainath Rao

    Full Text Available Emergence of drug resistant strains to currently available antibiotics has resulted in the quest for novel antimicrobial agents. Antimicrobial peptides (AMPs are receiving attention as alternatives to antibiotics. In this study, we used phage-display random peptide library to identify peptides binding to the cell surface of E. coli. The peptide with sequence RLLFRKIRRLKR (EC5 bound to the cell surface of E. coli and exhibited certain features common to AMPs and was rich in Arginine and Lysine residues. Antimicrobial activity of the peptide was tested in vitro by growth inhibition assays and the bacterial membrane permeabilization assay. The peptide was highly active against gram-negative organisms and showed significant bactericidal activity against E. coli and P. aeruginosa resulting in a reduction of 5 log(10 CFU/ml. In homologous plasma and platelets, incubation of EC5 with the bacteria resulted in significant reduction of E. coli and P. aeruginosa, compared to the peptide-free controls. The peptide was non-hemolytic and non-cytotoxic when tested on eukaryotic cells in culture. EC5 was able to permeabilize the outer membrane of E. coli and P. aeruginosa causing rapid depolarization of cytoplasmic membrane resulting in killing of the cells at 5 minutes of exposure. The secondary structure of the peptide showed a α-helical conformation in the presence of aqueous environment. The bacterial lipid interaction with the peptide was also investigated using Molecular Dynamic Simulations. Thus this study demonstrates that peptides identified to bind to bacterial cell surface through phage-display screening may additionally aid in identifying and developing novel antimicrobial peptides.

  20. Antiviral activity of tiazofurin and mycophenolic acid against Grapevine leafroll-associated virus 3 in Vitis vinifera explants.

    Science.gov (United States)

    Panattoni, A; D'Anna, F; Triolo, E

    2007-03-01

    The ability to control plant viral diseases with chemicals has great potential value for agriculture, but few chemicals are available to date due to the difficulty in obtaining effective drugs. IMP dehydrogenase is an enzyme which catalyzes the conversion of inosine 5'-monophosphate to xanthosine 5'-monophosphate in the de novo purine nucleotide synthetic pathway, and is considered a sensitive target for antiviral drugs. Two IMPDH inhibitors, tiazofurin (TR) and mycophenolic acid (MPA), were tested for their inhibitory effect on Grapevine leafroll-associated virus 3 (GLRaV-3) in in vitro grapevine explants. TR administration produced plantlets characterized by negative ELISA readings. No PCR products were obtained from these samples. This was confirmed by the absence of viral particles. MPA was essentially ineffective against GLRaV-3 replication in Sangiovese explants. This is the first report of GLRaV-3 eradication in grapevine explants following TR administration.

  1. A randomized, placebo controlled, double masked phase IB study evaluating the safety and antiviral activity of aprepitant, a neurokinin-1 receptor antagonist in HIV-1 infected adults.

    Directory of Open Access Journals (Sweden)

    Pablo Tebas

    Full Text Available BACKGROUND: Neurokinin-1 receptor (NK1R antagonists have anti-HIV activity in monocyte-derived macrophages, decrease CCR5 expression and improve natural killer cell function ex vivo. Aprepitant is a NK1R antagonist approved by FDA as an antiemetic. METHODS: We conducted a phase IB randomized, placebo controlled, double masked study to evaluate the safety, antiviral activity, pharmacokinetics and immune-modulatory effects of aprepitant in HIV-infected adults not receiving antiretroviral therapy, with CD4+ cell count ≥350 cells/mm(3 and plasma viral load ≥2,000 copies/ml. Subjects were stratified by viral load (< vs. ≥20,000 copies/ml and randomized within each stratum to receive aprepitant at 125 mg QD(Low, or 250 mg QD(High, or placebo(PL for 14 days, and followed for 42 days. RESULTS: Thirty subjects were randomized and 27 completed treatment (9, 8, 10 subjects in 125 (Low, 250 (High, and PL groups. 63% were male; 37% white; mean (SD age 43 (9.3 years. Geometric mean baseline viral load (copies/ml for Low, High, and PL was 15,709, 33,013, and 19,450, respectively. Mean (95%CI change in log10 viral load at day 14 for Low, High, and PL was -0.02(-0.24,+0.20, -0.05(-0.21,+0.10, and +0.04(-0.08,+0.16, respectively. The number of subjects with AEs was 4(44.4%, 5(62.5%, and 1(10% for Low, High, and PL. No Grade 4 AEs occurred. CONCLUSIONS: Adverse events of aprepitant were more common in the treated groups. At the dose used in this two-week phase IB study, aprepitant showed biological activity, but no significant antiviral activity. TRIAL REGISTRATION: ClinicalTrials.gov NCT00428519.

  2. The Personnel Competence as a Factor of Increasing the Efficiency of Exhibition and Fair Activity of the Company

    Directory of Open Access Journals (Sweden)

    Vladyslava Yermakova

    2017-06-01

    Full Text Available The article is devoted to theoretical grounding of personnel importance for the efficiency of trade fair-exhibition activity. Based on the analysis, generalization and systematization of scientific sources, the basic theoretical aspects of exhibitions involving personnel qualification and review personal sales as an important, specific marketing tools are highlighted.

  3. Viruses and Antiviral Immunity in Drosophila

    Science.gov (United States)

    Xu, Jie; Cherry, Sara

    2013-01-01

    Viral pathogens present many challenges to organisms, driving the evolution of a myriad of antiviral strategies to combat infections. A wide variety of viruses infect invertebrates, including both natural pathogens that are insect-restricted, and viruses that are transmitted to vertebrates. Studies using the powerful tools available in the model organism Drosophila have expanded our understanding of antiviral defenses against diverse viruses. In this review, we will cover three major areas. First, we will describe the tools used to study viruses in Drosophila. Second, we will survey the major viruses that have been studied in Drosophila. And lastly, we will discuss the well-characterized mechanisms that are active against these diverse pathogens, focusing on non-RNAi mediated antiviral mechanisms. Antiviral RNAi is discussed in another paper in this issue. PMID:23680639

  4. Viruses and antiviral immunity in Drosophila.

    Science.gov (United States)

    Xu, Jie; Cherry, Sara

    2014-01-01

    Viral pathogens present many challenges to organisms, driving the evolution of a myriad of antiviral strategies to combat infections. A wide variety of viruses infect invertebrates, including both natural pathogens that are insect-restricted, and viruses that are transmitted to vertebrates. Studies using the powerful tools in the model organism Drosophila have expanded our understanding of antiviral defenses against diverse viruses. In this review, we will cover three major areas. First, we will describe the tools used to study viruses in Drosophila. Second, we will survey the major viruses that have been studied in Drosophila. And lastly, we will discuss the well-characterized mechanisms that are active against these diverse pathogens, focusing on non-RNAi mediated antiviral mechanisms. Antiviral RNAi is discussed in another paper in this issue. Copyright © 2013 Elsevier Ltd. All rights reserved.

  5. A proanthocyanidin-rich extract from Cassia abbreviata exhibits antioxidant and hepatoprotective activities in vivo.

    Science.gov (United States)

    Sobeh, Mansour; Mahmoud, Mona F; Abdelfattah, Mohamed A O; Cheng, Haroan; El-Shazly, Assem M; Wink, Michael

    2018-03-01

    their diastereomers are the main components of the extract. The total phenolic content amounted for 474mg/g root extract expressed as gallic acid equivalent using the Folin-Ciocalteu method. The extract exhibited powerful antioxidant activity with EC50 of 6.3μg/mL in DPPH and 19.15mM FeSO4 equivalent/mg sample in FRAP assay. In C. elegans model, the extract (200μg/mL) was able to increase the survival rate by 44.56% and reduced the ROS level to 61.73%, compared to control group. Pretreatment of rats with 100mg extract/kg (b. wt.) reduced MDA by 47.36% and elevated GSH by 59.1%. The extract caused a significant reduction of ALT, AST and GGT activities by 11%, 35.7% and 65%, respectively. The findings of this study suggest that the proanthocyanidin-rich extract from C. abbreviata may be an interesting candidate for hepatoprotective activity in case of hepatocellular injury. Copyright © 2017 Elsevier B.V. All rights reserved.

  6. Poly(I:C induces antiviral immune responses in Japanese flounder (Paralichthys olivaceus that require TLR3 and MDA5 and is negatively regulated by Myd88.

    Directory of Open Access Journals (Sweden)

    Zhi-xia Zhou

    Full Text Available Polyinosinic:polycytidylic acid (poly(I:C is a ligand of toll-like receptor (TLR 3 that has been used as an immunostimulant in humans and mice against viral diseases based on its ability to enhance innate and adapt immunity. Antiviral effect of poly(I:C has also been observed in teleost, however, the underling mechanism is not clear. In this study, we investigated the potential and signaling mechanism of poly(I:C as an antiviral agent in a model of Japanese flounder (Paralichthys olivaceus infected with megalocytivirus. We found that poly(I:C exhibited strong antiviral activity and enhanced activation of head kidney macrophages and peripheral blood leukocytes. In vivo studies showed that (i TLR3 as well as MDA5 knockdown reduced poly(I:C-mediated immune response and antiviral activity to significant extents; (ii when Myd88 was overexpressed in flounder, poly(I:C-mediated antiviral activity was significantly decreased; (iii when Myd88 was inactivated, the antiviral effect of poly(I:C was significantly increased. Cellular study showed that (i the NF-κB activity induced by poly(I:C was upregulated in Myd88-overexpressing cells and unaffected in Myd88-inactivated cells; (ii Myd88 overexpression inhibited and upregulated the expression of poly(I:C-induced antiviral genes and inflammatory genes respectively; (iii Myd88 inactivation enhanced the expression of the antiviral genes induced by poly(I:C. Taken together, these results indicate that poly(I:C is an immunostimulant with antiviral potential, and that the immune response of poly(I:C requires TLR3 and MDA5 and is negatively regulated by Myd88 in a manner not involving NK-κB. These results provide insights to the working mechanism of poly(I:C, TLR3, and Myd88 in fish.

  7. Antiviral furanosesquiterpenes from Commiphora erythraea.

    Science.gov (United States)

    Cenci, Elio; Messina, Federica; Rossi, Elisabetta; Epifano, Francesco; Marcotullio, Maria Carla

    2012-02-01

    The crude methanolic extract obtained from C. erythraea resin was chromatographed on silica gel with solvent of increasing polarity. The extract and fractions were evaluated for cytotoxicity and antiviral activity [parainfluenza type 3 virus (PIV3)] by plaque forming units (PFU) reduction assay using HEp-2 cells (human larynx epidermoid carcinoma cell line). From the active fraction, five compounds were isolated and tested. Only two of these showed anti-PIV3 activity with a selectivity index (SI) of 66.6 and 17.5, respectively. Both the compounds are furanosesquiterpenoids.

  8. MHC and non-MHC genes regulate elimination of lymphocytic choriomeningitis virus and antiviral cytotoxic T lymphocyte and delayed-type hypersensitivity mediating T lymphocyte activity in parallel

    DEFF Research Database (Denmark)

    Thomsen, Allan Randrup; Marker, O

    1989-01-01

    The course of systemic infection with lymphocytic choriomeningitis virus was studied in mouse strains differing in the MHC or non-MHC background. Virus clearance rates differed significantly between H-2 identical strains as well as between congenic strains differing in the H-2L subregion, indicat......The course of systemic infection with lymphocytic choriomeningitis virus was studied in mouse strains differing in the MHC or non-MHC background. Virus clearance rates differed significantly between H-2 identical strains as well as between congenic strains differing in the H-2L subregion...... responsiveness measured in terms of virus-specific cytotoxicity and delayed-type hypersensitivity, whereas no correlation was found with regard to NK cell activity and antiviral antibody response. Analysis of F1 progeny between H-2 identical high and low responder strains showed that low responsiveness...

  9. Water extract of Pueraria lobata Ohwi has anti-viral activity against human respiratory syncytial virus in human respiratory tract cell lines

    Directory of Open Access Journals (Sweden)

    Tzeng-Jih Lin

    2013-12-01

    Full Text Available Human respiratory syncytial virus (HRSV infects all age groups and causes bronchiolitis, pneumonia, and acute respiratory distress syndrome with a significant mortality rate. To date, only ribavirin has been used to manage HRSV infection. However, ribavirin is expensive with an only modest effect. Furthermore, ribavirin has several side effects, which means it has limited clinical benefit. Pueraria lobata Ohwi (P. lobata is a common ingredient of Ge-Gen-Tang (Kakkon-to and Sheng-Ma-Ge-Gen-Tang (Shoma-kakkon-to, which are prescriptions of Chinese traditional medicine proven to have antiviral activity against HRSV. Therefore, it was hypothesized that P. lobata might be effective against HRSV. To find a cost-effective therapeutic modality, both human upper (HEp-2 and lower (A549 respiratory tract cell lines were used to test the hypothesis that P. lobata could inhibit HRSV-induced plaque formation. Results showed that the water extract of P. lobata was effective (p < 0.0001 against HRSV-induced plaque formation. P. lobata was more effective when given prior to viral inoculation (p < 0.0001 by inhibiting viral attachment (p < 0.0001 and penetration (p < 0.0001. However, supplementation with P. lobata could not stimulate interferon secretion after HRSV infection. In conclusion, P. lobata has antiviral activity against HRSV-induced plaque formation in airway mucosa mainly by inhibiting viral attachment and internalization. Further identification of effective constituents could contribute to the prevention of HRSV infection.

  10. Letermovir and inhibitors of the terminase complex: a promising new class of investigational antiviral drugs against human cytomegalovirus

    Directory of Open Access Journals (Sweden)

    Melendez DP

    2015-08-01

    Full Text Available Dante P Melendez,1,2 Raymund R Razonable1,2 1Division of Infectious Diseases, 2William J von Liebig Center for Transplantation and Clinical Regeneration, Mayo Clinic, Rochester, MN, USA Abstract: Infection with cytomegalovirus is prevalent in immunosuppressed patients. In solid organ transplant and hematopoietic stem cell transplant recipients, cytomegalovirus infection is associated with high morbidity and preventable mortality. Prevention and treatment of cytomegalovirus with currently approved antiviral drugs is often associated with side effects that sometimes preclude their use. Moreover, cytomegalovirus has developed mutations that confer resistance to standard antiviral drugs. During the last decade, there have been calls to develop novel antiviral drugs that could provide better options for prevention and treatment of cytomegalovirus. Letermovir (AIC246 is a highly specific antiviral drug that is currently undergoing clinical development for the management of cytomegalovirus infection. It acts by inhibiting the viral terminase complex. Letermovir is highly potent in vitro and in vivo against cytomegalovirus. Because of a distinct mechanism of action, it does not exhibit cross-resistance with other antiviral drugs. It is predicted to be active against strains that are resistant to ganciclovir, foscarnet, and cidofovir. To date, early-phase clinical trials suggest a very low incidence of adverse effects. Herein, we present a comprehensive review on letermovir, from its postulated novel mechanism of action to the results of most recent clinical studies. Keywords: cytomegalovirus, letermovir, AIC246, terminase, antivirals, transplantation 

  11. An M2-V27A channel blocker demonstrates potent in vitro and in vivo antiviral activities against amantadine-sensitive and -resistant influenza A viruses.

    Science.gov (United States)

    Hu, Yanmei; Musharrafieh, Rami; Ma, Chunlong; Zhang, Jiantao; Smee, Donald F; DeGrado, William F; Wang, Jun

    2017-04-01

    Adamantanes such as amantadine (1) and rimantadine (2) are FDA-approved anti-influenza drugs that act by inhibiting the wild-type M2 proton channel from influenza A viruses, thereby inhibiting the uncoating of the virus. Although adamantanes have been successfully used for more than four decades, their efficacy was curtailed by emerging drug resistance. Among the limited number of M2 mutants that confer amantadine resistance, the M2-V27A mutant was found to be the predominant mutant under drug selection pressure, thereby representing a high profile antiviral drug target. Guided by molecular dynamics simulations, we previously designed first-in-class M2-V27A inhibitors. One of the potent lead compounds, spiroadamantane amine (3), inhibits both the M2-WT and M2-V27A mutant with IC 50 values of 18.7 and 0.3 μM, respectively, in in vitro electrophysiological assays. Encouraged by these findings, in this study we further examine the in vitro and in vivo antiviral activity of compound 3 in inhibiting both amantadine-sensitive and -resistant influenza A viruses. Compound 3 not only had single to sub-micromolar EC 50 values against M2-WT- and M2-V27A-containing influenza A viruses in antiviral assays, but also rescued mice from lethal viral infection by either M2-WT- or M2-V27A-containing influenza A viruses. In addition, we report the design of two analogs of compound 3, and one was found to have improved in vitro antiviral activity over compound 3. Collectively, this study represents the first report demonstrating the in vivo antiviral efficacy of inhibitors targeting M2 mutants. The results suggest that inhibitors targeting drug-resistant M2 mutants are promising antiviral drug candidates worthy of further development. Copyright © 2017 Elsevier B.V. All rights reserved.

  12. PCBP2 enhances the antiviral activity of IFN-α against HCV by stabilizing the mRNA of STAT1 and STAT2.

    Directory of Open Access Journals (Sweden)

    Zhongshuai Xin

    Full Text Available Interferon-α (IFN-α is a natural choice for the treatment of hepatitis C, but half of the chronically infected individuals do not achieve sustained clearance of hepatitis C virus (HCV during treatment with IFN-α alone. The virus can impair IFN-α signaling and cellular factors that have an effect on the viral life cycles. We found that the protein PCBP2 is down-regulated in HCV-replicon containing cells (R1b. However, the effects and mechanisms of PCBP2 on HCV are unclear. To determine the effect of PCBP2 on HCV, overexpression and knockdown of PCBP2 were performed in R1b cells. Interestingly, we found that PCBP2 can facilitate the antiviral activity of IFN-α against HCV, although the RNA level of HCV was unaffected by either the overexpression or absence of PCBP2 in R1b cells. RIP-qRT-PCR and RNA half-life further revealed that PCBP2 stabilizes the mRNA of STAT1 and STAT2 through binding the 3'Untranslated Region (UTR of these two molecules, which are pivotal for the IFN-α anti-HCV effect. RNA pull-down assay confirmed that there were binding sites located in the C-rich tracts in the 3'UTR of their mRNAs. Stabilization of mRNA by PCBP2 leads to the increased protein expression of STAT1 and STAT2 and a consistent increase of phosphorylated STAT1 and STAT2. These effects, in turn, enhance the antiviral effect of IFN-α. These findings indicate that PCBP2 may play an important role in the IFN-α response against HCV and may benefit the HCV clinical therapy.

  13. The antiviral effect of jiadifenoic acids C against coxsackievirus B3

    Directory of Open Access Journals (Sweden)

    Miao Ge

    2014-08-01

    Full Text Available Coxsackievirus B type 3 (CVB3 is one of the major causative pathogens associated with viral meningitis and myocarditis, which are widespread in the human population and especially prevalent in neonates and children. These infections can result in dilated cardiomyopathy (DCM and other severe clinical complications. There are no vaccines or drugs approved for the prevention or therapy of CVB3-induced diseases. During screening for anti-CVB3 candidates in our previous studies, we found that jiadifenoic acids C exhibited strong antiviral activities against CVB3 as well as other strains of Coxsackie B viruses (CVBs. The present studies were carried out to evaluate the antiviral activities of jiadifenoic acids C. Results showed that jiadifenoic acids C could reduce CVB3 RNA and proteins synthesis in a dose-dependent manner. Jiadifenoic acids C also had a similar antiviral effect on the pleconaril-resistant variant of CVB3. We further examined the impact of jiadifenoic acids C on the synthesis of viral structural and non-structural proteins, finding that jiadifenoic acids C could reduce VP1 and 3D protein production. A time-course study with Vero cells showed that jiadifenoic acids C displayed significant antiviral activities at 0–6 h after CVB3 inoculation, indicating that jiadifenoic acids C functioned at an early step of CVB3 replication. However, jiadifenoic acids C had no prophylactic effect against CVB3. Taken together, we show that jiadifenoic acids C exhibit strong antiviral activities against all strains of CVB, including the pleconaril-resistant variant. Our study could provide a significant lead for anti-CVB3 drug development.

  14. Bioactivity of marine organisms. Part 3. Screening of marine algae of Indian coast for biological activity

    Digital Repository Service at National Institute of Oceanography (India)

    Kamat, S.Y.; Wahidullah, S.; Naik, C.G.; DeSouza, L.; Jayasree, V.; Ambiye, V.; Bhakuni, D.S.; Goel, A.K.; Garg, H.S.; Srimal, R.C.

    were diuretic, 3 hypoglycaemic, 3 hypotensive, 4 exhibited anti- implantation activity, cytokinin activity was observed in one and one showed adrenergic blocking action. The extracts neither , had anti-bacterial, anti-fungal and anti-viral activities...

  15. Infants of Depressed and Nondepressed Mothers Exhibit Differences in Frontal Brain Electrical Activity during the Expression of Negative Emotions.

    Science.gov (United States)

    Dawson, Geraldine; And Others

    1997-01-01

    Examined electrical brain activity during negative and positive emotion expression in infants of depressed and nondepressed mothers. Found that, compared with infants of nondepressed mothers, infants of depressed mothers exhibited increased EEG activation in the frontal but not parietal region when expressing negative emotions. There were no…

  16. A biomimetic approach to the synthesis of an antiviral marine steroidal orthoester.

    Science.gov (United States)

    Giner, José-Luis; Faraldos, Juan A

    2002-04-19

    Orthoesterol B, a marine natural product exhibiting antiviral activities, contains a [3.2.1]-bicyclic orthobutyrate bridging the steroid side chain and ring D. A biosynthetic reaction was proposed by which rearrangement of an epoxy ester results in the formation of the orthoester moiety. Steroidal model compounds incorporating 16-butyroxy and 20,22-epoxy groups were synthesized from tigogenin and were shown to rearrange to orthoesters under mild acidic catalysis.

  17. Targeting the kinase activities of ATR and ATM exhibits antitumoral activity in mouse models of MLL-rearranged AML.

    Science.gov (United States)

    Morgado-Palacin, Isabel; Day, Amanda; Murga, Matilde; Lafarga, Vanesa; Anton, Marta Elena; Tubbs, Anthony; Chen, Hua Tang; Ergan, Aysegul; Anderson, Rhonda; Bhandoola, Avinash; Pike, Kurt G; Barlaam, Bernard; Cadogan, Elaine; Wang, Xi; Pierce, Andrew J; Hubbard, Chad; Armstrong, Scott A; Nussenzweig, André; Fernandez-Capetillo, Oscar

    2016-09-13

    Among the various subtypes of acute myeloid leukemia (AML), those with chromosomal rearrangements of the MLL oncogene (AML-MLL) have a poor prognosis. AML-MLL tumor cells are resistant to current genotoxic therapies because of an attenuated response by p53, a protein that induces cell cycle arrest and apoptosis in response to DNA damage. In addition to chemicals that damage DNA, efforts have focused on targeting DNA repair enzymes as a general chemotherapeutic approach to cancer treatment. Here, we found that inhibition of the kinase ATR, which is the primary sensor of DNA replication stress, induced chromosomal breakage and death of mouse AML(MLL) cells (with an MLL-ENL fusion and a constitutively active N-RAS independently of p53. Moreover, ATR inhibition as a single agent exhibited antitumoral activity, both reducing tumor burden after establishment and preventing tumors from growing, in an immunocompetent allograft mouse model of AML(MLL) and in xenografts of a human AML-MLL cell line. We also found that inhibition of ATM, a kinase that senses DNA double-strand breaks, also promoted the survival of the AML(MLL) mice. Collectively, these data indicated that ATR or ATM inhibition represent potential therapeutic strategies for the treatment of AML, especially MLL-driven leukemias. Copyright © 2016, American Association for the Advancement of Science.

  18. Immersive Exhibitions

    DEFF Research Database (Denmark)

    Achiam, Marianne

    2015-01-01

    The immersive exhibition is a specialized exhibition genre in museums, which creates the illusion of time and place by representing key characteristics of a reference world and by integrating the visitor in this three-dimensionally reconstructed world (Mortensen 2010). A successful representation...... of the reference world depends on three criteria: whether the exhibition is staged as a coherent whole with all the displayed objects supporting the representation, whether the visitor is integrated as a component of the exhibition, and whether the content and message of the exhibition become dramatized...... as a result of the visitor’s interaction with the exhibit....

  19. Antimicrobial Peptides Containing Unnatural Amino Acid Exhibit Potent Bactericidal Activity against ESKAPE Pathogens

    Science.gov (United States)

    2013-01-01

    Laboratory Standards broth microdilution method. MIC is defined as the lowest concentration of the test antimicrobial that would inhibit the growth of the...idues exhibit negative hydrophobicity and by shortening the side chain the protonated nitrogen is moved closer to the peptide back- bone . This...it appears that back- bone flexibility after the hydrophobic or charged residue and the following Tic residue is more important in the interactions

  20. Human Exhibitions

    DEFF Research Database (Denmark)

    Andreassen, Rikke

    From 1870s to 1910s, more than 50 exhibitions of so-called exotic people took place in Denmark. Here large numbers of people of Asian and African origin were exhibited for the entertainment and ‘education’ of a mass audience. Several of these exhibitions took place in Copenhagen Zoo. Here differe...

  1. Antiviral Drugs: Seasonal Flu

    Centers for Disease Control (CDC) Podcasts

    2010-09-29

    In this podcast, Dr. Joe Bresee explains the nature of antiviral drugs and how they are used for seasonal flu.  Created: 9/29/2010 by National Center for Immunization and Respiratory Diseases (NCIRD).   Date Released: 9/29/2010.

  2. The FAI protein of group C streptococci targets B-cells and exhibits adjuvant activity.

    Science.gov (United States)

    Schulze, Kai; Goldmann, Oliver; Toppel, Antonia; Medina, Eva; Guzmán, Carlos A

    2005-02-03

    We have demonstrated that the fibrinogen-albumin-IgG receptor of group C streptococci (FAI) targets B-cells in vivo. We exploited the targeting properties of FAI to improve the immune responses stimulated by soluble antigens administered by the mucosal route. Enhanced systemic and mucosal immune responses were observed in mice after intranasal immunization when ovalbumin was fused to FAI or truncated derivatives. The FAI fragment encompassing the IgG- and fibrinogen-binding regions was the minimal domain exhibiting optimal carrier/adjuvant properties. The obtained results suggest that the FAI protein represents a useful tool to improve the immunogenicity of vaccine antigens.

  3. Induction and suppression of the innate antiviral responses by picornaviruses

    NARCIS (Netherlands)

    Feng, Q.|info:eu-repo/dai/nl/372641172

    2014-01-01

    On the front line of innate antiviral immune reactions is the type I interferon (IFN-α/β) system. IFN-α/β are small signaling molecules that can be produced by virtually all nucleated cells in our body upon virus infections, and induce a so-called “antiviral state” in neighboring cells by activating

  4. Cationic peptides from peptic hydrolysates of rice endosperm protein exhibit antimicrobial, LPS-neutralizing, and angiogenic activities.

    Science.gov (United States)

    Taniguchi, Masayuki; Kawabe, Junya; Toyoda, Ryu; Namae, Toshiki; Ochiai, Akihito; Saitoh, Eiichi; Tanaka, Takaaki

    2017-11-01

    In this study, we hydrolyzed rice endosperm protein (REP) with pepsin and generated 20 fractions containing multifunctional cationic peptides with varying isoelectric point (pI) values using ampholyte-free isoelectric focusing (autofocusing). Subsequently, we determined antimicrobial activities of each fraction against the pathogens Prophyromonas gingivalis, Propionibacterium acnes, Streptocossus mutans, and Candida albicans. Fractions 18, 19, and 20 had pI values greater than 12 and exhibited antimicrobial activity against P. gingivalis, P. acnes, and C. albicans, but not against S. mutans. In further experiments, we purified and identified cationic peptides from fractions 18, 19, and 20 using reversed-phase high-performance liquid chromatography and matrix-assisted laser/desorption ionization-time-of-flight mass spectroscopy. We also chemically synthesized five identified peptides (RSVSKSR, RRVIEPR, ERFQPMFRRPG, RVRQNIDNPNRADTYNPRAG, and VVRRVIEPRGLL) with pI values greater than 10.5 and evaluated antimicrobial, lipopolysaccharide (LPS)-neutralizing, and angiogenic activities. Among these synthetic peptides, only VVRRVIEPRGLL exhibited antimicrobial activity against P. gingivalis, with an IC 50 value of 87μM. However, all five cationic peptides exhibited LPS-neutralizing and angiogenic activities with little or no hemolytic activity against mammalian red blood cells at functional concentrations. These present data show dual or multiple functions of the five identified cationic peptides with little or no hemolytic activity. Therefore, fractions containing cationic peptides from REP hydrolysates have the potential to be used as dietary supplements and functional ingredients in food products. Copyright © 2017 Elsevier Inc. All rights reserved.

  5. Fungi from koala (Phascolarctos cinereus) faeces exhibit a broad range of enzyme activities against recalcitrant substrates.

    Science.gov (United States)

    Peterson, R A; Bradner, J R; Roberts, T H; Nevalainen, K M H

    2009-02-01

    Identification of fungi isolated from koala faeces and screening for their enzyme activities of biotechnological interest. Thirty-seven fungal strains were isolated from koala faeces and identified by the amplification and direct sequencing of the internal transcribed spacer (ITS) region of the ribosomal DNA. The fungi were screened for selected enzyme activities using agar plates containing a single substrate for each target class of enzyme. For xylanase, endoglucanase, ligninase (ligninolytic phenoloxidase) and protease over two-thirds of the isolates produced a clearing halo at 25 degrees C, indicating the secretion of active enzyme by the fungus, and one-third produced a halo indicating amylase, mannanase and tannase activity. Some isolates were also able to degrade crystalline cellulose and others displayed lipase activity. Many of the fungal isolates also produced active enzymes at 15 degrees C and some at 39 degrees C. Koala faeces, consisting of highly lignified fibre, undigested cellulose and phenolics, are a novel source of fungi with high and diverse enzyme activities capable of breaking down recalcitrant substrates. To our knowledge, this is the first time fungi from koala faeces have been identified using ITS sequencing and screened for their enzyme activities.

  6. Malignant T cells exhibit CD45 resistant Stat3 activation and proliferation in cutaneous

    DEFF Research Database (Denmark)

    Krejsgaard, Thorbjørn Frej; Helvad, Rikke; Ralfkiaer, Elisabeth

    2010-01-01

    -linking does not suppress the constitutive activation of Stat3 in the malignant T cells and there is no correlation between the level of activated Stat3 and the level of CD45 expression on the malignant T cells. Furthermore, in contrast to non-malignant T cells, the malignant T cells are protected against CD45...

  7. A novel video tracking method to evaluate the effect of influenza infection and antiviral treatment on ferret activity.

    Science.gov (United States)

    Oh, Ding Yuan; Barr, Ian G; Hurt, Aeron C

    2015-01-01

    Ferrets are the preferred animal model to assess influenza virus infection, virulence and transmission as they display similar clinical symptoms and pathogenesis to those of humans. Measures of disease severity in the ferret include weight loss, temperature rise, sneezing, viral shedding and reduced activity. To date, the only available method for activity measurement has been the assignment of an arbitrary score by a 'blind' observer based on pre-defined responsiveness scale. This manual scoring method is subjective and can be prone to bias. In this study, we described a novel video-tracking methodology for determining activity changes in a ferret model of influenza infection. This method eliminates the various limitations of manual scoring, which include the need for a sole 'blind' observer and the requirement to recognise the 'normal' activity of ferrets in order to assign relative activity scores. In ferrets infected with an A(H1N1)pdm09 virus, video-tracking was more sensitive than manual scoring in detecting ferret activity changes. Using this video-tracking method, oseltamivir treatment was found to ameliorate the effect of influenza infection on activity in ferret. Oseltamivir treatment of animals was associated with an improvement in clinical symptoms, including reduced inflammatory responses in the upper respiratory tract, lower body weight loss and a smaller rise in body temperature, despite there being no significant reduction in viral shedding. In summary, this novel video-tracking is an easy-to-use, objective and sensitive methodology for measuring ferret activity.

  8. Resistance of human leukocytes to vesicular stomatitis virus infection as one of the innate antiviral immune activities; participation of cell subpopulations.

    Directory of Open Access Journals (Sweden)

    Danuta Duś

    2008-02-01

    Full Text Available Among reactions of innate immunity, resistance of human peripheral blood leukocytes (PBL to viral infection seems important. The purpose of our study was to find, which of the subpopulations of PBL is the most responsible for the innate antiviral immunity of these cells. The innate immunity was measured by using the direct method of infection of leukocytes with vesicular stomatitis virus (VSV. The lack of VSV replication by infected leukocytes (0-1 log TCID50 was taken as an indicator for complete immunity; a low level of VSV (2-3 log for partial immunity; and high VSV titer (more than 4 log for no immunity. The resistance/innate immunity of whole PBL and subpopulations such as: adherent cells, fractions enriched in lymphocytes T, and lymphocytes B (separated on column with nylon wool, NK(+ and NK(- (separated by microbeads activated cell sorting MACS differ from each other. All fractions express higher resistance/innate immunity than the whole PBL. NK(+ cells were found the most resistant fraction of PBL to VSV infection. The results indicate that among the leukocytes in PBL the regulation mechanisms of innate immunity exist. The study on the mechanism of innate immunity regulation as well as the role of NK in innate immunity of PBL must be continued.

  9. Synthesis and antiviral activity evaluation of novel 2-phenyl-4-(D-arabino-4'-cycloaminobutyl)triazoles: acyclonucleosides containing unnatural bases.

    Science.gov (United States)

    Himanshu; Tyagi, Rahul; Olsen, Carl E; Errington, William; Parmar, Virinder S; Prasad, Ashok K

    2002-04-01

    Five 2-phenyl-4-(D-arabino-4'-cycloamino-3'-hydroxy-O-1',2'-isopropylidene-butyl)-2H-1,2,3-triazoles, acyclonucleosides containing unnatural bases have been synthesised by opening of the epoxide ring of 2-phenyl-4-(D-arabino-3',4'-epoxy-O-1',2'-isopropylidenebutyl)-2H-1,2,3-triazole with the corresponding cyclic amines in 70-85% yields. The starting arabino-epoxytriazole was prepared in five steps starting from D-glucose in an overall yield of 15%. All the five triazolylacyclonucleosides were unambiguously identified on the basis of their spectral data. The structure of one of the intermediates, that is 2-phenyl-4-(D-arabino-1',2',3',4'-tetrahydroxybutyl)-2H-1,2,3-triazole was confirmed by its X-ray crystallographic studies. These acyclonucleosides were subjected to antiviral activity evaluation in CEM-SS cell-based anti HIV assay with the lymphocytropic virus strains HIV-1(IIIB) and HIV-1(RF).

  10. Crystal and molecular structure of novel binuclear ten coordinated praseodymium(III with octadentateethylenediaminetetraacetate – Synthesis, characterization and antioxidant, antiviral and anticancer activities

    Directory of Open Access Journals (Sweden)

    R. Pradeep

    2017-03-01

    Full Text Available A novel ten coordinated binuclear hydrated praseodymium(III ethylenediaminetetraacetate with phenyl hydrazine has been synthesized and characterized by analytical, spectral and thermal techniques. The structure of the compound determined by X-ray crystallography reveals the binuclear nature of the complex with ten coordination around Pr(III ions. Neutral phenyl hydrazine molecules present outside the coordination sphere and four inner sphere water molecules found to occupy the coordination sites (each Pr(III ions possessing two coordinated water molecules. Among five more water molecules, four are involved in hydrogen bonding with phenyl hydrazine and EDTA4− and hence present in the second sphere. The remaining water molecule is present as bulk water. Interestingly, in the present case EDTA4− ions act as heptadentate ligand with one acetate group from each EDTA4− ion showing novel tridentate bridging behavior. The biological studies such as antioxidantal, antiviral and cytotoxicity studies reveal that this complex indeed shows promising activity.

  11. Exhibit Engineering

    DEFF Research Database (Denmark)

    Mortensen, Marianne Foss

    ) a synthesis of the findings from the first two studies with findings from the literature to generate two types of results: a coherent series of suggestions for a design iteration of the studied exhibit as well as a more general normative model for exhibit engineering. Finally, another perspective...

  12. Litopenaeus vannamei hemocyanin exhibits antitumor activity in S180 mouse model in vivo.

    Directory of Open Access Journals (Sweden)

    Shangjie Liu

    Full Text Available Hemocyanin is a multifunctional glycoprotein, which also plays multiple roles in immune defense. While it has been demonstrated that hemocyanin from some mollusks can induce potent immune response and is therefore undergoing clinical trials to be used in anti-tumor immunotherapy, little is currently known about how hemocyanin from arthropods affect tumors. In this study we investigated the anti-tumor activity of hemocyanin from Litopenaeus vannamei on Sarcoma-180 (S180 tumor-bearing mice model. Eight days treatment with 4mg/kg bodyweight of hemocyanin significantly inhibited the growth of S180 up to 49% as compared to untreated. Similarly, histopathology analysis showed a significant decrease in tumor cell number and density in the tissues of treated mice. Moreover, there was a significant increase in immune organs index, lymphocyte proliferation, NK cell cytotoxic activity and serum TNF-α level, suggesting that hemocyanin could improve the immunity of the S180 tumor-bearing mice. Additionally, there was a significant increase in superoxide dismutase (SOD activity and a decrease in the level of malondialdehyde (MDA in serum and liver, which further suggest that hemocyanin improved the anti-oxidant ability of the S180 tumor-bearing mice. Collectively, our data demonstrated that L. vannamei hemocyanin had a significant antitumor activity in mice.

  13. Litopenaeus vannamei hemocyanin exhibits antitumor activity in S180 mouse model in vivo

    Science.gov (United States)

    Aweya, Jude Juventus; Zheng, Zhou; Zhong, Mingqi; Chen, Jiehui; Wang, Fan

    2017-01-01

    Hemocyanin is a multifunctional glycoprotein, which also plays multiple roles in immune defense. While it has been demonstrated that hemocyanin from some mollusks can induce potent immune response and is therefore undergoing clinical trials to be used in anti-tumor immunotherapy, little is currently known about how hemocyanin from arthropods affect tumors. In this study we investigated the anti-tumor activity of hemocyanin from Litopenaeus vannamei on Sarcoma-180 (S180) tumor-bearing mice model. Eight days treatment with 4mg/kg bodyweight of hemocyanin significantly inhibited the growth of S180 up to 49% as compared to untreated. Similarly, histopathology analysis showed a significant decrease in tumor cell number and density in the tissues of treated mice. Moreover, there was a significant increase in immune organs index, lymphocyte proliferation, NK cell cytotoxic activity and serum TNF-α level, suggesting that hemocyanin could improve the immunity of the S180 tumor-bearing mice. Additionally, there was a significant increase in superoxide dismutase (SOD) activity and a decrease in the level of malondialdehyde (MDA) in serum and liver, which further suggest that hemocyanin improved the anti-oxidant ability of the S180 tumor-bearing mice. Collectively, our data demonstrated that L. vannamei hemocyanin had a significant antitumor activity in mice. PMID:28854214

  14. CotA, a multicopper oxidase from Bacillus pumilus WH4, exhibits manganese-oxidase activity.

    Directory of Open Access Journals (Sweden)

    Jianmei Su

    Full Text Available Multicopper oxidases (MCOs are a family of enzymes that use copper ions as cofactors to oxidize various substrates. Previous research has demonstrated that several MCOs such as MnxG, MofA and MoxA can act as putative Mn(II oxidases. Meanwhile, the endospore coat protein CotA from Bacillus species has been confirmed as a typical MCO. To study the relationship between CotA and the Mn(II oxidation, the cotA gene from a highly active Mn(II-oxidizing strain Bacillus pumilus WH4 was cloned and overexpressed in Escherichia coli strain M15. The purified CotA contained approximately four copper atoms per molecule and showed spectroscopic properties typical of blue copper oxidases. Importantly, apart from the laccase activities, the CotA also displayed substantial Mn(II-oxidase activities both in liquid culture system and native polyacrylamide gel electrophoresis. The optimum Mn(II oxidase activity was obtained at 53°C in HEPES buffer (pH 8.0 supplemented with 0.8 mM CuCl2. Besides, the addition of o-phenanthroline and EDTA both led to a complete suppression of Mn(II-oxidizing activity. The specific activity of purified CotA towards Mn(II was 0.27 U/mg. The Km, Vmax and kcat values towards Mn(II were 14.85±1.17 mM, 3.01×10(-6±0.21 M·min(-1 and 0.32±0.02 s(-1, respectively. Moreover, the Mn(II-oxidizing activity of the recombinant E. coli strain M15-pQE-cotA was significantly increased when cultured both in Mn-containing K liquid medium and on agar plates. After 7-day liquid cultivation, M15-pQE-cotA resulted in 18.2% removal of Mn(II from the medium. Furthermore, the biogenic Mn oxides were clearly observed on the cell surfaces of M15-pQE-cotA by scanning electron microscopy. To our knowledge, this is the first report that provides the direct observation of Mn(II oxidation with the heterologously expressed protein CotA, Therefore, this novel finding not only establishes the foundation for in-depth study of Mn(II oxidation mechanisms, but also offers

  15. Compounds from Sorindeia juglandifolia (Anacardiaceae exhibit potent anti-plasmodial activities in vitro and in vivo

    Directory of Open Access Journals (Sweden)

    Kamkumo Raceline G

    2012-11-01

    Full Text Available Abstract Background Discovering new lead compounds against malaria parasites is a crucial step to ensuring a sustainable global pipeline for effective anti-malarial drugs. As far as we know, no previous phytochemical or pharmacological investigations have been carried out on Sorindeia juglandifolia. This paper describes the results of an anti-malarial activity-driven investigation of the fruits of this Cameroonian plant. Methods Air-dried fruits were extracted by maceration using methanol. The extract was fractionated by flash chromatography followed by column chromatography over silica gel, eluting with gradients of hexane-ethyl acetate mixtures. Resulting fractions and compounds were tested in vitro against the Plasmodium falciparum chloroquine-resistant strain W2, against field isolates of P. falciparum, and against the P. falciparum recombinant cysteine protease falcipain-2. Promising fractions were assessed for acute toxicity after oral administration in mice. One of the promising isolated compounds was assessed in vivo against the rodent malaria parasite Plasmodium berghei. Results The main end-products of the activity-guided fractionation were 2,3,6-trihydroxy benzoic acid (1 and 2,3,6-trihydroxy methyl benzoate (2. Overall, nine fractions tested against P. falciparum W2 and falcipain-2 were active, with IC50 values of 2.3-11.6 μg/ml for W2, and 1.1-21.9 μg/ml for falcipain-2. Purified compounds (1 and (2 also showed inhibitory effects against P. falciparum W2 (IC50s 16.5 μM and 13.0 μM and falcipain-2 (IC50s 35.4 and 6.1 μM. In studies of P. falciparum isolates from Cameroon, the plant fractions demonstrated IC50 values of 0.14-19.4 μg/ml and compounds (1 and (2 values of 6.3 and 36.1 μM. In vivo assessment of compound (1 showed activity against P. berghei strain B, with mean parasitaemia suppressive dose and curative dose of 44.9 mg/kg and 42.2 mg/kg, respectively. Active fractions were found to be safe in mice after oral

  16. Secondary hyperalgesia phenotypes exhibit differences in brain activation during noxious stimulation

    DEFF Research Database (Denmark)

    Asghar, Mohammad Sohail; Pereira, Manuel Pedro; Werner, Mads Utke

    2015-01-01

    . To study differences in the propensity to develop central sensitization we examined differences in brain activity and anatomy according to individual phenotypical expression of secondary hyperalgesia by magnetic resonance imaging. Forty healthy volunteers received a first-degree burn-injury (47 °C, 7 min...... to central neuronal sensitization. Some individuals develop large areas of secondary hyperalgesia (high-sensitization responders), while others develop small areas (low-sensitization responders). The magnitude of each area is reproducible within individuals, and can be regarded as a phenotypic characteristic...... hyperalgesia areas after burn-injury. In addition, T1-weighted images were used to measure differences in gray-matter density in cortical and subcortical regions of the brain. We found significant differences in neuronal activity between high- and low-sensitization responders at baseline (before application...

  17. Platinum Dendritic-Flowers Prepared by Tellurium Nanowires Exhibit High Electrocatalytic Activity for Glycerol Oxidation.

    Science.gov (United States)

    Zuo, Yunpeng; Wu, Long; Cai, Kai; Li, Tingting; Yin, Wenmin; Li, Dian; Li, Na; Liu, Jiawei; Han, Heyou

    2015-08-19

    Dentritic Pt-based nanomaterials with enriched edge and corner atoms have recently attracted considerable attention as electrocatalysts. Meanwhile, Pt(111) facets are generally considered more active for the glycerol oxidation reaction (GOR). Thus, it is significant to construct the rational design and synthesis of dentritic Pt whose surface is mostly enclosed by {111} facets. Reported herein is a unique Pt-branched structure enriched by a large amount of valency unsaturated atoms prepared by the aggravation of the galvanic replacement strategy. The synthesis is developed to generate highly crystallized Pt nanoflowers using Te nanowires as a template. Furthermore, the electrochemical results show that Pt nanoflower is an excellent catalyst with higher mass activity and better structure stability than commercial Pt/C (20% Pt) for glycerol electro-oxidation. Besides, the template-broken approach could provide a novel potential way to synthesize Pt-based or other noble metals/alloys for their advanced functional applications.

  18. Tea tree oil exhibits antifungal activity against Botrytis cinerea by affecting mitochondria.

    Science.gov (United States)

    Li, Yonghua; Shao, Xingfeng; Xu, Jiayu; Wei, Yingying; Xu, Feng; Wang, Hongfei

    2017-11-01

    In order to investigate the effects of tea tree oil (TTO) on mitochondrial morphology and function in Botrytis cinerea, mycelia were treated with TTO at different concentrations. TTO at 2ml/l severely damaged mitochondria, resulting in matrix loss and increased mitochondrial irregularity. Mitochondrial membrane permeability was increased by TTO, as evidenced by a decrease in intracellular adenosine triphosphate (ATP) content and an increase in extracellular ATP content. Increasing concentrations of TTO decreased the activities of enzymes related to mitochondrial function and the tricarboxylic acid (TCA) cycle, affecting malic dehydrogenase, succinate dehydrogenase, ATPase, citrate synthetase, isocitrate dehydrogenase and α-ketoglutarate dehydrogenase, while sharply increasing the level of reactive oxygen species (ROS). These results suggest that mitochondrial damage, resulting in the disruption of the TCA cycle and accumulation of ROS, is involved in the mechanism of TTO antifungal activity against B. cinerea. Copyright © 2017 Elsevier Ltd. All rights reserved.

  19. IFN-gamma: Novel antiviral cytokines

    DEFF Research Database (Denmark)

    Ank, Nina; West, Hans; Paludan, Søren Riis

    2006-01-01

    and adaptive immune responses. Recently, a novel class of cytokines was discovered and named IFN-lambda (alternatively type III IFN or interleukin-28/29 [IL- 28/29]), based on IFN-like antiviral activity and induction of typical IFN-inducible genes. Here, we review the literature on IFN-lambda and discuss...

  20. Hawthorn (Crataegus monogyna Jacq.) extract exhibits atropine-sensitive activity in a cultured cardiomyocyte assay.

    Science.gov (United States)

    Salehi, Satin; Long, Shannon R; Proteau, Philip J; Filtz, Theresa M

    2009-01-01

    Hawthorn (Crataegus spp.) plant extract is used as a herbal alternative medicine for the prevention and treatment of various cardiovascular diseases. Recently, it was shown that hawthorn extract preparations caused negative chronotropic effects in a cultured neonatal murine cardiomyocyte assay, independent of beta-adrenergic receptor blockade. The aim of this study was to further characterize the effect of hawthorn extract to decrease the contraction rate of cultured cardiomyocytes. To test the hypothesis that hawthorn is acting via muscarinic receptors, the effect of hawthorn extract on atrial versus ventricular cardiomyocytes in culture was evaluated. As would be expected for activation of muscarinic receptors, hawthorn extract had a greater effect in atrial cells. Atrial and/or ventricular cardiomyocytes were then treated with hawthorn extract in the presence of atropine or himbacine. Changes in the contraction rate of cultured cardiomyocytes revealed that both muscarinic antagonists significantly attenuated the negative chronotropic activity of hawthorn extract. Using quinuclidinyl benzilate, L-[benzylic-4,4'-(3)H] ([(3)H]-QNB) as a radioligand antagonist, the effect of a partially purified hawthorn extract fraction to inhibit muscarinic receptor binding was quantified. Hawthorn extract fraction 3 dose-dependently inhibited [(3)H]-QNB binding to mouse heart membranes. Taken together, these findings suggest that decreased contraction frequency by hawthorn extracts in neonatal murine cardiomyocytes may be mediated via muscarinic receptor activation.

  1. A novel bacteriocin from Enterococcus faecalis 478 exhibits a potent activity against vancomycin-resistant enterococci.

    Science.gov (United States)

    Phumisantiphong, Uraporn; Siripanichgon, Kanokrat; Reamtong, Onrapak; Diraphat, Pornphan

    2017-01-01

    The emergence of multidrug-resistant enterococci (MDRE) and particularly vancomycin-resistant enterococci (VRE) is considered a serious health problem worldwide, causing the need for new antimicrobials. The aim of this study was to discover and characterize bacteriocin against clinical isolates of MDRE and VRE. Over 10,000 bacterial isolates from water, environment and clinical samples were screened. E. faecalis strain 478 isolated from human feces produced the highest antibacterial activity against several MDRE and VRE strains. The optimum condition for bacteriocin production was cultivation in MRS broth at 37°C, pH 5-6 for 16 hours. The bacteriocin-like substance produced from E. faecalis strain EF478 was stable at 60°C for at least 1 hour and retained its antimicrobial activity after storage at -20°C for 1 year, at 4°C for 6 months, and at 25°C for 2 months. A nano-HPLC electrospray ionization multi-stage tandem mass spectrometry (nLC-ESI-MS/MS) analysis showed that the amino acid sequences of the bacteriocin-like substance was similar to serine protease of E. faecalis, gi|488296663 (NCBI database), which has never been reported as a bacteriocin. This study reported a novel bacteriocin with high antibacterial activity against VRE and MDRE.

  2. Nanoparticles of cationic chimeric peptide and sodium polyacrylate exhibit striking antinociception activity at lower dose.

    Science.gov (United States)

    Gupta, Kshitij; Singh, Vijay P; Kurupati, Raj K; Mann, Anita; Ganguli, Munia; Gupta, Yogendra K; Singh, Yogendra; Saleem, Kishwar; Pasha, Santosh; Maiti, Souvik

    2009-02-20

    The current study investigates the performance of polyelectrolyte complexes based nanoparticles in improving the antinociceptive activity of cationic chimeric peptide-YFa at lower dose. Size, Zeta potential and morphology of the nanoparticles were determined. Size of the nanoparticles decreases and zeta potential increases with concomitant increase in charge ratio (Z(+/-)). The nanoparticles at Z(+/-)12 are spherical with 70+/-7 nm diameter in AFM and displayed positive surface charge and similar sizes (83+/-8 nm) by Zetasizer. The nanoparticles of Z(+/-) 12 are used in this study. Cytotoxicity by MTT assay on three different mammalian cell lines (liver, neuronal and kidney) revealed lower toxicity of nanoparticles. Hematological parameters were also not affected by nanoparticles compared to normal counts of water treated control group. Nanoparticles containing 10 mg/kg YFa produced increased antinociception, approximately 36%, in tail-flick latency test in mice, whereas the neat peptide at the same concentration did not show any antinociception activity. This enhancement in activity is attributed to the nanoparticle associated protection of peptide from proteolytic degradation. In vitro peptide release study in plasma also supported the antinociception profile of nanoparticles. Thus, our results suggest of a potential nanoparticle delivery system for cationic peptide drug candidates for improving their stability and bioavailability.

  3. A novel bacteriocin from Enterococcus faecalis 478 exhibits a potent activity against vancomycin-resistant enterococci.

    Directory of Open Access Journals (Sweden)

    Uraporn Phumisantiphong

    Full Text Available The emergence of multidrug-resistant enterococci (MDRE and particularly vancomycin-resistant enterococci (VRE is considered a serious health problem worldwide, causing the need for new antimicrobials. The aim of this study was to discover and characterize bacteriocin against clinical isolates of MDRE and VRE. Over 10,000 bacterial isolates from water, environment and clinical samples were screened. E. faecalis strain 478 isolated from human feces produced the highest antibacterial activity against several MDRE and VRE strains. The optimum condition for bacteriocin production was cultivation in MRS broth at 37°C, pH 5-6 for 16 hours. The bacteriocin-like substance produced from E. faecalis strain EF478 was stable at 60°C for at least 1 hour and retained its antimicrobial activity after storage at -20°C for 1 year, at 4°C for 6 months, and at 25°C for 2 months. A nano-HPLC electrospray ionization multi-stage tandem mass spectrometry (nLC-ESI-MS/MS analysis showed that the amino acid sequences of the bacteriocin-like substance was similar to serine protease of E. faecalis, gi|488296663 (NCBI database, which has never been reported as a bacteriocin. This study reported a novel bacteriocin with high antibacterial activity against VRE and MDRE.

  4. Pardaxin, a Fish Antimicrobial Peptide, Exhibits Antitumor Activity toward Murine Fibrosarcoma in Vitro and in Vivo

    Science.gov (United States)

    Wu, Shu-Ping; Huang, Tsui-Chin; Lin, Ching-Chun; Hui, Cho-Fat; Lin, Cheng-Hui; Chen, Jyh-Yih

    2012-01-01

    The antitumor activity of pardaxin, a fish antimicrobial peptide, has not been previously examined in in vitro and in vivo systems for treating murine fibrosarcoma. In this study, the antitumor activity of synthetic pardaxin was tested using murine MN-11 tumor cells as the study model. We show that pardaxin inhibits the proliferation of MN-11 cells and reduces colony formation in a soft agar assay. Transmission electron microscopy (TEM) showed that pardaxin altered the membrane structure similar to what a lytic peptide does, and also produced apoptotic features, such as hollow mitochondria, nuclear condensation, and disrupted cell membranes. A qRT-PCR and ELISA showed that pardaxin induced apoptosis, activated caspase-7 and interleukin (IL)-7r, and downregulated caspase-9, ATF 3, SOCS3, STAT3, cathelicidin, p65, and interferon (IFN)-γ suggesting that pardaxin induces apoptosis through the death receptor/nuclear factor (NF)-κB signaling pathway after 14 days of treatment in tumor-bearing mice. An antitumor effect was observed when pardaxin (25 mg/kg; 0.5 mg/day) was used to treat mice for 14 days, which caused significant inhibition of MN-11 cell growth in mice. Overall, these results indicate that pardaxin has the potential to be a novel therapeutic agent to treat fibrosarcomas. PMID:23015777

  5. Functional differences between antiviral activities of sulfonated and intact intravenous immunoglobulin preparations toward varicella-zoster virus and cytomegalovirus.

    Science.gov (United States)

    Yajima, Misako; Shiraki, Atsuko; Daikoku, Tohru; Oyama, Yukari; Yoshida, Yoshihiro; Shiraki, Kimiyasu

    2015-06-01

    Intravenous immunoglobulin (IVIG) is used to treat severe viral infection, especially varicella-zoster virus (VZV) and cytomegalovirus (CMV) infections. The neutralization antibody titers of eleven IVIG preparations from four companies were examined using VZV and CMV with and without complement. The neutralizing antibody titers of intact IgG preparations were three to six times higher after addition of complement. The effectiveness of the sulfonated IgG preparation was not enhanced by complement, but desulfonated IgG regained enhanced neutralization activity with complement. Antibody-dependent cellular cytotoxicity (ADCC) toward VZV-infected cells was observed with both intact and sulfonated IVIG and guinea pig splenocytes, but ADCC toward CMV-infected cells was not, although NK cell activity toward cells infected with VZV or CMV was detected by splenocytes. Sulfonated IVIG had no complement-activated neutralization of VZV and CMV but retained ADCC toward VZV with less activity after dilution than with intact IVIG. Because sulfonated IVIG is converted to the intact form after intravenous administration, it would show complement-enhanced neutralization and ADCC activity similar to that of intact IVIG in vivo. In this study we showed the effects of intact and sulfonated IgG on the functional activity of IgG against VZV and CMV. Copyright © 2015 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

  6. The Antiviral Mechanism of an Influenza A Virus Nucleoprotein-Specific Single-Domain Antibody Fragment

    Directory of Open Access Journals (Sweden)

    Leo Hanke

    2016-12-01

    Full Text Available Alpaca-derived single-domain antibody fragments (VHHs that target the influenza A virus nucleoprotein (NP can protect cells from infection when expressed in the cytosol. We found that one such VHH, αNP-VHH1, exhibits antiviral activity similar to that of Mx proteins by blocking nuclear import of incoming viral ribonucleoproteins (vRNPs and viral transcription and replication in the nucleus. We determined a 3.2-Å crystal structure of αNP-VHH1 in complex with influenza A virus NP. The VHH binds to a nonconserved region on the body domain of NP, which has been associated with binding to host factors and serves as a determinant of host range. Several of the NP/VHH interface residues determine sensitivity of NP to antiviral Mx GTPases. The structure of the NP/αNP-VHH1 complex affords a plausible explanation for the inhibitory properties of the VHH and suggests a rationale for the antiviral properties of Mx proteins. Such knowledge can be leveraged for much-needed novel antiviral strategies.

  7. One-dimensional poly(L-lysine)-block-poly(L-threonine) assemblies exhibit potent anticancer activity by enhancing membranolysis.

    Science.gov (United States)

    Chen, Yu-Fon; Shiau, Ai-Li; Chang, Sue-Joan; Fan, Nai-Shin; Wang, Chung-Teng; Wu, Chao-Liang; Jan, Jeng-Shiung

    2017-06-01

    Herein, we report the oncolytic activity of cationic, one-dimensional (1D) fibril assemblies formed from coil-sheet poly(L-lysine)-block-poly(L-threonine) (PLL-b-PLT) block copolypeptides for cancer therapy. The 1D fibril assemblies can efficiently interact with negatively charged cellular and mitochondrial membranes via electrostatic interactions, leading to necrosis via membrane lysis and apoptosis via the mitochondria-lytic effect. The concept is analogous to that of 1D drug carriers that exhibit enhanced cell penetration. In comparison to free PLL chains, PLL-b-PLT fibril assemblies exhibit selective cytotoxicity toward cancer cells, low hemolysis activity, enhanced membranolytic activity, and a different apoptosis pathway, which may be due to differences in the peptide-membrane interactions. Antitumor studies using a metastatic LL2 lung carcinoma model indicate that the fibril assemblies significantly inhibited tumor growth, improved survival in tumor-bearing mice and suppressed lung metastasis without obvious body weight loss. An additive efficacy was also observed for treatment with both PLL-b-PLT and cisplatin. These results support the feasibility of using 1D fibril assemblies as potential apoptotic anticancer therapeutics. We report that cationic, one-dimensional (1D) fibril assemblies formed by coil-sheet poly(L-lysine)-block-poly(L-threonine) (PLL-b-PLT) block copolypeptides exhibited potent anticancer activity by enhancing membranolysis. The 1D fibril assemblies can efficiently interact with negatively charged cellular and mitochondrial membranes via electrostatic interactions, leading to necrosis via membrane lysis and apoptosis via mitochondria-lytic effect. Moreover, the fibril assemblies exhibited low hemolytic activity and selective cytotoxicity toward cancer cell, which is advantageous as compared to PLL and most antimicrobial/anticancerous peptides. This study provides a new concept of using cationic, 1D fibril assemblies for cancer therapy

  8. Enantiomers of nifurtimox do not exhibit stereoselective anti-Trypanosoma cruzi activity, toxicity, or pharmacokinetic properties.

    Science.gov (United States)

    Moraes, Carolina B; White, Karen L; Braillard, Stéphanie; Perez, Catherine; Goo, Junghyun; Gaspar, Luis; Shackleford, David M; Cordeiro-da-Silva, Anabela; Thompson, R C Andrew; Freitas-Junior, Lucio; Charman, Susan A; Chatelain, Eric

    2015-01-01

    With the aim of improving the available drugs for the treatment of Chagas disease, individual enantiomers of nifurtimox were characterized. The results indicate that the enantiomers are equivalent in their in vitro activity against a panel of Trypanosoma cruzi strains; in vivo efficacy in a murine model of Chagas disease; in vitro toxicity and absorption, distribution, metabolism, and excretion characteristics; and in vivo pharmacokinetic properties. There is unlikely to be any therapeutic benefit of an individual nifurtimox enantiomer over the racemic mixture. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  9. Unciaphenol, an Oxygenated Analogue of the Bergman Cyclization Product of Uncialamycin Exhibits Anti-HIV Activity.

    Science.gov (United States)

    Williams, David E; Bottriell, Helen; Davies, Julian; Tietjen, Ian; Brockman, Mark A; Andersen, Raymond J

    2015-11-06

    Unciaphenol (2), an oxygenated analogue of the Bergman cyclization product of the enediyne uncialamycin (1), has been isolated along with 1 from cultures of the actinomycete Streptomyces uncialis. It is proposed that the C-22 OH substituent in 2 might arise from the attack of a nucleophilic oxygen species on the p-benzyne diradical intermediate IA in the Bergman cyclization of 1. 2 shows in vitro anti-HIV activity against viral strains that are resistant to clinically utilized anti-retroviral therapies.

  10. Letermovir and inhibitors of the terminase complex: a promising new class of investigational antiviral drugs against human cytomegalovirus.

    Science.gov (United States)

    Melendez, Dante P; Razonable, Raymund R

    2015-01-01

    Infection with cytomegalovirus is prevalent in immunosuppressed patients. In solid organ transplant and hematopoietic stem cell transplant recipients, cytomegalovirus infection is associated with high morbidity and preventable mortality. Prevention and treatment of cytomegalovirus with currently approved antiviral drugs is often associated with side effects that sometimes preclude their use. Moreover, cytomegalovirus has developed mutations that confer resistance to standard antiviral drugs. During the last decade, there have been calls to develop novel antiviral drugs that could provide better options for prevention and treatment of cytomegalovirus. Letermovir (AIC246) is a highly specific antiviral drug that is currently undergoing clinical development for the management of cytomegalovirus infection. It acts by inhibiting the viral terminase complex. Letermovir is highly potent in vitro and in vivo against cytomegalovirus. Because of a distinct mechanism of action, it does not exhibit cross-resistance with other antiviral drugs. It is predicted to be active against strains that are resistant to ganciclovir, foscarnet, and cidofovir. To date, early-phase clinical trials suggest a very low incidence of adverse effects. Herein, we present a comprehensive review on letermovir, from its postulated novel mechanism of action to the results of most recent clinical studies.

  11. Hydrogen Cyanide Produced by Pseudomonas chlororaphis O6 Exhibits Nematicidal Activity against Meloidogyne hapla

    Directory of Open Access Journals (Sweden)

    Beom Ryong Kang

    2018-02-01

    Full Text Available Root-knot nematodes (Meloidogyne spp. are parasites that attack many field crops and orchard trees, and affect both the quantity and quality of the products. A root-colonizing bacterium, Pseudomonas chlororaphis O6, possesses beneficial traits including strong nematicidal activity. To determine the molecular mechanisms involved in the nematicidal activity of P. chlororaphis O6, we constructed two mutants; one lacking hydrogen cyanide production, and a second lacking an insecticidal toxin, FitD. Root drenching with wild-type P. chlororaphis O6 cells caused juvenile mortality in vitro and in planta. Efficacy was not altered in the fitD mutant compared to the wild-type but was reduced in both bioassays for the mutant lacking hydrogen cyanide production. The reduced number of galls on tomato plants caused by the wild-type strain was comparable to that of a standard chemical nematicide. These findings suggest that hydrogen cyanide-producing root colonizers, such as P. chlororaphis O6, could be formulated as “green” nematicides that are compatible with many crops and offer agricultural sustainability.

  12. CXC Chemokines Exhibit Bactericidal Activity against Multidrug-Resistant Gram-Negative Pathogens

    Directory of Open Access Journals (Sweden)

    Matthew A. Crawford

    2017-11-01

    Full Text Available The continued rise and spread of antimicrobial resistance among bacterial pathogens pose a serious challenge to global health. Countering antimicrobial-resistant pathogens requires a multifaceted effort that includes the discovery of novel therapeutic approaches. Here, we establish the capacity of the human CXC chemokines CXCL9 and CXCL10 to kill multidrug-resistant Gram-negative bacteria, including New Delhi metallo-beta-lactamase-1-producing Klebsiella pneumoniae and colistin-resistant members of the family Enterobacteriaceae that harbor the mobile colistin resistance protein MCR-1 and thus possess phosphoethanolamine-modified lipid A. Colistin-resistant K. pneumoniae isolates affected by genetic mutation of the PmrA/PmrB two-component system, a chromosomally encoded regulator of lipopolysaccharide modification, and containing 4-amino-4-deoxy-l-arabinose-modified lipid A were also found to be susceptible to chemokine-mediated antimicrobial activity. However, loss of PhoP/PhoQ autoregulatory control, caused by disruption of the gene encoding the negative regulator MgrB, limited the bactericidal effects of CXCL9 and CXCL10 in a variable, strain-specific manner. Cumulatively, these findings provide mechanistic insight into chemokine-mediated antimicrobial activity, highlight disparities amongst determinants of colistin resistance, and suggest that chemokine-mediated bactericidal effects merit additional investigation as a therapeutic avenue for treating infections caused by multidrug-resistant pathogens.

  13. Long noncoding RNA linc00617 exhibits oncogenic activity in breast cancer.

    Science.gov (United States)

    Li, Hengyu; Zhu, Li; Xu, Lu; Qin, Keyu; Liu, Chaoqian; Yu, Yue; Su, Dongwei; Wu, Kainan; Sheng, Yuan

    2017-01-01

    Protein-coding genes account for only 2% of the human genome, whereas the vast majority of transcripts are noncoding RNAs including long noncoding RNAs. LncRNAs are involved in the regulation of a diverse array of biological processes, including cancer progression. An evolutionarily conserved lncRNA TUNA, was found to be required for pluripotency of mouse embryonic stem cells. In this study, we found the human ortholog of TUNA, linc00617, was upregulated in breast cancer samples. Linc00617 promoted motility and invasion of breast cancer cells and induced epithelial-mesenchymal-transition (EMT), which was accompanied by generation of stem cell properties. Moreover, knockdown of linc00617 repressed lung metastasis in vivo. We demonstrated that linc00617 upregulated the expression of stemness factor Sox2 in breast cancer cells, which was shown to promote the oncogenic activity of breast cancer cells by stimulating epithelial-to-mesenchymal transition and enhancing the tumor-initiating capacity. Thus, our data indicate that linc00617 functions as an important regulator of EMT and promotes breast cancer progression and metastasis via activating the transcription of Sox2. Together, it suggests that linc00617 may be a potential therapeutic target for aggressive breast cancer. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.

  14. Benzophenones from Mango Leaves Exhibit α-Glucosidase and NO Inhibitory Activities.

    Science.gov (United States)

    Pan, Jing; Yi, Xiaomin; Wang, Yihai; Chen, Guisi; He, Xiangjiu

    2016-10-12

    Mango (Mangifera indica L.) is a succulent tropical fruit. Bioactive phytochemical investigation has been carried out to the leaves of mango. Three new benzophenone glycosides, along with 14 known compounds, were purified and identified. The novel benzophenones were elucidated to be 2,4,4',6-tetrahydroxy-3'-methoxybenzophenone-3-C-β-d-glucopyranoside (1), 4,4',6-trihydroxybenzophenone-2-O-α-l-arabinofuranoside (7), and 4',6-dihydroxy-4-methoxybenzophenone-2-O-(2″),3-C-(1″)-1″-desoxy-α-l-fructofuranoside (11). The α-glucosidase inhibitory, NO production inhibitory, and antioxidant activities were assessed for the purified benzophenones and triterpenoids. Some benzophenones showed moderate α-glucosidase and NO inhibitory activities. The IC50 value of the α-glucosidase inhibitory of isolated compounds 1, 13, and 14 were 284.93 ± 20.29, 239.60 ± 25.00, and 297.37 ± 8.12 μM, respectively. Most compounds showed moderate effects to reduce the NO content in 50 and 100 μM. The above results of bioactivity powerfully demonstrated the phytochemicals from mango, especially benzophenones, probably partially rational for its antidiabetes and anti-inflammatory.

  15. Endophytic fungi isolated from oil-seed crop Jatropha curcas produces oil and exhibit antifungal activity.

    Directory of Open Access Journals (Sweden)

    Susheel Kumar

    Full Text Available Jatropha curcas L., a perennial plant grown in tropics and subtropics is popularly known for its potential as biofuel. The plant is reported to survive under varying environmental conditions having tolerance to stress and an ability to manage pest and diseases. The plant was explored for its endophytic fungi for use in crop protection. Endophytic fungi were isolated from leaf of Jatropha curcas, collected from New Delhi, India. Four isolates were identified as Colletotrichum truncatum, and other isolates were identified as Nigrospora oryzae, Fusarium proliferatum, Guignardia cammillae, Alternaria destruens, and Chaetomium sp. Dual plate culture bioassays and bioactivity assays of solvent extracts of fungal mycelia showed that isolates of Colletotrichum truncatum were effective against plant pathogenic fungi Fusarium oxysporum and Sclerotinia sclerotiorum. Isolate EF13 had highest activity against S. sclerotiorum. Extracts of active endophytic fungi were prepared and tested against S. sclerotiorum. Ethyl acetate and methanol extract of C. truncatum EF10 showed 71.7% and 70% growth inhibition, respectively. Hexane extracts of C. truncatum isolates EF9, EF10, and EF13 yielded oil and the oil from EF10 was similar to oil of the host plant, i.e., J. curcas.

  16. Mirror-image organometallic osmium arene iminopyridine halido complexes exhibit similar potent anticancer activity.

    Science.gov (United States)

    Fu, Ying; Soni, Rina; Romero, María J; Pizarro, Ana M; Salassa, Luca; Clarkson, Guy J; Hearn, Jessica M; Habtemariam, Abraha; Wills, Martin; Sadler, Peter J

    2013-11-04

    Four chiral Os(II) arene anticancer complexes have been isolated by fractional crystallization. The two iodido complexes, (S(Os),S(C))-[Os(η(6)-p-cym)(ImpyMe)I]PF6 (complex 2, (S)-ImpyMe: N-(2-pyridylmethylene)-(S)-1-phenylethylamine) and (R(Os),R(C))-[Os(η(6)-p-cym)(ImpyMe)I]PF6 (complex 4, (R)-ImpyMe: N-(2-pyridylmethylene)-(R)-1-phenylethylamine), showed higher anticancer activity (lower IC50 values) towards A2780 human ovarian cancer cells than cisplatin and were more active than the two chlorido derivatives, (S(Os),S(C))-[Os(η(6)-p-cym)(ImpyMe)Cl]PF6, 1, and (R(Os),R(C))-[Os(η(6)-p-cym)(ImpyMe)Cl]PF6, 3. The two iodido complexes were evaluated in the National Cancer Institute 60-cell-line screen, by using the COMPARE algorithm. This showed that the two potent iodido complexes, 2 (NSC: D-758116/1) and 4 (NSC: D-758118/1), share surprisingly similar cancer cell selectivity patterns with the anti-microtubule drug, vinblastine sulfate. However, no direct effect on tubulin polymerization was found for 2 and 4, an observation that appears to indicate a novel mechanism of action. In addition, complexes 2 and 4 demonstrated potential as transfer-hydrogenation catalysts for imine reduction. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  17. Alcoholic Extract of Eclipta alba Shows In Vitro Antioxidant and Anticancer Activity without Exhibiting Toxicological Effects

    Directory of Open Access Journals (Sweden)

    Navneet Kumar Yadav

    2017-01-01

    Full Text Available As per WHO estimates, 80% of people around the world use medicinal plants for the cure and prevention of various diseases including cancer owing to their easy availability and cost effectiveness. Eclipta alba has long been used in Ayurveda to treat liver diseases, eye ailments, and hair related disorders. The promising medicinal value of E. alba prompted us to study the antioxidant, nontoxic, and anticancer potential of its alcoholic extract. In the current study, we evaluated the in vitro cytotoxic and antioxidant effect of the alcoholic extract of Eclipta alba (AEEA in multiple cancer cell lines along with control. We have also evaluated its effect on different in vivo toxicity parameters. Here, we found that AEEA was found to be most active in most of the cancer cell lines but it significantly induced apoptosis in human breast cancer cell lines by disrupting mitochondrial membrane potential and DNA damage. Moreover, AEEA treatment inhibited migration in both MCF 7 and MDA-MB-231 cells in a dose dependent manner. Further, AEEA possesses robust in vitro antioxidant activity along with high total phenolic and flavonoid contents. In summary, our results indicate that Eclipta alba has enormous potential in complementary and alternative medicine for the treatment of cancer.

  18. Ortho-eugenol exhibits anti-nociceptive and anti-inflammatory activities.

    Science.gov (United States)

    Fonsêca, Diogo V; Salgado, Paula R R; Aragão Neto, Humberto de C; Golzio, Adriana M F O; Caldas Filho, Marcelo R D; Melo, Cynthia G F; Leite, Fagner C; Piuvezam, Marcia R; Pordeus, Liana Clébia de Morais; Barbosa Filho, José M; Almeida, Reinaldo N

    2016-09-01

    Ortho-eugenol is a much used phenylpropanoid whose ability to reduce pain and inflammation has never been studied. Researching ortho-eugenol's antinociceptive and anti-inflammatory activity, and its possible mechanisms of action is therefore of interest. The administration of vehicle, ortho-eugenol (50, 75 and 100mg/kg i.p.), morphine (6mg/kg, i.p.) or dexamethasone (2mg/kg, s.c.) occurred 30min before the completion of pharmacological tests. Pretreatment with ortho-eugenol did not change motor coordination test results, but reduced the number of writhes and licking times in the writhing test and glutamate test, respectively. The reaction time from thermal stimulus was significantly increased in the hot plate test after administration of ortho-eugenol. Treatment with yohimbine reversed the antinociceptive effect of ortho-eugenol, suggesting involvement of the adrenergic system. In anti-inflammatory tests, ortho-eugenol inhibited acetic acid induced vascular permeability and leukocyte migration, reducing TNF-α and IL-1β by virtue of its suppression of NF-κB and p38 phosphorylated forms in the peritonitis test. From these results, ortho-eugenol antinociceptive effects mediated by the adrenergic system and anti-inflammatory activity through regulation of proinflammatory cytokines and phosphorylation of NF-kB and p38 become evident for the first time. Copyright © 2016 Elsevier B.V. All rights reserved.

  19. Endophytic Fungi Isolated from Oil-Seed Crop Jatropha curcas Produces Oil and Exhibit Antifungal Activity

    Science.gov (United States)

    Kumar, Susheel; Kaushik, Nutan

    2013-01-01

    Jatropha curcas L., a perennial plant grown in tropics and subtropics is popularly known for its potential as biofuel. The plant is reported to survive under varying environmental conditions having tolerance to stress and an ability to manage pest and diseases. The plant was explored for its endophytic fungi for use in crop protection. Endophytic fungi were isolated from leaf of Jatropha curcas, collected from New Delhi, India. Four isolates were identified as Colletotrichum truncatum, and other isolates were identified as Nigrospora oryzae, Fusarium proliferatum, Guignardia cammillae, Alternaria destruens, and Chaetomium sp. Dual plate culture bioassays and bioactivity assays of solvent extracts of fungal mycelia showed that isolates of Colletotrichum truncatum were effective against plant pathogenic fungi Fusarium oxysporum and Sclerotinia sclerotiorum. Isolate EF13 had highest activity against S. sclerotiorum. Extracts of active endophytic fungi were prepared and tested against S. sclerotiorum. Ethyl acetate and methanol extract of C. truncatum EF10 showed 71.7% and 70% growth inhibition, respectively. Hexane extracts of C. truncatum isolates EF9, EF10, and EF13 yielded oil and the oil from EF10 was similar to oil of the host plant, i.e., J. curcas. PMID:23409154

  20. Cloning and expression of antiviral/ribosome-inactivating protein from Bougainvillea xbuttiana.

    Science.gov (United States)

    Choudhary, Nandlal; Kapoor, Harish C; Lodha, Madan L

    2008-03-01

    A full-length cDNA encoding ribosome-inactivating/antiviral protein (RIP/AVP)from the leaves of Bougainvillea x buttiana was isolated. The cDNA consisted of 1364 nucleotides with an open reading frame (ORF)of 960 nucleotides encoding a 35.49 kDa protein of 319 amino acids. The deduced amino acid sequence has a putative active domain conserved in RIPs/AVPs and shows a varying phylogenetic relationship to the RIPs from other plant species. The deduced protein has been designated BBAP1 (Bougainvillea x buttiana antiviral protein1). The ORF was cloned into an expression vector and expressed in E.coli as a fusion protein of approximately 78 kDa. The cleaved and purified recombinant BBAP1 exhibited ribosome-inhibiting rRNA N-glycosidase activity,and imparted a high level of resistance against the tobacco mosaic virus (TMV).

  1. A biomimetic collagen derived peptide exhibits anti-angiogenic activity in triple negative breast cancer.

    Directory of Open Access Journals (Sweden)

    Elena V Rosca

    Full Text Available We investigated the application of a mimetic 20 amino acid peptide derived from type IV collagen for treatment of breast cancer. We showed that the peptide induced a decrease of proliferation, adhesion, and migration of endothelial and tumor cells in vitro. We also observed an inhibition of triple negative MDA-MB-231 xenograft growth by 75% relative to control when administered intraperitoneally for 27 days at 10 mg/kg. We monitored in vivo the changes in vascular properties throughout the treatment using MRI and found that the vascular volume and permeability surface area product decreased significantly. The treatment also resulted in an increase of caspase-3 activity and in a reduction of microvascular density. The multiple mode of action of this peptide, i.e., anti-angiogenic, and anti-tumorigenic, makes it a viable candidate as a therapeutic agent as a monotherapy or in combination with other compounds.

  2. Thai Fruits Exhibit Antioxidant Activity and Induction of Antioxidant Enzymes in HEK-293 Cells.

    Science.gov (United States)

    Anantachoke, Natthinee; Lomarat, Pattamapan; Praserttirachai, Wasin; Khammanit, Ruksinee; Mangmool, Supachoke

    2016-01-01

    The cellular antioxidant enzymes play the important role of protecting the cells and organisms from the oxidative damage. Natural antioxidants contained in fruits have attracted considerable interest because of their presumed safety and potential nutritional value. Even though antioxidant activities of many fruits have been reported, the effects of phytochemicals contained in fruits on the induction of antioxidant enzymes in the cells have not been fully defined. In this study, we showed that extracts from Antidesma ghaesembilla , Averrhoa bilimbi , Malpighia glabra , Mangifera indica, Sandoricum koetjape , Syzygium malaccense, and Ziziphus jujuba inhibited H 2 O 2 -induced intracellular reactive oxygen species production in HEK-293 cells. Additionally, these Thai fruit extracts increased the mRNA and protein expressions of antioxidant enzymes, catalase, glutathione peroxidase-1, and manganese superoxide dismutase. The consumption of Thai fruits rich in phenolic compounds may reduce the risk of oxidative stress.

  3. Thai Fruits Exhibit Antioxidant Activity and Induction of Antioxidant Enzymes in HEK-293 Cells

    Directory of Open Access Journals (Sweden)

    Natthinee Anantachoke

    2016-01-01

    Full Text Available The cellular antioxidant enzymes play the important role of protecting the cells and organisms from the oxidative damage. Natural antioxidants contained in fruits have attracted considerable interest because of their presumed safety and potential nutritional value. Even though antioxidant activities of many fruits have been reported, the effects of phytochemicals contained in fruits on the induction of antioxidant enzymes in the cells have not been fully defined. In this study, we showed that extracts from Antidesma ghaesembilla, Averrhoa bilimbi, Malpighia glabra, Mangifera indica, Sandoricum koetjape, Syzygium malaccense, and Ziziphus jujuba inhibited H2O2-induced intracellular reactive oxygen species production in HEK-293 cells. Additionally, these Thai fruit extracts increased the mRNA and protein expressions of antioxidant enzymes, catalase, glutathione peroxidase-1, and manganese superoxide dismutase. The consumption of Thai fruits rich in phenolic compounds may reduce the risk of oxidative stress.

  4. Flavored black ginseng exhibited antitumor activity via improving immune function and inducing apoptosis.

    Science.gov (United States)

    Chen, Guilin; Li, Haijun; Gao, Yugang; Zhang, Lianxue; Zhao, Yan

    2017-05-24

    The objective of this project was to examine saponin and carbohydrate conversion, and to evaluate the antitumor activity of a novel ready-to-eat flavored black ginseng (FBG). The results of chemical experiments showed that common saponins in ginseng such as ginsenoside Re, Rg1, Rb1, etc., are almost completely converted to rare saponins and aglycones such as ginsenoside Rg5, protopanaxadiol (PPD), etc., and non-reducing sugars such as starch are almost completely degraded into reducing sugars as affected by garlic juice and high temperature processing. Furthermore, pharmacological experimental results showed that this novel FBG could inhibit the growth of tumors in H22 tumor-bearing mice dose-dependently at the dosage of 250, 500 and 1000 mg kg-1; meanwhile, the results of ELISA, H&E staining, western blotting and qRT-PCR show that FBG could improve immune function and induce tumor cell apoptosis.

  5. A biomimetic collagen derived peptide exhibits anti-angiogenic activity in triple negative breast cancer.

    Science.gov (United States)

    Rosca, Elena V; Penet, Marie-France; Mori, Noriko; Koskimaki, Jacob E; Lee, Esak; Pandey, Niranjan B; Bhujwalla, Zaver M; Popel, Aleksander S

    2014-01-01

    We investigated the application of a mimetic 20 amino acid peptide derived from type IV collagen for treatment of breast cancer. We showed that the peptide induced a decrease of proliferation, adhesion, and migration of endothelial and tumor cells in vitro. We also observed an inhibition of triple negative MDA-MB-231 xenograft growth by 75% relative to control when administered intraperitoneally for 27 days at 10 mg/kg. We monitored in vivo the changes in vascular properties throughout the treatment using MRI and found that the vascular volume and permeability surface area product decreased significantly. The treatment also resulted in an increase of caspase-3 activity and in a reduction of microvascular density. The multiple mode of action of this peptide, i.e., anti-angiogenic, and anti-tumorigenic, makes it a viable candidate as a therapeutic agent as a monotherapy or in combination with other compounds.

  6. Genetically engineered immunomodulatory Streptococcus thermophilus strains producing antioxidant enzymes exhibit enhanced anti-inflammatory activities.

    Science.gov (United States)

    Del Carmen, Silvina; de Moreno de LeBlanc, Alejandra; Martin, Rebeca; Chain, Florian; Langella, Philippe; Bermúdez-Humarán, Luis G; LeBlanc, Jean Guy

    2014-02-01

    The aims of this study were to develop strains of lactic acid bacteria (LAB) having both immunomodulatory and antioxidant properties and to evaluate their anti-inflammatory effects both in vitro, in different cellular models, and in vivo, in a mouse model of colitis. Different Lactobacillus delbrueckii subsp. bulgaricus and Streptococcus thermophilus strains were cocultured with primary cultures of mononuclear cells. Analysis of the pro- and anti-inflammatory cytokines secreted by these cells after coincubation with candidate bacteria revealed that L. delbrueckii subsp. bulgaricus CRL 864 and S. thermophilus CRL 807 display the highest anti-inflammatory profiles in vitro. Moreover, these results were confirmed in vivo by the determination of the cytokine profiles in large intestine samples of mice fed with these strains. S. thermophilus CRL 807 was then transformed with two different plasmids harboring the genes encoding catalase (CAT) or superoxide dismutase (SOD) antioxidant enzymes, and the anti-inflammatory effects of recombinant streptococci were evaluated in a mouse model of colitis induced by trinitrobenzenesulfonic acid (TNBS). Our results showed a decrease in weight loss, lower liver microbial translocation, lower macroscopic and microscopic damage scores, and modulation of the cytokine production in the large intestines of mice treated with either CAT- or SOD-producing streptococci compared to those in mice treated with the wild-type strain or control mice without any treatment. Furthermore, the greatest anti-inflammatory activity was observed in mice receiving a mixture of both CAT- and SOD-producing streptococci. The addition of L. delbrueckii subsp. bulgaricus CRL 864 to this mixture did not improve their beneficial effects. These findings show that genetically engineering a candidate bacterium (e.g., S. thermophilus CRL 807) with intrinsic immunomodulatory properties by introducing a gene expressing an antioxidant enzyme enhances its anti

  7. Magnesium lithospermate B and rosmarinic acid, two compounds present in Salvia miltiorrhiza, have potent antiviral activity against enterovirus 71 infections.

    Science.gov (United States)

    Chung, Yi-Ching; Hsieh, Feng-Chia; Lin, Ying-Ju; Wu, Tzong-Yuan; Lin, Cheng-Wen; Lin, Ching-Ting; Tang, Nou-Ying; Jinn, Tzyy-Rong

    2015-05-15

    The aim of this study was to identify the active ingredients responsible for the anti-EV71 activity produced by Salvia miltiorrhiza extracts. A pGS-EV71 IRES-based bicistronic reporter assay platform was used for rapid analysis of compounds that could specifically inhibit EV71 viral IRES-mediated translation. The analysis identified 2 caffeic acid derivatives, magnesium lithospermate B (MLB) and rosmarinic acid (RA), which suppressed EV71 IRES-mediated translation at concentrations of 30μg/ml. We also found that MLB and RA inhibited EV71 infection when they were added to RD cells during the viral absorption stage. MLB had a low IC50 value of 0.09mM and a high TI value of 10.52. In contrast, RA had an IC50 value of 0.50mM with a TI value of 2.97. MLB and RA (100µg/ml) also reduced EV71 viral particle production and significantly decreased VP1 protein production. We propose that these two derivatives inhibit EV71 viral entry into cells and viral IRES activity, thereby reducing viral particle production and viral RNA expression and blocking viral VP1 protein translation. This study provides useful information for the development of anti-EV71 assays and reagents by demonstrating a convenient EV71 IRES-based bicistronic assay platform to screen for anti-EV71 IRES activity, and also reports 2 compounds, MLB and RA, which are responsible for the anti-EV71 activity of S. miltiorrhiza. Copyright © 2015 Elsevier B.V. All rights reserved.

  8. Lab-Attenuated Rabies Virus Causes Abortive Infection and Induces Cytokine Expression in Astrocytes by Activating Mitochondrial Antiviral-Signaling Protein Signaling Pathway

    Directory of Open Access Journals (Sweden)

    Bin Tian

    2018-01-01

    Full Text Available Rabies is an ancient disease but remains endemic in most parts of the world and causes approximately 59,000 deaths annually. The mechanism through which the causative agent, rabies virus (RABV, evades the host immune response and infects the host central nervous system (CNS has not been completely elucidated thus far. Our previous studies have shown that lab-attenuated, but not wild-type (wt, RABV activates the innate immune response in the mouse and dog models. In this present study, we demonstrate that lab-attenuated RABV causes abortive infection in astrocytes, the most abundant glial cells in the CNS. Furthermore, we found that lab-attenuated RABV produces more double-stranded RNA (dsRNA than wt RABV, which is recognized by retinoic acid-inducible gene I (RIG-I or melanoma differentiation-associated protein 5 (MDA5. Activation of mitochondrial antiviral-signaling protein (MAVS, the common adaptor molecule for RIG-I and MDA5, results in the production of type I interferon (IFN and the expression of hundreds of IFN-stimulated genes, which suppress RABV replication and spread in astrocytes. Notably, lab-attenuated RABV replicates in a manner identical to that of wt RABV in MAVS−/− astrocytes. It was also found that lab-attenuated, but not wt, RABV induces the expression of inflammatory cytokines via the MAVS- p38/NF-κB signaling pathway. These inflammatory cytokines increase the blood–brain barrier permeability and thus enable immune cells and antibodies infiltrate the CNS parenchyma, resulting in RABV control and elimination. In contrast, wt RABV restricts dsRNA production and thus evades innate recognition by RIG-I/MDA5 in astrocytes, which could be one of the mechanisms by which wt RABV evades the host immune response in resident CNS cells. Our findings suggest that astrocytes play a critical role in limiting the replication of lab-attenuated RABV in the CNS.

  9. Orally Delivered Scorpion Antimicrobial Peptides Exhibit Activity against Pea Aphid (Acyrthosiphon pisum and Its Bacterial Symbionts

    Directory of Open Access Journals (Sweden)

    Karen Luna-Ramirez

    2017-08-01

    Full Text Available Aphids are severe agricultural pests that damage crops by feeding on phloem sap and vectoring plant pathogens. Chemical insecticides provide an important aphid control strategy, but alternative and sustainable control measures are required to avoid rapidly emerging resistance, environmental contamination, and the risk to humans and beneficial organisms. Aphids are dependent on bacterial symbionts, which enable them to survive on phloem sap lacking essential nutrients, as well as conferring environmental stress tolerance and resistance to parasites. The evolution of aphids has been accompanied by the loss of many immunity-related genes, such as those encoding antibacterial peptides, which are prevalent in other insects, probably because any harm to the bacterial symbionts would inevitably affect the aphids themselves. This suggests that antimicrobial peptides (AMPs could replace or at least complement conventional insecticides for aphid control. We fed the pea aphids (Acyrthosiphon pisum with AMPs from the venom glands of scorpions. The AMPs reduced aphid survival, delayed their reproduction, displayed in vitro activity against aphid bacterial symbionts, and reduced the number of symbionts in vivo. Remarkably, we found that some of the scorpion AMPs compromised the aphid bacteriome, a specialized organ that harbours bacterial symbionts. Our data suggest that scorpion AMPs holds the potential to be developed as bio-insecticides, and are promising candidates for the engineering of aphid-resistant crops.

  10. Monoterpenoid Terpinen-4-ol Exhibits Anticonvulsant Activity in Behavioural and Electrophysiological Studies

    Directory of Open Access Journals (Sweden)

    Franklin F. F. Nóbrega

    2014-01-01

    Full Text Available Terpinen-4-ol (4TRP is a monoterpenoid alcoholic component of essential oils obtained from several aromatic plants. We investigated the psychopharmacological and electrophysiological activities of 4TRP in male Swiss mice and Wistar rats. 4TRP was administered intraperitoneally (i.p. at doses of 25 to 200 mg/kg and intracerebroventricularly (i.c.v. at concentrations of 10, 20, and 40 ng/2 μL. For in vitro experiments, 4TRP concentrations were 0.1 mM and 1.0 mM. 4TRP (i.p. inhibited pentylenetetrazol- (PTZ- induced seizures, indicating anticonvulsant effects. Electroencephalographic recordings showed that 4TRP (i.c.v. protected against PTZ-induced seizures, corroborating the behavioural results. To determine whether 4TRP exerts anticonvulsant effects via regulation of GABAergic neurotransmission, we measured convulsions induced by 3-mercapto-propionic acid (3-MP. The obtained results showed involvement of the GABAergic system in the anticonvulsant action exerted by 4TRP, but flumazenil, a selective antagonist of the benzodiazepine site of the GABAA receptor, did not reverse the anticonvulsant effect, demonstrating that 4TRP does not bind to the benzodiazepine-binding site. Furthermore, 4TRP decreased the sodium current through voltage-dependent sodium channels, and thus its anticonvulsant effect may be related to changes in neuronal excitability because of modulation of these channels.

  11. Orally Delivered Scorpion Antimicrobial Peptides Exhibit Activity against Pea Aphid (Acyrthosiphon pisum) and Its Bacterial Symbionts

    Science.gov (United States)

    Luna-Ramirez, Karen; Skaljac, Marisa; Grotmann, Jens; Kirfel, Phillipp; Vilcinskas, Andreas

    2017-01-01

    Aphids are severe agricultural pests that damage crops by feeding on phloem sap and vectoring plant pathogens. Chemical insecticides provide an important aphid control strategy, but alternative and sustainable control measures are required to avoid rapidly emerging resistance, environmental contamination, and the risk to humans and beneficial organisms. Aphids are dependent on bacterial symbionts, which enable them to survive on phloem sap lacking essential nutrients, as well as conferring environmental stress tolerance and resistance to parasites. The evolution of aphids has been accompanied by the loss of many immunity-related genes, such as those encoding antibacterial peptides, which are prevalent in other insects, probably because any harm to the bacterial symbionts would inevitably affect the aphids themselves. This suggests that antimicrobial peptides (AMPs) could replace or at least complement conventional insecticides for aphid control. We fed the pea aphids (Acyrthosiphon pisum) with AMPs from the venom glands of scorpions. The AMPs reduced aphid survival, delayed their reproduction, displayed in vitro activity against aphid bacterial symbionts, and reduced the number of symbionts in vivo. Remarkably, we found that some of the scorpion AMPs compromised the aphid bacteriome, a specialized organ that harbours bacterial symbionts. Our data suggest that scorpion AMPs holds the potential to be developed as bio-insecticides, and are promising candidates for the engineering of aphid-resistant crops. PMID:28837113

  12. Paving asphalt products exhibit a lack of carcinogenic and mutagenic activity.

    Science.gov (United States)

    Goyak, Katy O; McKee, Richard H; Minsavage, Gary D; McGowan, Claude; Daughtrey, Wayne C; Freeman, James J

    2011-10-01

    A paving asphalt and a vacuum residuum (derived from crude oil by atmospheric and subsequent vacuum distillation and used as a blend stock for asphalt) were tested in skin carcinogenesis assays in mice and in optimized Ames assays for mutagenic activity. In the skin cancer tests, each substance was applied twice weekly for 104 weeks to the clipped backs of groups of 50 male C3H mice. Neither the paving asphalt nor the vacuum residuum (30% weight/volume and 75% weight/weight in US Pharmacopeia mineral oil, respectively) produced any tumors. The positive control benzo[a]pyrene (0.05% w/v in toluene) induced tumors in 46 of 50 mice, demonstrating the effectiveness of the test method. Salmonella typhimurium tester strain TA98 was used in the optimized Ames assay to evaluate mutagenic potential. Dimethylsulfoxide (DMSO) extractions of the substances were not mutagenic when tested up to toxic limits. Thus, under the conditions of these studies, neither the paving asphalt nor the vacuum residuum was carcinogenic or mutagenic.

  13. Fungi treated with small chemicals exhibit increased antimicrobial activity against facultative bacterial and yeast pathogens.

    Science.gov (United States)

    Zutz, Christoph; Bandian, Dragana; Neumayer, Bernhard; Speringer, Franz; Gorfer, Markus; Wagner, Martin; Strauss, Joseph; Rychli, Kathrin

    2014-01-01

    For decades, fungi have been the main source for the discovery of novel antimicrobial drugs. Recent sequencing efforts revealed a still high number of so far unknown "cryptic" secondary metabolites. The production of these metabolites is presumably epigenetically silenced under standard laboratory conditions. In this study, we investigated the effect of six small mass chemicals, of which some are known to act as epigenetic modulators, on the production of antimicrobial compounds in 54 spore forming fungi. The antimicrobial effect of fungal samples was tested against clinically facultative pathogens and multiresistant clinical isolates. In total, 30 samples of treated fungi belonging to six different genera reduced significantly growth of different test organisms compared to the untreated fungal sample (growth log reduction 0.3-4.3). For instance, the pellet of Penicillium restrictum grown in the presence of butyrate revealed significant higher antimicrobial activity against Staphylococcus (S.) aureus and multiresistant S. aureus strains and displayed no cytotoxicity against human cells, thus making it an ideal candidate for antimicrobial compound discovery. Our study shows that every presumable fungus, even well described fungi, has the potential to produce novel antimicrobial compounds and that our approach is capable of rapidly filling the pipeline for yet undiscovered antimicrobial substances.

  14. Synthesis and Antiviral Activity of 5‑(4‑Chlorophenyl-1,3,4-Thiadiazole Sulfonamides

    Directory of Open Access Journals (Sweden)

    Yuping Zhang

    2010-12-01

    Full Text Available Starting from 4-chlorobenzoic acid, 10 new 5-(4-chlorophenyl-N-substituted-N-1,3,4-thiadiazole-2-sulfonamide derivatives were synthesized in six-steps. Esterification of 4-chlorobenzoic acid with methanol and subsequent hydrazination, salt formation and cyclization afforded 5-(4-chlorophen-yl-1,3,4-thiadiazole-2-thiol (5. Conversion of this intermediate into sulfonyl chloride 6, followed by nucleophilic attack of the amines gave the title sulfonamides 7a-7j whose structures were confirmed by NMR, IR and elemental analysis. The bioassay tests showed that compounds 7b and 7i possessed certain anti-tobacco mosaic virus activity.

  15. Antiviral effect of cationic compounds on bacteriophages

    Directory of Open Access Journals (Sweden)

    Mai Huong eChatain-Ly

    2013-03-01

    Full Text Available The antiviral activity of several cationic compounds - cetytrimethylammonium (CTAB, chitosan, nisin and lysozyme - was investigated on the bacteriophage c2 (DNA head and non-contractile tail infecting Lactococcus strains and the bacteriophage MS2 (F-specific RNA infecting E.coli. Firstly, these activities were evaluated in a phosphate buffer pH 7- 10 mM. The CTAB had a virucidal effect on the Lactococcus bacteriophages, but not on the MS2. After 1 min of contact with 0.125 mM CTAB, the c2 population was reduced from 6 log(pfu/mL to 1,5 log(pfu/mL and completely deactivated at 1 mM. On the contrary, chitosan inhibited the MS2 more than it did the bacteriophages c2. No antiviral effect was observed for the nisin or the lysozyme on bacteriophages after 1 min of treatment. A 1 and 2.5 log reduction was respectively observed for nisin and lysozyme when the treatment time increased (5 or 10 min. These results showed that the antiviral effect depended both on the virus and structure of the antimicrobial compounds. The antiviral activity of these compounds was also evaluated in different physico-chemical conditions and in complex matrices. The antiviral activity of CTAB was impaired in acid pH and with an increase of the ionic strength. These results might be explained by the electrostatic interactions between cationic compounds and negatively charged particles such as bacteriophages or other compounds in a matrix. Milk proved to be protective suggesting the components of food could interfere with antimicrobial compounds.

  16. Exhibiting design

    DEFF Research Database (Denmark)

    Christensen, Line Hjorth

    2017-01-01

    This article explores how co-curatorial strategies and partnerships can work as driving forces for representing design, and how they can vitalize the exhibition as a media between enlightenment and experience. Focusing on Design Museum DK, drawing on historical as well as recent cases, it identif......This article explores how co-curatorial strategies and partnerships can work as driving forces for representing design, and how they can vitalize the exhibition as a media between enlightenment and experience. Focusing on Design Museum DK, drawing on historical as well as recent cases...

  17. Malignant T cells exhibit CD45 resistant Stat 3 activation and proliferation in cutaneous T cell lymphoma

    DEFF Research Database (Denmark)

    Krejsgaard, T; Helvad, Rikke; Ralfkiær, Elisabeth

    2010-01-01

    CD45 is a protein tyrosine phosphatase, which is well-known for regulating antigen receptor signalling in T and B cells via its effect on Src kinases. It has recently been shown that CD45 can also dephosphorylate Janus kinases (Jaks) and thereby regulate Signal transducer and activator...... of transcription (Stat) activation and cytokine-induced proliferation in lymphocytes. Consequently, CD45 dysregulation could be implicated in aberrant Jak/Stat activation and proliferation in lymphoproliferative diseases. Despite high expression of the CD45 ligand, Galectin-1, in skin lesions from cutaneous T......-cell lymphoma (CTCL), the malignant T cells exhibit constitutive activation of the Jak3/Stat3 signalling pathway and uncontrolled proliferation. We show that CD45 expression is down-regulated on malignant T cells when compared to non-malignant T cells established from CTCL skin lesions. Moreover, CD45 cross...

  18. Isotype modulates epitope specificity, affinity, and antiviral activities of anti-HIV-1 human broadly neutralizing 2F5 antibody.

    Science.gov (United States)

    Tudor, Daniela; Yu, Huifeng; Maupetit, Julien; Drillet, Anne-Sophie; Bouceba, Tahar; Schwartz-Cornil, Isabelle; Lopalco, Lucia; Tuffery, Pierre; Bomsel, Morgane

    2012-07-31

    The constant heavy chain (CH1) domain affects antibody affinity and fine specificity, challenging the paradigm that only variable regions contribute to antigen binding. To investigate the role of the CH1 domain, we constructed IgA2 from the broadly neutralizing anti-HIV-1 2F5 IgG1, and compared 2F5 IgA2 and IgG binding affinity and functional activities. We found that 2F5 IgA2 bound to the gp41 membrane proximal external region with higher affinity than IgG1. Functionally, compared with IgG1, 2F5 IgA2 more efficiently blocked HIV-1 transcytosis across epithelial cells and CD4(+) cell infection by R5 HIV-1. The 2F5 IgG1 and IgA2 acted synergistically to fully block HIV-1 transfer from Langerhans to autologous CD4(+) T cells and to inhibit CD4(+) T-cell infection. Epitope mapping performed by screening a random peptide library and in silico docking modeling suggested that along with the 2F5 IgG canonical ELDKWA epitope on gp41, the IgG1 recognized an additional 3D-conformational epitope on the gp41 C-helix. In contrast, the IgA2 epitope included a unique conformational motif on the gp41 N-helix. Overall, the CH1 region of 2F5 contributes to shape its epitope specificity, antibody affinity, and functional activities. In the context of sexually transmitted infections such as HIV-1/AIDS, raising a mucosal IgA-based vaccine response should complement an IgG-based vaccine response in blocking HIV-1 transmission.

  19. Isotype modulates epitope specificity, affinity, and antiviral activities of anti–HIV-1 human broadly neutralizing 2F5 antibody

    Science.gov (United States)

    Tudor, Daniela; Yu, Huifeng; Maupetit, Julien; Drillet, Anne-Sophie; Bouceba, Tahar; Schwartz-Cornil, Isabelle; Lopalco, Lucia; Tuffery, Pierre; Bomsel, Morgane

    2012-01-01

    The constant heavy chain (CH1) domain affects antibody affinity and fine specificity, challenging the paradigm that only variable regions contribute to antigen binding. To investigate the role of the CH1 domain, we constructed IgA2 from the broadly neutralizing anti–HIV-1 2F5 IgG1, and compared 2F5 IgA2 and IgG binding affinity and functional activities. We found that 2F5 IgA2 bound to the gp41 membrane proximal external region with higher affinity than IgG1. Functionally, compared with IgG1, 2F5 IgA2 more efficiently blocked HIV-1 transcytosis across epithelial cells and CD4+ cell infection by R5 HIV-1. The 2F5 IgG1 and IgA2 acted synergistically to fully block HIV-1 transfer from Langerhans to autologous CD4+ T cells and to inhibit CD4+ T-cell infection. Epitope mapping performed by screening a random peptide library and in silico docking modeling suggested that along with the 2F5 IgG canonical ELDKWA epitope on gp41, the IgG1 recognized an additional 3D-conformational epitope on the gp41 C-helix. In contrast, the IgA2 epitope included a unique conformational motif on the gp41 N-helix. Overall, the CH1 region of 2F5 contributes to shape its epitope specificity, antibody affinity, and functional activities. In the context of sexually transmitted infections such as HIV-1/AIDS, raising a mucosal IgA-based vaccine response should complement an IgG-based vaccine response in blocking HIV-1 transmission. PMID:22723360

  20. New ribosome-inactivating proteins with polynucleotide:adenosine glycosidase and antiviral activities from Basella rubra L. and bougainvillea spectabilis Willd.

    Science.gov (United States)

    Bolognesi, A; Polito, L; Olivieri, F; Valbonesi, P; Barbieri, L; Battelli, M G; Carusi, M V; Benvenuto, E; Del Vecchio Blanco, F; Di Maro, A; Parente, A; Di Loreto, M; Stirpe, F

    1997-12-01

    New single-chain (type 1) ribosome-inactivating proteins (RIPs) were isolated from the seeds of Basella rubra L. (two proteins) and from the leaves of Bougainvillea spectabilis Willd. (one protein). These RIPs inhibit protein synthesis both in a cell-free system, with an IC50 (concentration causing 50% inhibition) in the 10(-10) M range, and by various cell lines, with IC50S in the 10(-8)-10(-6) M range. All three RIPs released adenine not only from rat liver ribosomes but also from Escherichia coli rRNA, polyadenylic acid, herring sperm DNA, and artichoke mottled crinkle virus (AMCV) genomic RNA, thus being polynucleotide:adenosine glycosidases. The proteins from Basella rubra had toxicity to mice similar to that of most type 1 RIPs (Barbieri et al., 1993, Biochim Biophys Acta 1154: 237-282) with an LD50 (concentration that is 50% lethal) Bougainvillea spectabilis had an LD50 > 32 mg.kg-1. The N-terminal sequence of the two RIPs from Basella rubra had 80-93% identity, whereas it differed from the sequence of the RIP from Bougainvillea spectabilis. When tested with antibodies against various RIPs, the RIPs from Basella gave some cross-reactivity with sera against dianthin 32, and weak cross-reactivity with momordin I and momorcochin-S, whilst the RIP from Bougainvillea did not cross-react with any antiserum tested. An RIP from Basella rubra and one from Bougainvillea spectabilis were tested for antiviral activity, and both inhibited infection of Nicotiana benthamiana by AMCV.

  1. P1-Substituted Symmetry-Based Human Immunodeficiency Virus Protease Inhibitors with Potent Antiviral Activity against Drug-Resistant Viruses

    Energy Technology Data Exchange (ETDEWEB)

    DeGoey, David A.; Grampovnik, David J.; Chen, Hui-Ju; Flosi, William J.; Klein, Larry L.; Dekhtyar, Tatyana; Stoll, Vincent; Mamo, Mulugeta; Molla, Akhteruzzaman; Kempf, Dale J. (Abbott)

    2013-03-07

    Because there is currently no cure for HIV infection, patients must remain on long-term drug therapy, leading to concerns over potential drug side effects and the emergence of drug resistance. For this reason, new and safe antiretroviral agents with improved potency against drug-resistant strains of HIV are needed. A series of HIV protease inhibitors (PIs) with potent activity against both wild-type (WT) virus and drug-resistant strains of HIV was designed and synthesized. The incorporation of substituents with hydrogen bond donor and acceptor groups at the P1 position of our symmetry-based inhibitor series resulted in significant potency improvements against the resistant mutants. By this approach, several compounds, such as 13, 24, and 29, were identified that demonstrated similar or improved potencies compared to 1 against highly mutated strains of HIV derived from patients who previously failed HIV PI therapy. Overall, compound 13 demonstrated the best balance of potency against drug resistant strains of HIV and oral bioavailability in pharmacokinetic studies. X-ray analysis of an HIV PI with an improved resistance profile bound to WT HIV protease is also reported.

  2. Human Herpesvirus 6A Exhibits Restrictive Propagation with Limited Activation of the Protein Kinase R-eIF2α Stress Pathway.

    Science.gov (United States)

    Sharon, Eyal; Frenkel, Niza

    2017-05-01

    The eIF2α protein plays a critical role in the regulation of translation. The production of double-stranded RNA (dsRNA) during viral replication can activate protein kinase R (PKR), which phosphorylates eIF2α, leading to inhibition of the initial step of translation. Many viruses have evolved gene products targeting the PKR-eIF2a pathway, indicating its importance in antiviral defense. In the present study, we focused on alternations of PKR-eIF2a pathway during human herpesvirus 6A (HHV-6A) infection while monitoring viral gene expression and infectious viral yields. We have found increased phosphorylated PKR as well as phosphorylated eIF2α coincident with accumulation of the late gp82-105 viral protein. The level of total PKR was relatively constant, but it decreased by 144 h postinfection. The phosphorylation of eIF2a led to a moderate increase in activating transcription factor 4 (ATF4) accumulation, indicating moderate inhibition of protein translation during HHV-6A infection. The overexpression of PKR led to decreased viral propagation coincident with increased accumulation of phosphorylated PKR and phosphorylated eIF2a. Moreover, addition of a dominant negative PKR mutant resulted in a moderate increase in viral replication. HHV-6A exhibits relatively low efficiency of propagation of progeny virus secreted into the culture medium. This study suggests that the replicative strategy of HHV-6A involves a mild infection over a lengthy life cycle in culture, while preventing severe activation of the PKR-eIF2α pathway.IMPORTANCE Human herpesvirus 6A (HHV-6A) and HHV-6B are common, widely prevalent viruses, causing from mild to severe disease. Our study focused on the PKR-eIF2α stress pathway, which limits viral replication. The HHV-6 genome carries multiple genes transcribed from the two strands, predicting accumulation of dsRNAs which can activate PKR and inhibition of protein synthesis. We report that HHV-6A induced the accumulation of phosphorylated PKR and

  3. Antiviral activities of 2,6-diaminopurine-based acyclic nucleoside phosphonates against herpesviruses: In vitro study results with pseudorabies virus (PrV, SuHV-1)

    Czech Academy of Sciences Publication Activity Database

    Zouharová, D.; Lipenská, I.; Fojtiková, M.; Kulich, P.; Neca, J.; Slaný, M.; Kovařčík, K.; Turanek-Knotigová, P.; Hubatka, F.; Celechovská, H.; Mašek, J.; Koudelka, Š.; Procházka, L.; Eyer, L.; Plocková, J.; Bartheldyová, E.; Miller, A. D.; Růžek, Daniel; Raška, M.; Janeba, Zlatko; Turánek, J.

    2016-01-01

    Roč. 184, FEB 29 (2016), s. 84-93 ISSN 0378-1135 Institutional support: RVO:60077344 ; RVO:61388963 Keywords : Pseudorabies * Acyclic nucleoside phosphonates * DNA viruses * Cidofovir * Antiviral drugs * DNA polymerase Subject RIV: EE - Microbiology, Virology; CC - Organic Chemistry (UOCHB-X) Impact factor: 2.628, year: 2016

  4. Evaluation of the potential anti-viral activity of microRNAs in rainbow trout (Oncorhynchus mykiss)

    DEFF Research Database (Denmark)

    Bela-Ong, Dennis; Schyth, Brian Dall; Lorenzen, Niels

    2013-01-01

    Micro ribonucleic acids (miRNAs) are small (18-22 nucleotides) endogenous RNAs that potently mediate post-transcriptional silencing of a wide range of genes. They are emerging as critical regulators of cellular processes and some miRNAs have been demonstrated to possess direct antiviral effects. ...

  5. Small molecules with antiviral activity against the Ebola virus [v1; ref status: indexed, http://f1000r.es/523

    Directory of Open Access Journals (Sweden)

    Nadia Litterman

    2015-02-01

    Full Text Available The recent outbreak of the Ebola virus in West Africa has highlighted the clear shortage of broad-spectrum antiviral drugs for emerging viruses. There are numerous FDA approved drugs and other small molecules described in the literature that could be further evaluated for their potential as antiviral compounds. These molecules are in addition to the few new antivirals that have been tested in Ebola patients but were not originally developed against the Ebola virus, and may play an important role as we await an effective vaccine. The balance between using FDA approved drugs versus novel antivirals with minimal safety and no efficacy data in humans should be considered. We have evaluated 55 molecules from the perspective of an experienced medicinal chemist as well as using simple molecular properties and have highlighted 16 compounds that have desirable qualities as well as those that may be less desirable. In addition we propose that a collaborative database for sharing such published and novel information on small molecules is needed for the research community studying the Ebola virus.

  6. Antiviral lanostanoid triterpenes from the fungus Ganoderma pfeifferi.

    Science.gov (United States)

    Mothana, R A A; Awadh Ali, N A; Jansen, R; Wegner, U; Mentel, R; Lindequist, U

    2003-02-01

    Ganodermadiol, lucidadiol and applanoxidic acid G were isolated as first triterpenes from the European Basidiomycete Ganoderma pfeifferi. The compounds show antiviral activity against influenza virus type A and HSV type 1.

  7. La respuesta inmune antiviral

    Directory of Open Access Journals (Sweden)

    Rainel Sánchez de la Rosa

    1998-02-01

    Full Text Available Se expone que los virus son parásitos intracelulares obligados, puesto que no tienen metabolismo propio; esto obliga al sistema inmune a poner en marcha sus mecanismos más especializados para reconocer y eliminar, tanto a los virus libres, como a las células infectadas. Se señala que las células presentadoras de antígenos, los linfocitos B y los T unidos al complejo mayor de histocompatibilidad, forman parte de la organización de la respuesta inmune antiviral; la inducción de esta respuesta con proteínas, péptidos y ADN desnudo, son alternativas actuales tanto en la prevención como en el tratamiento de las infecciones viralesIt is explained that viruses are compulsory intracellular parasites, since they don't have their own metabolism, which makes the immune system to start its mest specialized mechanisms to recognize and eliminate the free viruses and the infected cells. It is stated that the cells presenting antigens, and the B and T lymphocytes together with the major histocompatibility complex, are part of the organization of the immune antiviral response. The induction of this response with proteins, peptides and naked DNA are the present alternatives for the prevention and treatment of viral infections

  8. Museum Exhibit

    Science.gov (United States)

    1991-01-01

    A TSP from NASA Tech Briefs provided the solution to an electrical problem at a Florida museum. When a model train would not start without a jerk, a Marshall Space Flight Center development called pulse width control was adapted. The new circuit enables the train to start smoothly and reduces construction and maintenance costs. The same technology is also used in another hands-on exhibit. Applications of other TSPs are anticipated.

  9. Recombinant Nox4 cytosolic domain produced by a cell or cell-free base systems exhibits constitutive diaphorase activity

    Energy Technology Data Exchange (ETDEWEB)

    Nguyen, Minh Vu Chuong, E-mail: mvchuong@yahoo.fr [GREPI AGIM FRE 3405 CNRS-UJF, Universite Joseph Fourier, Grenoble (France); Zhang, Leilei [GREPI AGIM FRE 3405 CNRS-UJF, Universite Joseph Fourier, Grenoble (France); Lhomme, Stanislas; Mouz, Nicolas [PX' Therapeutics, MINATEC/Batiment de Haute Technologie, Grenoble (France); Lenormand, Jean-Luc [HumProTher Laboratory, TheReX/TIMC-IMAG UMR 5525 CNRS UJF, Universite Joseph Fourier, UFR de Medecine, Domaine de la Merci, 38706 La Tronche (France); Lardy, Bernard; Morel, Francoise [GREPI AGIM FRE 3405 CNRS-UJF, Universite Joseph Fourier, Grenoble (France)

    2012-03-16

    Highlights: Black-Right-Pointing-Pointer A comparison of two bacterial cell and cell-free protein expression systems is presented. Black-Right-Pointing-Pointer Soluble and active truncated Nox4 proteins are produced. Black-Right-Pointing-Pointer Nox4 has a constitutive diaphorase activity which is independent of cytosolic factors. Black-Right-Pointing-Pointer Isoform Nox4B is unable to initiate the first electronic transfer step. Black-Right-Pointing-Pointer Findings contribute to the understanding of the mechanism of Nox4 oxidase activity. -- Abstract: The membrane protein NADPH (nicotinamide adenine dinucleotide phosphate) oxidase Nox4 constitutively generates reactive oxygen species differing from other NADPH oxidases activity, particularly in Nox2 which needs a stimulus to be active. Although the precise mechanism of production of reactive oxygen species by Nox2 is well characterized, the electronic transfer throughout Nox4 remains unclear. Our study aims to investigate the initial electronic transfer step (diaphorase activity) of the cytosolic tail of Nox4. For this purpose, we developed two different approaches to produce soluble and active truncated Nox4 proteins. We synthesized soluble recombinant proteins either by in vitro translation or by bacteria induction. While proteins obtained by bacteria induction demonstrate an activity of 4.4 {+-} 1.7 nmol/min/nmol when measured against iodonitro tetrazolium chloride and 20.5 {+-} 2.8 nmol/min/nmol with cytochrome c, the soluble proteins produced by cell-free expression system exhibit a diaphorase activity with a turn-over of 26 {+-} 2.6 nmol/min/nmol when measured against iodonitro tetrazolium chloride and 48 {+-} 20.2 nmol/min/nmol with cytochrome c. Furthermore, the activity of the soluble proteins is constitutive and does not need any stimulus. We also show that the cytosolic tail of the isoform Nox4B lacking the first NADPH binding site is unable to demonstrate any diaphorase activity pointing out the

  10. Inducible Interleukin 32 (IL-32) Exerts Extensive Antiviral Function via Selective Stimulation of Interferon λ1 (IFN-λ1)*

    Science.gov (United States)

    Li, Yongkui; Xie, Jiajia; Xu, Xiupeng; Liu, Li; Wan, Yushun; Liu, Yingle; Zhu, Chengliang; Zhu, Ying

    2013-01-01

    Interleukin (IL)-32 has been recognized as a proinflammatory cytokine that participates in responses to viral infection. However, little is known about how IL-32 is induced in response to viral infection and the mechanisms of IL-32-mediated antiviral activities. We discovered that IL-32 is elevated by hepatitis B virus (HBV) infection both in vitro and in vivo and that HBV induced IL-32 expression at the level of both transcription and post-transcription. Furthermore, microRNA-29b was found to be a key factor in HBV-regulated IL-32 expression by directly targeting the mRNA 3′-untranslated region of IL-32. Antiviral analysis showed that IL-32 was not sufficient to alter HBV replication in HepG2.2.15 cells. To mimic the viremic phase of viral infection, freshly isolated peripheral blood mononuclear cells were treated with IL-32γ, the secretory isoform, and the supernatants were used for antiviral assays. Surprisingly, these supernatants exhibited extensive antiviral activity against multiplex viruses besides HBV. Thus, we speculated that the IL-32γ-treated peripheral blood mononuclear cells produced and secreted an unknown antiviral factor. Using antibody neutralization assays, we identified the factor as interferon (IFN)-λ1 and not IFN-α. Further studies indicated that IL-32γ effectively inhibited HBV replication in a hydrodynamic injection mouse model. Clinical data showed that elevated levels of IFN-λ1 both in serum and liver tissue of HBV patients were positively correlated to the increased levels of IL-32. Our results demonstrate that elevated IL-32 levels during viral infection mediate antiviral effects by stimulating the expression of IFN-λ1. PMID:23729669

  11. Randomized Phase I: Safety, Immunogenicity and Mucosal Antiviral Activity in Young Healthy Women Vaccinated with HIV-1 Gp41 P1 Peptide on Virosomes.

    Science.gov (United States)

    Leroux-Roels, Geert; Maes, Cathy; Clement, Frédéric; van Engelenburg, Frank; van den Dobbelsteen, Marieke; Adler, Michael; Amacker, Mario; Lopalco, Lucia; Bomsel, Morgane; Chalifour, Anick; Fleury, Sylvain

    2013-01-01

    Mucosal antibodies harboring various antiviral activities may best protect mucosal surfaces against early HIV-1 entry at mucosal sites and they should be ideally induced by prophylactic HIV-1 vaccines for optimal prevention of sexually transmitted HIV-1. A phase I, double-blind, randomized, placebo-controlled trial was conducted in twenty-four healthy HIV-uninfected young women. The study objectives were to assess the safety, tolerability and immunogenicity of virosomes harboring surface HIV-1 gp41-derived P1 lipidated peptides (MYM-V101). Participants received placebo or MYM-V101 vaccine at 10 μg/dose or 50 μg/dose intramuscularly at week 0 and 8, and intranasally at week 16 and 24. MYM-V101 was safe and well-tolerated at both doses administered by the intramuscular and intranasal routes, with the majority of subjects remaining free of local and general symptoms. P1-specific serum IgGs and IgAs were induced in all high dose recipients after the first injection. After the last vaccination, vaginal and rectal P1-specific IgGs could be detected in all high dose recipients. Approximately 63% and 43% of the low and high dose recipients were respectively tested positive for vaginal P1-IgAs, while 29% of the subjects from the high dose group tested positive for rectal IgAs. Serum samples had total specific IgG and IgA antibody concentrations ≥ 0.4 μg/mL, while mucosal samples were usually below 0.01 μg/mL. Vaginal secretions from MYM-V101 vaccinated subjects were inhibiting HIV-1 transcytosis but had no detectable neutralizing activity. P1-specific Th1 responses could not be detected on PBMC. This study demonstrates the excellent safety and tolerability of MYM-V101, eliciting systemic and mucosal antibodies in the majority of subjects. Vaccine-induced mucosal anti-gp41 antibodies toward conserved gp41 motifs were harboring HIV-1 transcytosis inhibition activity and may contribute to reduce sexually-transmitted HIV-1. ClinicalTrials.gov NCT01084343.

  12. Randomized Phase I: Safety, Immunogenicity and Mucosal Antiviral Activity in Young Healthy Women Vaccinated with HIV-1 Gp41 P1 Peptide on Virosomes.

    Directory of Open Access Journals (Sweden)

    Geert Leroux-Roels

    Full Text Available Mucosal antibodies harboring various antiviral activities may best protect mucosal surfaces against early HIV-1 entry at mucosal sites and they should be ideally induced by prophylactic HIV-1 vaccines for optimal prevention of sexually transmitted HIV-1. A phase I, double-blind, randomized, placebo-controlled trial was conducted in twenty-four healthy HIV-uninfected young women. The study objectives were to assess the safety, tolerability and immunogenicity of virosomes harboring surface HIV-1 gp41-derived P1 lipidated peptides (MYM-V101. Participants received placebo or MYM-V101 vaccine at 10 μg/dose or 50 μg/dose intramuscularly at week 0 and 8, and intranasally at week 16 and 24. MYM-V101 was safe and well-tolerated at both doses administered by the intramuscular and intranasal routes, with the majority of subjects remaining free of local and general symptoms. P1-specific serum IgGs and IgAs were induced in all high dose recipients after the first injection. After the last vaccination, vaginal and rectal P1-specific IgGs could be detected in all high dose recipients. Approximately 63% and 43% of the low and high dose recipients were respectively tested positive for vaginal P1-IgAs, while 29% of the subjects from the high dose group tested positive for rectal IgAs. Serum samples had total specific IgG and IgA antibody concentrations ≥ 0.4 μg/mL, while mucosal samples were usually below 0.01 μg/mL. Vaginal secretions from MYM-V101 vaccinated subjects were inhibiting HIV-1 transcytosis but had no detectable neutralizing activity. P1-specific Th1 responses could not be detected on PBMC. This study demonstrates the excellent safety and tolerability of MYM-V101, eliciting systemic and mucosal antibodies in the majority of subjects. Vaccine-induced mucosal anti-gp41 antibodies toward conserved gp41 motifs were harboring HIV-1 transcytosis inhibition activity and may contribute to reduce sexually-transmitted HIV-1.ClinicalTrials.gov NCT01084343.

  13. Curcumin-Free Turmeric Exhibits Activity against Human HCT-116 Colon Tumor Xenograft: Comparison with Curcumin and Whole Turmeric

    Directory of Open Access Journals (Sweden)

    Sahdeo Prasad

    2017-12-01

    Full Text Available Extensive research within last two decades has indicated that curcumin extracted from turmeric (Curcuma longa, exhibits anticancer potential, in part through the modulation of inflammatory pathways. However, the residual antitumor activity of curcumin-free turmeric (CFT relative to curcumin or turmeric is not well-understood. In the present study, therefore, we determined activities of these agents in both in vitro and in vivo models of human HCT-116 colorectal cancer (CRC. When examined in an in vitro antiproliferative, clonogenic or anti-inflammatory assay system, we found that curcumin was highly active whereas turmeric and CFT had relatively poor activity against CRC cells. However, when examined in vivo at an oral dose of either 100 or 500 mg/kg given to nude mice bearing CRC xenografts, all three preparations of curcumin, turmeric, and CFT similarly suppressed the growth of the xenograft. The effect of CFT on suppression of tumor growth was dose-dependent, with 500 mg/kg tending to be more effective than 100 mg/kg. Interestingly, 100 mg/kg curcumin or turmeric was found to be more effective than 500 mg/kg. When examined in vivo for the expression of biomarkers associated with cell survival (cIAP-1, Bcl-2, and survivin, proliferation (Ki-67 and cyclin D1 and metastasis (ICAM-1 and VEGF, all were down-modulated. These agents also suppressed inflammatory transcription factors (NF-κB and STAT3 in tumor cells. Overall, our results with CFT provide evidence that turmeric must contain additional bioactive compounds other than curcumin that, in contrast to curcumin, exhibit greater anticancer potential in vivo than in vitro against human CRC. Moreover, our study highlights the fact that the beneficial effects of turmeric and curcumin in humans may be more effectively realized at lower doses, whereas CFT could be given at higher doses without loss in favorable activity.

  14. Potential Antiviral Agents from Marine Fungi: An Overview

    Directory of Open Access Journals (Sweden)

    Soheil Zorofchian Moghadamtousi

    2015-07-01

    Full Text Available Biodiversity of the marine world is only partially subjected to detailed scientific scrutiny in comparison to terrestrial life. Life in the marine world depends heavily on marine fungi scavenging the oceans of lifeless plants and animals and entering them into the nutrient cycle by. Approximately 150 to 200 new compounds, including alkaloids, sesquiterpenes, polyketides, and aromatic compounds, are identified from marine fungi annually. In recent years, numerous investigations demonstrated the tremendous potential of marine fungi as a promising source to develop new antivirals against different important viruses, including herpes simplex viruses, the human immunodeficiency virus, and the influenza virus. Various genera of marine fungi such as Aspergillus, Penicillium, Cladosporium, and Fusarium were subjected to compound isolation and antiviral studies, which led to an illustration of the strong antiviral activity of a variety of marine fungi-derived compounds. The present review strives to summarize all available knowledge on active compounds isolated from marine fungi with antiviral activity.

  15. Potential Antiviral Agents from Marine Fungi: An Overview

    Science.gov (United States)

    Zorofchian Moghadamtousi, Soheil; Nikzad, Sonia; Abdul Kadir, Habsah; Abubakar, Sazaly; Zandi, Keivan

    2015-01-01

    Biodiversity of the marine world is only partially subjected to detailed scientific scrutiny in comparison to terrestrial life. Life in the marine world depends heavily on marine fungi scavenging the oceans of lifeless plants and animals and entering them into the nutrient cycle by. Approximately 150 to 200 new compounds, including alkaloids, sesquiterpenes, polyketides, and aromatic compounds, are identified from marine fungi annually. In recent years, numerous investigations demonstrated the tremendous potential of marine fungi as a promising source to develop new antivirals against different important viruses, including herpes simplex viruses, the human immunodeficiency virus, and the influenza virus. Various genera of marine fungi such as Aspergillus, Penicillium, Cladosporium, and Fusarium were subjected to compound isolation and antiviral studies, which led to an illustration of the strong antiviral activity of a variety of marine fungi-derived compounds. The present review strives to summarize all available knowledge on active compounds isolated from marine fungi with antiviral activity. PMID:26204947

  16. Lactoferrin. Antiviral activity of lactoferrin

    NARCIS (Netherlands)

    Swart, P J; Kuipers, E M; Smit, C; Van Der Strate, B W; Harmsen, M C; Meijer, D K

    1998-01-01

    A series of native and chemically derivatized lactoferrins (Lfs) purified from milk and colostrum were assayed in vitro for their anti-HIV and anti-HCMV-cytopathic effects in MT4 cells and fibroblasts respectively. All Lfs from bovine and human milk or colostrum were able to completely block HCMV

  17. Human Exhibitions

    DEFF Research Database (Denmark)

    Andreassen, Rikke

    of displayed people, connecting the attitudes and science of the past with both our (continued) modern fascination with ‘the exotic’, and contemporary language and popular culture. As such, it will be of interest to scholars of sociology, anthropology and history working in the areas of gender and sexuality...... light on the staging of exhibitions, the daily life of the exhibitees, the wider connections between shows across Europe and the thinking of the time on matters of race, science, gender and sexuality. A window onto contemporary racial understandings, the book presents interviews with the descendants...

  18. Human Exhibitions

    DEFF Research Database (Denmark)

    Andreassen, Rikke

    , this book draws on unique archival material, including photographs, documentary evidence and newspaper articles, newly discovered in Copenhagen. This opens for new insights and perspectives on these European exhibitions. The book employs post-colonial and feminist approaches to the material to shed fresh...... of displayed people, connecting the attitudes and science of the past with both our (continued) modern fascination with ‘the exotic’, and contemporary language and popular culture. As such, it will be of interest to scholars of sociology, anthropology and history working in the areas of gender and sexuality...

  19. Plant-produced anti-dengue virus monoclonal antibodies exhibit reduced antibody-dependent enhancement of infection activity.

    Science.gov (United States)

    Dent, Matthew; Hurtado, Jonathan; Paul, Amber M; Sun, Haiyan; Lai, Huafang; Yang, Ming; Esqueda, Adrian; Bai, Fengwei; Steinkellner, Herta; Chen, Qiang

    2016-12-01

    The mAb E60 has the potential to be a desirable therapeutic molecule since it efficiently neutralizes all four serotypes of dengue virus (DENV). However, mammalian-cell-produced E60 exhibits antibody-dependent enhancement of infection (ADE) activity, rendering it inefficacious in vivo, and treated animals more susceptible to developing more severe diseases during secondary infection. In this study, we evaluated a plant-based expression system for the production of therapeutically suitable E60. The mAb was transiently expressed in Nicotiana benthamianaWT and a ∆XFT line, a glycosylation mutant lacking plant-specific N-glycan residues. The mAb was efficiently expressed and assembled in leaves and exhibited highly homogenous N-glycosylation profiles, i.e. GnGnXF3 or GnGn structures, depending on the expression host. Both E60 glycovariants demonstrated equivalent antigen-binding specificity and in vitro neutralization potency against DENV serotypes 2 and 4 compared with their mammalian-cell-produced counterpart. By contrast, plant-produced E60 exhibited reduced ADE activity in Fc gamma receptor expressing human cells. Our results suggest the ability of plant-produced antibodies to minimize ADE, which may lead to the development of safe and highly efficacious antibody-based therapeutics against DENV and other ADE-prone viral diseases. Our study provides so far unknown insight into the relationship between mAb N-glycosylation and ADE, which contributes to our understanding of how sugar moieties of antibodies modulate Fc-mediated functions and viral pathogenesis.

  20. A Meloidogyne incognita effector is imported into the nucleus and exhibits transcriptional activation activity in planta.

    Science.gov (United States)

    Zhang, Lei; Davies, Laura J; Elling, Axel A

    2015-01-01

    Root-knot nematodes are sedentary biotrophic endoparasites that maintain a complex interaction with their host plants. Nematode effector proteins are synthesized in the oesophageal glands of nematodes and secreted into plant tissue through a needle-like stylet. Effectors characterized to date have been shown to mediate processes essential for nematode pathogenesis. To gain an insight into their site of action and putative function, the subcellular localization of 13 previously isolated Meloidogyne incognita effectors was determined. Translational fusions were created between effectors and EGFP-GUS (enhanced green fluorescent protein-β-glucuronidase) reporter genes, which were transiently expressed in tobacco leaf cells. The majority of effectors localized to the cytoplasm, with one effector, 7H08, imported into the nuclei of plant cells. Deletion analysis revealed that the nuclear localization of 7H08 was mediated by two novel independent nuclear localization domains. As a result of the nuclear localization of the effector, 7H08 was tested for the ability to activate gene transcription. 7H08 was found to activate the expression of reporter genes in both yeast and plant systems. This is the first report of a plant-parasitic nematode effector with transcriptional activation activity. © 2014 BSPP AND JOHN WILEY & SONS LTD.