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Sample records for antiviral drug oseltamivir

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

    Energy Technology Data Exchange (ETDEWEB)

    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

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

    International Nuclear Information System (INIS)

    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

  3. 75 FR 20429 - Amended Authorizations of Emergency Use of Certain Antiviral Drugs Zanamivir and Oseltamivir...

    Science.gov (United States)

    2010-04-19

    ... Register (74 FR 38628, August 4, 2009), as was the notice of the April 27, 2009, Authorizations (74 FR... and oseltamivir phosphate capsules deployed from the Strategic National Stockpile (SNS) that were... addition to those held in or deployed from the SNS that were beyond or would be beyond their...

  4. Oseltamivir

    Directory of Open Access Journals (Sweden)

    Tullu M

    2009-01-01

    Full Text Available Oseltamivir, a selective neuraminidase enzyme inhibitor, has gained worldwide attention in view of Influenza A (H1N1 pandemic. It is one of the most important drugs effective against the novel influenza virus. Oseltamivir is used for the treatment of uncomplicated acute illness due to influenza infection. Early initiation of treatment with the drug provides greater clinical benefits. The drug can also be effectively used for prophylaxis. Oseltamivir is readily absorbed from the gastrointestinal tract and is converted to the active metabolite- oseltamivir carboxylate, which has a wider distribution in the body. Oseltamivir carboxylate is eliminated in the urine with a half-life of 6-10 h. The drug is generally well-tolerated and does not have many clinically significant drug interactions. Nausea and vomiting are the commonest adverse effects associated with its use. The standard adult dose for treatment is 75 mg twice a day for five days and the dose for prophylaxis is 75 mg once daily for at least seven days following contact with an infected individual. The dose needs to be adjusted in patients with renal failure but no adjustments are required in patients with hepatic impairment. Although most of the influenza virus strains are sensitive to oseltamivir, development of drug resistance may limit the clinical utility of the drug in the future.

  5. Triple combination of amantadine, ribavirin, and oseltamivir is highly active and synergistic against drug resistant influenza virus strains in vitro.

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    Jack T Nguyen

    Full Text Available The rapid emergence and subsequent spread of the novel 2009 Influenza A/H1N1 virus (2009 H1N1 has prompted the World Health Organization to declare the first pandemic of the 21st century, highlighting the threat of influenza to public health and healthcare systems. Widespread resistance to both classes of influenza antivirals (adamantanes and neuraminidase inhibitors occurs in both pandemic and seasonal viruses, rendering these drugs to be of marginal utility in the treatment modality. Worldwide, virtually all 2009 H1N1 and seasonal H3N2 strains are resistant to the adamantanes (rimantadine and amantadine, and the majority of seasonal H1N1 strains are resistant to oseltamivir, the most widely prescribed neuraminidase inhibitor (NAI. To address the need for more effective therapy, we evaluated the in vitro activity of a triple combination antiviral drug (TCAD regimen composed of drugs with different mechanisms of action against drug-resistant seasonal and 2009 H1N1 influenza viruses. Amantadine, ribavirin, and oseltamivir, alone and in combination, were tested against amantadine- and oseltamivir-resistant influenza A viruses using an in vitro infection model in MDCK cells. Our data show that the triple combination was highly synergistic against drug-resistant viruses, and the synergy of the triple combination was significantly greater than the synergy of any double combination tested (P<0.05, including the combination of two NAIs. Surprisingly, amantadine and oseltamivir contributed to the antiviral activity of the TCAD regimen against amantadine- and oseltamivir-resistant viruses, respectively, at concentrations where they had no activity as single agents, and at concentrations that were clinically achievable. Our data demonstrate that the TCAD regimen composed of amantadine, ribavirin, and oseltamivir is highly synergistic against resistant viruses, including 2009 H1N1. The TCAD regimen overcomes baseline drug resistance to both classes of

  6. Removal of the antiviral agent oseltamivir and its biological activity by oxidative processes

    International Nuclear Information System (INIS)

    The antiviral agent oseltamivir acid (OA, the active metabolite of Tamiflu®) may occur at high concentrations in wastewater during pandemic influenza events. To eliminate OA and its antiviral activity from wastewater, ozonation and advanced oxidation processes were investigated. For circumneutral pH, kinetic measurements yielded second-order rate constants of 1.7 ± 0.1 × 105 and 4.7 ± 0.2 × 109 M−1 s−1 for the reaction of OA with ozone and hydroxyl radical, respectively. During the degradation of OA by both oxidants, the antiviral activity of the treated aqueous solutions was measured by inhibition of neuraminidase activity of two different viral strains. A transient, moderate (two-fold) increase in antiviral activity was observed in solutions treated up to a level of 50% OA transformation, while for higher degrees of transformation the activity corresponded to that caused exclusively by OA. OA was efficiently removed by ozonation in a wastewater treatment plant effluent, suggesting that ozonation can be applied to remove OA from wastewater. - Highlights: ► Oseltamivir acid (OA) is oxidized by ozone and hydroxyl radical. ► Kinetics: We determined rate constants for the reaction with these oxidants. ► The specific activity of OA as neuraminidase inhibitor disappeared during oxidation. ► Ozonation and advanced oxidation can effectively remove OA from wastewaters. - Ozone and hydroxyl radical treatment processes can degrade aqueous oseltamivir acid and remove its antiviral activity.

  7. Drug Repurposing Identifies Inhibitors of Oseltamivir-Resistant Influenza Viruses.

    Science.gov (United States)

    Bao, Ju; Marathe, Bindumadhav; Govorkova, Elena A; Zheng, Jie J

    2016-03-01

    The neuraminidase (NA) inhibitor, oseltamivir, is a widely used anti-influenza drug. However, oseltamivir-resistant H1N1 influenza viruses carrying the H275Y NA mutation spontaneously emerged as a result of natural genetic drift and drug treatment. Because H275Y and other potential mutations may generate a future pandemic influenza strain that is oseltamivir-resistant, alternative therapy options are needed. Herein, we show that a structure-based computational method can be used to identify existing drugs that inhibit resistant viruses, thereby providing a first line of pharmaceutical defense against this possible scenario. We identified two drugs, nalidixic acid and dorzolamide, that potently inhibit the NA activity of oseltamivir-resistant H1N1 viruses with the H275Y NA mutation at very low concentrations, but have no effect on wild-type H1N1 NA even at a much higher concentration, suggesting that the oseltamivir-resistance mutation itself caused susceptibility to these drugs. PMID:26833677

  8. 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.

  9. Removal of the antiviral agent oseltamivir and its biological activity by oxidative processes.

    Science.gov (United States)

    Mestankova, Hana; Schirmer, Kristin; Escher, Beate I; von Gunten, Urs; Canonica, Silvio

    2012-02-01

    The antiviral agent oseltamivir acid (OA, the active metabolite of Tamiflu(®)) may occur at high concentrations in wastewater during pandemic influenza events. To eliminate OA and its antiviral activity from wastewater, ozonation and advanced oxidation processes were investigated. For circumneutral pH, kinetic measurements yielded second-order rate constants of 1.7 ± 0.1 × 10(5) and 4.7 ± 0.2 × 10(9) M(-1) s(-1) for the reaction of OA with ozone and hydroxyl radical, respectively. During the degradation of OA by both oxidants, the antiviral activity of the treated aqueous solutions was measured by inhibition of neuraminidase activity of two different viral strains. A transient, moderate (two-fold) increase in antiviral activity was observed in solutions treated up to a level of 50% OA transformation, while for higher degrees of transformation the activity corresponded to that caused exclusively by OA. OA was efficiently removed by ozonation in a wastewater treatment plant effluent, suggesting that ozonation can be applied to remove OA from wastewater. PMID:22230064

  10. Emerging antiviral drugs.

    Science.gov (United States)

    De Clercq, Erik

    2008-09-01

    Foremost among the newly described antiviral agents that may be developed into drugs are, for the treatment of human papilloma virus (HPV) infections, cPrPMEDAP; for the treatment of herpes simplex virus (HSV) infections, BAY 57-1293; for the treatment of varicella-zoster virus (VZV) infections, FV-100 (prodrug of Cf 1743); for the treatment of cytomegalovirus (CMV) infections, maribavir; for the treatment of poxvirus infections, ST-246; for the treatment of hepatitis B virus (HBV) infections, tenofovir disoproxil fumarate (TDF) (which in the meantime has already been approved in the EU); for the treatment of various DNA virus infections, the hexadecyloxypropyl (HDP) and octadecyloxyethyl (ODE) prodrugs of cidofovir; for the treatment of orthomyxovirus infections (i.e., influenza), peramivir; for the treatment of hepacivirus infections (i.e., hepatitis C), the protease inhibitors telaprevir and boceprevir, the nucleoside RNA replicase inhibitors (NRRIs) PSI-6130 and R1479, and various non-nucleoside RNA replicase inhibitors (NNRRIs); for the treatment of human immunodeficiency virus (HIV) infections, integrase inhibitors (INIs) such as elvitegravir, nucleoside reverse transcriptase inhibitors (NRTIs) such as apricitabine, non-nucleoside reverse transcriptase inhibitors (NNRTIs) such as rilpivirine and dapivirine; and for the treatment of both HCV and HIV infections, cyclosporin A derivatives such as the non-immunosuppressive Debio-025. PMID:18764719

  11. Antiviral activity of the oseltamivir and Melissa officinalis L. essential oil against avian influenza A virus (H9N2).

    Science.gov (United States)

    Pourghanbari, Gholamhosein; Nili, Hasan; Moattari, Afagh; Mohammadi, Ali; Iraji, Aida

    2016-06-01

    Lemon balm derivatives are going to acquire a novelty as natural and potent remedy for treatment of viral infections since the influenza viruses are developing resistance to the current antivirals widely. Oseltamivir, Melissa officinalis essential oil (MOEO) and their synergistic efficacy against avian influenza virus (AIV) subtype H9N2 were evaluated in vitro in MDCK cells at different time exposure by using TCID50, HA, Real Time PCR and HI assay. The results showed that MOEO could inhibit replication of AVI through the different virus replication phase (P ≤ 0.05). Also the highest antiviral activity of MOEO was seen when AIV incubated with MOEO before cell infection. The TCID50/ml was reduced 1.3-2.1, 2.3-2.8, 3.7-4.5 log 10 than control group (5.6 log 10), HAU/50 µl was decreased 85-94, 71.4-94, 71.4-94 % and viral genome copy number/µl was brought down 68-95, 90-100, 89.6-99.9 % at pre-infection, post-infection and simultaneous stage, respectively. Hemagglutination inhibition result showed the MOEO was not able to inhibit agglutination of the chicken red blood cell (cRBC). Replication of the AVI was suppressed by the different concentration of oseltamivir completely or near 100 %. Also oseltamivir showed a synergistic activity with MOEO especially when oseltamivir concentration reduced under 0.005 mg/ml. The chemical composition was examined by GC-MS analysis and Its main constituents were identified as monoterpenaldehydes citral a, citral b. In conclusion, the findings of the study showed that lemon balm essential oil could inhibit influenza virus replication through different replication cycle steps especially throughout the direct interaction with the virus particles. PMID:27366768

  12. 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.

  13. Influenza Round Table: Antiviral Drugs

    Centers for Disease Control (CDC) Podcasts

    2009-11-04

    In this podcast, Dr. Joe Bresee explains the nature of antiviral drugs and how they are used.  Created: 11/4/2009 by National Center for Immunization and Respiratory Diseases (NCIRD).   Date Released: 11/4/2009.

  14. Adverse drug reaction profile of oseltamivir in children

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    Prashant S Dalvi

    2011-01-01

    Full Text Available Aim: To monitor and evaluate the pattern of ADRs to oseltamivir in pediatric population suffering from H1N1 influenza at a tertiary care hospital. Materials and Methods: Children offered oseltamivir for treatment and chemoprophylaxis were monitored for adverse events by direct questioning for symptoms and clinical examination on day 5 and day 10. Assessment of neurological events was done by asking the parents or guardians regarding development of specific symptoms. Adverse events obtained were analyzed for severity, causality and age-group wise. Results: Out of 191 children (median age, 3 years, 69 (36.1% developed ADRs. Most common symptoms were vomiting (16.2% followed by diarrhea (12.0%, ear disorders (8.9%, and insomnia (6.8%. The incidence of neuropsychiatric symptoms was 12.6% which were mild-to-moderate on severity scale. There was no significant difference in the incidence of adverse events between children less than 1 year and other age groups. Conclusion: Oseltamivir is well tolerated in Indian children with suspected or confirmed H1N1 influenza. Our study also indicates safety of oseltamivir in infants.

  15. The Use of Antiviral Drugs for Influenza: Guidance for Practitioners 2012/2013

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    Fred Y Aoki

    2012-01-01

    Seasonal influenza in 2012/2013 is predicted to be caused by two human influenza A and one influenza B strain, all of which are anticipated to remain generally susceptible to oseltamivir.The predicted strains are A/California/7/2009 (H1N1 pdm09-like, A/Victoria/361/2011 (H3N2-like and B/Wisconsin/1/2010-like (Yamagata lineage. All are included in the seasonal influenza vaccine and are susceptible to oseltamivir.Swine-variant H3N2v, which has rarely caused infection in humans exposed to infected swine within the past year in the United States, is susceptible to oseltamivir. It is not included in the current seasonal influenza vaccine.It is still considered that initiation of antiviral therapy more than 36 h to 48 h after onset of symptoms is beneficial in patients hospitalized with complicated influenza and severe illness.Oseltamivir continues to be recommended for the treatment of influenza in pregnant women.The use of antiviral drugs among measures to control outbreaks of influenza in closed facilities such as correctional institutions is now included in the present document.

  16. Can antiviral drugs contain pandemic influenza transmission?

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    Niels G Becker

    Full Text Available Antiviral drugs dispensed during the 2009 influenza pandemic generally failed to contain transmission. This poses the question of whether preparedness for a future pandemic should include plans to use antiviral drugs to mitigate transmission.Simulations using a standard transmission model that allows for infected arrivals and delayed vaccination show that attempts to contain transmission require relatively few antiviral doses. In contrast, persistent use of antiviral drugs when the reproduction number remains above 1 use very many doses and are unlikely to reduce the eventual attack rate appreciably unless the stockpile is very large. A second model, in which the community has a household structure, shows that the effectiveness of a strategy of dispensing antiviral drugs to infected households decreases rapidly with time delays in dispensing the antivirals. Using characteristics of past pandemics it is estimated that at least 80% of primary household cases must present upon show of symptoms to have a chance of containing transmission by dispensing antiviral drugs to households. To determine data needs, household outbreaks were simulated with 50% receiving antiviral drugs early and 50% receiving antiviral drugs late. A test to compare the size of household outbreaks indicates that at least 100-200 household outbreaks need to be monitored to find evidence that antiviral drugs can mitigate transmission of the newly emerged virus.Use of antiviral drugs in an early attempt to contain transmission should be part of preparedness plans for a future influenza pandemic. Data on the incidence of the first 350 cases and the eventual attack rates of the first 200 hundred household outbreaks should be used to estimate the initial reproduction number R and the effectiveness of antiviral drugs to mitigate transmission. Use of antiviral drugs to mitigate general transmission should cease if these estimates indicate that containment of transmission is unlikely.

  17. Oseltamivir Resistance in Influenza A(H6N2 Caused by an R292K Substitution in Neuraminidase Is Not Maintained in Mallards without Drug Pressure.

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    Anna Gillman

    Full Text Available Wild waterfowl is the natural reservoir of influenza A virus (IAV; hosted viruses are very variable and provide a source for genetic segments which can reassort with poultry or mammalian adapted IAVs to generate novel species crossing viruses. Additionally, wild waterfowl act as a reservoir for highly pathogenic IAVs. Exposure of wild birds to the antiviral drug oseltamivir may occur in the environment as its active metabolite can be released from sewage treatment plants to river water. Resistance to oseltamivir, or to other neuraminidase inhibitors (NAIs, in IAVs of wild waterfowl has not been extensively studied.In a previous in vivo Mallard experiment, an influenza A(H6N2 virus developed oseltamivir resistance by the R292K substitution in the neuraminidase (NA, when the birds were exposed to oseltamivir. In this study we tested if the resistance could be maintained in Mallards without drug exposure. Three variants of resistant H6N2/R292K virus were each propagated during 17 days in five successive pairs of naïve Mallards, while oseltamivir exposure was decreased and removed. Daily fecal samples were analyzed for viral presence, genotype and phenotype.Within three days without drug exposure no resistant viruses could be detected by NA sequencing, which was confirmed by functional NAI sensitivity testing. We conclude that this resistant N2 virus could not compete in fitness with wild type subpopulations without oseltamivir drug pressure, and thus has no potential to circulate among wild birds. The results of this study contrast to previous observations of drug induced resistance in an avian H1N1 virus, which was maintained also without drug exposure in Mallards. Experimental observations on persistence of NAI resistance in avian IAVs resemble NAI resistance seen in human IAVs, in which resistant N2 subtypes do not circulate, while N1 subtypes with permissive mutations can circulate without drug pressure. We speculate that the phylogenetic

  18. Enabling the intestinal absorption of highly polar antiviral agents: ion-pair facilitated membrane permeation of zanamivir heptyl ester and guanidino oseltamivir.

    Science.gov (United States)

    Miller, Jonathan M; Dahan, Arik; Gupta, Deepak; Varghese, Sheeba; Amidon, Gordon L

    2010-08-01

    Antiviral drugs often suffer from poor intestinal permeability, preventing their delivery via the oral route. The goal of this work was to enhance the intestinal absorption of the low-permeability antiviral agents zanamivir heptyl ester (ZHE) and guanidino oseltamivir (GO) utilizing an ion-pairing approach, as a critical step toward making them oral drugs. The counterion 1-hydroxy-2-naphthoic acid (HNAP) was utilized to enhance the lipophilicity and permeability of the highly polar drugs. HNAP substantially increased the log P of the drugs by up to 3.7 log units. Binding constants (K(11(aq))) of 388 M(-1) for ZHE-HNAP and 2.91 M(-1) for GO-HNAP were obtained by applying a quasi-equilibrium transport model to double-reciprocal plots of apparent octanol-buffer distribution coefficients versus HNAP concentration. HNAP enhanced the apparent permeability (P(app)) of both compounds across Caco-2 cell monolayers in a concentration-dependent manner, as substantial P(app) (0.8-3.0 x 10(-6) cm/s) was observed in the presence of 6-24 mM HNAP, whereas no detectable transport was observed without counterion. Consistent with a quasi-equilibrium transport model, a linear relationship with slope near 1 was obtained from a log-log plot of Caco-2 P(app) versus HNAP concentration, supporting the ion-pair mechanism behind the permeability enhancement. In the rat jejunal perfusion assay, the addition of HNAP failed to increase the effective permeability (P(eff)) of GO. However, the rat jejunal permeability of ZHE was significantly enhanced by the addition of HNAP in a concentration-dependent manner, from essentially zero without HNAP to 4.0 x 10(-5) cm/s with 10 mM HNAP, matching the P(eff) of the high-permeability standard metoprolol. The success of ZHE-HNAP was explained by its >100-fold stronger K(11(aq)) versus GO-HNAP, making ZHE-HNAP less prone to dissociation and ion-exchange with competing endogenous anions and able to remain intact during membrane permeation. Overall, this

  19. What You Should Know about Flu Antiviral Drugs

    Science.gov (United States)

    ... this? Submit What's this? Submit Button Past Newsletters What You Should Know About Flu Antiviral Drugs Language: ... that can be used to treat flu illness. What are antiviral drugs? Antiviral drugs are prescription medicines ( ...

  20. Oseltamivir-conjugated polymeric micelles prepared by RAFT living radical polymerization as a new active tumor targeting drug delivery platform.

    Science.gov (United States)

    Kapishon, Vitaliy; Allison, Stephanie; Whitney, Ralph A; Cunningham, Michael F; Szewczuk, Myron R; Neufeld, Ronald J

    2016-02-23

    Targeted drug delivery using polymeric nanostructures has been at the forefront of cancer research, engineered for safer, more efficient and effective use of chemotherapy. Here, we designed a new polymeric micelle delivery system for active tumor targeting followed by micelle-drug internalization via receptor-induced endocytosis. We recently reported that oseltamivir phosphate targets and inhibits Neu1 sialidase activity associated with receptor tyrosine kinases such as epidermal growth factor receptors (EGFRs) which are overexpressed in cancer cells. By decorating micelles with oseltamivir, we investigated whether they actively targeted human pancreatic PANC1 cancer cells. Amphiphilic block copolymers with oseltamivir conjugated at the hydrophilic end, oseltamivir-pPEGMEMA-b-pMMA (oseltamivir-poly(polyethylene glycol methyl ether methacrylate)-block-poly(methyl methacrylate), were synthesized using reversible addition-fragmentation chain transfer (RAFT) living radical polymerization. Oseltamivir-conjugated micelles have self-assembling properties to give worm-like micellar structures with molecular weight of 80 000 g mol(-1). Oseltamivir-conjugated water soluble pPEGMEMA, dose dependently, both inhibited sialidase activity associated with Neu1, and reduced viability of PANC1 cells. In addition, oseltamivir-conjugated micelles, labelled with a hydrophobic fluorescent dye within the micelle core, were subsequently internalized by PANC1 cells. Blocking cell surface Neu1 with anti-Neu1 antibody, reduced internalization of oseltamivir-conjugated micelles, demonstrating that Neu1 binding linked to sialidase inhibition were prerequisite steps for subsequent internalization of the micelles. The mechanism of internalization is likely that of receptor-induced endocytosis demonstrating potential as a new nanocarrier system for not only targeting a tumor cell, but also for directly reducing viability through Neu1 inhibition, followed by intracellular delivery of hydrophobic

  1. Coadministration of Hedera helix L. Extract Enabled Mice to Overcome Insufficient Protection against Influenza A/PR/8 Virus Infection under Suboptimal Treatment with Oseltamivir.

    Science.gov (United States)

    Hong, Eun-Hye; Song, Jae-Hyoung; Shim, Aeri; Lee, Bo-Ra; Kwon, Bo-Eun; Song, Hyuk-Hwan; Kim, Yeon-Jeong; Chang, Sun-Young; Jeong, Hyeon Gun; Kim, Jong Geal; Seo, Sang-Uk; Kim, HyunPyo; Kwon, YongSoo; Ko, Hyun-Jeong

    2015-01-01

    Several anti-influenza drugs that reduce disease manifestation exist, and although these drugs provide clinical benefits in infected patients, their efficacy is limited by the emergence of drug-resistant influenza viruses. In the current study, we assessed the therapeutic strategy of enhancing the antiviral efficacy of an existing neuraminidase inhibitor, oseltamivir, by coadministering with the leaf extract from Hedera helix L, commonly known as ivy. Ivy extract has anti-inflammatory, antibacterial, antifungal, and antihelminthic properties. In the present study, we investigated its potential antiviral properties against influenza A/PR/8 (PR8) virus in a mouse model with suboptimal oseltamivir that mimics a poor clinical response to antiviral drug treatment. Suboptimal oseltamivir resulted in insufficient protection against PR8 infection. Oral administration of ivy extract with suboptimal oseltamivir increased the antiviral activity of oseltamivir. Ivy extract and its compounds, particularly hedrasaponin F, significantly reduced the cytopathic effect in PR8-infected A549 cells in the presence of oseltamivir. Compared with oseltamivir treatment alone, coadministration of the fraction of ivy extract that contained the highest proportion of hedrasaponin F with oseltamivir decreased pulmonary inflammation in PR8-infected mice. Inflammatory cytokines and chemokines, including tumor necrosis factor-alpha and chemokine (C-C motif) ligand 2, were reduced by treatment with oseltamivir and the fraction of ivy extract. Analysis of inflammatory cell infiltration in the bronchial alveolar of PR8-infected mice revealed that CD11b+Ly6G+ and CD11b+Ly6Cint cells were recruited after virus infection; coadministration of the ivy extract fraction with oseltamivir reduced infiltration of these inflammatory cells. In a model of suboptimal oseltamivir treatment, coadministration of ivy extract fraction that includes hedrasaponin F increased protection against PR8 infection that could be

  2. Coadministration of Hedera helix L. Extract Enabled Mice to Overcome Insufficient Protection against Influenza A/PR/8 Virus Infection under Suboptimal Treatment with Oseltamivir.

    Directory of Open Access Journals (Sweden)

    Eun-Hye Hong

    Full Text Available Several anti-influenza drugs that reduce disease manifestation exist, and although these drugs provide clinical benefits in infected patients, their efficacy is limited by the emergence of drug-resistant influenza viruses. In the current study, we assessed the therapeutic strategy of enhancing the antiviral efficacy of an existing neuraminidase inhibitor, oseltamivir, by coadministering with the leaf extract from Hedera helix L, commonly known as ivy. Ivy extract has anti-inflammatory, antibacterial, antifungal, and antihelminthic properties. In the present study, we investigated its potential antiviral properties against influenza A/PR/8 (PR8 virus in a mouse model with suboptimal oseltamivir that mimics a poor clinical response to antiviral drug treatment. Suboptimal oseltamivir resulted in insufficient protection against PR8 infection. Oral administration of ivy extract with suboptimal oseltamivir increased the antiviral activity of oseltamivir. Ivy extract and its compounds, particularly hedrasaponin F, significantly reduced the cytopathic effect in PR8-infected A549 cells in the presence of oseltamivir. Compared with oseltamivir treatment alone, coadministration of the fraction of ivy extract that contained the highest proportion of hedrasaponin F with oseltamivir decreased pulmonary inflammation in PR8-infected mice. Inflammatory cytokines and chemokines, including tumor necrosis factor-alpha and chemokine (C-C motif ligand 2, were reduced by treatment with oseltamivir and the fraction of ivy extract. Analysis of inflammatory cell infiltration in the bronchial alveolar of PR8-infected mice revealed that CD11b+Ly6G+ and CD11b+Ly6Cint cells were recruited after virus infection; coadministration of the ivy extract fraction with oseltamivir reduced infiltration of these inflammatory cells. In a model of suboptimal oseltamivir treatment, coadministration of ivy extract fraction that includes hedrasaponin F increased protection against PR8

  3. Clinical relevance of HCV antiviral drug resistance.

    Science.gov (United States)

    Welsch, C; Zeuzem, S

    2012-10-01

    The approval of direct-acting antiviral agents (DAAs) against the hepatitis C virus (HCV) NS3 protease revolutionized antiviral therapy in chronic hepatitis C. They mark the beginning of an era with drugs designed to inhibit specific viral proteins involved in the virus life cycle rather than the nonspecific antiviral activity of interferon. Upcoming generations of antivirals are expected that lead to viral eradication in most patients who undergo treatment with hope held for years that HCV can be cured without interferon. Antiviral drug resistance plays a key role in DAA-treatment failure. Knowledge on molecular escape mechanisms of resistant variants, their time to wild-type reversal and potential persistence is of upmost importance to design treatment strategies for patients with previous DAA-treatment failure. PMID:23006585

  4. Antiviral Drug Resistance of Human Cytomegalovirus

    OpenAIRE

    Lurain, Nell S.; Chou, Sunwen

    2010-01-01

    Summary: The study of human cytomegalovirus (HCMV) antiviral drug resistance has enhanced knowledge of the virological targets and the mechanisms of antiviral activity. The currently approved drugs, ganciclovir (GCV), foscarnet (FOS), and cidofovir (CDV), target the viral DNA polymerase. GCV anabolism also requires phosphorylation by the virus-encoded UL97 kinase. GCV resistance mutations have been identified in both genes, while FOS and CDV mutations occur only in the DNA polymerase gene. Co...

  5. Vaccines and Antiviral Drugs in Pandemic Preparedness

    OpenAIRE

    Arnold S. Monto

    2006-01-01

    While measures such as closing schools and social distancing may slow the effects of pandemic influenza, only vaccines and antiviral drugs are clearly efficacious in preventing infection or treating illness. Unless the pandemic strain closely resembles one already recognized, vaccine will not be available early. However, studies can be conducted beforehand to address questions concerning vaccine dose, frequency of inoculation, and need for adjuvants. In contrast, antiviral drugs, particularly...

  6. The Use of Antiviral Drugs for Influenza: Guidance for Practitioners 2012/2013

    OpenAIRE

    Fred Y Aoki; Allen, Upton D.; H Grant Stiver; Evans, Gerald A

    2012-01-01

    The present article addresses the use of antiviral drugs in the management of seasonal influenza illness for the 2012/2013 season. It updates the previous document published in 2011 (1). Noteworthy guidance updates since 2011 include the following: Seasonal influenza in 2012/2013 is predicted to be caused by two human influenza A and one influenza B strain, all of which are anticipated to remain generally susceptible to oseltamivir.The predicted strains are A/California/7/2009 (H1N1) pdm09...

  7. Antiviral Drug Resistance: Mechanisms and Clinical Implications

    OpenAIRE

    Strasfeld, Lynne; Chou, Sunwen

    2010-01-01

    Antiviral drug resistance is an increasing concern in immunocompromised patient populations, where ongoing viral replication and prolonged drug exposure lead to the selection of resistant strains. Rapid diagnosis of resistance can be made by associating characteristic viral mutations with resistance to various drugs as determined by phenotypic assays. Management of drug resistance includes optimization of host factors and drug delivery, selection of alternative therapies based on knowledge of...

  8. Bell's Palsy: Treatment with Steroids and Antiviral Drugs

    Science.gov (United States)

    ... PATIENTS and their FAMILIES BELL’S PALSY: TREATMENT WITH STEROIDS AND ANTIVIRAL DRUGS This information sheet is provided to help you understand the role of steroids and antiviral drugs for treating Bell’s palsy. Neurologists ...

  9. Oseltamivir (Tamiflu® in the environment, resistance development in influenza A viruses of dabbling ducks and the risk of transmission of an oseltamivir-resistant virus to humans – a review

    Directory of Open Access Journals (Sweden)

    Josef D. Järhult

    2012-06-01

    Full Text Available The antiviral drug oseltamivir (Tamiflu® is a cornerstone in influenza pandemic preparedness plans worldwide. However, resistance to the drug is a growing concern. The active metabolite oseltamivir carboxylate (OC is not degraded in surface water or sewage treatment plants and has been detected in river water during seasonal influenza outbreaks. The natural influenza reservoir, dabbling ducks, can thus be exposed to OC in aquatic environments. Environmental-like levels of OC induce resistance development in influenza A/H1N1 virus in mallards. There is a risk of resistance accumulation in influenza viruses circulating among wild birds when oseltamivir is used extensively. By reassortment or direct transmission, oseltamivir resistance can be transmitted to humans potentially causing a resistant pandemic or human-adapted highly-pathogenic avian influenza virus. There is a need for more research on resistance development in the natural influenza reservoir and for a prudent use of antivirals.

  10. Drug: D00900 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available D00900 Drug Oseltamivir phosphate (JAN/USAN); Tamiflu (TN) C16H28N2O4. H3PO4 410.1818 410.3997 D ... 08093 Therapeutic category: 6250 ATC code: J05AH02 influenza virus A, B neuraminidase inhibitor Transporter: SLC ... P drug classification [BR:br08302] Antivirals Anti-influenza ... Agents Oseltamivir D00900 Oseltamivir phosphate (J ...

  11. H274Y's Effect on Oseltamivir Resistance: What Happens Before the Drug Enters the Binding Site.

    Science.gov (United States)

    Yusuf, Muhammad; Mohamed, Nornisah; Mohamad, Suriyati; Janezic, Dusanka; Damodaran, K V; Wahab, Habibah A

    2016-01-25

    Increased reports of oseltamivir (OTV)-resistant strains of the influenza virus, such as the H274Y mutation on its neuraminidase (NA), have created some cause for concern. Many studies have been conducted in the attempt to uncover the mechanism of OTV resistance in H274Y NA. However, most of the reported studies on H274Y focused only on the drug-bound system, so the direct effects of the mutation on NA itself prior to drug binding still remain unclear. Therefore, molecular dynamics simulations of NA in apo form, followed by principal component analysis and interaction energy calculations, were performed to investigate the structural changes of the NA binding site as a result of the H274Y mutation. It was observed that the disruption of the NA binding site due to the H274Y mutation was initiated by the repulsive effect of Y274 on the 250-loop, which in turn altered the hydrogen-bonding network around residue 274. The rotated W295 side chain caused the upward movement of the 340-loop. Consequently, sliding box docking results suggested that the binding pathway of OTV was compromised because of the disruption of this binding site. This study also highlighted the importance of the functional group at C6 of the sialic acid mimicry. It is hoped that these results will improve the understanding of OTV resistance and shed some light on the design of a novel anti-influenza drug. PMID:26703840

  12. Antiviral drug discovery: broad-spectrum drugs from nature.

    OpenAIRE

    Martinez, J P; Sasse, F; Brönstrup, M; Diez, J; Meyerhans, A

    2015-01-01

    Covering: up to April 2014. The development of drugs with broad-spectrum antiviral activities is a long pursued goal in drug discovery. It has been shown that blocking co-opted host-factors abrogates the replication of many viruses, yet the development of such host-targeting drugs has been met with scepticism mainly due to toxicity issues and poor translation to in vivo models. With the advent of new and more powerful screening assays and prediction tools, the idea of a drug that can efficien...

  13. Pharmacological Characterization of the Spectrum of Antiviral Activity and Genetic Barrier to Drug Resistance of M2-S31N Channel Blockers.

    Science.gov (United States)

    Ma, Chunlong; Zhang, Jiantao; Wang, Jun

    2016-09-01

    Adamantanes (amantadine and rimantadine) are one of the two classes of Food and Drug Administration-approved antiviral drugs used for the prevention and treatment of influenza A virus infections. They inhibit viral replication by blocking the wild-type (WT) M2 proton channel, thus preventing viral uncoating. However, their use was discontinued due to widespread drug resistance. Among a handful of drug-resistant mutants, M2-S31N is the predominant mutation and persists in more than 95% of currently circulating influenza A strains. We recently designed two classes of M2-S31N inhibitors, S31N-specific inhibitors and S31N/WT dual inhibitors, which are represented by N-[(5-cyclopropyl-1,2-oxazol-3-yl)methyl]adamantan-1-amine (WJ379) and N-[(5-bromothiophen-2-yl)methyl]adamantan-1-amine (BC035), respectively. However, their antiviral activities against currently circulating influenza A viruses and their genetic barrier to drug resistance are unknown. In this report, we evaluated the therapeutic potential of these two classes of M2-S31N inhibitors (WJ379 and BC035) by profiling their antiviral efficacy against multidrug-resistant influenza A viruses, in vitro drug resistance barrier, and synergistic effect with oseltamivir. We found that M2-S31N inhibitors were active against several influenza A viruses that are resistant to one or both classes of Food and Drug Administration-approved anti-influenza drugs. In addition, M2-S31N inhibitors display a higher in vitro genetic barrier to drug resistance than amantadine. The antiviral effect of WJ379 was also synergistic with oseltamivir carboxylate. Overall, these results reaffirm that M2-S31N inhibitors are promising antiviral drug candidates that warrant further development. PMID:27385729

  14. Sales of oseltamivir in Norway prior to the emergence of oseltamivir resistant influenza A(H1N1 viruses in 2007–08

    Directory of Open Access Journals (Sweden)

    Hungnes Olav

    2009-05-01

    Full Text Available Abstract Background An unprecedented high proportion of oseltamivir resistant influenza A(H1N1 viruses emerged in the 2007–08 influenza season. In Norway, two thirds of all tested A(H1N1 viruses were resistant to the antiviral drug. In order to see if this emergence could be explained by a drug induced selection pressure, we analysed data on the sales of oseltamivir in Norway for the years 2002–07. Methods We used data from two sources; the Norwegian Drug Wholesales Statistics Database and the Norwegian Prescription Database (NorPD, for the years 2002–2007. We calculated courses sold of oseltamivir (Tamiflu® per 1000 inhabitants per year. Results Our data showed that, except for the years 2005 and 2006, sales of oseltamivir were low in Norway; courses sold per 1000 inhabitants varied between 0.17–1.64. The higher sales in 2005 and 2006 we believe were caused by private stockpiling in fear of a pandemic, and do not represent actual usage. Conclusion A drug induced selection pressure was probably not the cause of the emergence of oseltamivir resistant influenza A(H1N1 viruses in 2007–08 in Norway.

  15. Oseltamivir PK/PD Modeling and Simulation to Evaluate Treatment Strategies against Influenza-Pneumococcus Coinfection.

    Science.gov (United States)

    Boianelli, Alessandro; Sharma-Chawla, Niharika; Bruder, Dunja; Hernandez-Vargas, Esteban A

    2016-01-01

    Influenza pandemics and seasonal outbreaks have shown the potential of Influenza A virus (IAV) to enhance susceptibility to a secondary infection with the bacterial pathogen Streptococcus pneumoniae (Sp). The high morbidity and mortality rate revealed the poor efficacy of antiviral drugs and vaccines to fight IAV infections. Currently, the most effective treatment for IAV is by antiviral neuraminidase inhibitors. Among them, the most frequently stockpiled is Oseltamivir which reduces viral release and transmission. However, effectiveness of Oseltamivir is compromised by the emergence of resistant IAV strains and secondary bacterial infections. To date, little attention has been given to evaluate how Oseltamivir treatment strategies alter Influenza viral infection in presence of Sp coinfection and a resistant IAV strain emergence. In this paper we investigate the efficacy of current approved Oseltamivir treatment regimens using a computational approach. Our numerical results suggest that the curative regimen (75 mg) may yield 47% of antiviral efficacy and 9% of antibacterial efficacy. An increment in dose to 150 mg (pandemic regimen) may increase the antiviral efficacy to 49% and the antibacterial efficacy to 16%. The choice to decrease the intake frequency to once per day is not recommended due to a significant reduction in both antiviral and antibacterial efficacy. We also observe that the treatment duration of 10 days may not provide a clear improvement on the antiviral and antibacterial efficacy compared to 5 days. All together, our in silico study reveals the success and pitfalls of Oseltamivir treatment strategies within IAV-Sp coinfection and calls for testing the validity in clinical trials. PMID:27379214

  16. Oseltamivir PK/PD Modeling and Simulation to Evaluate Treatment Strategies against Influenza-Pneumococcus Coinfection

    Science.gov (United States)

    Boianelli, Alessandro; Sharma-Chawla, Niharika; Bruder, Dunja; Hernandez-Vargas, Esteban A.

    2016-01-01

    Influenza pandemics and seasonal outbreaks have shown the potential of Influenza A virus (IAV) to enhance susceptibility to a secondary infection with the bacterial pathogen Streptococcus pneumoniae (Sp). The high morbidity and mortality rate revealed the poor efficacy of antiviral drugs and vaccines to fight IAV infections. Currently, the most effective treatment for IAV is by antiviral neuraminidase inhibitors. Among them, the most frequently stockpiled is Oseltamivir which reduces viral release and transmission. However, effectiveness of Oseltamivir is compromised by the emergence of resistant IAV strains and secondary bacterial infections. To date, little attention has been given to evaluate how Oseltamivir treatment strategies alter Influenza viral infection in presence of Sp coinfection and a resistant IAV strain emergence. In this paper we investigate the efficacy of current approved Oseltamivir treatment regimens using a computational approach. Our numerical results suggest that the curative regimen (75 mg) may yield 47% of antiviral efficacy and 9% of antibacterial efficacy. An increment in dose to 150 mg (pandemic regimen) may increase the antiviral efficacy to 49% and the antibacterial efficacy to 16%. The choice to decrease the intake frequency to once per day is not recommended due to a significant reduction in both antiviral and antibacterial efficacy. We also observe that the treatment duration of 10 days may not provide a clear improvement on the antiviral and antibacterial efficacy compared to 5 days. All together, our in silico study reveals the success and pitfalls of Oseltamivir treatment strategies within IAV-Sp coinfection and calls for testing the validity in clinical trials. PMID:27379214

  17. Biodistribution and metabolism of the anti-influenza drug [11C]oseltamivir and its active metabolite [11C]Ro 64-0802 in mice

    International Nuclear Information System (INIS)

    Introduction: Oseltamivir phosphate (Tamiflu) is an orally active anti-influenza drug, which is hydrolyzed by esterase to its carboxylate metabolite Ro 64-0802 with potent activity to inhibit the influenza virus. The abnormal behavior and death associated with the use of oseltamivir have developed into a major problem in Japan where Tamiflu is often prescribed for seasonal influenza. It is critical to determine the amount of oseltamivir and Ro 64-0802 in the human brain and to elucidate the relationship between their amounts and neuropsychiatric side effects. The aim of this study was to evaluate [11C]oseltamivir and [11C]Ro 64-0802 in mice as promising positron emission tomography (PET) ligands for measuring their amounts in living brains. Methods: Whole-body biodistribution of [11C]oseltamivir and [11C]Ro 64-0802 was determined in mice using the dissection method and micro-PET. In vitro and in vivo metabolite assay was performed in the plasma and brain of mice. Results: Between 1 and 60 min after injection of [11C]oseltamivir and [11C]Ro 64-0802, 0.20-0.06% and 0.39-0.03% ID/g were detected in the mouse brains, respectively (dissection method). Radioactivity concentrations in the living brains between 0 and 90 min after injection were measured at standardized uptake values of 0.25-0.05 for [11C]oseltamivir and 0.38-0.02 for [11C]Ro 64-0802 (micro-PET). In vivo metabolite assay demonstrated the presence of [11C]oseltamivir and [11C]Ro 64-0802 in the brains after [11C]oseltamivir injection. Conclusion: This study determined the distribution and metabolism of [11C]oseltamivir and [11C]Ro 64-0802 in mice. PET could be used to measure their amounts in the living brain and to elucidate the relationship between the amounts in the brain and the side effects of Tamiflu in the central nervous system

  18. Biodistribution and metabolism of the anti-influenza drug [{sup 11}C]oseltamivir and its active metabolite [{sup 11}C]Ro 64-0802 in mice

    Energy Technology Data Exchange (ETDEWEB)

    Hatori, Akiko; Arai, Takuya; Yanamoto, Kazuhiko; Yamasaki, Tomoteru; Kawamura, Kazunori; Yui, Joji; Konno, Fujiko; Nakao, Ryuji; Suzuki, Kazutoshi [Department of Molecular Probes, Molecular Imaging Center, National Institute of Radiological Sciences (NIRS), Inage-ku, Chiba 263-8555 (Japan); Zhang Mingrong [Department of Molecular Probes, Molecular Imaging Center, National Institute of Radiological Sciences (NIRS), Inage-ku, Chiba 263-8555 (Japan)], E-mail: zhang@nirs.go.jp

    2009-01-15

    Introduction: Oseltamivir phosphate (Tamiflu) is an orally active anti-influenza drug, which is hydrolyzed by esterase to its carboxylate metabolite Ro 64-0802 with potent activity to inhibit the influenza virus. The abnormal behavior and death associated with the use of oseltamivir have developed into a major problem in Japan where Tamiflu is often prescribed for seasonal influenza. It is critical to determine the amount of oseltamivir and Ro 64-0802 in the human brain and to elucidate the relationship between their amounts and neuropsychiatric side effects. The aim of this study was to evaluate [{sup 11}C]oseltamivir and [{sup 11}C]Ro 64-0802 in mice as promising positron emission tomography (PET) ligands for measuring their amounts in living brains. Methods: Whole-body biodistribution of [{sup 11}C]oseltamivir and [{sup 11}C]Ro 64-0802 was determined in mice using the dissection method and micro-PET. In vitro and in vivo metabolite assay was performed in the plasma and brain of mice. Results: Between 1 and 60 min after injection of [{sup 11}C]oseltamivir and [{sup 11}C]Ro 64-0802, 0.20-0.06% and 0.39-0.03% ID/g were detected in the mouse brains, respectively (dissection method). Radioactivity concentrations in the living brains between 0 and 90 min after injection were measured at standardized uptake values of 0.25-0.05 for [{sup 11}C]oseltamivir and 0.38-0.02 for [{sup 11}C]Ro 64-0802 (micro-PET). In vivo metabolite assay demonstrated the presence of [{sup 11}C]oseltamivir and [{sup 11}C]Ro 64-0802 in the brains after [{sup 11}C]oseltamivir injection. Conclusion: This study determined the distribution and metabolism of [{sup 11}C]oseltamivir and [{sup 11}C]Ro 64-0802 in mice. PET could be used to measure their amounts in the living brain and to elucidate the relationship between the amounts in the brain and the side effects of Tamiflu in the central nervous system.

  19. Compliance to oseltamivir among two populations in Oxfordshire, United Kingdom affected by influenza A(H1N1pdm09, November 2009--a waste water epidemiology study.

    Directory of Open Access Journals (Sweden)

    Andrew C Singer

    Full Text Available Antiviral provision remains the focus of many pandemic preparedness plans, however, there is considerable uncertainty regarding antiviral compliance rates. Here we employ a waste water epidemiology approach to estimate oseltamivir (Tamiflu® compliance. Oseltamivir carboxylate (oseltamivir's active metabolite was recovered from two waste water treatment plant (WWTP catchments within the United Kingdom at the peak of the autumnal wave of the 2009 Influenza A (H1N1pdm09 pandemic. Predictions of oseltamivir consumption from detected levels were compared with two sources of national government statistics to derive compliance rates. Scenario and sensitivity analysis indicated between 3-4 and 120-154 people were using oseltamivir during the study period in the two WWTP catchments and a compliance rate between 45-60%. With approximately half the collected antivirals going unused, there is a clear need to alter public health messages to improve compliance. We argue that a near real-time understanding of drug compliance at the scale of the waste water treatment plant (hundreds to millions of people can potentially help public health messages become more timely, targeted, and demographically sensitive, while potentially leading to less mis- and un-used antiviral, less wastage and ultimately a more robust and efficacious pandemic preparedness plan.

  20. Oseltamivir-resistant pandemic (H1N1) 2009 virus infection in England and Scotland, 2009-2010.

    Science.gov (United States)

    Calatayud, Laurence; Lackenby, Angie; Reynolds, Arlene; McMenamin, Jim; Phin, Nick F; Zambon, Maria; Pebody, Richard

    2011-10-01

    Oseltamivir has been widely used for pandemic (H1N1) 2009 virus infection, and by April 30, 2010, a total of 285 resistant cases were reported worldwide, including 45 in the United Kingdom. To determine risk factors for emergence of oseltamivir resistance and severe infection, a case-control study was conducted in the United Kingdom. Study participants were hospitalized in England or Scotland during January 4, 2009-April 30, 2010. Controls had confirmed oseltamivir-sensitive pandemic (H1N1) 2009 virus infections, and case-patients had confirmed oseltamivir-resistant infections. Of 28 case-patients with available information, 21 (75%) were immunocompromised; 31 of 33 case-patients (94%) received antiviral drugs before a sample was obtained. After adjusting for confounders, case-patients remained significantly more likely than controls to be immunocompromised and at higher risk for showing development of respiratory complications. Selective drug pressure likely explains the development of oseltamivir resistance, especially among immunocompromised patients. Monitoring of antiviral resistance is strongly recommended in this group. PMID:22000349

  1. Oseltamivir-Resistant Pandemic (H1N1) 2009 Virus Infection in England and Scotland, 2009–2010

    Science.gov (United States)

    Lackenby, Angie; Reynolds, Arlene; McMenamin, Jim; Phin, Nick F.; Zambon, Maria C.; Pebody, Richard

    2011-01-01

    Oseltamivir has been widely used for pandemic (H1N1) 2009 virus infection, and by April 30, 2010, a total of 285 resistant cases were reported worldwide, including 45 in the United Kingdom. To determine risk factors for emergence of oseltamivir resistance and severe infection, a case–control study was conducted in the United Kingdom. Study participants were hospitalized in England or Scotland during January 4, 2009–April 30, 2010. Controls had confirmed oseltamivir-sensitive pandemic (H1N1) 2009 virus infections, and case-patients had confirmed oseltamivir-resistant infections. Of 28 case-patients with available information, 21 (75%) were immunocompromised; 31 of 33 case-patients (94%) received antiviral drugs before a sample was obtained. After adjusting for confounders, case-patients remained significantly more likely than controls to be immunocompromised and at higher risk for showing development of respiratory complications. Selective drug pressure likely explains the development of oseltamivir resistance, especially among immunocompromised patients. Monitoring of antiviral resistance is strongly recommended in this group. PMID:22000349

  2. Simultaneous determination of 14 antiviral drugs and relevant metabolites in chicken muscle by UPLC-MS/MS after QuEChERS preparation.

    Science.gov (United States)

    Mu, Pengqian; Xu, Nana; Chai, Tingting; Jia, Qi; Yin, Zhiqiang; Yang, Shuming; Qian, Yongzhong; Qiu, Jing

    2016-06-15

    A fast method for the simultaneous determination of 14 antiviral drugs and relevant metabolites in chicken muscle by ultra-high liquid chromatography tandem mass spectrometry (UPLC-MS/MS) was developed. The analytes included anti-influenza drugs (amantadine, rimantadine, oseltamivir, oseltamivir carboxylate, memantine, arbidol, and moroxydine), anti-herpes drugs (acyclovir, ganciclovir, famciclovir, penciclovir, ribavirin and its main metabolite TCONH2), and an immunomodulator (imiquimod). The samples were pretreated using a modified QuEChERS (Quick, Easy, Cheap, Effective, Rugged and Safe) method. The determination of the target compounds was conducted in less than 11.0min, and specificity was ensured by the use of multiple reaction monitoring (MRM) acquisition mode. Good linearities (R(2)>0.9928) were obtained in the range of 0.1-100μg/L, and the recovery rates were 56.2-113.4% with RSDs of 1.7-10.3% for intra-day precision and 2.4-8.8% for inter-day precision. The LODs and LOQs of all analytes were in the ranges of 0.02-1.0 and 0.05-2.5μg/kg, respectively. An analysis of real samples suggested that this method is simple, sensitive, reliable and practical for the detection of antiviral drugs in animal tissue. PMID:27174693

  3. Drug: D08306 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available D08306 Drug Oseltamivir (INN); Agucort (TN) C16H28N2O4 312.2049 312.4045 D08306.gif Antiviral; E ... nzyme inhibitor, neuraminidase, influenza ... virus [DS:H00398] Same as: C08092 ATC code: J05AH0 ... 2 influenza virus A, B neuraminidase inhibitor map07044 Antivir ...

  4. Synaptic and Behavioral Interactions of Oseltamivir (Tamiflu) with Neurostimulants

    OpenAIRE

    Izumi, Yukitoshi; Tokuda, Kazuhiro; O’Dell, Kazuko A.; Charles F. Zorumski; Narahashi, Toshio

    2008-01-01

    Oseltamivir (Tamiflu), a neuraminidase inhibitor, is widely used for treatment of influenza. Because abnormal behaviors have been observed in some Japanese teenagers following oseltamivir use, its safety has been questioned. Oseltamivir is known to alter neuronal function and behavior in animals, particularly when administered in combination with ethanol. Based on this, we hypothesized that interactions of oseltamivir with other drugs may result in altered CNS excitability. We found that inje...

  5. The treatment of influenza with antiviral drugs

    OpenAIRE

    Stiver, Grant

    2003-01-01

    Influenza vaccination with current inactivated vaccines homologous to the prevalent wild-type virus can reduce influenza illness in 75%–80% of healthy adults. Vaccine is recommended for all individuals with chronic underlying diseases and for those aged 65 years or older. Although influenza vaccination is still advocated for patients with blunted immunity, protection rates are not as high, running at 40% for frail institutionalized elderly people. The influenza antiviral agents amantadine or ...

  6. Aminoadamantanes versus other antiviral drugs for chronic hepatitis C

    DEFF Research Database (Denmark)

    Lamers, Mieke H; Broekman, Mark; Drenth, Joost Ph;

    2014-01-01

    aminoadamantanes for patients with chronic hepatitis C would show strong benefits, it is probably better to focus on the assessments of other direct acting antiviral drugs. We found no evidence assessing other aminoadamantanes in randomised clinical trials in order to recommend or refute their use....... months after the end of treatment) in approximately 40% to 80% of treated patients, depending on viral genotype. Recently, a new class of drugs have emerged for hepatitis C infection, the direct acting antivirals, which in combination with standard therapy or alone can lead to sustained virological...... response in 80% or more of treated patients. Aminoadamantanes, mostly amantadine, are antiviral drugs used for the treatment of patients with chronic hepatitis C. We have previously systematically reviewed amantadine versus placebo or no intervention and found no significant effects of the amantadine on...

  7. Oseltamivir and Neuropsychiatric Behaviors – A Case Report on an Adolescent Teen and Evaluation of the Literature

    Directory of Open Access Journals (Sweden)

    Tsz-Yin SO

    2009-11-01

    Full Text Available OBJECTIVE: To illustrate a case of oseltamivir induced neuropsychiatric behaviors in an adolescent teen. CASE SUMMARY: A 15-year-old previously healthy adolescent presented to the emergency department with acute onset of altered mental status after taking two doses of oseltamivir prescribed to him by his primary care physician for presumed influenza infection. A thorough examination at the hospital, which included a urine drug screen, complete blood count, complete metabolic panel, urine and blood cultures, head computed tomography, and chest radiograph, did not indicate any other clinical conditions that could explain his abnormal behaviors. No other medications were given to him in the hospital. About 20 hours after the last dose of oseltamivir, he awoke from a nap and his mental status was completely back to baseline. He had no memory of the events transpired in the past 24 hours and was discharged home with no further incidence.DISSCUSION: Oseltamivir is an anti-viral agent that is often used as treatment and prophylaxis for influenza infection. Neuropsychiatric adverse events such as hallucination and delirium can potentially occur with this agent. This rare adverse event may be due to the binding of the medication to the enzyme sialidase causing increase in dopamine activity. Most of the reports were in young Japanese children less than 16 years old. Some studies have shown a causal relationship with oseltamivir leading to this adverse event, while some have failed to do so, probably due to flaws in their analytical method. The Naranjo ADR probability scale showed a possible causality between neuropsychiatric behaviors and oseltamivir administration in this patient.CONCLUSIONS: Oseltamivir is an effective anti-viral for influenza infection if started early in the course of the illness. Clinicians should monitor for neuropsychiatric symptoms when starting patients on this medication.

  8. Flu Resistance to Antiviral Drug in North Carolina

    Centers for Disease Control (CDC) Podcasts

    2011-12-19

    Dr. Katrina Sleeman, Associate Service Fellow at CDC, discusses resistance to an antiviral flu drug in North Carolina.  Created: 12/19/2011 by National Center for Emerging and Zoonotic Infectious Diseases (NCEZID).   Date Released: 12/19/2011.

  9. INVESTMENT IN ANTIVIRAL DRUGS : A REAL OPTIONS APPROACH

    NARCIS (Netherlands)

    Attema, Arthur E.; Lugner, Anna K.; Feenstra, Talitha L.

    2010-01-01

    Real options analysis is a promising approach to model investment under uncertainty. We employ this approach to value stockpiling of antiviral drugs as a precautionary measure against a possible influenza pandemic. Modifications of the real options approach to include risk attitude and deviations fr

  10. H1N1 Flu and Antiviral Drugs

    Centers for Disease Control (CDC) Podcasts

    2009-05-02

    This podcast discusses the use of antiviral drugs for treating and preventing the H1N1 flu virus.  Created: 5/2/2009 by Coordinating Center for Infectious Diseases, National Center for Immunization and Respiratory Diseases, Influenza Division (CCID/NCIRD/ID).   Date Released: 5/2/2009.

  11. Approved Antiviral Drugs over the Past 50 Years.

    Science.gov (United States)

    De Clercq, Erik; Li, Guangdi

    2016-07-01

    Since the first antiviral drug, idoxuridine, was approved in 1963, 90 antiviral drugs categorized into 13 functional groups have been formally approved for the treatment of the following 9 human infectious diseases: (i) HIV infections (protease inhibitors, integrase inhibitors, entry inhibitors, nucleoside reverse transcriptase inhibitors, nonnucleoside reverse transcriptase inhibitors, and acyclic nucleoside phosphonate analogues), (ii) hepatitis B virus (HBV) infections (lamivudine, interferons, nucleoside analogues, and acyclic nucleoside phosphonate analogues), (iii) hepatitis C virus (HCV) infections (ribavirin, interferons, NS3/4A protease inhibitors, NS5A inhibitors, and NS5B polymerase inhibitors), (iv) herpesvirus infections (5-substituted 2'-deoxyuridine analogues, entry inhibitors, nucleoside analogues, pyrophosphate analogues, and acyclic guanosine analogues), (v) influenza virus infections (ribavirin, matrix 2 protein inhibitors, RNA polymerase inhibitors, and neuraminidase inhibitors), (vi) human cytomegalovirus infections (acyclic guanosine analogues, acyclic nucleoside phosphonate analogues, pyrophosphate analogues, and oligonucleotides), (vii) varicella-zoster virus infections (acyclic guanosine analogues, nucleoside analogues, 5-substituted 2'-deoxyuridine analogues, and antibodies), (viii) respiratory syncytial virus infections (ribavirin and antibodies), and (ix) external anogenital warts caused by human papillomavirus infections (imiquimod, sinecatechins, and podofilox). Here, we present for the first time a comprehensive overview of antiviral drugs approved over the past 50 years, shedding light on the development of effective antiviral treatments against current and emerging infectious diseases worldwide. PMID:27281742

  12. Searching for antiviral drugs for human papillomaviruses.

    Science.gov (United States)

    Underwood, M R; Shewchuk, L M; Hassell, A M; Phelps, W C

    2000-12-01

    The human papillomaviruses (HPVs) are ubiquitous human pathogens that cause a wide variety of benign and pre-malignant epithelial tumours. Of the almost 100 different types of HPV that have been characterized to date, approximately two dozen specifically infect genital and oral mucosa. Mucosal HPVs are most frequently sexually transmitted and, with an incidence roughly twice that of herpes simplex virus infection, are considered one of the most common sexually transmitted diseases throughout the world. A subset of genital HPVs, termed 'high-risk' HPVs, is highly associated with the development of genital cancers including cervical carcinoma. The absence of a simple monolayer cell culture system for analysis and propagation of the virus has substantially retarded progress in the development of diagnostic and therapeutic strategies for HPV infection. In spite of these difficulties, great progress has been made in the elucidation of the molecular controls of virus gene expression, replication and pathogenesis. With this knowledge and some important new tools, there is great potential for the development of improved diagnostic and prognostic tests, prophylactic and therapeutic vaccines, and traditional antiviral medicines. PMID:11142617

  13. Anti-Viral Drugs for Human Adenoviruses

    Directory of Open Access Journals (Sweden)

    Chor Wing Sing

    2010-10-01

    Full Text Available There are many stages in the development of a new drug for viral infection and such processes are even further complicated for adenovirus by the fact that there are at least 51 serotypes, forming six distinct groups (A–F, with different degree of infectivity. This review attempts to address the importance of developing pharmaceuticals for adenovirus and also review recent development in drug discovery for adenovirus, including newer strategies such as microRNA approaches. Different drug screening strategies will also be discussed.

  14. Coadministration of Hedera helix L. Extract Enabled Mice to Overcome Insufficient Protection against Influenza A/PR/8 Virus Infection under Suboptimal Treatment with Oseltamivir

    OpenAIRE

    Eun-Hye Hong; Jae-Hyoung Song; Aeri Shim; Bo-Ra Lee; Bo-Eun Kwon; Hyuk-Hwan Song; Yeon-Jeong Kim; Sun-Young Chang; Hyeon Gun Jeong; Jong Geal Kim; Sang-Uk Seo; HyunPyo Kim; YongSoo Kwon; Hyun-Jeong Ko

    2015-01-01

    Several anti-influenza drugs that reduce disease manifestation exist, and although these drugs provide clinical benefits in infected patients, their efficacy is limited by the emergence of drug-resistant influenza viruses. In the current study, we assessed the therapeutic strategy of enhancing the antiviral efficacy of an existing neuraminidase inhibitor, oseltamivir, by coadministering with the leaf extract from Hedera helix L, commonly known as ivy. Ivy extract has anti-inflammatory, antiba...

  15. Carrier-Mediated Prodrug Uptake to Improve the Oral Bioavailability of Polar Drugs: An Application to an Oseltamivir Analogue.

    Science.gov (United States)

    Incecayir, Tuba; Sun, Jing; Tsume, Yasuhiro; Xu, Hao; Gose, Tomoka; Nakanishi, Takeo; Tamai, Ikumi; Hilfinger, John; Lipka, Elke; Amidon, Gordon L

    2016-02-01

    The goal of this study was to improve the intestinal mucosal cell membrane permeability of the poorly absorbed guanidino analogue of a neuraminidase inhibitor, oseltamivir carboxylate (GOC) using a carrier-mediated strategy. Valyl amino acid prodrug of GOC with isopropyl-methylene-dioxy linker (GOC-ISP-Val) was evaluated as the potential substrate for intestinal oligopeptide transporter, hPEPT1 in Xenopus laevis oocytes heterologously expressing hPEPT1, and an intestinal mouse perfusion system. The diastereomers of GOC-ISP-Val were assessed for chemical and metabolic stability. Permeability of GOC-ISP-Val was determined in Caco-2 cells and mice. Diastereomer 2 was about 2 times more stable than diastereomer 1 in simulated intestinal fluid and rapidly hydrolyzed to the parent drug in cell homogenates. The prodrug had a 9 times-enhanced apparent permeability (P(app)) in Caco-2 cells compared with the parent drug. Both diastereomer exhibited high effective permeability (P(eff)) in mice, 6.32 ± 3.12 and 5.20 ± 2.81 × 10(-5) cm/s for diastereomer 1 and 2, respectively. GOC-ISP-Val was found to be a substrate of hPEPT1. Overall, this study indicates that the prodrug, GOC-ISP-Val, seems to be a promising oral anti-influenza agent that has sufficient stability at physiologically relevant pHs before absorption, significantly improved permeability via hPEPT1 and potentially rapid activation in the intestinal cells. PMID:26869437

  16. Antiviral resistance and the control of pandemic influenza.

    Directory of Open Access Journals (Sweden)

    Marc Lipsitch

    2007-01-01

    Full Text Available BACKGROUND: The response to the next influenza pandemic will likely include extensive use of antiviral drugs (mainly oseltamivir, combined with other transmission-reducing measures. Animal and in vitro studies suggest that some strains of influenza may become resistant to oseltamivir while maintaining infectiousness (fitness. Use of antiviral agents on the scale anticipated for the control of pandemic influenza will create an unprecedented selective pressure for the emergence and spread of these strains. Nonetheless, antiviral resistance has received little attention when evaluating these plans. METHODS AND FINDINGS: We designed and analyzed a deterministic compartmental model of the transmission of oseltamivir-sensitive and -resistant influenza infections during a pandemic. The model predicts that even if antiviral treatment or prophylaxis leads to the emergence of a transmissible resistant strain in as few as 1 in 50,000 treated persons and 1 in 500,000 prophylaxed persons, widespread use of antivirals may strongly promote the spread of resistant strains at the population level, leading to a prevalence of tens of percent by the end of a pandemic. On the other hand, even in circumstances in which a resistant strain spreads widely, the use of antivirals may significantly delay and/or reduce the total size of the pandemic. If resistant strains carry some fitness cost, then, despite widespread emergence of resistance, antivirals could slow pandemic spread by months or more, and buy time for vaccine development; this delay would be prolonged by nondrug control measures (e.g., social distancing that reduce transmission, or use of a stockpiled suboptimal vaccine. Surprisingly, the model suggests that such nondrug control measures would increase the proportion of the epidemic caused by resistant strains. CONCLUSIONS: The benefits of antiviral drug use to control an influenza pandemic may be reduced, although not completely offset, by drug resistance

  17. A case for developing antiviral drugs against polio.

    Science.gov (United States)

    Collett, Marc S; Neyts, Johan; Modlin, John F

    2008-09-01

    Polio eradication is within sight. In bringing the world close to this ultimate goal, the Global Polio Eradication Initiative (GPEI) has relied exclusively on the live, attenuated oral poliovirus vaccine (OPV). However, as eradication nears, continued OPV use becomes less tenable due to the incidence of vaccine associated paralytic poliomyelitis (VAPP) in vaccine recipients and disease caused by circulating vaccine-derived polioviruses (cVDPVs) in contacts. Once wild poliovirus transmission has been interrupted globally, OPV use will stop. This will leave the inactivated poliovirus vaccine (IPV) as the only weapon to defend a polio-free world. Outbreaks caused by cVDPVs are expected post-OPV cessation, and accidental or deliberate releases of virus could also occur. There are serious doubts regarding the ability of IPV alone to control outbreaks. Here, we argue that antiviral drugs against poliovirus be added to the arsenal. Anti-poliovirus drugs could be used to treat the infected and protect the exposed, acting rapidly on their own to contain an outbreak and used as a complement to IPV. While there are no polio antiviral drugs today, the technological feasibility of developing such drugs and their probability of clinical success have been established by over three decades of drug development targeting the related rhinoviruses and non-polio enteroviruses (NPEVs). Because of this history, there are known compounds with anti-poliovirus activity in vitro that represent excellent starting points for polio drug development. Stakeholders must come to understand the potential public health benefits of polio drugs, the feasibility of their development, and the relatively modest costs involved. Given the timelines for eradication and those for drug development, the time for action is now. PMID:18513807

  18. Virus susceptibility and clinical effectiveness of anti-influenza drugs during the 2010–2011 influenza season in Russia

    OpenAIRE

    I.A. Leneva; E.I. Burtseva; S.B. Yatsyshina; I.T. Fedyakina; E.S. Kirillova; E.P. Selkova; Osipova, E.; V. V. Maleev

    2016-01-01

    Background: Antiviral drugs are critical adjuncts to influenza vaccination. This study determined the in vitro susceptibilities of influenza A and B viruses isolated in the 2010–2011 season in Russia to the neuraminidase inhibitor oseltamivir and the hemagglutinin fusion inhibitor umifenovir and clinical efficacy of this antiviral drugs in this season. Methods: The antiviral potency of these drugs against A(H1N1)pdm09 virus in mice was assessed. Importantly, the clinical effectiveness of o...

  19. Epidemiological Characteristics of Novel Influenza A (H1N1) in Antiviral Drug Users in Korea

    OpenAIRE

    Kyunghi Choi; Sung-il Cho; Masahiro Hashizume; Ho Kim

    2012-01-01

    Soon after the first novel influenza A (H1N1) death was documented in Korea on August 15, 2009, prompt treatment with antiviral drugs was recommended when an infection was suspected. Free antiviral drugs were distributed to patients who met the case definition in the treatment guidelines, and patients prescribed the antiviral drugs were included in the Antiviral Drug Surveillance System (ADSS). A total of 2,825,821 patients were reported to the ADSS from September 1 to December 31, 2009. Odds...

  20. Antiviral drug profile of human influenza A & B viruses circulating in India: 2004-2011

    Directory of Open Access Journals (Sweden)

    V A Potdar

    2014-01-01

    Full Text Available Background & objectives: Recent influenza antiviral resistance studies in South East Asia, Europe and the United States reveal adamantane and neuraminidase inhibitor (NAIs resistance. This study was undertaken to evaluate antiviral resistance in influenza viruses isolated from various parts of India, during 2004 to 2011. Methods: Influenza viruses were analyzed genetically for known resistance markers by M2 and NA gene sequencing. Influenza A/H1N1 (n=206, A/H3N2 (n=371 viruses for amantadine resistance and A/H1N1 (n=206, A/H3N2 (n=272 and type B (n=326 for oseltamivir resistance were sequenced. Pandemic (H1N1 (n= 493 isolates were tested for H274Y mutation by real time reverse transcription (rRT-PCR. Randomly selected resistant and sensitive influenza A/H1N1 and A/H3N2 viruses were confirmed by phenotypic assay. Results: Serine to asparagine (S3IN mutation was detected in six isolates of 2007-2008.One dual-resistant A/H1N1 was detected for the first time in India with leucine to phenylalanine (L26F mutation in M2 gene and H274Y mutation in NA gene. A/H3N2 viruses showed an increase in resistance to amantadine from 22.5 per cent in 2005 to 100 per cent in 2008 onwards with S3IN mutation. Fifty of the 61 (82% A/H1N1 viruses tested in 2008-2009 were oseltamivir resistant with H274Y mutation, while all A/H3N2, pandemic A/H1N1 and type B isolates remained sensitive. Genetic results were also confirmed by phenotypic analysis of randomly selected 50 resistant A/H1N1 and 40 sensitive A/H3N2 isolates. Interpretation & conclusions: Emergence of influenza viruses resistant to amantadine and oseltamivir in spite of negligible usage of antivirals emphasizes the need for continuous monitoring of antiviral resistance.

  1. The use of antiviral drugs for influenza: Guidance for practitioners, 2012/2013; Paediatric summary

    OpenAIRE

    Allen, Upton D.

    2013-01-01

    This practice point summarizes the use of antiviral drugs to manage influenza illness in children and youth for the 2012/2013 season. It excerpts a recently published, full-length update of Canadian recommendations for clinicians on the use of antiviral drugs for the prevention and treatment of influenza, with a focus on paediatric antiviral therapy. Detailed information on the selective use of chemoprophylaxis can be found in the source document, which also highlights the importance of secon...

  2. Occurrence and fate of oseltamivir carboxylate (Tamiflu) and amantadine in sewage treatment plants.

    Science.gov (United States)

    Ghosh, Gopal Chandra; Nakada, Norihide; Yamashita, Naoyuki; Tanaka, Hiroaki

    2010-09-01

    We investigated the occurrence and fate of the two antiviral drugs oseltamivir carboxylate (OC)-the active metabolite of Tamiflu-and amantadine (AMT) at three sewage treatment plants (STPs) during the 2008-2009 and 2009-2010 influenza seasons in Japan. Both compounds were detected in all samples analyzed. The concentrations in raw influents at the STPs ranged from 140 to 460 ng L(-1) OC and from 184 to 538 ng L(-1) AMT. Primary treatment gave no substantial removal of the drugs (OC, 2-9%; AMT, 7-17%). Biological nutrient-removal-based secondary treatment (anoxic-oxic-anoxic-oxic and anaerobic-anoxic-oxic) removed 20-37% of OC, whereas extended-aeration-based conventional activated sludge treatment removed ozonation removed >90%. Ozonation after secondary treatment in STPs will be necessary during an influenza pandemic to reduce the risks associated with the widespread use of antiviral drugs. PMID:20692015

  3. Clinical pharmacokinetic drug interactions associated with artemisinin derivatives and HIV-antivirals

    OpenAIRE

    Kiang, Tony K.L.; Kyle J Wilby; Ensom, Mary H H

    2014-01-01

    Management of HIV and malaria co-infection is challenging due to potential drug-drug interactions between antimalarial and HIV-antiviral drugs. Little is known of the clinical significance of these drug interactions, and this review provides a comprehensive summary and critical evaluation of the literature. Specifically, drug interactions between WHO-recommended artemisinin combination therapies (ACT) and HIV-antivirals are discussed. An extensive literature search produced eight articles det...

  4. Curious discoveries in antiviral drug development: the role of serendipity.

    Science.gov (United States)

    De Clercq, Erik

    2015-07-01

    Antiviral drug development has often followed a curious meandrous route, guided by serendipity rather than rationality. This will be illustrated by ten examples. The polyanionic compounds (i) polyethylene alanine (PEA) and (ii) suramin were designed as an antiviral agent (PEA) or known as an antitrypanosomal agent (suramin), before they emerged as, respectively, a depilatory agent, or reverse transcriptase inhibitor. The 2',3'-dideoxynucleosides (ddNs analogues) (iii) have been (and are still) used in the "Sanger" DNA sequencing technique, although they are now commercialized as nucleoside reverse transcriptase inhibitors (NRTIs) in the treatment of HIV infections. (E)-5-(2-Bromovinyl)-2'-deoxyuridine (iv) was discovered as a selective anti-herpes simplex virus compound and is now primarily used for the treatment of varicella-zoster virus infections. The prototype of the acyclic nucleoside phosphonates (ANPs), (S)-9-(3-hydroxy-2-phosphonylmethoxypropyl)adenine [(S)-HPMPA], (v) was never commercialized, although it gave rise to several marketed products (cidofovir, adefovir, and tenofovir). 1-[2-(Hydroxyethoxy)methyl]-6-(phenylthio)thymine (vi) and TIBO (tetrahydroimidazo[4,5,1-jk][1,4-benzodiazepin-2(1H)]-one and -thione) (vii) paved the way to a number of compounds (i.e., nevirapine, delavirdine, etravirine, and rilpivirine), which are now collectively called non-NRTIs. The bicyclam AMD3100 (viii) was originally described as an anti-HIV agent before it became later marketed as a stem cell mobilizer. The S-adenosylhomocysteine hydrolase inhibitors (ix), while active against a broad range of (-)RNA viruses and poxviruses may be particularly effective against Ebola virus, and for (x) the O-ANP derivatives, the potential application range encompasses virtually all DNA viruses. PMID:25726922

  5. Oseltamivir-resistant influenza A(H1N1pdm2009 strains found in Brazil are endowed with permissive mutations, which compensate the loss of fitness imposed by antiviral resistance

    Directory of Open Access Journals (Sweden)

    Thiago Moreno Lopes e Souza

    2015-02-01

    Full Text Available The 2009 pandemic influenza A virus outbreak led to the systematic use of the neuraminidase (NA inhibitor oseltamivir (OST. Consequently, OST-resistant strains, carrying the mutation H275Y, emerged in the years after the pandemics, with a prevalence of 1-2%. Currently, OST-resistant strains have been found in community settings, in untreated individuals. To spread in community settings, H275Y mutants must contain additional mutations, collectively called permissive mutations. We display the permissive mutations in NA of OST-resistant A(H1N1pdm09 virus found in Brazilian community settings. The NAs from 2013 are phylogenetically distinct from those of 2012, indicating a tendency of positive selection of NAs with better fitness. Some previously predicted permissive mutations, such as V241I and N369K, found in different countries, were also detected in Brazil. Importantly, the change D344N, also predicted to compensate loss of fitness imposed by H275Y mutation, was found in Brazil, but not in other countries in 2013. Our results reinforce the notion that OST-resistant A(H1N1pdm09 strains with compensatory mutations may arise in an independent fashion, with samples being identified in different states of Brazil and in different countries. Systematic circulation of these viral strains may jeopardise the use of the first line of anti-influenza drugs in the future.

  6. SOME ASPECTS OF THE MARKETING STUDIES FOR THE PHARMACEUTICAL MARKET OF ANTIVIRAL DRUGS

    Directory of Open Access Journals (Sweden)

    A. G. Salnikova

    2015-01-01

    Full Text Available Antiviral drugs are widely used in medicinal practice. They suppress the originator and stimulate the protection of an organism. The drugs are used for the treatment of flu and ARVI, herpetic infections, virus hepatitis, HIV-infection. Contemporary pharmaceutical market is represented by a wide range of antiviral drugs. Marketing studies are conducted to develop strategies, used for the enhancement of pharmacy organization activity efficiency. Conduction of the marketing researches of pharmaceutical market is the purpose of this study. We have used State Registry of Drugs, State Record of Drugs, List of vital drugs, questionnaires of pharmaceutical workers during our work. Historical, sociological, mathematical methods, and a method of expert evaluation were used in the paper. As the result of the study we have made the following conclusions. We have studied and generalized the literature data about classification and application of antiviral drugs, marketing, competition. The assortment of antiviral drugs on the pharmaceutical market of the Russian Federation was also studied. We have conducted an analysis for the obtainment of the information about antiviral drugs by pharmaceutical workers. We have determined the competitiveness of antiviral drugs, and on the basis of the research conducted we have submitted an offer for pharmaceutical organizations to form the range of antiviral drugs.

  7. Cost-Benefit of Stockpiling Drugs for Influenza Pandemic

    OpenAIRE

    Balicer, Ran D.; Huerta, Michael; Davidovitch, Nadav; Grotto, Itamar

    2005-01-01

    We analyzed strategies for the use of stockpiled antiviral drugs in the context of a future influenza pandemic and estimated cost-benefit ratios. Current stockpiling of oseltamivir appears to be cost-saving to the economy under several treatment strategies, including therapeutic treatment of patients and postexposure prophylactic treatment of patients' close contacts.

  8. Oseltamivir-Resistant Flu

    Centers for Disease Control (CDC) Podcasts

    2012-04-13

    Dr. Aaron Storms, an Epidemic Intelligence Service (EIS) officer at CDC, discusses his paper about oseltamivir-resistant H1N1flu.  Created: 4/13/2012 by National Center for Emerging and Zoonotic Infectious Diseases (NCEZID).   Date Released: 4/17/2012.

  9. 5α-reductase inhibitors, antiviral and anti-tumor activities of some steroidal cyanopyridinone derivatives.

    Science.gov (United States)

    Al-Mohizea, Abdullah M; Al-Omar, Mohamed A; Abdalla, Mohamed M; Amr, Abdel-Galil E

    2012-01-01

    We herein report the 5α-reductase inhibitors, antiviral and anti-tumor activities of some synthesized heterocyclic cyanopyridone and cyanothiopyridone derivatives fused with steroidal structure. Initially the acute toxicity of the compounds was assayed via the determination of their LD(50). All the compounds, except 3b, were interestingly less toxic than the reference drug (Prednisolone(®)). Seventeen heterocyclic derivatives containing a cyanopyridone or cyanothiopyridone rings fused to a steroidal moiety were synthesized and screened for their 5α-reductase inhibitors, antiviral and anti-tumor activities comparable to that of Anastrozole, Bicalutamide, Efavirenz, Capravirine, Ribavirin, Oseltamivir and Amantadine as the reference drugs. Some of the compounds exhibited better 5α-reductase inhibitors, antiviral and anti-tumor activities than the reference drugs. The detailed 5α-reductase inhibitors, antiviral and anti-tumor activities of the synthesized compounds were reported. PMID:22057085

  10. Oseltamivir Treatment for Children with Influenza-Like Illness in China: A Cost-Effectiveness Analysis

    Science.gov (United States)

    Shen, Kunling; Xiong, Tengbin; Tan, Seng Chuen; Wu, Jiuhong

    2016-01-01

    Background Influenza is a common viral respiratory infection that causes epidemics and pandemics in the human population. Oseltamivir is a neuraminidase inhibitor—a new class of antiviral therapy for influenza. Although its efficacy and safety have been established, there is uncertainty regarding whether influenza-like illness (ILI) in children is best managed by oseltamivir at the onset of illness, and its cost-effectiveness in children has not been studied in China. Objective To evaluate the cost-effectiveness of post rapid influenza diagnostic test (RIDT) treatment with oseltamivir and empiric treatment with oseltamivir comparing with no antiviral therapy against influenza for children with ILI. Methods We developed a decision-analytic model based on previously published evidence to simulate and evaluate 1-year potential clinical and economic outcomes associated with three managing strategies for children presenting with symptoms of influenza. Model inputs were derived from literature and expert opinion of clinical practice and research in China. Outcome measures included costs and quality-adjusted life year (QALY). All the interventions were compared with incremental cost-effectiveness ratios (ICER). Results In base case analysis, empiric treatment with oseltamivir consistently produced the greatest gains in QALY. When compared with no antiviral therapy, the empiric treatment with oseltamivir strategy is very cost effective with an ICER of RMB 4,438. When compared with the post RIDT treatment with oseltamivir, the empiric treatment with oseltamivir strategy is dominant. Probabilistic sensitivity analysis projected that there is a 100% probability that empiric oseltamivir treatment would be considered as a very cost-effective strategy compared to the no antiviral therapy, according to the WHO recommendations for cost-effectiveness thresholds. The same was concluded with 99% probability for empiric oseltamivir treatment being a very cost-effective strategy

  11. Debate Regarding Oseltamivir Use for Seasonal and Pandemic Influenza

    Science.gov (United States)

    Kelly, Heath

    2016-01-01

    A debate about the market-leading influenza antiviral medication, oseltamivir, which initially focused on treatment for generally mild illness, has been expanded to question the wisdom of stockpiling for use in future influenza pandemics. Although randomized controlled trial evidence confirms that oseltamivir will reduce symptom duration by 17–25 hours among otherwise healthy adolescents and adults with community-managed disease, no randomized controlled trials have examined the effectiveness of oseltamivir against more serious outcomes. Observational studies, although criticized on methodologic grounds, suggest that oseltamivir given early can reduce the risk for death by half among persons hospitalized with confirmed infection caused by influenza A(H1N1)pdm09 and influenza A(H5N1) viruses. However, available randomized controlled trial data may not be able to capture the effect of oseltamivir use among hospitalized patients with severe disease. We assert that data on outpatients with relatively mild disease should not form the basis for policies on the management of more severe disease. PMID:27191818

  12. Determining the Quality of Oseltamivir (Tamiflu)

    Centers for Disease Control (CDC) Podcasts

    2008-02-04

    The possibility of an avian flu pandemic has given Tamiflu attention. Because of fear of a pandemic, this drug has been in high demand. Unfortunately, this demand has prompted production of counterfeit Tamiflu. CDC's Dr. Mike Green discusses a test that is simple and affordable and can test the quality of products purported to be oseltamivir (Tamiflu).  Created: 2/4/2008 by Emerging Infectious Diseases.   Date Released: 2/20/2008.

  13. Development of Potent Antiviral Drugs Inspired by Viral Hexameric DNA-Packaging Motors with Revolving Mechanism.

    Science.gov (United States)

    Pi, Fengmei; Zhao, Zhengyi; Chelikani, Venkata; Yoder, Kristine; Kvaratskhelia, Mamuka; Guo, Peixuan

    2016-09-15

    The intracellular parasitic nature of viruses and the emergence of antiviral drug resistance necessitate the development of new potent antiviral drugs. Recently, a method for developing potent inhibitory drugs by targeting biological machines with high stoichiometry and a sequential-action mechanism was described. Inspired by this finding, we reviewed the development of antiviral drugs targeting viral DNA-packaging motors. Inhibiting multisubunit targets with sequential actions resembles breaking one bulb in a series of Christmas lights, which turns off the entire string. Indeed, studies on viral DNA packaging might lead to the development of new antiviral drugs. Recent elucidation of the mechanism of the viral double-stranded DNA (dsDNA)-packaging motor with sequential one-way revolving motion will promote the development of potent antiviral drugs with high specificity and efficiency. Traditionally, biomotors have been classified into two categories: linear and rotation motors. Recently discovered was a third type of biomotor, including the viral DNA-packaging motor, beside the bacterial DNA translocases, that uses a revolving mechanism without rotation. By analogy, rotation resembles the Earth's rotation on its own axis, while revolving resembles the Earth's revolving around the Sun (see animations at http://rnanano.osu.edu/movie.html). Herein, we review the structures of viral dsDNA-packaging motors, the stoichiometries of motor components, and the motion mechanisms of the motors. All viral dsDNA-packaging motors, including those of dsDNA/dsRNA bacteriophages, adenoviruses, poxviruses, herpesviruses, mimiviruses, megaviruses, pandoraviruses, and pithoviruses, contain a high-stoichiometry machine composed of multiple components that work cooperatively and sequentially. Thus, it is an ideal target for potent drug development based on the power function of the stoichiometries of target complexes that work sequentially. PMID:27356896

  14. Antiviral resistance during pandemic influenza: implications for stockpiling and drug use

    Directory of Open Access Journals (Sweden)

    Bowman Christopher S

    2009-01-01

    Full Text Available Abstract Background The anticipated extent of antiviral use during an influenza pandemic can have adverse consequences for the development of drug resistance and rationing of limited stockpiles. The strategic use of drugs is therefore a major public health concern in planning for effective pandemic responses. Methods We employed a mathematical model that includes both sensitive and resistant strains of a virus with pandemic potential, and applies antiviral drugs for treatment of clinical infections. Using estimated parameters in the published literature, the model was simulated for various sizes of stockpiles to evaluate the outcome of different antiviral strategies. Results We demonstrated that the emergence of highly transmissible resistant strains has no significant impact on the use of available stockpiles if treatment is maintained at low levels or the reproduction number of the sensitive strain is sufficiently high. However, moderate to high treatment levels can result in a more rapid depletion of stockpiles, leading to run-out, by promoting wide-spread drug resistance. We applied an antiviral strategy that delays the onset of aggressive treatment for a certain amount of time after the onset of the outbreak. Our results show that if high treatment levels are enforced too early during the outbreak, a second wave of infections can potentially occur with a substantially larger magnitude. However, a timely implementation of wide-scale treatment can prevent resistance spread in the population, and minimize the final size of the pandemic. Conclusion Our results reveal that conservative treatment levels during the early stages of the outbreak, followed by a timely increase in the scale of drug-use, will offer an effective strategy to manage drug resistance in the population and avoid run-out. For a 1918-like strain, the findings suggest that pandemic plans should consider stockpiling antiviral drugs to cover at least 20% of the population.

  15. Human cytomegalovirus antiviral drug resistance in hematopoietic stem cell transplantation: current state of the art.

    Science.gov (United States)

    Campos, Ana Bela; Ribeiro, Joana; Boutolleau, David; Sousa, Hugo

    2016-05-01

    Human cytomegalovirus (HCMV) infection is a major cause of morbidity and mortality in allogeneic hematopoietic stem cell transplant recipients. The significant clinical impact of HCMV infection and progression to HCMV disease among allogeneic hematopoietic stem cell transplant recipients has been reduced by prophylactic, preemptive, and curative treatments using ganciclovir, valganciclovir, foscarnet, and cidofovir. Resistance to (val)ganciclovir results from mutations localized in HCMV UL97 gene (encoding the pUL97 phosphotransferase), UL54 gene (encoding the pUL54 DNA polymerase), or both genes, whereas foscarnet and cidofovir resistance results from mutations localized within UL54 gene only. This review is focused on HCMV antiviral drug resistance, including the functions of target genes of antivirals, the mechanisms of antiviral resistance, the different mutations in pUL97 and pUL54 that have been identified in either clinical isolates or laboratory strains, and their impact on HCMV susceptibility to antiviral drugs. It emphasizes the importance of proving that observed genetic changes confer resistance so they can be distinguished from polymorphisms. Because of the emergence of HCMV resistance to currently available drugs, novel drugs are urgently needed for the therapeutic management of HCMV-resistant infections in hematopoietic stem cell transplant patients. Copyright © 2016 John Wiley & Sons, Ltd. PMID:26990717

  16. A simple, rapid, and sensitive system for the evaluation of anti-viral drugs in rats

    International Nuclear Information System (INIS)

    Highlights: ► We established a novel, simple and rapid in vivo system for evaluation of anti-HIV-1 drugs with rats. ► The system may be applicable for other antiviral drugs, and/or useful for initial screening in vivo. ► In this system, TRI-1144 displayed the most potent anti-HIV-1 activity in vivo. -- Abstract: The lack of small animal models for the evaluation of anti-human immunodeficiency virus type 1 (HIV-1) agents hampers drug development. Here, we describe the establishment of a simple and rapid evaluation system in a rat model without animal infection facilities. After intraperitoneal administration of test drugs to rats, antiviral activity in the sera was examined by the MAGI assay. Recently developed inhibitors for HIV-1 entry, two CXCR4 antagonists, TF14016 and FC131, and four fusion inhibitors, T-20, T-20EK, SC29EK, and TRI-1144, were evaluated using HIV-1IIIB and HIV-1BaL as representative CXCR4- and CCR5-tropic HIV-1 strains, respectively. CXCR4 antagonists were shown to only possess anti-HIV-1IIIB activity, whereas fusion inhibitors showed both anti-HIV-1IIIB and anti-HIV-1BaL activities in rat sera. These results indicate that test drugs were successfully processed into the rat sera and could be detected by the MAGI assay. In this system, TRI-1144 showed the most potent and sustained antiviral activity. Sera from animals not administered drugs showed substantial anti-HIV-1 activity, indicating that relatively high dose or activity of the test drugs might be needed. In conclusion, the novel rat system established here, “phenotypic drug evaluation”, may be applicable for the evaluation of various antiviral drugs in vivo.

  17. AVALIAÇÃO DO TRATAMENTO REALIZADO COM O ANTIVIRAL FOSFATO DE OSELTAMIVIR (TAMIFLU® E OS EXAMES LABORATORIAIS DE PACIENTES DIAGNOSTICADOS COM GRIPE A SUBTIPO H1N1 EM UM HOSPITAL DA CIDADE DE TOLEDO – PARANÁ, BRASIL

    Directory of Open Access Journals (Sweden)

    Kiara Regina Canzi

    2015-12-01

    Full Text Available O fosfato de oseltamivir, uma pró-droga do carboxilato de oseltamivir, é um inibidor potente e seletivo das enzimas neuraminidase. A atividade da enzima viral, neuraminidase, é importante tanto para a entrada do vírus em células não infectadas quanto para a liberação de partículas virais. O carboxilato de oseltamivir inibe a neuraminidase do vírus da gripe de ambos os tipos: Influenza A e B, impedindo a replicação do mesmo. 46 pacientes com idades entre 1 e 76 anos de idade, de ambos os sexos, internados em um Hospital na cidade de Toledo durante o período de Junho de 2009 a Janeiro de 2010, com casos confirmados ou suspeitos de gripe A subtipo H1N1. Durante o período de internamento, foi avaliado o uso do Fosfato de Oseltamivir, bem como reações adversas e tempo de uso do medicamento e os exames empregados para auxiliar o diagnóstico (Hemograma completo e a gasometria arterial. O tempo de uso do medicamento não excedeu o preconizado, o qual foi de 5 (cinco dias ininterruptos, e entre as reações adversas ou efeitos colaterais estão náusea (43,47%, cefaléia (8,69% e vômitos (17,39%. As alterações laboratoriais evidenciam leucócitos normais (média de 9.145 mL, plaquetas de 246.166 mm³, pH sanguíneo (gasometria arterial levemente ácido e PO2 (mmHg e SO2 abaixo dos valores de referência. A abordagem da infecção pelo vírus Influenza A H1N1 2009 representa desafio epidemiológico-clinico-laboratorial-terapêutico em todo o mundo. Logo, requer esforço coletivo para impedir o seu avanço e os riscos de letalidade e mortalidade incluídos em sua disseminação.

  18. Caulerpin as a potential antiviral drug against herpes simplex virus type 1

    Directory of Open Access Journals (Sweden)

    Nathália Regina Porto Vieira Macedo

    2012-08-01

    Full Text Available About 80% of the human adult population is infected with HSV-1. Although there are many anti-HSV-1 drugs available (acyclovir, ganciclovir, valaciclovir, foscarnet, their continuous use promotes the selection of resistant strains, mainly in ACV patients. In addition to resistance, the drugs also have toxicity, particularly when administration is prolonged. The study of new molecules isolated from green algae with potential antiviral activity represents a good opportunity for the development of antiviral drugs. Caulerpin, the major product from the marine algae Caulerpa Lamouroux (Caulerpales, is known for its biological activities such as antioxidant, antifungal, acetylcholinesterase inhibitor (AChE and antibacterial activity. In this work, we show that caulerpin could be an alternative to acyclovir as an anti-HSV-1 drug that inhibits the alpha and beta phases of the replication cycle.

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

    OpenAIRE

    Park KwiSung; Yeo SangGu; Baek KyoungAh; Cheon DooSung; Choi YoungJin; Park JoonSoo; Lee SooJin

    2011-01-01

    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 a...

  20. Current Landscape of Antiviral Drug Discovery [version 1; referees: 2 approved

    Directory of Open Access Journals (Sweden)

    Wade Blair

    2016-02-01

    Full Text Available Continued discovery and development of new antiviral medications are paramount for global human health, particularly as new pathogens emerge and old ones evolve to evade current therapeutic agents. Great success has been achieved in developing effective therapies to suppress human immunodeficiency virus (HIV and hepatitis B virus (HBV; however, the therapies are not curative and therefore current efforts in HIV and HBV drug discovery are directed toward longer-acting therapies and/or developing new mechanisms of action that could potentially lead to cure, or eradication, of the virus. Recently, exciting early clinical data have been reported for novel antivirals targeting respiratory syncytial virus (RSV and influenza (flu. Preclinical data suggest that these new approaches may be effective in treating high-risk patients afflicted with serious RSV or flu infections. In this review, we highlight new directions in antiviral approaches for HIV, HBV, and acute respiratory virus infections.

  1. 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.

  2. A review of antiviral drugs and other compounds with activity against feline herpesvirus type 1.

    Science.gov (United States)

    Thomasy, Sara M; Maggs, David J

    2016-07-01

    Feline herpesvirus type 1 (FHV-1) is a common and important cause of ocular surface disease, dermatitis, respiratory disease, and potentially intraocular disease in cats. Many antiviral drugs developed for the treatment of humans infected with herpesviruses have been used to treat cats infected with FHV-1. Translational use of drugs in this manner ideally requires methodical investigation of their in vitro efficacy against FHV-1 followed by pharmacokinetic and safety trials in normal cats. Subsequently, placebo-controlled efficacy studies in experimentally inoculated animals should be performed followed, finally, by carefully designed and monitored clinical trials in client-owned animals. This review is intended to provide a concise overview of the available literature regarding the efficacy of antiviral drugs and other compounds with proven or putative activity against FHV-1, as well as a discussion of their safety in cats. PMID:27091747

  3. Parallel shRNA and CRISPR-Cas9 screens enable antiviral drug target identification.

    Science.gov (United States)

    Deans, Richard M; Morgens, David W; Ökesli, Ayşe; Pillay, Sirika; Horlbeck, Max A; Kampmann, Martin; Gilbert, Luke A; Li, Amy; Mateo, Roberto; Smith, Mark; Glenn, Jeffrey S; Carette, Jan E; Khosla, Chaitan; Bassik, Michael C

    2016-05-01

    Broad-spectrum antiviral drugs targeting host processes could potentially treat a wide range of viruses while reducing the likelihood of emergent resistance. Despite great promise as therapeutics, such drugs remain largely elusive. Here we used parallel genome-wide high-coverage short hairpin RNA (shRNA) and clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9 screens to identify the cellular target and mechanism of action of GSK983, a potent broad-spectrum antiviral with unexplained cytotoxicity. We found that GSK983 blocked cell proliferation and dengue virus replication by inhibiting the pyrimidine biosynthesis enzyme dihydroorotate dehydrogenase (DHODH). Guided by mechanistic insights from both genomic screens, we found that exogenous deoxycytidine markedly reduced GSK983 cytotoxicity but not antiviral activity, providing an attractive new approach to improve the therapeutic window of DHODH inhibitors against RNA viruses. Our results highlight the distinct advantages and limitations of each screening method for identifying drug targets, and demonstrate the utility of parallel knockdown and knockout screens for comprehensive probing of drug activity. PMID:27018887

  4. Dynamics of an HBV Model with Drug Resistance Under Intermittent Antiviral Therapy

    Science.gov (United States)

    Zhang, Ben-Gong; Tanaka, Gouhei; Aihara, Kazuyuki; Honda, Masao; Kaneko, Shuichi; Chen, Luonan

    2015-06-01

    This paper studies the dynamics of the hepatitis B virus (HBV) model and the therapy regimens of HBV disease. First, we propose a new mathematical model of HBV with drug resistance, and then analyze its qualitative and dynamical properties. Combining the clinical data and theoretical analysis, we demonstrate that our model is biologically plausible and also computationally viable. Second, we demonstrate that the intermittent antiviral therapy regimen is one of the possible strategies to treat this kind of complex disease. There are two main advantages of this regimen, i.e. it not only may delay the development of drug resistance, but also may reduce the duration of on-treatment time compared with the long-term continuous medication. Moreover, such an intermittent antiviral therapy can reduce the adverse side effects. Our theoretical model and computational results provide qualitative insight into the progression of HBV, and also a possible new therapy for HBV disease.

  5. The chemical bases of the various AIDS epidemics: recreational drugs, anti-viral chemotherapy and malnutrition

    Indian Academy of Sciences (India)

    Peter Duesberg; Claus Koehnlein; David Rasnick

    2003-06-01

    In 1981 a new epidemic of about two-dozen heterogeneous diseases began to strike non-randomly growing numbers of male homosexuals and mostly male intravenous drug users in the US and Europe. Assuming immunodeficiency as the common denominator the US Centers for Disease Control (CDC) termed the epidemic, AIDS, for acquired immunodeficiency syndrome. From 1981–1984 leading researchers including those from the CDC proposed that recreational drug use was the cause of AIDS, because of exact correlations and of drug-specific diseases. However, in 1984 US government researchers proposed that a virus, now termed human immunodeficiency virus (HIV), is the cause of the non-random epidemics of the US and Europe but also of a new, sexually random epidemic in Africa. The virus-AIDS hypothesis was instantly accepted, but it is burdened with numerous paradoxes, none of which could be resolved by 2003: Why is there no HIV in most AIDS patients, only antibodies against it? Why would HIV take 10 years from infection to AIDS? Why is AIDS not self-limiting via antiviral immunity? Why is there no vaccine against AIDS? Why is AIDS in the US and Europe not random like other viral epidemics? Why did AIDS not rise and then decline exponentially owing to antiviral immunity like all other viral epidemics? Why is AIDS not contagious? Why would only HIV carriers get AIDS who use either recreational or anti-HIV drugs or are subject to malnutrition? Why is the mortality of HIV-antibody-positives treated with anti-HIV drugs 7–9%, but that of all (mostly untreated) HIV-positives globally is only 1.4%? Here we propose that AIDS is a collection of chemical epidemics, caused by recreational drugs, anti-HIV drugs, and malnutrition. According to this hypothesis AIDS is not contagious, not immunogenic, not treatable by vaccines or antiviral drugs, and HIV is just a passenger virus. The hypothesis explains why AIDS epidemics strike non-randomly if caused by drugs and randomly if caused by

  6. The Use of Antiviral Drugs for Influenza: Recommended Guidelines for Practitioners

    OpenAIRE

    Allen, Upton D.; Fred Y Aoki; H Grant Stiver; for the Canadian Paediatric Society and the Association of Medical Microbiology and Infectious Disease Canada

    2006-01-01

    The present document outlines current guidelines and supporting literature relating to the use of antiviral drugs for chemoprophylaxis and influenza illness therapy in paediatric and adult settings. The focus is on the management of influenza in interpandemic periods. Where appropriate, the areas in need of additional research are identified. It will be necessary to update aspects of these guidelines as new information emerges. The recommendations that follow represent the results of a joint ...

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

    Science.gov (United States)

    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. PMID:25680890

  8. Influenza vaccines and influenza antiviral drugs in Africa: are they available and do guidelines for their use exist?

    OpenAIRE

    Duque, Jazmin; McMorrow, Meredith L.; Adam L Cohen

    2014-01-01

    Background Influenza viruses cause significant morbidity and mortality in Africa, particularly among high-risk groups, but influenza vaccines and antiviral drugs may not be commonly available and used. The main aim of this study was to determine the availability and use of influenza vaccines and antiviral drugs as well as to describe existing related guidelines and policies in Africa. Methods A self-administered survey was distributed among key influenza experts in 40 African countries. Resul...

  9. Guidance on The Use of Antiviral Drugs for Influenza in Acute Care Facilities in Canada, 2014-2015

    OpenAIRE

    H Grant Stiver; Evans, Gerald A; Fred Y Aoki; Allen, Upton D.; Michel Laverdière

    2015-01-01

    This article represents the second update to the AMMI Canada Guidelines document on the use of antiviral drugs for influenza. The article aims to inform health care professionals of the increased risk for influenza in long-term care facilities due to a documented mismatch between the components chosen for this season’s vaccine and currently circulating influenza strains. Adjusted recommendations for the use of antiviral drugs for influenza in the acute care setting for this season are provide...

  10. Studies of Retroviral Reverse Transcriptase and Flaviviral Protease Enzymes as Antiviral Drug Targets : Applications in Antiviral Drug Discovery & Therapy

    OpenAIRE

    Junaid, Muhammad

    2012-01-01

    Viruses are a major threat to humans due to their unique adaptability, evolvability and  capability to control their hosts as parasites and genetic elements. HIV/AIDS is the third largest cause of death by infectious diseases in the world, and drug resistance due to the viral mutations is still the leading cause of treatment failure. The flaviviruses, such as Dengue virus (DEN) and Japanese encephalitis virus (JEV), represent other major cause of morbidity and mortality, and the areas where t...

  11. 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 

  12. The Use of Antiviral Drugs for Influenza: Recommended Guidelines for Practitioners

    Directory of Open Access Journals (Sweden)

    Upton D Allen

    2006-01-01

    Full Text Available The present document outlines current guidelines and supporting literature relating to the use of antiviral drugs for chemoprophylaxis and influenza illness therapy in paediatric and adult settings. The focus is on the management of influenza in interpandemic periods. Where appropriate, the areas in need of additional research are identified. It will be necessary to update aspects of these guidelines as new information emerges. The recommendations that follow represent the results of a joint effort supported by the Canadian Paediatric Society and the Association of Medical Microbiology and Infectious Disease Canada.

  13. Reaction of cis- and trans-Dichlorotetra(Dimethylsulfoxide)Ruthenium(II) With the Antiviral Drug Acyclovir

    OpenAIRE

    Koutsodimou, Aglaia; Natile, Giovanni

    2000-01-01

    NMR was used to investigate the reaction of cis- and trans-[RuCl2(DMSO)4] with the antiviral drug acyclovir, a guanine derivative containing the acyclic (2-hydroxo) ethoxymethyl pendant linked to N(9). Studies were performed in aqueous solutions at ambient temperature and at 37 °C, and at various molar ratios. Both isomers yielded two compounds, a monoadduct and a bisadduct, the relative yields being dependent upon the metal to ligand concentration ratios. The products derived from the two Ru...

  14. Using ICR and SCID mice as animal models for smallpox to assess antiviral drug efficacy.

    Science.gov (United States)

    Titova, Ksenya A; Sergeev, Alexander A; Zamedyanskaya, Alena S; Galahova, Darya O; Kabanov, Alexey S; Morozova, Anastasia A; Bulychev, Leonid E; Sergeev, Artemiy A; Glotova, Tanyana I; Shishkina, Larisa N; Taranov, Oleg S; Omigov, Vladimir V; Zavjalov, Evgenii L; Agafonov, Alexander P; Sergeev, Alexander N

    2015-09-01

    The possibility of using immunocompetent ICR mice and immunodeficient SCID mice as model animals for smallpox to assess antiviral drug efficacy was investigated. Clinical signs of the disease did not appear following intranasal (i.n.) challenge of mice with strain Ind-3a of variola virus (VARV), even when using the highest possible dose of the virus (5.2 log10 p.f.u.). The 50 % infective doses (ID50) of VARV, estimated by the virus presence or absence in the lungs 3 and 4 days post-infection, were 2.7 ± 0.4 log10 p.f.u. for ICR mice and 3.5 ± 0.7 log10 p.f.u. for SCID mice. After i.n. challenge of ICR and SCID mice with VARV 30 and 50 ID50, respectively, steady reproduction of the virus occurred only in the respiratory tract (lungs and nose). Pathological inflammatory destructive changes were revealed in the respiratory tract and the primary target cells for VARV (macrophages and epithelial cells) in mice, similar to those in humans and cynomolgus macaques. The use of mice to assess antiviral efficacies of NIOCH-14 and ST-246 demonstrated the compliance of results with those described in scientific literature, which opens up the prospect of their use as an animal model for smallpox to develop anti-smallpox drugs intended for humans. PMID:26067292

  15. A method for evaluating antiviral drug susceptibility of Epstein-Barr virus

    Directory of Open Access Journals (Sweden)

    Charlotte A Romain

    2010-01-01

    Full Text Available Charlotte A Romain1, Henry H Balfour Jr1,2, Heather E Vezina1,3, Carol J Holman11Department of Laboratory Medicine and Pathology, 2Department of Pediatrics, 3Department of Experimental and Clinical Pharmacology, University of Minnesota, Minneapolis, MN, USAAbstract: We developed an in vitro Epstein-Barr virus (EBV drug susceptibility assay using P3HR1 cells or lymphoblastoid cells from subjects with infectious mononucleosis, which were grown in the presence of various concentrations of acyclovir (ACV, ganciclovir (GCV or R-9-[4-hydroxy-2-(hydroxymethylbutyl]guanine (H2G and 12-O-tetradecanoyl-phorbol-13-acetate (TPA. On day 7, total cellular DNA was extracted and EBV DNA was detected using an in-house quantitative real-time polymerase chain reaction (PCR method. All three drugs had in vitro activity against EBV in both the laboratory standard producer cell line P3HR1 and in subject-derived lymphoblastoid cell lines. The median 50% inhibitory concentrations (IC50s in P3HR1 cells were: ACV, 3.4 μM; GCV, 2.6 μM; and H2G, 2.7 μM and in 3 subject-derived cells were: ACV, 2.5 μM; GCV, 1.7 μM; and H2G, 1.9 μM. Our assay can be used to screen candidate anti-EBV drugs. Because we can measure the IC50 of patients’ strains of EBV, this assay may also be useful for monitoring viral resistance especially in immunocompomised hosts receiving antiviral drugs for prevention or treatment of EBV diseases.Keywords: Epstein-Barr virus, ganciclovir, acyclovir, valomaciclovir, H2G, antivirals

  16. A novel corneal explant model system to evaluate antiviral drugs against feline herpesvirus type 1 (FHV-1).

    Science.gov (United States)

    Pennington, Matthew R; Fort, Michael W; Ledbetter, Eric C; Van de Walle, Gerlinde R

    2016-06-01

    Feline herpesvirus type-1 (FHV-1) is the most common viral cause of ocular surface disease in cats. Many antiviral drugs are used to treat FHV-1, but require frequent topical application and most lack well-controlled in vivo studies to justify their clinical use. Therefore, better validation of current and novel treatment options are urgently needed. Here, we report on the development of a feline whole corneal explant model that supports FHV-1 replication and thus can be used as a novel model system to evaluate the efficacy of antiviral drugs. The anti-herpes nucleoside analogues cidofovir and acyclovir, which are used clinically to treat ocular herpesvirus infection in cats and have previously been evaluated in traditional two-dimensional feline cell cultures in vitro, were evaluated in this explant model. Both drugs suppressed FHV-1 replication when given every 12 h, with cidofovir showing greater efficacy. In addition, the potential efficacy of the retroviral integrase inhibitor raltegravir against FHV-1 was evaluated in cell culture as well as in the explant model. Raltegravir was not toxic to feline cells or corneas, and most significantly, inhibited FHV-1 replication at 500 µM in both systems. Importantly, this drug was effective when given only once every 24 h. Taken together, our data indicate that the feline whole corneal explant model is a useful tool for the evaluation of antiviral drugs and, furthermore, that raltegravir appears a promising novel antiviral drug to treat ocular herpesvirus infection in cats. PMID:26959283

  17. Prescription of antiviral drugs during the 2009 influenza pandemic: an observational study using electronic medical files of general practitioners in the Netherlands

    OpenAIRE

    Hooiveld, M; Groep, T. van de; Verheij, Th.J.M.; Sande, M A; Verheij, R.A.; Tacken, M.A.; van Essen, G. A.

    2013-01-01

    Background: After the clinical impact of the A(H1N1) pdm09 virus was considered to be mild, treatment with antiviral drugs was recommended only to patients who were at risk for severe disease or who had a complicated course of influenza. We investigated to what extent antiviral prescriptions in primary care practices were in accordance with the recommendations, what proportion of patients diagnosed with influenza had been prescribed antiviral drugs, and to what extent prescriptions related to...

  18. Antiviral Chemistry & Chemotherapy's current antiviral agents FactFile 2008 (2nd edition): RNA viruses.

    Science.gov (United States)

    De Clercq, Erik; Field, Hugh J

    2008-01-01

    Among the RNA viruses, other than the retroviruses (that is, HIV), which are dealt with separately in the current FactFile, the most important targets for the development of antiviral agents at the moment are the orthomyxoviruses (that is, influenza), the hepaciviruses (that is, hepatitis C virus [HCV]) and, to a lesser extent, the picornaviruses. Although the uncoating inhibitors amantadine and rimantadine were the first known inhibitors of influenza A, the neuraminidase inhibitors oseltamivir, zanamivir and peramivir have now become the prime antiviral drugs for the treatment of influenza A and B virus infections. For HCV infections, standard treatment consists of the combination of pegylated interferon-alpha with ribavirin, but several other antivirals targeted at specific viral functions such as the HCV protease and/ or polymerase may be expected to soon take an important share of this important market. Still untapped is the potential of a variety of uncoating inhibitors, as well as protease and/or polymerase inhibitors against the wide spectrum of picornaviruses. While ribavirin has been available for 35 years as a broad-spectrum anti-RNA virus agent, relatively new and unexplored is favipiravir (T-705) accredited with activity against influenza as well as flaviviruses, bunyaviruses and arenaviruses. PMID:18727441

  19. Assessment of Antiviral Properties of Peramivir against H7N9 Avian Influenza Virus in an Experimental Mouse Model.

    Science.gov (United States)

    Farooqui, Amber; Huang, Linxi; Wu, Suwu; Cai, Yingmu; Su, Min; Lin, Pengzhou; Chen, Weihong; Fang, Xibin; Zhang, Li; Liu, Yisu; Zeng, Tiansheng; Paquette, Stephane G; Khan, Adnan; Kelvin, Alyson A; Kelvin, David J

    2015-12-01

    The H7N9 influenza virus causes a severe form of disease in humans. Neuraminidase inhibitors, including oral oseltamivir and injectable peramivir, are the first choices of antiviral treatment for such cases; however, the clinical efficacy of these drugs is questionable. Animal experimental models are essential for understanding the viral replication kinetics under the selective pressure of antiviral agents. This study demonstrates the antiviral activity of peramivir in a mouse model of H7N9 avian influenza virus infection. The data show that repeated administration of peramivir at 30 mg/kg of body weight successfully eradicated the virus from the respiratory tract and extrapulmonary tissues during the acute response, prevented clinical signs of the disease, including neuropathy, and eventually protected mice against lethal H7N9 influenza virus infection. Early treatment with peramivir was found to be associated with better disease outcomes. PMID:26369969

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

    Science.gov (United States)

    Yu, Debin; Zhao, Mingzhi; Dong, Liwei; Zhao, Lu; Zou, Mingwei; Sun, Hetong; Zhang, Mengying; Liu, Hongyu; Zou, Zhihua

    2016-01-01

    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 expression of the antiviral genes MxA and OAS and two of them, analog-6 and -7, displayed an unexpected high potency that is higher than that of type I IFN (IFN-α2a) in activating the IFN-stimulated response element (ISRE)-luciferase reporter. Importantly, both analog-6 and -7 effectively inhibited replication of hepatitis C virus in Huh-7.5.1 cells, with an IC50 that is comparable to that of IFN-α2a; and consistent with the roles of IFN-λ in mucosal epithelia, both analogs potently inhibited replication of H3N2 influenza A virus in A549 cells. Together, these studies identified two IFN-λ analogs as candidates to be developed as novel antiviral biologics. PMID:26792983

  1. Influenza neuraminidase inhibitors: antiviral action and mechanisms of resistance

    Science.gov (United States)

    McKimm‐Breschkin, Jennifer L.

    2012-01-01

    Please cite this paper as: McKimm‐Breschkin (2012) Influenza neuraminidase inhibitors: Antiviral action and mechanisms of resistance. Influenza and Other Respiratory Viruses 7(Suppl. 1), 25–36. There are two major classes of antivirals available for the treatment and prevention of influenza, the M2 inhibitors and the neuraminidase inhibitors (NAIs). The M2 inhibitors are cheap, but they are only effective against influenza A viruses, and resistance arises rapidly. The current influenza A H3N2 and pandemic A(H1N1)pdm09 viruses are already resistant to the M2 inhibitors as are many H5N1 viruses. There are four NAIs licensed in some parts of the world, zanamivir, oseltamivir, peramivir, and a long‐acting NAI, laninamivir. This review focuses on resistance to the NAIs. Because of differences in their chemistry and subtle differences in NA structures, resistance can be both NAI‐ and subtype specific. This results in different drug resistance profiles, for example, the H274Y mutation confers resistance to oseltamivir and peramivir, but not to zanamivir, and only in N1 NAs. Mutations at E119, D198, I222, R292, and N294 can also reduce NAI sensitivity. In the winter of 2007–2008, an oseltamivir‐resistant seasonal influenza A(H1N1) strain with an H274Y mutation emerged in the northern hemisphere and spread rapidly around the world. In contrast to earlier evidence of such resistant viruses being unfit, this mutant virus remained fully transmissible and pathogenic and became the major seasonal A(H1N1) virus globally within a year. This resistant A(H1N1) virus was displaced by the sensitive A(H1N1)pdm09 virus. Approximately 0·5–1·0% of community A(H1N1)pdm09 isolates are currently resistant to oseltamivir. It is now apparent that variation in non‐active site amino acids can affect the fitness of the enzyme and compensate for mutations that confer high‐level oseltamivir resistance resulting in minimal impact on enzyme function. PMID:23279894

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

    Directory of Open Access Journals (Sweden)

    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

  3. Diagnostic imaging of herpes simplex virus encephalitis using a radiolabeled antiviral drug: autoradiographic assessment in an animal model

    International Nuclear Information System (INIS)

    To develop a new approach to the diagnosis of herpes simplex encephalitis, we used a radiolabeled antiviral drug, 2'-fluoro-5-methyl-1-beta-D-arabinosyluracil labeled with carbon 14 ([14C]FMAU), as a probe for selectively imaging brain infection in a rat model by quantitative autoradiography. A high correlation was found between focal infection, as defined by immunoperoxidase viral antigen staining, and increased regional [14C]FMAU uptake in brain sections. Two potential sources of false-positive imaging were defined: high concentrations of drug in the choroid plexus because of its higher permeability compared with brain, and drug sequestration by proliferating uninfected cell populations. Our results support the soundness of the proposed strategy of using a labeled antiviral drug that is selectively phosphorylated by herpes simplex virus type 1 thymidine kinase in conjunction with scanning methods for human diagnosis, and also define some of the factors that must be taken into account when planning clinical application

  4. H1N1流感病毒D151G突变株对奥司他韦的抗药性研究及药物筛选%Drug resistance of mutation D151 G of H1 N1 influenza virus to oseltamivir and drug screening

    Institute of Scientific and Technical Information of China (English)

    石会娜; 栗海波; 刘伟

    2011-01-01

    目的:观察H1N1流感病毒D151G突变株对奥司他韦的抗药性,筛选对D151G突变神经氨酸酶具有抑制作用的化合物.方法:采用分子动力学模拟和MM-GBSA自由能计算方法判断H1N1流感病毒D151G突变株对奥司他韦的抗药性;应用分子对接软件Autodoek从ZINC数据库筛选与D151G突变神经氨酸酶结合能力较强的化合物.结果:D151G突变神经氨酸酶与奥司他韦的结合能比野生型神经氨酸酶与奥司他韦的结合能降低了-4.61kcal/mol;筛选出的5个化合物及奥司他韦与D151G突变神经氨酸酶的结合能分别为-7.56、-7.71、-7.88、-7.89、-9.09和-7.21 kcal/mol.结论:H1N1流感病毒D151G突变株对奥司他韦具有抗药性,筛选出的5个化合物中,4-[1-(1-金刚烷基氧化羧基)乙氨基]-3-氨基-4-氧代-丁酸与D151G突变神经氨酸酶的结合能力最强.%Aim:To observe whether mutation D151G of H1N1 influenza virus exhibits drug resistance to oseltamivir and select compounds to which mutation D151G of HIM influenza virus is sensitive. Methods:Molecular dynamics simulation and MM-GBSA methods were performed to judge the resistance of mutation D1S1G of H1N1 influenza virus to oseltamivir; molecular docking software Autodock was applied to select some compounds from ZINC database, which had higher affinity to D151G mutated neuraminidase than oseltamivir. Results: The binding energy of D151G mutated neuraminidase to oseltamivir decreased by -4.61 keal/mol with respect to wild-type complex. The binding energies of five compounds and oseltamivir to D151G mutated neuraminidase were -7.56, -7.71, -7.88, -7.89, -9.09 and -7.21 kcal/mol,respectively. Conclusion; Mutation D151G of H1N1 influenza virus exhibits drug resistance to oseltamivir. 4-[ l-( 1-adaman-tyloxycarbonyl) ethylamino] -3-amino-4-oxo-butanoic acid has highest affinity to D1S1G mutated neuraminidase among five candidate compounds.

  5. High throughput screening for small molecule enhancers of the interferon signaling pathway to drive next-generation antiviral drug discovery.

    Directory of Open Access Journals (Sweden)

    Dhara A Patel

    Full Text Available Most of current strategies for antiviral therapeutics target the virus specifically and directly, but an alternative approach to drug discovery might be to enhance the immune response to a broad range of viruses. Based on clinical observation in humans and successful genetic strategies in experimental models, we reasoned that an improved interferon (IFN signaling system might better protect against viral infection. Here we aimed to identify small molecular weight compounds that might mimic this beneficial effect and improve antiviral defense. Accordingly, we developed a cell-based high-throughput screening (HTS assay to identify small molecules that enhance the IFN signaling pathway components. The assay is based on a phenotypic screen for increased IFN-stimulated response element (ISRE activity in a fully automated and robust format (Z'>0.7. Application of this assay system to a library of 2240 compounds (including 2160 already approved or approvable drugs led to the identification of 64 compounds with significant ISRE activity. From these, we chose the anthracycline antibiotic, idarubicin, for further validation and mechanism based on activity in the sub-µM range. We found that idarubicin action to increase ISRE activity was manifest by other members of this drug class and was independent of cytotoxic or topoisomerase inhibitory effects as well as endogenous IFN signaling or production. We also observed that this compound conferred a consequent increase in IFN-stimulated gene (ISG expression and a significant antiviral effect using a similar dose-range in a cell-culture system inoculated with encephalomyocarditis virus (EMCV. The antiviral effect was also found at compound concentrations below the ones observed for cytotoxicity. Taken together, our results provide proof of concept for using activators of components of the IFN signaling pathway to improve IFN efficacy and antiviral immune defense as well as a validated HTS approach to identify

  6. High frequency of antiviral drug resistance and non-b subtypes in HIV-1 patients failing antiviral therapy in Cuba

    Science.gov (United States)

    Kouri, Vivian; Alemán, Yoan; Pérez, Lissette; Pérez, Jorge; Fonseca, Carlos; Correa, Consuelo; Aragonés, Carlos; Campos, Jorge; Álvarez, Delmis; Schrooten, Yoeri; Vinken, Lore; Limia, Celia; Soto, Yudira; Vandamme, Anne-Mieke; Van Laethem, Kristel

    2014-01-01

    Introduction Emergence of HIV-1 drug resistance may limit the sustained benefits of antiretroviral therapy (ART) in settings with limited laboratory monitoring and drug options. The objective is to implement the surveillance of drug resistance and subtypes in HIV-1 patients failing ART in Cuba. Methods This study compiled clinical and genotypic drug resistance data 588 ART-experienced HIV-1 patients attending a clinical center in Havana in 2009–2013. Drug resistance testing was performed as part of routine clinical care. Drug resistance mutations and levels were determined using Rega version 8.0.2. Results Eighty-three percent received solely ART containing at least three drugs. Patients from 2009 to 2010 were longer treated (median: 4.9 vs 2.7 years) and exposed to more ART regimens (median: 4 vs 2 regimens) compared to patients from 2011–2013. Nucleoside reverse transcriptase inhibitor (NRTI), non-nucleoside RTI (NNRTI) and PI mutations were present in 83.5, 77.4 and 52.0%. Full-class resistance (FCR) to NRTI, NNRTI, PI and multidrug resistance (MDR) were detected in 25.0, 33.7, 11.4 and 6.3%. FCR to NRTI, NNRTI, PI and MDR were present in 12.8, 28.7, 0 and 0% after first-line failure (164 patients) and in 23.1, 34.6, 3.8 and 3.1% after second-line failure (130 patients). Subtype B (32.5%), BG recombinants (19.6%) and CRF19_cpx (16.2%) were the most prevalent genetic forms. Subtype distribution did not change significantly between 2009–2010 and 2011–2013, except for BG recombinants that increased from 12.2 to 21.3% (p=0.002). Conclusions Our study found a high prevalence of drug resistance and supports the need for appropriate laboratory monitoring in clinical practice and access to drug options in case of virological failure. PMID:25397499

  7. High frequency of antiviral drug resistance and non-b subtypes in HIV-1 patients failing antiviral therapy in Cuba

    Directory of Open Access Journals (Sweden)

    Vivian Kouri

    2014-11-01

    Full Text Available Introduction: Emergence of HIV-1 drug resistance may limit the sustained benefits of antiretroviral therapy (ART in settings with limited laboratory monitoring and drug options. The objective is to implement the surveillance of drug resistance and subtypes in HIV-1 patients failing ART in Cuba. Methods: This study compiled clinical and genotypic drug resistance data 588 ART-experienced HIV-1 patients attending a clinical center in Havana in 2009–2013. Drug resistance testing was performed as part of routine clinical care. Drug resistance mutations and levels were determined using Rega version 8.0.2. Results: Eighty-three percent received solely ART containing at least three drugs. Patients from 2009 to 2010 were longer treated (median: 4.9 vs 2.7 years and exposed to more ART regimens (median: 4 vs 2 regimens compared to patients from 2011–2013. Nucleoside reverse transcriptase inhibitor (NRTI, non-nucleoside RTI (NNRTI and PI mutations were present in 83.5, 77.4 and 52.0%. Full-class resistance (FCR to NRTI, NNRTI, PI and multidrug resistance (MDR were detected in 25.0, 33.7, 11.4 and 6.3%. FCR to NRTI, NNRTI, PI and MDR were present in 12.8, 28.7, 0 and 0% after first-line failure (164 patients and in 23.1, 34.6, 3.8 and 3.1% after second-line failure (130 patients. Subtype B (32.5%, BG recombinants (19.6% and CRF19_cpx (16.2% were the most prevalent genetic forms. Subtype distribution did not change significantly between 2009–2010 and 2011–2013, except for BG recombinants that increased from 12.2 to 21.3% (p=0.002. Conclusions: Our study found a high prevalence of drug resistance and supports the need for appropriate laboratory monitoring in clinical practice and access to drug options in case of virological failure.

  8. Oseltamivir produces hypothermic and neuromuscular effects by inhibition of nicotinic acetylcholine receptor functions: comparison to procaine and bupropion.

    Science.gov (United States)

    Fukushima, Akihiro; Chazono, Kaori; Hashimoto, Yuichi; Iwajima, Yui; Yamamoto, Shohei; Maeda, Yasuhiro; Ohsawa, Masahiro; Ono, Hideki

    2015-09-01

    Oseltamivir, an anti-influenza virus drug, induces marked hypothermia in normal mice. We have proposed that the hypothermic effect arises from inhibition of the nicotinic acetylcholine receptor function of sympathetic ganglion neurons which innervate the brown adipose tissue (a heat generator). It has been reported that local anesthetics inhibit nicotinic acetylcholine receptor function by acting on its ionic channels, and that bupropion, a nicotinic antagonist, induces hypothermia. In this study, we compared the effects of oseltamivir, procaine and bupropion on body temperature, cardiovascular function and neuromuscular transmission. Intraperitoneal administration of oseltamivir (100mg/kg), procaine (86.6mg/kg) and bupropion (86.7mg/kg) lowered the core body temperature of normal mice. At lower doses (10-30mg/kg oseltamivir, 8.7-26mg/kg procaine and bupropion), when administered subcutaneously, the three drugs antagonized the hypothermia induced by intraperitoneal injection of nicotine (1mg/kg). In anesthetized rats, intravenous oseltamivir (30-100mg/kg), procaine (10mg/kg) and bupropion (10mg/kg) induced hypotension and bradycardia. Oseltamivir alone (100mg/kg) did not inhibit neuromuscular twitch contraction of rats, but at 3-30mg/kg it augmented the muscle-relaxing effect of d-tubocurarine. Similar effects were observed when lower doses of procaine (10-30mg/kg) and bupropion (3-10mg/kg) were administered, suggesting that systemic administration of oseltamivir inhibits muscular nicotinic acetylcholine receptors. These results support the idea that the hypothermic effect of oseltamivir is due to its effects on sympathetic ganglia which innervate the brown adipose tissue, and suggest that oseltamivir may exert non-selective ion channel blocking effects like those of ester-type local anesthetics. PMID:26049014

  9. Oseltamivir compounding in the hospital pharmacy during the (H1N1 influenza pandemic

    Directory of Open Access Journals (Sweden)

    Márcia Lúcia de Mário Marin

    2010-01-01

    Full Text Available AIMS: Pandemics impose large demands on the health care system. The supply of appropriate chemotherapeutic agents, namely oseltamivir solution, presented a serious challenge in the recent influenza pandemic. This study reports on the rational series of pharmacotechnical steps that were followed to appropriately handle bulk oseltamivir powder to meet the increased demand. METHODS: During a six-week period in August and September of 2009, a task force was created in the Central Pharmacy of Hospital das Clínicas to convert imported oseltamivir phosphate into ready-to-use solution for utilization by physicians and public health authorities. The protocol included dissolution, physico-chemical tests and the bottling of a liquid microdose formulation for emergency room and outpatient dispensing with adequate quality control during all phases. RESULTS: The successful production routine was based on a specially designed flowchart according to which a batch of 33210 g of oseltamivir powder was converted into 32175 solution units during the aforementioned period with a net loss of only 2.6%. The end products were bottles containing 50 ml of 15 mg/mL oseltamivir solution. The measured concentration was stable and accurate (97.5% - 102.0% of the nominal value. The drug was prescribed as both a prophylactic and therapeutic agent. DISCUSSION: Hospital pharmacies are conventionally engaged in the manipulation of medical prescriptions and specialty drugs. They are generally responsible for only small-scale equipment used for manufacturing and quality-control procedures. The compounding of oseltamivir was a unique effort dictated by exceptional circumstances. CONCLUSION: The shortage of oseltamivir solution for clinical use was solved by emergency operationalization of a semi-industrial process in which bulk powder was converted into practical vials for prompt delivery.

  10. A Review of the Antiviral Susceptibility of Human and Avian Influenza Viruses over the Last Decade

    Directory of Open Access Journals (Sweden)

    Ding Yuan Oh

    2014-01-01

    Full Text Available Antivirals play an important role in the prevention and treatment of influenza infections, particularly in high-risk or severely ill patients. Two classes of influenza antivirals have been available in many countries over the last decade (2004–2013, the adamantanes and the neuraminidase inhibitors (NAIs. During this period, widespread adamantane resistance has developed in circulating influenza viruses rendering these drugs useless, resulting in the reliance on the most widely available NAI, oseltamivir. However, the emergence of oseltamivir-resistant seasonal A(H1N1 viruses in 2008 demonstrated that NAI-resistant viruses could also emerge and spread globally in a similar manner to that seen for adamantane-resistant viruses. Previously, it was believed that NAI-resistant viruses had compromised replication and/or transmission. Fortunately, in 2013, the majority of circulating human influenza viruses remain sensitive to all of the NAIs, but significant work by our laboratory and others is now underway to understand what enables NAI-resistant viruses to retain the capacity to replicate and transmit. In this review, we describe how the susceptibility of circulating human and avian influenza viruses has changed over the last ten years and describe some research studies that aim to understand how NAI-resistant human and avian influenza viruses may emerge in the future.

  11. Potential for Drug-Drug Interactions between Antiretrovirals and HCV Direct Acting Antivirals in a Large Cohort of HIV/HCV Coinfected Patients

    OpenAIRE

    Poizot-Martin, Isabelle; Naqvi, Alissa; Obry-Roguet, Véronique; Valantin, Marc-Antoine; Cuzin, Lise; Billaud, Eric; Cheret, Antoine; Rey, David; Jacomet, Christine; Duvivier, Claudine; Pugliese, Pascal; Pradat, Pierre; Cotte, Laurent

    2015-01-01

    Objectives Development of direct acting antivirals (DAA) offers new benefits for patients with chronic hepatitis C. The combination of these drugs with antiretroviral treatment (cART) is a real challenge in HIV/HCV coinfected patients. The aim of this study was to describe potential drug-drug interactions between DAAs and antiretroviral drugs in a cohort of HIV/HCV coinfected patients. Methods Cross-sectional study of all HIV/HCV coinfected patients attending at least one visit in 2012 in the...

  12. Guidance for Practitioners on the Use of Antiviral Drugs to Control Influenza Outbreaks in Long-Term Care Facilities in Canada, 2014-2015 Season

    OpenAIRE

    Fred Y Aoki; Allen, Upton D.; H Grant Stiver; Michel Laverdière; Danuta Skowronski; Evans, Gerald A

    2015-01-01

    The AMMI Canada Guidelines document ‘The use of antiviral drugs for influenza: A foundation document for practitioners’, published in the Autumn 2013 issue of the Journal, outlines the recommendations for the use of antiviral drugs to treat influenza. This article, which represents the first of two updates to these guidelines published in the current issue of the Journal, aims to inform health care professionals of the increased risk for influenza in long-term care facilities due to a documen...

  13. A human genome-wide loss-of-function screen identifies effective chikungunya antiviral drugs.

    Science.gov (United States)

    Karlas, Alexander; Berre, Stefano; Couderc, Thérèse; Varjak, Margus; Braun, Peter; Meyer, Michael; Gangneux, Nicolas; Karo-Astover, Liis; Weege, Friderike; Raftery, Martin; Schönrich, Günther; Klemm, Uwe; Wurzlbauer, Anne; Bracher, Franz; Merits, Andres; Meyer, Thomas F; Lecuit, Marc

    2016-01-01

    Chikungunya virus (CHIKV) is a globally spreading alphavirus against which there is no commercially available vaccine or therapy. Here we use a genome-wide siRNA screen to identify 156 proviral and 41 antiviral host factors affecting CHIKV replication. We analyse the cellular pathways in which human proviral genes are involved and identify druggable targets. Twenty-one small-molecule inhibitors, some of which are FDA approved, targeting six proviral factors or pathways, have high antiviral activity in vitro, with low toxicity. Three identified inhibitors have prophylactic antiviral effects in mouse models of chikungunya infection. Two of them, the calmodulin inhibitor pimozide and the fatty acid synthesis inhibitor TOFA, have a therapeutic effect in vivo when combined. These results demonstrate the value of loss-of-function screening and pathway analysis for the rational identification of small molecules with therapeutic potential and pave the way for the development of new, host-directed, antiviral agents. PMID:27177310

  14. Oseltamivir in human avian influenza infection

    OpenAIRE

    Smith, James R.

    2010-01-01

    Avian influenza A viruses continue to cause disease outbreaks in humans, and extrapulmonary infection is characteristic. In vitro studies demonstrate the activity of oseltamivir against avian viruses of the H5, H7 and H9 subtypes. In animal models of lethal infection, oseltamivir treatment and prophylaxis limit viral replication and improve survival. Outcomes are influenced by the virulence of the viral strain, dosage regimen and treatment delay; it is also critical for the compound to act sy...

  15. Structures of Two Coronavirus Main Proteases: Implications for Substrate Binding and Antiviral Drug Design

    Energy Technology Data Exchange (ETDEWEB)

    Xue, Xiaoyu; Yu, Hongwei; Yang, Haitao; Xue, Fei; Wu, Zhixin; Shen, Wei; Li, Jun; Zhou, Zhe; Ding, Yi; Zhao, Qi; Zhang, Xuejun C.; Liao, Ming; Bartlam, Mark; Rao, Zihe (SCAU); (Tsinghua); (Chinese Aca. Sci.)

    2008-07-21

    Coronaviruses (CoVs) can infect humans and multiple species of animals, causing a wide spectrum of diseases. The coronavirus main protease (M{sup pro}), which plays a pivotal role in viral gene expression and replication through the proteolytic processing of replicase polyproteins, is an attractive target for anti-CoV drug design. In this study, the crystal structures of infectious bronchitis virus (IBV) MP{sup pro} and a severe acute respiratory syndrome CoV (SARS-CoV) M{sup pro} mutant (H41A), in complex with an N-terminal autocleavage substrate, were individually determined to elucidate the structural flexibility and substrate binding of M{sup pro}. A monomeric form of IBV M{sup pro} was identified for the first time in CoV M{sup pro} structures. A comparison of these two structures to other available M{sup pro} structures provides new insights for the design of substrate-based inhibitors targeting CoV M{sup pro}s. Furthermore, a Michael acceptor inhibitor (named N3) was cocrystallized with IBV M{sup pro} and was found to demonstrate in vitro inactivation of IBV M{sup pro} and potent antiviral activity against IBV in chicken embryos. This provides a feasible animal model for designing wide-spectrum inhibitors against CoV-associated diseases. The structure-based optimization of N3 has yielded two more efficacious lead compounds, N27 and H16, with potent inhibition against SARS-CoV M{sup pro}.

  16. Oseltamivir

    Science.gov (United States)

    ... system such as azathioprine (Imuran); cyclosporine (Neoral, Sandimmune); cancer chemotherapy medications; methotrexate (Rheumatrex); sirolimus (Rapamune); oral steroids such as dexamethasone ( ...

  17. Oseltamivir

    Science.gov (United States)

    ... as a stuffy or runny nose, sore throat, cough, muscle or joint aches, tiredness, headache, fever, and ... liquid, such as regular or sugar-free chocolate syrup, corn syrup, caramel topping, or light brown sugar ...

  18. 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.

  19. Oseltamivir (Tamiflu) Induced Depressive Episode in a Female Adolescent

    OpenAIRE

    Chung, Sungho; Joung, Yoo Sook

    2010-01-01

    Oseltamivir was developed for prophylactic and therapeutic use against influenza, specifically targeting the viral enzyme's highly-conserved active site. In recent years, there have been case reports of neuropsychiatric events during or after oseltamivir treatment, in Japan and other countries. However, a search of the literature revealed no such cases in South Korea. We present the case of a 15-year-old female adolescent diagnosed with depressive episode after taking oseltamivir. Oseltamivir...

  20. Identification of transformation products of antiviral drugs formed during biological wastewater treatment and their occurrence in the urban water cycle.

    Science.gov (United States)

    Funke, Jan; Prasse, Carsten; Ternes, Thomas A

    2016-07-01

    The fate of five antiviral drugs (abacavir, emtricitabine, ganciclovir, lamivudine and zidovudine) was investigated in biological wastewater treatment. Investigations of degradation kinetics were accompanied by the elucidation of formed transformation products (TPs) using activated sludge lab experiments and subsequent LC-HRMS analysis. Degradation rate constants ranged between 0.46 L d(-1) gSS(-1) (zidovudine) and 55.8 L d(-1) gSS(-1) (abacavir). Despite these differences of the degradation kinetics, the same main biotransformation reaction was observed for all five compounds: oxidation of the terminal hydroxyl-moiety to the corresponding carboxylic acid (formation of carboxy-TPs). In addition, the oxidation of thioether moieties to sulfoxides was observed for emtricitabine and lamivudine. Antiviral drugs were detected in influents of municipal wastewater treatment plants (WWTPs) with concentrations up to 980 ng L(-1) (emtricitabine), while in WWTP effluents mainly the TPs were found with concentration levels up to 1320 ng L(-1) (carboxy-abacavir). Except of zidovudine none of the original antiviral drugs were detected in German rivers and streams, whereas the concentrations of the TPs ranged from 16 ng L(-1) for carboxy-lamivudine up to 750 ng L(-1) for carboxy-acyclovir. These concentrations indicate an appreciable portion from WWTP effluents present in rivers and streams, as well as the high environmental persistence of the carboxy-TPs. As a result three of the carboxylic TPs were detected in finished drinking water. PMID:27082694

  1. Marine natural seaweed products as potential antiviral drugs against Bovine viral diarrhea virus

    Directory of Open Access Journals (Sweden)

    Ana Maria Viana Pinto

    2012-08-01

    Full Text Available Bovine viral diarrhea virus (BVDV is an etiologic agent that causes important economic losses in the world. It is endemic in cattle herds in most parts of the world. The purpose of this study was to evaluate the in vitro cytotoxic effect and antiviral properties of several marine natural products obtained from seaweeds: the indole alkaloid caulerpin (CAV, 1 and three diterpenes: 6-hydroxydichotoma-3,14-diene-1,17-dial (DA, 2, 10,18-diacetoxy-8-hydroxy-2,6-dolabelladiene (DB1, 3 and 8,10,18-trihydroxy-2,6-dolabelladiene (DB3, 4. The screening to evaluate the cytotoxicity of compounds did not show toxic effects to MDBK cells. The antiviral activity of the compounds was measured by the inhibition of the cytopathic effect on infected cells by plaque assay (PA and EC50 values were calculated for CAV (EC=2,0± 5.8, DA (EC 2,8± 7.7, DB1 (EC 2,0±9.7, and DB3 (EC 2,3±7.4. Acyclovir (EC50 322± 5.9 was used in all experiments as the control standard. Although the results of the antiviral activity suggest that all compounds are promising as antiviral agents against BVDV, the Selectivity Index suggests that DB1 is the safest of the compounds tested.

  2. The Need for Development of New HIV-1 Reverse Transcriptase and Integrase Inhibitors in the Aftermath of Antiviral Drug Resistance

    Directory of Open Access Journals (Sweden)

    Mark A. Wainberg

    2012-01-01

    Full Text Available The use of highly active antiretroviral therapy (HAART involves combinations of drugs to achieve maximal virological response and reduce the potential for the emergence of antiviral resistance. There are two broad classes of reverse transcriptase inhibitors, the nucleoside reverse transcriptase inhibitors (NRTIs and nonnucleoside reverse transcriptase inhibitors (NNRTIs. Since the first classes of such compounds were developed, viral resistance against them has necessitated the continuous development of novel compounds within each class. This paper considers the NRTIs and NNRTIs currently in both preclinical and clinical development or approved for second line therapy and describes the patterns of resistance associated with their use, as well as the underlying mechanisms that have been described. Due to reasons of both affordability and availability, some reverse transcriptase inhibitors with low genetic barrier are more commonly used in resource-limited settings. Their use results to the emergence of specific patterns of antiviral resistance and so may require specific actions to preserve therapeutic options for patients in such settings. More recently, the advent of integrase strand transfer inhibitors represents another major step forward toward control of HIV infection, but these compounds are also susceptible to problems of HIV drug resistance.

  3. Influenza Resistance to Antiviral Drugs: Virus characterization, mechanism and clinical impact

    OpenAIRE

    Vries, Erhard

    2014-01-01

    markdownabstract__Abstract__ Each year, approximately 5-10% of the world population is infected with the influenza viruses resulting in significant morbidity and an estimated 250.000 to 500.000 deaths every year. Among individuals at increased risk of developing severe influenza disease are those with a compromised immune system. For them being able to effectively suppress viral replication antiviral therapy can be crucial. However, in immunocompromised patients the currently available antivi...

  4. Chemical Analysis and Transplacental Transfer of Oseltamivir and Oseltamivir Carboxylic Acid in Pregnant Rats

    OpenAIRE

    Lin, Chia-Chun; Yen, Jiin-Cherng; Wu, Yu-Tse; Lin, Lie-Chwen; Tsai, Tung-Hu

    2012-01-01

    In view of the limited information on the pharmacokinetics of oseltamivir (OSE) during pregnancy, this study aims to evaluate the placental transportation of OSE and its active metabolite oseltamivir carboxylic acid (OCA) in rats. A validated liquid chromatography-tandem mass spectrometry (LC-MS/MS) system coupled to an in vivo transplacental model has been developed to determine OSE and OCA in the placenta, amniotic fluids and fetus of 13-day pregnant Sprague-Dawley rats. Concentrations of O...

  5. Meeting report: 4th ISIRV antiviral group conference: Novel antiviral therapies for influenza and other respiratory viruses.

    Science.gov (United States)

    McKimm-Breschkin, Jennifer L; Fry, Alicia M

    2016-05-01

    The International Society for Influenza and other Respiratory Virus Diseases (isirv) held its 4th Antiviral Group Conference at the University of Texas on 2-4 June, 2015. With emerging resistance to the drugs currently licensed for treatment and prophylaxis of influenza viruses, primarily the neuraminidase inhibitor oseltamivir phosphate (Tamiflu) and the M2 inhibitors amantadine and rimantadine, and the lack of effective interventions against other respiratory viruses, the 3-day programme focused on the discovery and development of inhibitors of several virus targets and key host cell factors involved in virus replication or mediating the inflammatory response. Virus targets included the influenza haemagglutinin, neuraminidase and M2 proteins, and both the respiratory syncytial virus and influenza polymerases and nucleoproteins. Therapies for rhinoviruses and MERS and SARS coronaviruses were also discussed. With the emerging development of monoclonal antibodies as therapeutics, the potential implications of antibody-dependent enhancement of disease were also addressed. Topics covered all aspects from structural and molecular biology to preclinical and clinical studies. The importance of suitable clinical trial endpoints and regulatory issues were also discussed from the perspectives of both industry and government. This meeting summary provides an overview, not only for the conference participants, but also for those interested in the current status of antivirals for respiratory viruses. PMID:26872862

  6. Increasing oral absorption of polar neuraminidase inhibitors: a prodrug transporter approach applied to oseltamivir analogue.

    Science.gov (United States)

    Gupta, Deepak; Varghese Gupta, Sheeba; Dahan, Arik; Tsume, Yasuhiro; Hilfinger, John; Lee, Kyung-Dall; Amidon, Gordon L

    2013-02-01

    Poor oral absorption is one of the limiting factors in utilizing the full potential of polar antiviral agents. The neuraminidase target site requires a polar chemical structure for high affinity binding, thus limiting oral efficacy of many high affinity ligands. The aim of this study was to overcome this poor oral absorption barrier, utilizing prodrug to target the apical brush border peptide transporter 1 (PEPT1). Guanidine oseltamivir carboxylate (GOCarb) is a highly active polar antiviral agent with insufficient oral bioavailability (4%) to be an effective therapeutic agent. In this report we utilize a carrier-mediated targeted prodrug approach to improve the oral absorption of GOCarb. Acyloxy(alkyl) ester based amino acid linked prodrugs were synthesized and evaluated as potential substrates of mucosal transporters, e.g., PEPT1. Prodrugs were also evaluated for their chemical and enzymatic stability. PEPT1 transport studies included [(3)H]Gly-Sar uptake inhibition in Caco-2 cells and cellular uptake experiments using HeLa cells overexpressing PEPT1. The intestinal membrane permeabilities of the selected prodrugs and the parent drug were then evaluated for epithelial cell transport across Caco-2 monolayers, and in the in situ rat intestinal jejunal perfusion model. Prodrugs exhibited a pH dependent stability with higher stability at acidic pHs. Significant inhibition of uptake (IC(50) 30-fold increase in affinity compared to GOCarb. The l-valyl prodrug exhibited significant enhancement of uptake in PEPT1/HeLa cells and compared favorably with the well-absorbed valacyclovir. Transepithelial permeability across Caco-2 monolayers showed that these amino acid prodrugs have a 2-5-fold increase in permeability as compared to the parent drug and showed that the l-valyl prodrug (P(app) = 1.7 × 10(-6) cm/s) has the potential to be rapidly transported across the epithelial cell apical membrane. Significantly, only the parent drug (GOCarb) appeared in the basolateral

  7. Increasing Oral Absorption of Polar Neuraminidase Inhibitors: A Prodrug Transporter Approach Applied to Oseltamivir Analogue

    Science.gov (United States)

    Gupta, Deepak; Gupta, Sheeba Varghese; Dahan, Arik; Tsume, Yasuhiro; Hilfinger, John; Lee, Kyung-Dall; Amidon, Gordon L.

    2013-01-01

    Poor oral absorption is one of the limiting factors in utilizing the full potential of polar antiviral agents. The neuraminidase target site requires a polar chemical structure for high affinity binding, thus limiting oral efficacy of many high affinity ligands. The aim of this study was to overcome this poor oral absorption barrier, utilizing prodrug to target the apical brush border peptide transporter 1 (PEPT1). Guanidine oseltamivir carboxylate (GOCarb) is a highly active polar antiviral agent (prodrug) with insufficient oral bioavailability (4%) to be an effective therapeutic agent. In this report we utilize a carrier-mediated targeted prodrug approach to improve the oral absorption of GOCarb. Acyloxy(alkyl) ester based amino acid linked prodrugs were synthesized and evaluated as potential substrates of mucosal transporters e.g. PEPT1. Prodrugs were also evaluated for their chemical and enzymatic stability. PEPT1 transport studies included [3H]Gly-Sar uptake inhibition and cellular uptake experiments using HeLa cells over-expressing PEPT1. The intestinal membrane permeability of the selected prodrugs and the parent drug were then evaluated for epithelial cell transport across Caco-2 monolayers, and in the in-situ rat intestinal jejunal perfusion model. Prodrugs exhibited a pH dependent stability with higher stability at acidic pHs. Significant inhibition of uptake (IC50 30 fold increase in affinity compared to GOCarb. The L-valyl prodrug exhibited significant enhancement of uptake in PEPT1/HeLa cells, and compared favorably with the well absorbed valacyclovir. Transepithelial permeability across Caco-2 monolayers showed that these amino acid prodrugs have a 2–5 fold increase in permeability as compared to the parent drug and showed that the L-valyl prodrug (Papp = 1.7×10−6 cm/sec) has the potential to be a rapidly transported across the epithelial cell apical membrane. Significantly, only the parent drug (GOCarb) appeared in the basolateral compartment

  8. Oseltamivir derivatives suitable for click chemistry

    Czech Academy of Sciences Publication Activity Database

    Kožíšek, Milan; Konvalinka, Jan; Řezáčová, Pavlína; Machara, A.; Albinana, C. B.

    Praha: Czech Chemical Society, 2015. s. 56. [Liblice 2015. Advances in Organic , Bioorganic and Pharmaceutical Chemistry /50./. 06.11.2015-08.11.2015, Olomouc] R&D Projects: GA ČR GA13-19561S Institutional support: RVO:61388963 Keywords : oseltamivir * Tamiphosphor * virostatics Subject RIV: CC - Organic Chemistry

  9. [Naturally occurring oseltamivir resistance in influenza A.

    DEFF Research Database (Denmark)

    Madsen, Laura; Nielsen, Alex; Lundgren, Jens

    2010-01-01

    During the last two influenza seasons, one of the predominant influenza A types (H1N1) has developed complete resistance to oseltamivir, the primary treatment option. The virus does, however, remain sensitive to zanamavir and amantadine. There is no unequivocal explanation for this slide in the d...

  10. A double-blind, randomized, placebo-controlled multicenter study of oseltamivir phosphate for treatment of influenza infection in China

    Institute of Scientific and Technical Information of China (English)

    龙芸; 蔡伯蔷; 王孟昭; 朱元珏

    2003-01-01

    main adverse events following test drug were gastrointestinal symptoms, neurological symptoms and rashes. Conclusion Oseltamivir was effective and well tolerated as treatment of early naturally acquired influenza.

  11. A comparative study of the interaction of Tamiflu and Oseltamivir carboxylate with bovine serum albumin.

    Science.gov (United States)

    Vishkaee, Tahereh Sadigh; Mohajerani, Niloufar; Nafisi, Shohreh

    2013-02-01

    Oseltamivir phosphate (Tamiflu) is a pro-drug that is metabolized to its active form (Oseltamivir carboxylate), after oral administration. OC inhibits influenza A and B neuraminidases in vitro and OP inhibits influenza virus infection and replication in vitro. Serum albumin is the most abundant of the proteins in the circulatory system of a wide variety of organisms and plays an important role in the transport and deposition of many drugs. The aim of this study was to examine the interaction of BSA with Tamiflu and Oseltamivir carboxylate in aqueous solution at physiological conditions, using a constant protein concentration and various drug contents. FTIR, UV-Vis spectroscopic methods were used to determine the drugs binding mode, the binding constant and the effects of drug complexation on protein secondary structure. Structural analysis showed that OP and OC bind BSA with overall binding constants of K(OP-BSA)=1.88 (±0.16)×10(4)M(-1) and K(OC-BSA)=5.7 (±0.09)×10(2)M(-1). Drug complexation alters protein conformation by major reduction of α-helix and random coil and increase of β-sheet and turn structures that indicate a partial protein destabilization. The results suggest that BSA might act as carrier proteins for OP in delivering it to target molecules. PMID:23353784

  12. Dengue Virus Reporter Replicon is a Valuable Tool for Antiviral Drug Discovery and Analysis of Virus Replication Mechanisms

    Science.gov (United States)

    Kato, Fumihiro; Hishiki, Takayuki

    2016-01-01

    Dengue, the most prevalent arthropod-borne viral disease, is caused by the dengue virus (DENV), a member of the Flaviviridae family, and is a considerable public health threat in over 100 countries, with 2.5 billion people living in high-risk areas. However, no specific antiviral drug or licensed vaccine currently targets DENV infection. The replicon system has all the factors needed for viral replication in cells. Since the development of replicon systems, transient and stable reporter replicons, as well as reporter viruses, have been used in the study of various virological aspects of DENV and in the identification of DENV inhibitors. In this review, we summarize the DENV reporter replicon system and its applications in high-throughput screening (HTS) for identification of anti-DENV inhibitors. We also describe the use of this system in elucidation of the mechanisms of virus replication and viral dynamics in vivo and in vitro. PMID:27164125

  13. Dengue Virus Reporter Replicon is a Valuable Tool for Antiviral Drug Discovery and Analysis of Virus Replication Mechanisms.

    Science.gov (United States)

    Kato, Fumihiro; Hishiki, Takayuki

    2016-01-01

    Dengue, the most prevalent arthropod-borne viral disease, is caused by the dengue virus (DENV), a member of the Flaviviridae family, and is a considerable public health threat in over 100 countries, with 2.5 billion people living in high-risk areas. However, no specific antiviral drug or licensed vaccine currently targets DENV infection. The replicon system has all the factors needed for viral replication in cells. Since the development of replicon systems, transient and stable reporter replicons, as well as reporter viruses, have been used in the study of various virological aspects of DENV and in the identification of DENV inhibitors. In this review, we summarize the DENV reporter replicon system and its applications in high-throughput screening (HTS) for identification of anti-DENV inhibitors. We also describe the use of this system in elucidation of the mechanisms of virus replication and viral dynamics in vivo and in vitro. PMID:27164125

  14. 磷酸奥司他韦预防甲型H1N1流感时引起不良反应206例报道%Report of 206 cases of adverse drug reactions in using oseltamivir to prevent influenza A H1N1 influenza

    Institute of Scientific and Technical Information of China (English)

    董伟; 王艳彩

    2011-01-01

    AIM To analyse the adverse drug reactions (ADRs) occurred in people who took oseltamivir phosphate to prevent influenza A H1N1 influenza. METHODS The ADRs of 2 978 cases who took oseltamivir phosphate 75 mg once daily for 7 d to prevent influenza A H1N1 influenza were recorded every day and 2 790 cases with intact data were carried out statistical analysis. RESULTS There were 206 cases of ADRs, with the total ADRs incidence rate of 7.38%. Cases with the main clinical manifestations of enteron symptoms such as diarrhea, nausea, and bellyache etc.were 157, with the incidence rate of 5.62%. The incidenec rate of ADRs was low in rash, otalgia, tachycardia, foreign body sensation of esophagus and nosebleed and insomnia etc. CONCLUSION The ADRs of oseltamivir phosphate in the prevention of influenza A HIN1 influenza mainly were enteron symptoms which do not affect the treatment in general. But if such symptoms as rash or tachyeardia occur, the drug should be immediately stopped and symptomatic treatment must be given.%目的 分析磷酸奥司他韦预防甲型H1N1流感时人群不良反应发生情况.方法 对2978例服用磷酸奥司他韦75㎎,qd,共7 d预防甲型H1N1型流感者逐日记录其不良反应并将2790例资料完整者进行分析统计.结果 206例出现不良反应,总不良反应发生率为7.38%,以腹泻、恶心、腹痛等消化道症状为主,共157例,发生率为5.62%.皮疹、耳痛、心动过速、食管异物感、鼻出血、失眠等发生率低.结论 磷酸奥司他韦预防甲型H1N1流感时不良反应以消化道症状为主,一般不影响治疗.如出现皮疹、心动过速等应停药并给予对症处理.

  15. Theoretical studies on the susceptibility of oseltamivir against variants of 2009 A/H1N1 influenza neuraminidase.

    Science.gov (United States)

    Li, Lin; Li, Youyong; Zhang, Liling; Hou, Tingjun

    2012-10-22

    The outbreak and high speed global spread of the new strain of influenza A/H1N1 virus in 2009 posed a serious threat to global health. It is more likely that drug-resistant influenza strains will arise after the extensive use of anti-influenza drugs. Consequently, the identification of the potential resistant sites for drugs in advance and the understanding of the corresponding molecular mechanisms that cause drug resistance are quite important in the design of new drug candidates with better potency to combat drug resistance. Here, we performed molecular simulations to evaluate the potency of oseltamivir to combat drug resistance caused by the mutations in 2009 A/H1N1 neuraminidase (NA). We examined three representative drug-resistant mutations in NA, consisting of H274Y, N294S, and Y252H. First, a theoretical structure of A/H1N1 NA in complex with oseltamivir was constructed using homology modeling. Then, molecular dynamics (MD) simulations, molecular mechanics/Poisson-Boltzmann surface area (MM/PBSA) calculations, and MM/GBSA free energy decomposition were used to characterize the binding of oseltamivir with the wild type (WT) and three mutated NAs. Our predictions show that N294S and H274Y, two popular drug-resistant mutations in different variants of NA, still cause significant resistance to oseltamivir. However, the Y252H mutation does not impair the interactions between oseltamivir and A/H1N1 NA. An examination of individual energy components shows that the loss of polar interactions is the key source for the resistance of the studied mutations to oseltamivir. Moreover, free energy decomposition analysis and structural analysis reveal that the N294S or H274Y mutation triggers the large-scale conformational changes of the binding pocket and then impairs the affinity of oseltamivir. We expect that our results will be useful for the rational design of NA inhibitors with high potency against drug-resistant A/H1N1 mutants. PMID:22998323

  16. Public health management of antiviral drugs during the 2009 H1N1 influenza pandemic: a survey of local health departments in California

    Directory of Open Access Journals (Sweden)

    Hunter Jennifer C

    2012-01-01

    Full Text Available Abstract Background The large-scale deployment of antiviral drugs from the Strategic National Stockpile during the 2009 H1N1 influenza response provides a unique opportunity to study local public health implementation of the medical countermeasure dispensing capability in a prolonged event of national significance. This study aims to describe the range of methods used by local health departments (LHDs in California to manage antiviral activities and to gain a better understanding of the related challenges experienced by health departments and their community partners. Methods This research employed a mixed-methods approach. First, a multi-disciplinary focus group of pandemic influenza planners from key stakeholder groups in California was convened in order to generate ideas and identify critical themes related to the local implementation of antiviral activities during the H1N1 influenza response. These qualitative data informed the development of a web-based survey, which was distributed to all 61 LHDs in California for the purpose of assessing the experiences of a representative sample of local health agencies in a large region. Results Forty-four LHDs participated in this study, representing 72% of the local public health agencies in California. While most communities dispensed a modest number of publicly purchased antivirals, LHDs nevertheless drew on their previous work and engaged in a number of antiviral activities, including: acquiring, allocating, distributing, dispensing, tracking, developing guidance, and communicating to the public and clinical community. LHDs also identified specific antiviral challenges presented by the H1N1 pandemic, including: reconciling multiple sources and versions of antiviral guidance, determining appropriate uses and recipients of publicly purchased antivirals, and staffing shortages. Conclusions The 2009 H1N1 influenza pandemic presented an unusual opportunity to learn about the role of local public health

  17. Synthesis of an antiviral drug precursor from chitin using a saprophyte as a whole-cell catalyst

    Directory of Open Access Journals (Sweden)

    Steiger Matthias G

    2011-12-01

    Full Text Available Abstract Background Recent incidents, such as the SARS and influenza epidemics, have highlighted the need for readily available antiviral drugs. One important precursor currently used for the production of Relenza, an antiviral product from GlaxoSmithKline, is N-acetylneuraminic acid (NeuNAc. This substance has a considerably high market price despite efforts to develop cost-reducing (biotechnological production processes. Hypocrea jecorina (Trichoderma reesei is a saprophyte noted for its abundant secretion of hydrolytic enzymes and its potential to degrade chitin to its monomer N-acetylglucosamine (GlcNAc. Chitin is considered the second most abundant biomass available on earth and therefore an attractive raw material. Results In this study, we introduced two enzymes from bacterial origin into Hypocrea, which convert GlcNAc into NeuNAc via N-acetylmannosamine. This enabled the fungus to produce NeuNAc from the cheap starting material chitin in liquid culture. Furthermore, we expressed the two recombinant enzymes as GST-fusion proteins and developed an enzyme assay for monitoring their enzymatic functionality. Finally, we demonstrated that Hypocrea does not metabolize NeuNAc and that no NeuNAc-uptake by the fungus occurs, which are important prerequisites for a potential production strategy. Conclusions This study is a proof of concept for the possibility to engineer in a filamentous fungus a bacterial enzyme cascade, which is fully functional. Furthermore, it provides the basis for the development of a process for NeuNAc production as well as a general prospective design for production processes that use saprophytes as whole-cell catalysts.

  18. Antiviral activity of the plant extracts from Thuja orientalis, Aster spathulifolius, and Pinus thunbergii against influenza virus A/PR/8/34.

    Science.gov (United States)

    Won, Ji-Na; Lee, Seo-Yong; Song, Dae-sub; Poo, Haryoung

    2013-01-01

    Influenza viruses cause significant morbidity and mortality in humans through epidemics or pandemics. Currently, two classes of anti-influenza virus drugs, M2 ion-channel inhibitors (amantadin and rimantadine) and neuraminidase inhibitors (oseltamivir and zanamivir), have been used for the treatment of the influenza virus infection. Since the resistance to these drugs has been reported, the development of a new antiviral agent is necessary. In this study, we examined the antiviral efficacy of the plant extracts against the influenza A/PR/8/34 infection. In vitro, the antiviral activities of the plant extracts were investigated using the cell-based screening. Three plant extracts, Thuja orientalis, Aster spathulifolius, and Pinus thunbergii, were shown to induce a high cell viability rate after the infection with the influenza A/PR/8/34 virus. The antiviral activity of the plant extracts also increased as a function of the concentration of the extracts and these extracts significantly reduced the visible cytopathic effect caused by virus infections. Furthermore, the treatment with T. orientalis was shown to have a stronger inhibitory effect than that with A. spathulifolius or P. thunbergii. These results may suggest that T. orientalis has anti-influenza A/PR/8/34 activity. PMID:23314378

  19. Antiviral Polymer Therapeutics

    DEFF Research Database (Denmark)

    Smith, Anton Allen Abbotsford

    2014-01-01

    The field of drug delivery is in essence an exercise in engineered pharmacokinetics. Methods of doing so have been developed through the introduction of a vehicle carrying the drug, either by encapsulation or covalent attachment. The emergence of polymer therapeutics in anticancer therapy has...... the examples of polymer therapeutics being applied as an antiviral treatment are few and far in-between. This work aims to explore antiviral therapeutics, specifically in context of hepatitis virus C (HCV) and HIV. The current treatment of hepatitis C consists of a combination of drugs, of which ribavirin...

  20. Crystal Structures, Thermal Analysis, and Dissolution Behavior of New Solid Forms of the Antiviral Drug Arbidol with Dicarboxylic Acids

    Directory of Open Access Journals (Sweden)

    Alex N. Manin

    2015-12-01

    Full Text Available Salts of the antiviral drug arbidol (umifenovir (Arb with maleate (Mlc and fumarate (Fum anions have been obtained, and their crystal structures have been described. The crystal structure of arbidol maleate has been redetermined by single crystal X-ray diffraction at 180K. A new arbidol cocrystal in zwitterion form with succinic acid (Suc has also been found and characterized. The arbidol zwitterion was not previously seen in any of the drug crystal forms, and the [Arb + Suc] cocrystal seems to be the first found instance. Analysis of the conformational preferences of the arbidol molecule in the crystal structures has shown that it adopts two types of conformations, namely “open” and “closed” ones. Thermal stability of the arbidol salts and cocrystal have been analyzed by means of differential scanning calorimetry, thermogravimetric, and mass-spectrometry analysis. The dissolution study of the arbidol salts and cocrystal performed in aqueous buffer solutions with pH 1.2 and 6.8 has shown that both the salts and the cocrystal dissolve incongruently to form an arbidol hydrochloride monohydrate at pH 1.2 and an arbidol base at pH 6.8, respectively. The cocrystal reaches the highest solubility level in both pH 1.2 and pH 6.8 solutions.

  1. HIV-1 Reverse Transcriptase and Antiviral Drug Resistance (Part 1 of 2)

    OpenAIRE

    Das, Kalyan; Arnold, Eddy

    2013-01-01

    HIV-1 reverse transcriptase (RT) contributes to the development of resistance to all anti-AIDS drugs by introducing mutations into the viral genome. At the molecular level, mutations in RT result in resistance to RT inhibitors. Eight nucleoside/nucleotide analogs (NRTIs) and five non-nucleoside inhibitors (NNRTIs) are approved HIV-1 drugs. Structures of RT have been determined in complexes with substrates and/or inhibitors, and the structures have revealed different conforma...

  2. Prolonged influenza virus shedding and emergence of antiviral resistance in immunocompromised patients and ferrets.

    Directory of Open Access Journals (Sweden)

    Erhard van der Vries

    Full Text Available Immunocompromised individuals tend to suffer from influenza longer with more serious complications than otherwise healthy patients. Little is known about the impact of prolonged infection and the efficacy of antiviral therapy in these patients. Among all 189 influenza A virus infected immunocompromised patients admitted to ErasmusMC, 71 were hospitalized, since the start of the 2009 H1N1 pandemic. We identified 11 (15% cases with prolonged 2009 pandemic virus replication (longer than 14 days, despite antiviral therapy. In 5 out of these 11 (45% cases oseltamivir resistant H275Y viruses emerged. Given the inherent difficulties in studying antiviral efficacy in immunocompromised patients, we have infected immunocompromised ferrets with either wild-type, or oseltamivir-resistant (H275Y 2009 pandemic virus. All ferrets showed prolonged virus shedding. In wild-type virus infected animals treated with oseltamivir, H275Y resistant variants emerged within a week after infection. Unexpectedly, oseltamivir therapy still proved to be partially protective in animals infected with resistant virus. Immunocompromised ferrets offer an attractive alternative to study efficacy of novel antiviral therapies.

  3. Persistent Infection of Drug-resistant Influenza A Virus during Chemotherapy for Malignant Lymphoma.

    Science.gov (United States)

    Kawakami, Toru; Hirabayashi, Yukio; Kawakami, Fumihiro; Isobe, Rei; Kaneko, Naoto; Mimura, Yuto; Ito, Toshiro; Furuta, Kiyoshi; Shimazaki, Mami; Nakazawa, Hideyuki; Kitano, Kiyoshi

    2016-01-01

    We herein report the case of an 80-year-old man with malignant lymphoma who became persistently infected with influenza A virus. Although he was repeatedly treated with NA inhibitors, such as oseltamivir or peramivir, nasal cavity swab tests for influenza A antigen continued to be positive for more than 2 months. Virological analyses revealed that he was infected with the NA inhibitor-resistant A (H3N2) virus possessing an R292K substitution in the NA protein. These findings suggest that a drug-resistant influenza virus strain might selectively survive antiviral therapy in elderly patients with refractory malignant lymphoma undergoing multiple chemotherapies. PMID:27374689

  4. Effect of an Echinacea-Based Hot Drink Versus Oseltamivir in Influenza Treatment: A Randomized, Double-Blind, Double-Dummy, Multicenter, Noninferiority Clinical Trial

    OpenAIRE

    Karel Rauš; Stephan Pleschka; Peter Klein, MSc; Roland Schoop, MSc; Peter Fisher

    2015-01-01

    Background: Echinacea has antiviral activity against influenza viruses in vitro and has traditionally been used for treatment of colds and flu. Objectives: This randomized, double-blind, double-dummy, multicenter, controlled clinical trial compared a new echinacea formulation with the neuraminidase inhibitor oseltamivir, the gold standard treatment for influenza. Methods: Following informed consent, 473 patients with early influenza symptoms (≤48 hours) were recruited in primary care in...

  5. Virus-encoded chemokine receptors--putative novel antiviral drug targets

    DEFF Research Database (Denmark)

    Rosenkilde, Mette M

    2005-01-01

    Large DNA viruses, in particular herpes- and poxviruses, have evolved proteins that serve as mimics or decoys for endogenous proteins in the host. The chemokines and their receptors serve key functions in both innate and adaptive immunity through control of leukocyte trafficking, and have as such a...... receptors. The chemokine receptors belong to the superfamily of G-protein coupled 7TM receptors that per se are excellent drug targets. At present, non-peptide antagonists have been developed against many chemokine receptors. The potentials of the virus-encoded chemokine receptors as drug targets--ie. as...

  6. Quantifying antiviral activity optimizes drug combinations against hepatitis C virus infection

    Energy Technology Data Exchange (ETDEWEB)

    Koizumi, Yoshiki [School of Medicine, College of Medical, Pharmaceutical and Health Sciences, Kanazawa University, Ishikawa, Japan; Nakajim, Syo [Department of Virology II, National Institute of Infectious Diseases, Tokyo, Japan; Department of Applied Biological Sciences, Faculty of Science and Technology, Tokyo University of Sciences, Chiba, J; Ohash, Hirofumi [Department of Virology II, National Institute of Infectious Diseases, Tokyo, Japan: Department of Applied Biological Sciences, Faculty of Science and Technology, Tokyo University of Sciences, Chiba, J; Tanaka, Yasuhito [Department of Virology and Liver Unit, Nagoya City University Graduate School of Medicinal Sciences, Nagoya, Japan; Wakita, Takaji [Department of Virology II, National Institute of Infectious Diseases, Tokyo, Japan; Perelson, Alan S. [Los Alamos National Laboratory; Iwami, Shingo [Department of Biology, Faculty of Sciences, Kyushu University, Fukuoka, Japan: PRESTO, JST, Saitama, Japan: CREST, JST, Saitama, Japan; Watashi, Koichi [Department of Virology II, National Institute of Infectious Diseases, Tokyo, Japan: Department of Applied Biological Sciences, Faculty of Science and Technology, Tokyo University of Sciences, Chiba, J

    2016-03-21

    Cell culture study combing a mathematical model and computer simulation quantifies the anti-hepatitis C virus drug efficacy at any concentrations and any combinations in preclinical settings, and can obtain rich basic evidences for selecting optimal treatments prior to costly clinical trials.

  7. Biophysical studies on the interaction of platinum(II) complex containing antiviral drug ribavirin with human serum albumin.

    Science.gov (United States)

    Shahabadi, Nahid; Hadidi, Saba; Kalar, Zeinab Mirzaei

    2016-07-01

    This study describes HSA binding properties of a platinum(II) complex with an antiviral drug ligand; ribavirin. Spectroscopic analysis of the emission quenching at different temperatures and UV-vis spectra revealed that the quenching mechanism of HSA by Pt(II) complex is static quenching mechanism. The binding constants and the number of binding sites were determined by fluorescence quenching method. Pt(II) complex binding is characterized by one high affinity binding site. Through the site marker competitive experiment, site I was assigned to possess high affinity binding site for Pt(II) complex. The calculated thermodynamic parameters (ΔG, ΔH and ΔS) confirmed that the binding reaction is spontaneous, and hydrophobic forces played a major role in the reaction. Fluorescence quenching studies showed that the binding affinity of Pt(II) complex with HSA in the buffer solution at different pH values is: Kb (pH3.0)>Kb (pH9.0)>Kb (pH7.4). The CD spectrum shows the binding of Pt(II) complex leads to a change in the α-helical structure of HSA. CD spectroscopy studies further indicated the influence of pH on the complexation process and the alteration in the protein conformation upon binding. PMID:27183492

  8. The antiviral drug valacyclovir successfully suppresses salivary gland hypertrophy virus (SGHV in laboratory colonies of Glossina pallidipes.

    Directory of Open Access Journals (Sweden)

    Adly M M Abd-Alla

    Full Text Available Many species of tsetse flies are infected with a virus that causes salivary gland hypertrophy (SGH symptoms associated with a reduced fecundity and fertility. A high prevalence of SGH has been correlated with the collapse of two laboratory colonies of Glossina pallidipes and colony maintenance problems in a mass rearing facility in Ethiopia. Mass-production of G. pallidipes is crucial for programs of tsetse control including the sterile insect technique (SIT, and therefore requires a management strategy for this virus. Based on the homology of DNA polymerase between salivary gland hypertrophy virus and herpes viruses at the amino acid level, two antiviral drugs, valacyclovir and acyclovir, classically used against herpes viruses were selected and tested for their toxicity on tsetse flies and their impact on virus replication. While long term per os administration of acyclovir resulted in a significant reduction of productivity of the colonies, no negative effect was observed in colonies fed with valacyclovir-treated blood. Furthermore, treatment of a tsetse colony with valacyclovir for 83 weeks resulted in a significant reduction of viral loads and consequently suppression of SGH symptoms. The combination of initial selection of SGHV-negative flies by non-destructive PCR, a clean feeding system, and valacyclovir treatment resulted in a colony that was free of SGH syndromes in 33 weeks. This is the first report of the use of a drug to control a viral infection in an insect and of the demonstration that valacyclovir can be used to suppress SGH in colonies of G. pallidipes.

  9. Biochemical Effects Of Ribavirin (Antiviral And Ddb (Hepato Protective Drugs In Albino Rats

    Directory of Open Access Journals (Sweden)

    Soliman S. Ibrahim, Amr Shalaby and Mahmoud Rabeh

    2005-09-01

    Full Text Available The present investigation has been designed to through spot light on the efficiency of these two drugs in treatment of hepatitis patients. Cortisol, antigliadin (1gG , total protein (TP albumin (ALB , Iron (Fe , alanine aminotransferase (ALT , aspartic aminotransferase (AST and alkaline phosphatase (ALP were determined in serum of normal mature male and female albino rats that injected intraperitoneally day after day with 1mg/kg body weight of each drug separately for 3 months. The cortisol level and ALP showed significant increase in each of ribavirin or DDB treated animals, while the IgG concentration in ribavirin treated animals increased significantly, but it is did not vary greatly from that of the control in DDB treated animals. On the other hand both ribavirin and DDB treated male and female rats showed significant decrease in the ALT in serum while serum AST elicited non significant decrease in each of ribavirin and DDB treated male and female. With respect to serum TP and ALB levels the result showed significant decrease in ribavirin and non significant decrease in DDB treated male and female rats. Furthermore, the serum Fe level in ribavirin treated male and female rats increased significantly but it is did not vary greatly from that of the control in DDB treated animal.

  10. Oseltamivir resistance among influenza viruses: surveillance in northern Viet Nam, 2009–2012

    Directory of Open Access Journals (Sweden)

    Nguyen Thi Kim Phuong

    2013-06-01

    Full Text Available Introduction: Antiviral resistance has been reported in seasonal influenza A viruses and avian influenza A(H5N1 viruses in Viet Nam, raising concerns about the efficacy of treatment. Methods: We analysed specimens from two sources during the period 2009–2012: influenza-positive samples from influenza-like illness patients at sentinel clinics in northern Viet Nam and isolates from patients with confirmed A(H5N1 infections. Pyrosequencing was used to detect mutations: H275Y [for A(H1N1 and A(H5N1], E119V [for A(H3N2] and I117V [for A(H5N1]. A neuraminidase inhibition assay was used to determine the Inhibitory Concentration 50 (IC50 values for all influenza A and B isolates. Results: There were 341 influenza A positive samples identified; influenza A(H1N1pdm09 was identified most frequently (n = 215. In 2009, oseltamivir resistance was observed in 100% (19 of 19 of seasonal A(H1N1 isolates and 1.4% (3/215 of A(H1N1pdm09 isolates. This H275Y mutation was not found in influenza subtypes A(H5N1 or A(H3N2 isolates. Discussion: In Viet Nam, seasonal and A(H5N1 influenza vaccines are not currently available; thus, effective treatment is required. The presence of oseltamivir-resistant viruses is therefore a concern. Active surveillance for oseltamivir resistance among influenza viruses circulating in Viet Nam should be continued.

  11. Clinical Implications of Antiviral Resistance in Influenza

    Directory of Open Access Journals (Sweden)

    Timothy C. M. Li

    2015-09-01

    Full Text Available Influenza is a major cause of severe respiratory infections leading to excessive hospitalizations and deaths globally; annual epidemics, pandemics, and sporadic/endemic avian virus infections occur as a result of rapid, continuous evolution of influenza viruses. Emergence of antiviral resistance is of great clinical and public health concern. Currently available antiviral treatments include four neuraminidase inhibitors (oseltamivir, zanamivir, peramivir, laninamivir, M2-inibitors (amantadine, rimantadine, and a polymerase inhibitor (favipiravir. In this review, we focus on resistance issues related to the use of neuraminidase inhibitors (NAIs. Data on primary resistance, as well as secondary resistance related to NAI exposure will be presented. Their clinical implications, detection, and novel therapeutic options undergoing clinical trials are discussed.

  12. Discovery of potential drugs for human-infecting H7N9 virus containing R294K mutation

    Directory of Open Access Journals (Sweden)

    He JY

    2014-12-01

    Full Text Available Jiao-Yu He,1,* Cheng Li,2,* Guo Wu3 1College of Life Sciences and Key Laboratory for Bio-resources of Ministry of Education, Sichuan University, 2College of Agronomy, Sichuan Agricultural University, 3College of Life Sciences, Sichuan Normal University, Chengdu, People’s Republic of China *These authors contributed equally to this work Background: After the first epidemic wave from February through May 2013, the influenza A (H7N9 virus emerged and has followed a second epidemic wave since June 2013. As of June 27, 2014, the outbreak of H7N9 had caused 450 confirmed cases of human infection, with 165 deaths included. The case-fatality rate of all confirmed cases is about 36%, making the H7N9 virus a significant threat to people’s health. At present, neuraminidase inhibitors are the only licensed antiviral medications available to treat H7N9 infections in humans. Oseltamivir is the most commonly used inhibitor, and it is also a front-line drug for the threatening H7N9. Unfortunately, it has been reported that patients treated with oseltamivir can induce R294K (Arg294Lys substitution in the H7N9 virus, which is a rare mutation and can reduce the antiviral efficacy of inhibitors. Even worse, deaths caused by such mutation after oseltamivir treatment have already been reported, indicating that the need to find substitutive neuraminidase inhibitors for currently available drugs to treat drug-resistant H7N9 is really pressing.Materials and methods: First, the structure of H7N9 containing the R294K substitution was downloaded from the Protein Data Bank, and structural information of approved drugs was downloaded from the ZINC (ZINC Is Not Commercial database. Taking oseltamivir carboxylate as a reference drug, we then filtered these molecules through virtual screening to find out potential inhibitors targeting the mutated H7N9 virus. For further evaluation, we carried out a 14 ns molecular dynamic simulation for each H7N9–drug complex and

  13. Analysis of Oseltamivir Resistance Substitutions in Influenza Virus Glycoprotein Neuraminidase using a Lentivirus-Based Surrogate Assay System

    Institute of Scientific and Technical Information of China (English)

    Jennifer Tisoncik-Go; Katie S Cordero; Lijun Rong

    2013-01-01

    Influenza A virus poses a great threat to global health,and oseltamivir (trade marked as Tamiflu),which targets influenza surface glycoprotein neuraminidase (NA),is used clinically as a major anti-influenza treatment.However,certain substitutions in NA can render an influenza virus resistant to this drug.In this study,using a lentiviral pseudotyping system,which alleviates the safety concerns of studying highly pathogenic influenza viruses such as avian influenza H5N 1,that utilizes influenza surface glycoproteins (hemagglutinin or HA,and NA) and an HIV-core combined with a luciferase reporter gene as a surrogate assay,we first assessed the functionality of NA by measuring pseudovirion release in the absence or presence of oseltamivir.We demonstrated that oseltamivir displays a dose-dependent inhibition on NA activity.In contrast,a mutant NA (H274Y) is more resistant to oseltamivir treatment.In addition,the effects of several previously reported substitution NA mutants were examined as well.Our results demonstrate that this lentivirus-based pseudotyping system provides a quick,safe,and effective way to assess resistance to neuraminidase inhibitors.And we believe that as new mutations appear in influenza isolates,their impact on the effectiveness of current and future anti-NA can be quickly and reliably evaluated by this assay.

  14. Synthesis and Antiviral Evaluation of 6-(Trifluoromethylbenzyl) and 6-(Fluorobenzyl) Analogues of HIV Drugs Emivirine and GCA-186

    DEFF Research Database (Denmark)

    El-Brollosy, Nasser R.; Sørensen, Esben R.; Pedersen, Erik Bjerreg.;

    2008-01-01

    antiviral activity against HIV-1 wild type and mutants resistant to non-nucleoside RT inhibitors. The biological test results showed that the most of theses compounds showed good activity against wild type HIV-1. Among them, compound 1-(ethoxymethyl)-6-(3-fluorobenzyl)-5-isopropyluracil (9i) showed the...

  15. Prediction of the Pharmacodynamically Linked Variable of Oseltamivir Carboxylate for Influenza A Virus Using an In Vitro Hollow-Fiber Infection Model System▿

    OpenAIRE

    McSharry, James J.; Weng, Qingmei; Brown, Ashley; Kulawy, Robert; Drusano, George L.

    2009-01-01

    MDCK cells transfected with the human β-galactoside α-2,6-sialyltransferase 1 gene (AX-4 cells) were used to determine the drug susceptibility and pharmacodynamically linked variable of oseltamivir for influenza virus. For dose-ranging studies, five hollow-fiber units were charged with 102 A/Sydney/5/97 (H3N2) influenza virus-infected AX-4 cells and 108 uninfected AX-4 cells. Each unit was treated continuously with different oseltamivir carboxylate concentrations in virus growth medium for 6 ...

  16. A randomized, crossover study to evaluate the pharmacokinetics of amantadine and oseltamivir administered alone and in combination.

    Directory of Open Access Journals (Sweden)

    Dennis Morrison

    Full Text Available UNLABELLED: The threat of potential pandemic influenza requires a reevaluation of licensed therapies for the prophylaxis or treatment of avian H5N1 infection that may adapt to man. Among the therapies considered for use in pandemic influenza is the co-administration of ion channel and neuraminidase inhibitors, both to potentially increase efficacy as well as to decrease the emergence of resistant isolates. To better understand the potential for drug interactions, a cross-over, randomized, open-label trial was conducted with amantadine, 100 mg po bid, and oseltamivir, 75 mg po bid, given alone or in combination for 5 days. Each subject (N = 17 served as their own control and was administered each drug alone or in combination, with appropriate wash-out. Co-administration with oseltamivir had no clinically significant effect on the pharmacokinetics (PK of amantadine [mean ratios (90% CI for AUC(0-12 0.93 (0.89, 0.98 and C(max 0.96 (0.90, 1.02]. Similarly, amantadine co-administration did not affect oseltamivir PK [AUC(0-12 0.92 (0.86, 0.99 and C(max 0.85 (0.73, 0.99] or the PK of the metabolite, oseltamivir carboxylate [AUC(0-12 0.98 (0.95, 1.02 and C(max 0.95 (0.89, 1.01]. In this small trial there was no evidence of an increase in adverse events. Although many more subjects would need to be studied to rule out a synergistic increase in adverse events, the combination in this small human drug-drug interaction trial appears safe and without pharmacokinetic consequences. TRIAL REGISTRATION: ClinicalTrials.gov NCT00416962.

  17. 流行性感冒和禽流感的抗病毒治疗%Antiviral treatment for influenza and avian influenza

    Institute of Scientific and Technical Information of China (English)

    沈银忠; 卢洪洲

    2013-01-01

      Early antiviral treatment is a key measure to improve the prognosis of the patients with influenza and avian influenza. At present the antiviral influenza drugs used in the clinic can be roughly divided into two categories according to their mechanisms. One category is to act on the viral surface glycoproteins neuraminidase and the other on the ion channel M2 protein. The common antiviral influenza drugs used mainly in China are oseltamivir, zanamivir, amantadine and rimantadine now. The antiviral influenza treatment should be given as early as possible after its occurrence within 48 h. In case of lack of drug resistance test results, influenza A virus can be treated with oseltamivir, zanamivir, amantadine or rimantadine, and influenza B virus with oseltamivir or zanamivir. The drug resistance analysis shows that type A H1N1 influenza, H5N1 and H7N9 avian influenzas should be treated with neuraminidase inhibitors firstly, and the course of its treatment is usually 5 days. But for the patients with severe diseases, the dosages should be increased and treatment time prolonged. Emergence of drug resistance of virus has brought a challenge for the antiviral treatment. Joint anti-influenza virus treatment may be considered to be used in the treatment of the infections caused by the resistant influenza virus.%  早期抗病毒治疗是改善流行性感冒和禽流感患者预后的关键。目前临床用于抗流感病毒的药物按作用机制可大致分为两类,一类作用于病毒表面的糖蛋白神经氨酸酶,另一类作用于离子通道M2蛋白。我国目前常用的抗流感病毒药物主要有奥司他韦、扎那米韦、金刚烷胺和金刚乙胺。抗流感病毒治疗应在发病后48 h内尽早进行;在缺乏耐药检测结果的情况下,甲型流感病毒可选用奥司他韦、扎那米韦、金刚烷胺或金刚乙胺进行治疗,乙型流感病毒选用奥司他韦或扎那米韦治疗。耐药

  18. Antiviral Prophylaxis and Isolation for the Control of Pandemic Influenza

    OpenAIRE

    Qingxia Zhang; Dingcheng Wang

    2014-01-01

    Before effective vaccines become available, antiviral drugs are considered as the major control strategies for a pandemic influenza. However, perhaps such control strategies can be severely hindered by the low-efficacy of antiviral drugs. For this reason, using antiviral drugs and an isolation strategy is included in our study. A compartmental model that allows for imported exposed individuals and asymptomatic cases is used to evaluate the effectiveness of control strategies via antiviral pro...

  19. Diversity of Pharmacological Properties in Chinese and European Medicinal Plants: Cytotoxicity, Antiviral and Antitrypanosomal Screening of 82 Herbal Drugs

    OpenAIRE

    Thomas Efferth; Marin, Jose J. G.; Stefan Kahl; Dorothea Kaufmann; Ashour, Mohamed L; Blazquez, Alba G; Romero, Marta R.; Michael Wink; Florian Herrmann

    2011-01-01

    In an extensive screening, the antiviral, antitrypanosomal and anticancer properties of extracts from 82 plants used in traditional Chinese medicine and European phytomedicine were determined. Several promising plants that were highly effective against hepatitis B virus (HBV), bovine viral diarrhoea virus (BVDV)—a flavivirus used here as a surrogate in vitro model of hepatitis C virus, trypanosomes (Trypanosoma brucei brucei) and several cancer cell lines were identified. Six aqueous extracts...

  20. Use of Antiviral Drugs to Reduce Household Transmission of Pandemic (H1N1) 2009, United Kingdom1

    OpenAIRE

    Pebody, Richard G.; Harris, Ross; Kafatos, George; Chamberland, Mary; Campbell, Colin; Jonathan S Nguyen-Van-Tam; McLean, Estelle; Andrews, Nick; Peter J White; Wynne-Evans, Edward; Green, Jon; Ellis, Joanna; Wreghitt, Tim; Bracebridge, Sam; Ihekweazu, Chikwe

    2011-01-01

    The United Kingdom implemented a containment strategy for pandemic (H1N1) 2009 through administering antiviral agents (AVs) to patients and their close contacts. This observational household cohort study describes the effect of AVs on household transmission. We followed 285 confirmed primary cases in 259 households with 761 contacts. At 2 weeks, the confirmed secondary attack rate (SAR) was 8.1% (62/761) and significantly higher in persons 50 years of age (18.9% vs. 1.2%, p

  1. Efficacy of combined antiviral therapy with pegylated interferon α-2a and ribavirin for chronic hepatitis C infection in intravenous drug users

    Directory of Open Access Journals (Sweden)

    Ružić Maja

    2010-01-01

    Full Text Available Introduction. Hepatitis C Virus infection represents not just a medical, but also a socio-economic problem. It is estimated that among 170 million infected, 60% belongs to the category of intravenous drug users (IDUs. Objective. The aim of this paper was to compare the response to the combined therapy of pegylated interferon alfa 2a and ribavirin, in the group of patients with HCV infection who were intravenous drug users (IDUs and in patients who were identified in the other way of transmission of HCV. Also to identify the influence of the therapy on diseases of addiction, during the course of HCV infection and on the effects of the combined therapy of pegylated interferon alfa 2a and ribavirin. Methods. We conducted a retrospective-prospective study, on 60 patients, treated with combined antiviral therapy-pegylated interferon alfa 2a and ribavirin. 30 patients were from the group of IDUs, and 30 patients from other epidemiological groups. Results. There were significant differences between the age of the patients (30.2±7.1 vs. 39.3±11.2 years; p=0.002, but no significant difference in the duration of the HCV infection between the two groups of patients (8.9±7.4 vs. 13.1±7.0 years; p>0.05. A large number of the patients in the group of IDUs had a problem with the abstinence of the drug abuse. In this group, there was the influence of alcohol (30% and other substances with potential hepatotoxicity: marihuana (23.3% and psycho-active drugs (73.6%. Staging of the liver fibrosis was not influenced by those two parameters and was similar in both groups (p>0.05. The genotype 3a was dominant in intravenous drug users (50.0% and genotype 1b in the control group of the patients (76.6%. In both groups, SVR was achieved at a higher percentage (86% vs. 70.00%; p>0.05, but among the intravenous drug users the relapses of HCV infection were at a lower percentage (3.3% vs. 20.0%; p=0.044. Side effects were noticed in solitary cases in both of the examined

  2. Diversity of Pharmacological Properties in Chinese and European Medicinal Plants: Cytotoxicity, Antiviral and Antitrypanosomal Screening of 82 Herbal Drugs

    Directory of Open Access Journals (Sweden)

    Thomas Efferth

    2011-09-01

    Full Text Available In an extensive screening, the antiviral, antitrypanosomal and anticancer properties of extracts from 82 plants used in traditional Chinese medicine and European phytomedicine were determined. Several promising plants that were highly effective against hepatitis B virus (HBV, bovine viral diarrhoea virus (BVDV—a flavivirus used here as a surrogate in vitro model of hepatitis C virus, trypanosomes (Trypanosoma brucei brucei and several cancer cell lines were identified. Six aqueous extracts from Celosia cristata, Ophioglossum vulgatum, Houttuynia cordata, Selaginella tamariscina, Alpinia galanga and Alpinia oxyphylla showed significant antiviral effects against BVDV without toxic effects on host embryonic bovine trachea (EBTr cells, while Evodia lepta, Hedyotis diffusa and Glycyrrhiza spp. demonstrated promising activities against the HBV without toxic effects on host human hepatoblastoma cells transfected with HBV-DNA (HepG2 2.2.15 cells. Seven organic extracts from Alpinia oxyphylla, Coptis chinensis, Kadsura longipedunculata, Arctium lappa, Panax ginseng, Panax notoginseng and Saposhnikovia divaricata inhibited T. b. brucei. Moreover, among fifteen water extracts that combined high antiproliferative activity (IC50 0.5–20 µg/mL and low acute in vitro toxicity (0–10% reduction in cell viability at IC50, Coptis chinensis presented the best beneficial characteristics. In conclusion, traditional herbal medicine from Europe and China still has a potential for new therapeutic targets and therapeutic applications.

  3. Therapeutic targeting of Neu1 sialidase with oseltamivir phosphate (Tamiflu® disables cancer cell survival in human pancreatic cancer with acquired chemoresistance

    Directory of Open Access Journals (Sweden)

    O’Shea LK

    2014-01-01

    Full Text Available Leah K O'Shea,1 Samar Abdulkhalek,1 Stephanie Allison,2 Ronald J Neufeld,2 Myron R Szewczuk11Department of Biomedical and Molecular Sciences, 2Department of Chemical Engineering, Queen's University, Kingston, ON, CanadaBackground: Resistance to drug therapy, along with high rates of metastasis, contributes to the low survival rate in patients diagnosed with pancreatic cancer. An alternate treatment for human pancreatic cancer involving targeting of Neu1 sialidase with oseltamivir phosphate (Tamiflu® was investigated in human pancreatic cancer (PANC1 cells with acquired resistance to cisplatin and gemcitabine. Its efficacy in overcoming the intrinsic resistance of the cell to chemotherapeutics and metastasis was evaluated.Methods: Microscopic imaging, immunocytochemistry, immunohistochemistry, and WST-1 cell viability assays were used to evaluate cell survival, morphologic changes, and expression levels of E-cadherin, N-cadherin, and VE-cadherin before and after treatment with oseltamivir phosphate in PANC1 cells with established resistance to cisplatin, gemcitabine, or a combination of the two agents, and in archived paraffin-embedded PANC1 tumors grown in RAGxCγ double mutant mice.Results: Oseltamivir phosphate overcame the chemoresistance of PANC1 to cisplatin and gemcitabine alone or in combination in a dose-dependent manner, and disabled the cancer cell survival mechanism(s. Oseltamivir phosphate also reversed the epithelial-mesenchymal transition characteristic of the phenotypic E-cadherin to N-cadherin changes associated with resistance to drug therapy. Low-dose oseltamivir phosphate alone or in combination with gemcitabine in heterotopic xenografts of PANC1 tumors growing in RAGxCγ double mutant mice did not prevent metastatic spread to the liver and lung.Conclusion: Therapeutic targeting of Neu1 sialidase with oseltamivir phosphate at the growth factor receptor level disables the intrinsic signaling platform for cancer cell survival

  4. Bench to Bed Evidences for Pharmacokinetic and Pharmacodynamic Interactions Involving Oseltamivir and Chinese Medicine

    Directory of Open Access Journals (Sweden)

    Qi Chang

    2014-01-01

    Full Text Available Oseltamivir (OA, an ethyl ester prodrug of oseltamivir carboxylate (OC, is clinically used as a potent and selective inhibitor of neuraminidase. Chinese medicines have been advocated to combine with conventional drug for avian influenza. The current study aims to investigate the potential pharmacokinetic and pharmacodynamic interactions of a Chinese medicine formula, namely, Yin Qiao San and Sang Ju Yin (CMF1, commonly used for anti-influenza in combination with OA in both rat and human, and to reveal the underlined mechanisms. It was found that although Cmax, AUC and urinary recovery of OC, as well as metabolic ratio (AUCOC/AUCOA, were significantly decreased in a dose-dependent manner following combination use of CMF1 and OA in rat studies (P<0.01, such coadministration in 14 healthy volunteers only resulted in a trend of minor decrease in the related parameters. Further mechanistic studies found that although CMF1 could reduce absorption and metabolism of OA, it appears to enhance viral inhibition of OA (P<0.01. In summary, although there was potential interaction between OA and CMF1 found in rat studies, its clinical impact was expected to be minimal. The coadministration of OA and CMF1 at the clinical recommended dosages is, therefore, considered to be safe.

  5. The mechanisms of delayed onset type adverse reactions to oseltamivir.

    Science.gov (United States)

    Hama, Rokuro

    2016-09-01

    Oseltamivir is recommended for the treatment and prophylaxis of influenza in persons at higher risk for influenza complications such as individuals with diabetes, neuropsychiatric illnesses, and respiratory, cardiac, renal, hepatic or haematological diseases. However, a recent Cochrane review reported that reduction of antibody production, renal disorders, hyperglycaemia, psychiatric disorders, and QT prolongation may be related to oseltamivir use. The underlying mechanisms are reviewed. There is decisive evidence that administration of a clinically compatible dose of oseltamivir in mice challenged by a respiratory syncytial virus (RSV) that lacks a neuraminidase gene showed symptom-relieving effects and inhibition of viral clearance. These effects were accompanied by decreased level of T cell surface sialoglycosphingolipid (ganglioside) GM1 that is regulated by the endogenous neuraminidase in response to viral challenge. Clinical and non-clinical evidence supports the view that the usual dose of oseltamivir suppresses pro-inflammatory cytokines such as interferon-gamma, interleukin-6, and tumour necrosis factor-alpha almost completely with partial suppression of viral shedding in human influenza virus infection experiment. Animal toxicity tests support the clinical evidence with regard to renal and cardiac disorders (bradycardia and QT prolongation) and do not disprove the metabolic effect. Reduction of antibody production and cytokine induction and renal, metabolic, cardiac, and prolonged psychiatric disorders after oseltamivir use may be related to inhibition of the host's endogenous neuraminidase. While the usual clinical dose of zanamivir may not have this effect, a higher dose or prolonged administration of zanamivir and other neuraminidase inhibitors may induce similar delayed reactions, including reduction of the antibody and/or cytokine production. PMID:27251370

  6. A Quantitative Measurement of Antiviral Activity of Anti-Human Immunodeficiency Virus Type 1 Drugs against Simian Immunodeficiency Virus Infection: Dose-Response Curve Slope Strongly Influences Class-Specific Inhibitory Potential

    OpenAIRE

    Deng, Kai; Zink, M. Christine; Clements, Janice E; Siliciano, Robert F.

    2012-01-01

    Simian immunodeficiency virus (SIV) infection in macaques is so far the best animal model for human immunodeficiency virus type 1 (HIV-1) studies, but suppressing viral replication in infected animals remains challenging. Using a novel single-round infectivity assay, we quantitated the antiviral activities of antiretroviral drugs against SIV. Our results emphasize the importance of the dose-response curve slope in determining the inhibitory potential of antiretroviral drugs and provide useful...

  7. Viability of a Drug-Resistant Human Immunodeficiency Virus Type 1 Protease Variant: Structural Insights for Better Antiviral Therapy

    OpenAIRE

    Prabu-Jeyabalan, Moses; Ellen A. Nalivaika; King, Nancy M.; Schiffer, Celia A.

    2003-01-01

    Under the selective pressure of protease inhibitor therapy, patients infected with human immunodeficiency virus (HIV) often develop drug-resistant HIV strains. One of the first drug-resistant mutations to arise in the protease, particularly in patients receiving indinavir or ritonavir treatment, is V82A, which compromises the binding of these and other inhibitors but allows the virus to remain viable. To probe this drug resistance, we solved the crystal structures of three natural substrates ...

  8. Towards antivirals against chikungunya virus.

    Science.gov (United States)

    Abdelnabi, Rana; Neyts, Johan; Delang, Leen

    2015-09-01

    Chikungunya virus (CHIKV) has re-emerged in recent decades, causing major outbreaks of chikungunya fever in many parts of Africa and Asia, and since the end of 2013 also in Central and South America. Infections are usually associated with a low mortality rate, but can proceed into a painful chronic stage, during which patients may suffer from polyarthralgia and joint stiffness for weeks and even several years. There are no vaccines or antiviral drugs available for the prevention or treatment of CHIKV infections. Current therapy therefore consists solely of the administration of analgesics, antipyretics and anti-inflammatory agents to relieve symptoms. We here review molecules that have been reported to inhibit CHIKV replication, either as direct-acting antivirals, host-targeting drugs or those that act via a yet unknown mechanism. This article forms part of a symposium in Antiviral Research on "Chikungunya discovers the New World." PMID:26119058

  9. Development of robust in vitro RNA-dependent RNA polymerase assay as a possible platform for antiviral drug testing against dengue.

    Science.gov (United States)

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

    2016-10-01

    NS5 is the largest and most conserved protein among the four dengue virus (DENV) serotypes. It has been the target of interest for antiviral drug development due to its major role in replication. NS5 consists of two domains, the N-terminal methyltransferase domain and C-terminal catalytic RNA-dependent RNA polymerase (RdRp) domain. It is an unstable protein and is prone to inactivation upon prolonged incubation at room temperature, thus affecting the inhibitor screening assays. In the current study, we expressed and purified DENV RdRp alone in Esherichia coli (E. coli) cells. The N-terminally His-tagged construct of DENV RdRp was transformed into E. coli expression strain BL-21 (DE3) pLysS cells. Protein expression was induced with isopropyl-β-D-thiogalactopyranoside (IPTG) at a final concentration of 0.4mM. The induced cultures were then grown for 20h at 18°C and cells were harvested by centrifugation at 6000xg for 15min at 4°C. The recombinant protein was purified using HisTrap affinity column (Ni-NTA) and then the sample was subjected to size exclusion chromatography, which successfully removed the degradation product obtained during the previous purification step. The in vitro polymerase activity of RdRp was successfully demonstrated using homopolymeric polycytidylic acid (poly(rC)) RNA template. This study describes the high level production of enzymatically active DENV RdRp protein which can be used to develop assays for testing large number of compounds in a high-throughput manner. RdRp has the de novo initiation activity and the in vitro polymerase assays for the protein provide a platform for highly robust and efficient antiviral compound screening systems. PMID:27542741

  10. Use of antiviral drugs to reduce household transmission of pandemic (H1N1) 2009, United Kingdom.

    Science.gov (United States)

    Pebody, Richard G; Harris, Ross; Kafatos, George; Chamberland, Mary; Campbell, Colin; Nguyen-Van-Tam, Jonathan S; McLean, Estelle; Andrews, Nick; White, Peter J; Wynne-Evans, Edward; Green, Jon; Ellis, Joanna; Wreghitt, Tim; Bracebridge, Sam; Ihekweazu, Chikwe; Oliver, Isabel; Smith, Gillian; Hawkins, Colin; Salmon, Roland; Smyth, Bryan; McMenamin, Jim; Zambon, Maria; Phin, Nick; Watson, John M

    2011-06-01

    The United Kingdom implemented a containment strategy for pandemic (H1N1) 2009 through administering antiviral agents (AVs) to patients and their close contacts. This observational household cohort study describes the effect of AVs on household transmission. We followed 285 confirmed primary cases in 259 households with 761 contacts. At 2 weeks, the confirmed secondary attack rate (SAR) was 8.1% (62/761) and significantly higher in persons 50 years of age (18.9% vs. 1.2%, p<0.001). Early (<48 hours) treatment of primary case-patients reduced SAR (4.5% vs. 10.6%, p = 0.003). The SAR in child contacts was 33.3% (10/30) when the primary contact was a woman and 2.9% (1/34) when the primary contact was a man (p = 0.010). Of 53 confirmed secondary case-patients, 45 had not received AV prophylaxis. The effectiveness of AV prophylaxis in preventing infection was 92%. PMID:21749759

  11. Influenza A/H1N1 2009 pneumonia in kidney transplant recipients: characteristics and outcomes following high-dose oseltamivir exposure.

    Science.gov (United States)

    Watcharananan, S P; Suwatanapongched, T; Wacharawanichkul, P; Chantratitaya, W; Mavichak, V; Mossad, S B

    2010-04-01

    We report 2 cases of severe pneumonia due to the novel pandemic influenza A/H1N1 2009 in kidney transplant recipients. Our patients initially experienced influenza-like illness that rapidly progressed to severe pneumonia within 48 h. The patients became hypoxic and required non-invasive ventilation. The novel influenza A/H1N1 2009 was identified from their nasal swabs. These cases were treated successfully with a relatively high dose of oseltamivir, adjusted for their renal function. Clinical improvement was documented only after a week of antiviral therapy. Despite early antiviral treatment, we showed that morbidity following novel pandemic influenza A/H1N1 2009 infection is high among kidney transplant recipients. PMID:20102550

  12. Using mutagenesis to explore conserved residues in the RNA-binding groove of influenza A virus nucleoprotein for antiviral drug development.

    Science.gov (United States)

    Liu, Chia-Lin; Hung, Hui-Chen; Lo, Shou-Chen; Chiang, Ching-Hui; Chen, I-Jung; Hsu, John T-A; Hou, Ming-Hon

    2016-01-01

    Nucleoprotein (NP) is the most abundant type of RNA-binding viral protein in influenza A virus-infected cells and is necessary for viral RNA transcription and replication. Recent studies demonstrated that influenza NP is a valid target for antiviral drug development. The surface of the groove, covered with numerous conserved residues between the head and body domains of influenza A NP, plays a crucial role in RNA binding. To explore the mechanism by which NP binds RNA, we performed a series of site-directed mutagenesis in the RNA-binding groove, followed by surface plasmon resonance (SPR), to characterize the interactions between RNA and NP. Furthermore, a role of Y148 in NP stability and NP-RNA binding was evaluated. The aromatic residue of Y148 was found to stack with a nucleotide base. By interrupting the stacking interaction between Y148 and an RNA base, we identified an influenza virus NP inhibitor, (E, E)-1,7-bis(4-hydroxy-3-methoxyphenyl) -1,6-heptadiene-3,5-dione; this inhibitor reduced the NP's RNA-binding affinity and hindered viral replication. Our findings will be useful for the development of new drugs that disrupt the interaction between RNA and viral NP in the influenza virus. PMID:26916998

  13. 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.

  14. Anti-Influenza Neuraminidase Inhibitor Oseltamivir Phosphate Induces Canine Mammary Cancer Cell Aggressiveness

    OpenAIRE

    Joana T de Oliveira; Santos, Ana L.; Catarina Gomes; Rita Barros; Cláudia Ribeiro; Nuno Mendes; de Matos, Augusto J.; M. Helena Vasconcelos; Maria José Oliveira; Celso A Reis; Fátima Gärtner

    2015-01-01

    Oseltamivir phosphate is a widely used anti-influenza sialidase inhibitor. Sialylation, governed by sialyltransferases and sialidases, is strongly implicated in the oncogenesis and progression of breast cancer. In this study we evaluated the biological behavior of canine mammary tumor cells upon oseltamivir phosphate treatment (a sialidase inhibitor) in vitro and in vivo. Our in vitro results showed that oseltamivir phosphate impairs sialidase activity leading to increased sialylation in CMA0...

  15. Oseltamivir use and outcomes during the 2009 influenza A H1N1 pandemic in Taiwan

    OpenAIRE

    Liu, Chia-Hung; Wang, Jiun-Ling; Su, Chia-Ping; Chuang, Jen-Hsiang; Chang, Chia-Hsuin; Lai, Mei-Shu

    2013-01-01

    Background The Taiwan CDC provided free oseltamivir to all patients with influenza infections confirmed by rapid testing or who had clinical warning symptoms during the 2009 H1N1 influenza pandemic in Taiwan. However, oseltamivir utilization patterns, cost, and outcomes among oseltamivir-treated patients remained unclear. Method A population-level, observational cohort study was conducted using the Taiwan National Health Insurance Database from January to December 2009 to describe the use of ...

  16. Contact transmission of influenza virus between ferrets imposes a looser bottleneck than respiratory droplet transmission allowing propagation of antiviral resistance.

    Science.gov (United States)

    Frise, Rebecca; Bradley, Konrad; van Doremalen, Neeltje; Galiano, Monica; Elderfield, Ruth A; Stilwell, Peter; Ashcroft, Jonathan W; Fernandez-Alonso, Mirian; Miah, Shahjahan; Lackenby, Angie; Roberts, Kim L; Donnelly, Christl A; Barclay, Wendy S

    2016-01-01

    Influenza viruses cause annual seasonal epidemics and occasional pandemics. It is important to elucidate the stringency of bottlenecks during transmission to shed light on mechanisms that underlie the evolution and propagation of antigenic drift, host range switching or drug resistance. The virus spreads between people by different routes, including through the air in droplets and aerosols, and by direct contact. By housing ferrets under different conditions, it is possible to mimic various routes of transmission. Here, we inoculated donor animals with a mixture of two viruses whose genomes differed by one or two reverse engineered synonymous mutations, and measured the transmission of the mixture to exposed sentinel animals. Transmission through the air imposed a tight bottleneck since most recipient animals became infected by only one virus. In contrast, a direct contact transmission chain propagated a mixture of viruses suggesting the dose transferred by this route was higher. From animals with a mixed infection of viruses that were resistant and sensitive to the antiviral drug oseltamivir, resistance was propagated through contact transmission but not by air. These data imply that transmission events with a looser bottleneck can propagate minority variants and may be an important route for influenza evolution. PMID:27430528

  17. Oseltamivir-resistant pandemic (H1N12009 in Yemen - case report

    Directory of Open Access Journals (Sweden)

    Al-Kohlani Abdulhakeem

    2010-05-01

    Full Text Available Abstract Background During the influenza season of 2007-08, oseltamivir-resistant influenza A (H1N1 viruses emerged in several countries in Europe, North America, and Asia. Despite substantial prevalence of oseltamivir-resistant viruses, few data are available on the clinical profile of subjects infected with these viruses. Objectives: to describe the first oseltamivir-resistant (H1N1 influenza virus pandemic 2009 from the Eastern Mediterranean Region including Yemen and to determine the evidence by clinical presentation of children infected with these oseltamivir - resistant viruses. Methodology History, physical examination and laboratory investigations including Complete Blood Count, chest x-ray, blood cultures, CSF examination, LFTs, RFTs, blood for sugar, H1N1 test and oseltamivir resistance test. Results Nasal swabs indicated positivity on both H1N1 test and the RNP gene (Human R Nase P gene that serves as internal positive control for Human RNA. Both clinical specimens presented the mutation S31N in the M2 gene associated with resistance to adamantanes and H274Y in NA gene associated with resistance to oseltamivir. This was the first diagnosed case of resistance to oseltamivir in Yemen and also it is the first reported case of oseltamivir resistance virus in the Eastern Mediterranean Region. Conclusion The pattern of resistance found in the oseltamivir resistant isolate collected from Yemen is the same as has been reported elsewhere in other WHO regions. Clinical description and outcomes are not different from what is described elsewhere.

  18. Evaluation of Antiviral Compounds Against Avian Influenza

    OpenAIRE

    Call, Evan W.

    1991-01-01

    Tests in vitro for antiviral activity against avian influenza viruses, A/Turkey/Sanpete/85 (H6N8) and A/Turkey/Sanpete/86 (H10N9), isolated in Sanpete County, Utah, utilized known antiviral agents, amantadine•HCl (adamantanamine hydrochloride) and ribavirin (1-β-D ribofuranosyl-1,2,4-triazole-3-carboxamide). The testing involved evaluation of seven drug concentrations. Maximum tolerated dose, minimum inhibitory concentration and therapeutic indexes were determined for each drug used. Both dru...

  19. TARGETING OF ANTIVIRAL DRUGS TO LYMPHOCYTES-T4 - ANTI-HIV ACTIVITY OF NEOGLYCOPROTEIN AZTMP CONJUGATES INVITRO

    NARCIS (Netherlands)

    MOLEMA, G; JANSEN, RW; PAUWELS, R; DECLERCQ, E; MEIJER, DKF

    1990-01-01

    The delivery of the anti-HIV agent 3'-azido-3'-deoxythymidine (AZT), in its 5'-monophosphate form, (in)to human T-lymphocyte MT-4 cells in vitro through covalent coupling to neoglycoproteins was investigated. In vivo application of this drug targeting concept may lead to increased efficacy and/or di

  20. Potent Antiviral HIV-1 Protease Inhibitor GRL-02031 Adapts to the Structures of Drug Resistant Mutants with Its P1;#8242;-Pyrrolidinone Ring

    Energy Technology Data Exchange (ETDEWEB)

    Chang, Yu-Chung E.; Yu, XiaXia; Zhang, Ying; Tie, Yunfeng; Wang, Yuan-Fang; Yashchuk, Sofiya; Ghosh, Arun K.; Harrison, Robert W.; Weber, Irene T. (GSU); (Purdue); (GSI); (CDC)

    2012-11-14

    GRL-02031 (1) is an HIV-1 protease (PR) inhibitor containing a novel P1' (R)-aminomethyl-2-pyrrolidinone group. Crystal structures at resolutions of 1.25-1.55 {angstrom} were analyzed for complexes of 1 with the PR containing major drug resistant mutations, PR{sub I47V}, PR{sub L76V}, PR{sub V82A}, and PR{sub N88D}. Mutations of I47V and V82A alter residues in the inhibitor-binding site, while L76V and N88D are distal mutations having no direct contact with the inhibitor. Substitution of a smaller amino acid in PR{sub I47V} and PR{sub L76V} and the altered charge of PR{sub N88D} are associated with significant local structural changes compared to the wild-type PR{sub WT}, while substitution of alanine in PR{sub V82A} increases the size of the S1' subsite. The P1' pyrrolidinone group of 1 accommodates to these local changes by assuming two different conformations. Overall, the conformation and interactions of 1 with PR mutants resemble those of PR{sub WT} with similar inhibition constants in good agreement with the antiviral potency on multidrug resistant HIV-1.

  1. Evaluation of the role of the antioxidant silymarin in modulating the in vivo genotoxicity of the antiviral drug ribavirin in mice.

    Science.gov (United States)

    Noshy, Magda M; Hussien, Nahed A; El-Ghor, Akmal A

    2013-04-15

    Ribavirin (1-β-d-ribofuranosyl-1,2,4-triazole-3-carboxamide) is a widely used broad-spectrum antiviral drug. Recently, several reports revealed genotoxic effects of ribavirin in vivo and in vitro, which were correlated with the production of reactive oxygen species (ROS). This study aimed to evaluate the genotoxicity of ribavirin and to investigate the role of the natural antioxidant silymarin to modulate this genotoxicity. Male albino mice (age, 8-10 weeks) were injected intraperitoneally (i.p.) with ribavirin at three dose levels (20, 75 and 130 mg/kg bw) either in a single injection (acute treatment) or in multiple injections on five consecutive days (sub-acute treatment). Other comparable groups were treated with silymarin (70 mg/kg bw) 1h before the injection with ribavirin. Mice were sacrificed at different sampling times (24, 48 and 72 h) after the last ribavirin treatment. Micronucleus (MN) and single-strand conformation polymorphism (SSCP) assays were used to assess genotoxic and cytotoxic effects of ribavirin and to evaluate the protective effect of the pre-treatment with silymarin. Our results reveal genotoxic and cytotoxic effects of ribavirin in the MN assay. Pre-treatment with silymarin reduced the toxicity of ribavirin. In the SSCP assay, ribavirin treatment did not induce any mutations in the two selected sites in the D-loop of mitochondrial DNA (mtDNA). PMID:23402882

  2. Neuraminidase inhibitor R-125489 - A promising drug for treating influenza virus: Steered molecular dynamics approach

    International Nuclear Information System (INIS)

    Highlights: → We study binding affinity of R-125489 and its prodrug CS-8958 to neuraminidase of pathogenic influenza viruses by molecular dynamics simulations. → It is shown that, in agreement with experiments, R-125489 binds to neuraminidase more tightly than CS-8958. → We predict that R-125489 can be used to treat not only wild-type but also tamiflu-resistant N294S, H274Y variants of A/H5N1 virus. → The high correlation between theoretical and experimental data implies that SMD is a very promising tool for drug design. -- Abstract: Two neuraminidase inhibitors, oseltamivir and zanamivir, are important drug treatments for influenza. Oseltamivir-resistant mutants of the influenza virus A/H1N1 and A/H5N1 have emerged, necessitating the development of new long-acting antiviral agents. One such agent is a new neuraminidase inhibitor R-125489 and its prodrug CS-8958. An atomic level understanding of the nature of this antiviral agents binding is still missing. We address this gap in our knowledge by applying steered molecular dynamics (SMD) simulations to different subtypes of seasonal and highly pathogenic influenza viruses. We show that, in agreement with experiments, R-125489 binds to neuraminidase more tightly than CS-8958. Based on results obtained by SMD and the molecular mechanics-Poisson-Boltzmann surface area method, we predict that R-125489 can be used to treat not only wild-type but also tamiflu-resistant N294S, H274Y variants of A/H5N1 virus as its binding affinity does not vary much across these systems. The high correlation level between theoretically determined rupture forces and experimental data on binding energies for the large number of systems studied here implies that SMD is a promising tool for drug design.

  3. Neuraminidase inhibitor R-125489 - A promising drug for treating influenza virus: Steered molecular dynamics approach

    Energy Technology Data Exchange (ETDEWEB)

    Mai, Binh Khanh [Institute for Computational Science and Technology, 6 Quarter, Linh Trung Ward, Thu Duc District, Ho Chi Minh City (Viet Nam); Li, Mai Suan, E-mail: masli@ifpan.edu.pl [Institute of Physics, Polish Academy of Sciences, Al. Lotnikow 32/46, 02-668 Warsaw (Poland)

    2011-07-08

    Highlights: {yields} We study binding affinity of R-125489 and its prodrug CS-8958 to neuraminidase of pathogenic influenza viruses by molecular dynamics simulations. {yields} It is shown that, in agreement with experiments, R-125489 binds to neuraminidase more tightly than CS-8958. {yields} We predict that R-125489 can be used to treat not only wild-type but also tamiflu-resistant N294S, H274Y variants of A/H5N1 virus. {yields} The high correlation between theoretical and experimental data implies that SMD is a very promising tool for drug design. -- Abstract: Two neuraminidase inhibitors, oseltamivir and zanamivir, are important drug treatments for influenza. Oseltamivir-resistant mutants of the influenza virus A/H1N1 and A/H5N1 have emerged, necessitating the development of new long-acting antiviral agents. One such agent is a new neuraminidase inhibitor R-125489 and its prodrug CS-8958. An atomic level understanding of the nature of this antiviral agents binding is still missing. We address this gap in our knowledge by applying steered molecular dynamics (SMD) simulations to different subtypes of seasonal and highly pathogenic influenza viruses. We show that, in agreement with experiments, R-125489 binds to neuraminidase more tightly than CS-8958. Based on results obtained by SMD and the molecular mechanics-Poisson-Boltzmann surface area method, we predict that R-125489 can be used to treat not only wild-type but also tamiflu-resistant N294S, H274Y variants of A/H5N1 virus as its binding affinity does not vary much across these systems. The high correlation level between theoretically determined rupture forces and experimental data on binding energies for the large number of systems studied here implies that SMD is a promising tool for drug design.

  4. Chiral analysis of anti-acquired immunodeficiency syndrome drug, 9-(R)-[2-(phosphonomethoxy)propyl]adenine (tenofovir), and related antiviral acyclic nucleoside phosphonates by CE using beta-CD as chiral selector

    Czech Academy of Sciences Publication Activity Database

    Šolínová, Veronika; Kašička, Václav; Sázelová, Petra; Holý, Antonín

    2009-01-01

    Roč. 30, č. 12 (2009), s. 2245-2254. ISSN 0173-0835 R&D Projects: GA ČR(CZ) GA203/06/1044; GA ČR(CZ) GA203/08/1428; GA AV ČR 1QS400550501; GA MŠk 1M0508 Institutional research plan: CEZ:AV0Z40550506 Keywords : antiviral drugs * capillary electrophoresis * enantioseparation Subject RIV: CB - Analytical Chemistry, Separation Impact factor: 3.077, year: 2009

  5. Nitazoxanide: a first-in-class broad-spectrum antiviral agent.

    Science.gov (United States)

    Rossignol, Jean-François

    2014-10-01

    Originally developed and commercialized as an antiprotozoal agent, nitazoxanide was later identified as a first-in-class broad-spectrum antiviral drug and has been repurposed for the treatment of influenza. A Phase 2b/3 clinical trial recently published in The Lancet Infectious Diseases found that oral administration of nitazoxanide 600mg twice daily for five days reduced the duration of clinical symptoms and reduced viral shedding compared to placebo in persons with laboratory-confirmed influenza. The same study also suggested a potential benefit for subjects with influenza-like illness who did not have influenza or other documented respiratory viral infection. From a chemical perspective, nitazoxanide is the scaffold for a new class of drugs called thiazolides. These small-molecule drugs target host-regulated processes involved in viral replication. Nitazoxanide is orally bioavailable and safe with extensive post-marketing experience involving more than 75 million adults and children. A new dosage formulation of nitazoxanide is presently undergoing global Phase 3 clinical development for the treatment of influenza. Nitazoxanide inhibits a broad range of influenza A and B viruses including influenza A(pH1N1) and the avian A(H7N9) as well as viruses that are resistant to neuraminidase inhibitors. It is synergistic with neuraminidase inhibitors, and combination therapy with oseltamivir is being studied in humans as part of ongoing Phase 3 clinical development. Nitazoxanide also inhibits the replication of a broad range of other RNA and DNA viruses including respiratory syncytial virus, parainfluenza, coronavirus, rotavirus, norovirus, hepatitis B, hepatitis C, dengue, yellow fever, Japanese encephalitis virus and human immunodeficiency virus in cell culture assays. Clinical trials have indicated a potential role for thiazolides in treating rotavirus and norovirus gastroenteritis and chronic hepatitis B and chronic hepatitis C. Ongoing and future clinical development

  6. Structure-Based Tetravalent Zanamivir with Potent Inhibitory Activity against Drug-Resistant Influenza Viruses.

    Science.gov (United States)

    Fu, Lifeng; Bi, Yuhai; Wu, Yan; Zhang, Shanshan; Qi, Jianxun; Li, Yan; Lu, Xuancheng; Zhang, Zhenning; Lv, Xun; Yan, Jinghua; Gao, George F; Li, Xuebing

    2016-07-14

    Zanamivir and oseltamivir are principal influenza antiviral drugs that target viral neuraminidase (NA), but resistant viruses containing mutant NAs with diminished drug affinity are increasingly emerging. Using the structural knowledge of both drug-binding sites and their spatial arrangement on the homotetrameric NA, we have developed a tetravalent zanamivir (TZ) molecule that exhibited marked increases in NA binding affinity, inhibition of NA enzyme activity, and in vitro plus in vivo antiviral efficacy over zanamivir. TZ functioned against both human seasonal H3N2 and avian H7N9 viruses, including drug-resistant mutants. Crystal structure of a resistant N9 NA in complex with TZ explained the function, which showed that four zanamivir residues simultaneously bound to all four monomers of NA. The design method of TZ described in this study may be useful to develop drugs or ligands that target proteins with multiple binding sites. The potent anti-influenza activity of TZ makes it attractive for further development. PMID:27341624

  7. Small molecules with antiviral activity against the Ebola virus

    OpenAIRE

    Nadia Litterman; Christopher Lipinski; Sean Ekins

    2015-01-01

    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 r...

  8. 磷酸奥司他韦的临床应用进展%Progress in clinical application of Oseltamivir Phosphate

    Institute of Scientific and Technical Information of China (English)

    王新敏; 薛继军; 陈富新

    2014-01-01

    Oseltamivir phosphate is a kind of high-efficiency anti-influenza virus drug. Oseltamivir, alone or combined with chinese traditional patent medicine, plays an important role in the treatment of Influenza A( H1N1), Bird flu and Hand-foot-mouth disease,and has low incidence of adverse reactions, clinical application is safe and effective.%磷酸奥司他韦是一种高效的抗流感病毒药物,单独或联合中成药使用在抗甲型H1N1流感、抗禽流感、辅助治疗小儿手足口病等治疗中疗效显著,且毒副作用小,临床应用安全有效。

  9. Conformational Analysis, Molecular Structure and Solid State Simulation of the Antiviral Drug Acyclovir (Zovirax) Using Density Functional Theory Methods

    Science.gov (United States)

    Alvarez-Ros, Margarita Clara; Palafox, Mauricio Alcolea

    2014-01-01

    The five tautomers of the drug acyclovir (ACV) were determined and optimised at the MP2 and B3LYP quantum chemical levels of theory. The stability of the tautomers was correlated with different parameters. On the most stable tautomer N1 was carried out a comprehensive conformational analysis, and the whole conformational parameters (R, β, Φ, φ1, φ2, φ3, φ4, φ5) were studied as well as the NBO Natural atomic charges. The calculations were carried out with full relaxation of all geometrical parameters. The search located at least 78 stable structures within 8.5 kcal/mol electronic energy range of the global minimum, and classified in two groups according to the positive or negative value of the torsional angle φ1. In the nitrogen atoms and in the O2' and O5' oxygen atoms of the most stable conformer appear a higher reactivity than in the natural nucleoside deoxyguanosine. The solid state was simulated through a dimer and tetramer forms and the structural parameters were compared with the X-ray crystal data available. Several general conclusions were emphasized. PMID:24915059

  10. Conformational Analysis, Molecular Structure and Solid State Simulation of the Antiviral Drug Acyclovir (Zovirax Using Density Functional Theory Methods

    Directory of Open Access Journals (Sweden)

    Margarita Clara Alvarez-Ros

    2014-06-01

    Full Text Available The five tautomers of the drug acyclovir (ACV were determined and optimised at the MP2 and B3LYP quantum chemical levels of theory. The stability of the tautomers was correlated with different parameters. On the most stable tautomer N1 was carried out a comprehensive conformational analysis, and the whole conformational parameters (R, β, Φ, φ1, φ2, φ3, φ4, φ5 were studied as well as the NBO Natural atomic charges. The calculations were carried out with full relaxation of all geometrical parameters. The search located at least 78 stable structures within 8.5 kcal/mol electronic energy range of the global minimum, and classified in two groups according to the positive or negative value of the torsional angle j1. In the nitrogen atoms and in the O2' and O5' oxygen atoms of the most stable conformer appear a higher reactivity than in the natural nucleoside deoxyguanosine. The solid state was simulated through a dimer and tetramer forms and the structural parameters were compared with the X-ray crystal data available. Several general conclusions were emphasized.

  11. Antibacterial, antifungal, and antiviral activities of the lipophylic extracts of Pistacia vera.

    Science.gov (United States)

    Ozçelik, Berrin; Aslan, Mustafa; Orhan, Ilkay; Karaoglu, Taner

    2005-01-01

    In the present study, antibacterial, antifungal, and antiviral properties of 15 lipohylic extracts obtained from different parts (leaf, branch, stem, kernel, shell skins, seeds) of Pistacia vera were screened against both standard and the isolated strains of Escherichia coli, Pseudomonas aeruginosa, Enterococcus faecalis, Staphylococcus aureus, Candida albicans and C. parapsilosis by microdilution method. Both Herpes simplex (DNA) and Parainfluenza viruses (RNA) were used for the determination of antiviral activity of the P. vera extracts by using Vero cell line. Ampicilline, ofloxocine, ketoconazole, fluconazole, acyclovir and oseltamivir were used as the control agents. The extracts showed little antibacterial activity between the range of 128-256 microg/ml concentrations whereas they had noticeable antifungal activity at the same concentrations. Kernel and seed extracts showed significant antiviral activity compared to the rest of the extracts as well as the controls. PMID:15881833

  12. Intra- and inter-pandemic variations of antiviral, antibiotics and decongestants in wastewater treatment plants and receiving rivers.

    Directory of Open Access Journals (Sweden)

    Andrew C Singer

    Full Text Available The concentration of eleven antibiotics (trimethoprim, oxytetracycline, ciprofloxacin, azithromycin, cefotaxime, doxycycline, sulfamethoxazole, erythromycin, clarithromycin, ofloxacin, norfloxacin, three decongestants (naphazoline, oxymetazoline, xylometazoline and the antiviral drug oseltamivir's active metabolite, oseltamivir carboxylate (OC, were measured weekly at 21 locations within the River Thames catchment in England during the month of November 2009, the autumnal peak of the influenza A[H1N1]pdm09 pandemic. The aim was to quantify the pharmaceutical response to the pandemic and compare this to drug use during the late pandemic (March 2010 and the inter-pandemic periods (May 2011. A large and small wastewater treatment plant (WWTP were sampled in November 2009 to understand the differential fate of the analytes in the two WWTPs prior to their entry in the receiving river and to estimate drug users using a wastewater epidemiology approach. Mean hourly OC concentrations in the small and large WWTP's influent were 208 and 350 ng/L (max, 2070 and 550 ng/L, respectively. Erythromycin was the most concentrated antibiotic measured in Benson and Oxford WWTPs influent (max=6,870 and 2,930 ng/L, respectively. Napthazoline and oxymetazoline were the most frequently detected and concentrated decongestant in the Benson WWTP influent (1650 and 67 ng/L and effluent (696 and 307 ng/L, respectively, but were below detection in the Oxford WWTP. OC was found in 73% of November 2009's weekly river samples (max=193 ng/L, but only in 5% and 0% of the late- and inter-pandemic river samples, respectively. The mean river concentration of each antibiotic during the pandemic largely fell between 17-74 ng/L, with clarithromycin (max=292 ng/L and erythromycin (max=448 ng/L yielding the highest single measure. In general, the concentration and frequency of detecting antibiotics in the river increased during the pandemic. OC was uniquely well-suited for the wastewater

  13. Preparation of molecularly imprinted solid-phase microextraction fiber for the selective removal and extraction of the antiviral drug abacavir in environmental and biological matrices.

    Science.gov (United States)

    Terzopoulou, Zoi; Papageorgiou, Myrsini; Kyzas, George Z; Bikiaris, Dimitrios N; Lambropoulou, Dimitra A

    2016-03-24

    In the present study, a molecularly imprinted solid-phase microextraction fiber (MIP-SPMEf) was synthesized and applied for the selective removal and extraction of the antiviral drug, abacavir (ABA). Morphology and structure characterization of fibers were performed by scanning electron microscopy and Fourier transform infrared spectra, respectively. The effects on the adsorption behavior of the process parameters were studied and the equilibrium data were fitted by the Langmuir, Freundlich and Langmuir-Freundlich models. The maximum adsorption capability (Qmax) was determined by Langmuir- Freundlich model and was 149 mg/g for MIP-SPMEf. In the next step, SPME methodology followed by liquid desorption and liquid chromatography with mass spectrometry (LC/MS) has been developed and evaluated for the determination of the target compound in environmental and biological matrices (surface waters, wastewaters and urine). Parameters that could influence SPME efficiency were investigated. Then, optimization of stirring speed, extraction time and salt content was carried out by using a central composite design (CCD) and response surface methodology (RSM). A quadratic model between dependent and independent variables was built. Under the optimum conditions (extraction time 40 min, stirring rate 650 rpm and salt content 0.3% NaCl w/v) the validated method presented a high sensitivity and selectivity with LODs and LOQs in the range of 10.1-13.6 and 33.3-43.9 ng/L, respectively. The developed method was successfully applied to the analysis of ABA in real samples. The percentage extraction efficiency ranged from 88 to 99% revealing good accuracy and absence of matrix effects. PMID:26944990

  14. Mathematical Modeling of Hepatitis C Prevalence Reduction with Antiviral Treatment Scale-Up in Persons Who Inject Drugs in Metropolitan Chicago.

    Directory of Open Access Journals (Sweden)

    Desarae Echevarria

    Full Text Available New direct-acting antivirals (DAAs provide an opportunity to combat hepatitis C virus (HCV infection in persons who inject drugs (PWID. Here we use a mathematical model to predict the impact of a DAA-treatment scale-up on HCV prevalence among PWID and the estimated cost in metropolitan Chicago.To estimate the HCV antibody and HCV-RNA (chronic infection prevalence among the metropolitan Chicago PWID population, we used empirical data from three large epidemiological studies. Cost of DAAs is assumed $50,000 per person.Approximately 32,000 PWID reside in metropolitan Chicago with an estimated HCV-RNA prevalence of 47% or 15,040 cases. Approximately 22,000 PWID (69% of the total PWID population attend harm reduction (HR programs, such as syringe exchange programs, and have an estimated HCV-RNA prevalence of 30%. There are about 11,000 young PWID (<30 years old with an estimated HCV-RNA prevalence of 10% (PWID in these two subpopulations overlap. The model suggests that the following treatment scale-up is needed to reduce the baseline HCV-RNA prevalence by one-half over 10 years of treatment [cost per year, min-max in millions]: 35 per 1,000 [$50-$77] in the overall PWID population, 19 per 1,000 [$20-$26] for persons in HR programs, and 5 per 1,000 [$3-$4] for young PWID.Treatment scale-up could dramatically reduce the prevalence of chronic HCV infection among PWID in Chicago, who are the main reservoir for on-going HCV transmission. Focusing treatment on PWID attending HR programs and/or young PWID could have a significant impact on HCV prevalence in these subpopulations at an attainable cost.

  15. Antiviral activity of silymarin against chikungunya virus

    OpenAIRE

    Rafidah Lani; Pouya Hassandarvish; Chun Wei Chiam; Ehsan Moghaddam; Justin Jang Hann Chu; Kai Rausalu; Andres Merits; Stephen Higgs; Dana Vanlandingham; Sazaly Abu Bakar; Keivan Zandi

    2015-01-01

    The mosquito-borne chikungunya virus (CHIKV) causes chikungunya fever, with clinical presentations such as severe back and small joint pain, and debilitating arthritis associated with crippling pains that persist for weeks and even years. Although there are several studies to evaluate the efficacy of drugs against CHIKV, the treatment for chikungunya fever is mainly symptom-based and no effective licensed vaccine or antiviral are available. Here, we investigated the antiviral activity of thre...

  16. Anti-influenza neuraminidase inhibitor oseltamivir phosphate induces canine mammary cancer cell aggressiveness.

    Science.gov (United States)

    de Oliveira, Joana T; Santos, Ana L; Gomes, Catarina; Barros, Rita; Ribeiro, Cláudia; Mendes, Nuno; de Matos, Augusto J; Vasconcelos, M Helena; Oliveira, Maria José; Reis, Celso A; Gärtner, Fátima

    2015-01-01

    Oseltamivir phosphate is a widely used anti-influenza sialidase inhibitor. Sialylation, governed by sialyltransferases and sialidases, is strongly implicated in the oncogenesis and progression of breast cancer. In this study we evaluated the biological behavior of canine mammary tumor cells upon oseltamivir phosphate treatment (a sialidase inhibitor) in vitro and in vivo. Our in vitro results showed that oseltamivir phosphate impairs sialidase activity leading to increased sialylation in CMA07 and CMT-U27 canine mammary cancer cells. Surprisingly, oseltamivir phosphate stimulated, CMT-U27 cell migration and invasion capacity in vitro, in a dose-dependent manner. CMT-U27 tumors xenograft of oseltamivir phosphate-treated nude mice showed increased sialylation, namely α2,6 terminal structures and SLe(x) expression. Remarkably, a trend towards increased lung metastases was observed in oseltamivir phosphate-treated nude mice. Taken together, our findings revealed that oseltamivir impairs canine mammary cancer cell sialidase activity, altering the sialylation pattern of canine mammary tumors, and leading, surprisingly, to in vitro and in vivo increased mammary tumor aggressiveness. PMID:25850034

  17. Anti-influenza neuraminidase inhibitor oseltamivir phosphate induces canine mammary cancer cell aggressiveness.

    Directory of Open Access Journals (Sweden)

    Joana T de Oliveira

    Full Text Available Oseltamivir phosphate is a widely used anti-influenza sialidase inhibitor. Sialylation, governed by sialyltransferases and sialidases, is strongly implicated in the oncogenesis and progression of breast cancer. In this study we evaluated the biological behavior of canine mammary tumor cells upon oseltamivir phosphate treatment (a sialidase inhibitor in vitro and in vivo. Our in vitro results showed that oseltamivir phosphate impairs sialidase activity leading to increased sialylation in CMA07 and CMT-U27 canine mammary cancer cells. Surprisingly, oseltamivir phosphate stimulated, CMT-U27 cell migration and invasion capacity in vitro, in a dose-dependent manner. CMT-U27 tumors xenograft of oseltamivir phosphate-treated nude mice showed increased sialylation, namely α2,6 terminal structures and SLe(x expression. Remarkably, a trend towards increased lung metastases was observed in oseltamivir phosphate-treated nude mice. Taken together, our findings revealed that oseltamivir impairs canine mammary cancer cell sialidase activity, altering the sialylation pattern of canine mammary tumors, and leading, surprisingly, to in vitro and in vivo increased mammary tumor aggressiveness.

  18. Antiviral Strategies for Pandemic and Seasonal Influenza

    OpenAIRE

    Fang Fang; Maria Hedlund; Larson, Jeffrey L.

    2010-01-01

    While vaccines are the primary public health response to seasonal and pandemic flu, short of a universal vaccine there are inherent limitations to this approach. Antiviral drugs provide valuable alternative options for treatment and prophylaxis of influenza. Here, we will review drugs and drug candidates against influenza with an emphasis on the recent progress of a host-targeting entry-blocker drug candidate, DAS181, a sialidase fusion protein.

  19. Combinations of Oseltamivir and T-705 Extend the Treatment Window for Highly Pathogenic Influenza A(H5N1) Virus Infection in Mice

    Science.gov (United States)

    Marathe, Bindumadhav M.; Wong, Sook-San; Vogel, Peter; Garcia-Alcalde, Fernando; Webster, Robert G.; Webby, Richard J.; Najera, Isabel; Govorkova, Elena A.

    2016-01-01

    Current anti-influenza therapy depends on administering drugs soon after infection, which is often impractical. We assessed whether combinations of oseltamivir (a neuraminidase inhibitor) and T-705 (a nonspecific inhibitor of viral polymerases) could extend the window for treating lethal infection with highly pathogenic A(H5N1) influenza virus in mice. Combination therapy protected 100% of mice, even when delayed until 96 h postinoculation. Compared to animals receiving monotherapy, mice receiving combination therapy had reduced viral loads and restricted viral spread in lung tissues, limited lung damage, and decreased inflammatory cytokine production. Next-generation sequencing showed that virus populations in T-705–treated mice had greater genetic variability, with more frequent transversion events, than did populations in control and oseltamivir-treated mice, but no substitutions associated with resistance to oseltamivir or T-705 were detected. Thus, combination therapy extended the treatment window for A(H5N1) influenza infection in mice and should be considered for evaluation in a clinical setting. PMID:27221530

  20. Combinations of Oseltamivir and T-705 Extend the Treatment Window for Highly Pathogenic Influenza A(H5N1) Virus Infection in Mice.

    Science.gov (United States)

    Marathe, Bindumadhav M; Wong, Sook-San; Vogel, Peter; Garcia-Alcalde, Fernando; Webster, Robert G; Webby, Richard J; Najera, Isabel; Govorkova, Elena A

    2016-01-01

    Current anti-influenza therapy depends on administering drugs soon after infection, which is often impractical. We assessed whether combinations of oseltamivir (a neuraminidase inhibitor) and T-705 (a nonspecific inhibitor of viral polymerases) could extend the window for treating lethal infection with highly pathogenic A(H5N1) influenza virus in mice. Combination therapy protected 100% of mice, even when delayed until 96 h postinoculation. Compared to animals receiving monotherapy, mice receiving combination therapy had reduced viral loads and restricted viral spread in lung tissues, limited lung damage, and decreased inflammatory cytokine production. Next-generation sequencing showed that virus populations in T-705-treated mice had greater genetic variability, with more frequent transversion events, than did populations in control and oseltamivir-treated mice, but no substitutions associated with resistance to oseltamivir or T-705 were detected. Thus, combination therapy extended the treatment window for A(H5N1) influenza infection in mice and should be considered for evaluation in a clinical setting. PMID:27221530

  1. Determining Mechanism of Action of Antivirals for Respiratory Illness

    Science.gov (United States)

    Rodriguez, Irma; Dobrovolny, Hana

    2015-03-01

    Viral infections in the respiratory tract are common in humans and can cause serious illness and death. Drug treatment is the principal line of protection against many of these illnesses and many compounds are tested as antivirals. Often the efficacy of these antivirals are determined before a mechanism of action is understood. We use mathematical models to represent the evolution of these diseases and establish which experiments can help determine the mechanism of action of antivirals.

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

    OpenAIRE

    Paul Schnitzler; Jürgen Reichling; Akram Astani

    2011-01-01

    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 infectio...

  3. Effectiveness of Personal Protective Equipment and Oseltamivir Prophylaxis during Avian Influenza A (H7N7) Epidemic, the Netherlands, 2003

    OpenAIRE

    te Beest, Dennis E.; van Boven, Michiel; Bos, Marian E H; Stegeman, Arjan; Koopmans, Marion P.G.

    2010-01-01

    We analyzed the effectiveness of personal protective equipment and oseltamivir use during the 2003 avian influenza A (H7N7) epidemic in the Netherlands by linking databases containing information about farm visits, human infections, and use of oseltamivir and personal protective equipment. Using a stringent case definition, based on self-reported conjunctivitis combined with a positive hemagglutination-inhibition assay, we found that prophylactic treatment with oseltamivir significantly reduc...

  4. In Vitro Antiviral Activity of Favipiravir (T-705) against Drug-Resistant Influenza and 2009 A(H1N1) Viruses▿

    OpenAIRE

    Sleeman, Katrina; Mishin, Vasiliy P.; Deyde, Varough M.; Furuta, Yousuke; Klimov, Alexander I; Larisa V Gubareva

    2010-01-01

    Favipiravir (T-705) has previously been shown to have a potent antiviral effect against influenza virus and some other RNA viruses in both cell culture and in animal models. Currently, favipiravir is undergoing clinical evaluation for the treatment of influenza A and B virus infections. In this study, favipiravir was evaluated in vitro for its ability to inhibit the replication of a representative panel of seasonal influenza viruses, the 2009 A(H1N1) strains, and animal viruses with pandemic ...

  5. Antiviral activity of silymarin against chikungunya virus.

    Science.gov (United States)

    Lani, Rafidah; Hassandarvish, Pouya; Chiam, Chun Wei; Moghaddam, Ehsan; Chu, Justin Jang Hann; Rausalu, Kai; Merits, Andres; Higgs, Stephen; Vanlandingham, Dana; Abu Bakar, Sazaly; Zandi, Keivan

    2015-01-01

    The mosquito-borne chikungunya virus (CHIKV) causes chikungunya fever, with clinical presentations such as severe back and small joint pain, and debilitating arthritis associated with crippling pains that persist for weeks and even years. Although there are several studies to evaluate the efficacy of drugs against CHIKV, the treatment for chikungunya fever is mainly symptom-based and no effective licensed vaccine or antiviral are available. Here, we investigated the antiviral activity of three types of flavonoids against CHIKV in vitro replication. Three compounds: silymarin, quercetin and kaempferol were evaluated for their in vitro antiviral activities against CHIKV using a CHIKV replicon cell line and clinical isolate of CHIKV of Central/East African genotype. A cytopathic effect inhibition assay was used to determine their activities on CHIKV viral replication and quantitative reverse transcription PCR was used to calculate virus yield. Antiviral activity of effective compound was further investigated by evaluation of CHIKV protein expression using western blotting for CHIKV nsP1, nsP3, and E2E1 proteins. Briefly, silymarin exhibited significant antiviral activity against CHIKV, reducing both CHIKV replication efficiency and down-regulating production of viral proteins involved in replication. This study may have important consequence for broaden the chance of getting the effective antiviral for CHIKV infection. PMID:26078201

  6. First Fatal Oseltamivir-Resistant 2009 Pandemic Influenza A (H1N1) Case in an Adult in Korea

    OpenAIRE

    Hong, Seung-Dok; Park, Seong-Hwan; Kang, Seung-Ji; Kwon, Yong Soo; Kee, Seung-Jung; Park, Kyung-Hwa; Jung, Sook-In; Jang, Hee-Chang

    2011-01-01

    It has been suggested that oseltamivir-resistant influenza viruses harboring the H274/275Y mutation are less virulent than are those that are oseltamivir-sensitive, and fatality attributed to infection with an oseltamivir-resistant virus is very rare. Here we report the first fatal adult case of oseltamivir-resistant 2009 pandemic influenza A (H1N1) in Korea. A 60-year-old Korean male who had hypertension, diabetes mellitus, chronic kidney disease, and dilated cardiomyopathy visited Chonnam N...

  7. Antiviral therapy of decompensated hepatitis B virus-related cirrhosis

    Institute of Scientific and Technical Information of China (English)

    CHEN Guang-cheng; YU Tao; HUANG Kai-hong; CHEN Qi-kui

    2012-01-01

    Objective To review the development,mechanism,necessity and limitation of antiviral therapy in decompensated hepatitis B virus-related cirrhosis.Data sources Most information was pulled from a literature search (Pubmed 2000 to 2011) using the keywords of antiviral and decompensated hepatitis B virus-related cirrhosis.Relevant book chapters were also reviewed.Study selection Well-controlled,prospective landmark studies and review articles on antiviral therapy in decompesated hepatitis B virus-related cirrhosis were selected.Results Specific antiviral agents not only control viral replication,which permits liver transplantation,but also improve liver function so significantly that patients could be removed from the transplant waiting list.However,the emergence of drug-resistant mutants can result in treatment failure.Combination therapy is a save-strategy in drug-resistant.Conclusions Although the treatment of end-stage liver disease is still a challenge worldwide,antiviral therapy has altered the natural history of hepatitis B patients with decompensated cirrhosis.The approval of the new generation of antivirals is opening new perspectives for finding the optimal antiviral treatment for patients with decompensated cirrhosis and preventing antiviral resistance.A combination of antivirals may be one of the future strategies for fulfilling these goals.

  8. Quantitative Analysis of a Parasitic Antiviral Strategy

    OpenAIRE

    Kim, Hwijin; Yin, John

    2004-01-01

    We extended a computer simulation of viral intracellular growth to study a parasitic antiviral strategy that diverts the viral replicase toward parasite growth. This strategy inhibited virus growth over a wide range of conditions, while minimizing host cell perturbations. Such parasitic strategies may inhibit the development of drug-resistant virus strains.

  9. In vitro and in vivo stability of oseltamivir within a bioequivalence trial.

    Science.gov (United States)

    Grigoriev, Alexander; Borisova, Irina; Yaroshenko, Irina; Sidorova, Alla

    2016-05-01

    A simple, precise, and rapid method to simultaneously determine the levels of oseltamivir (OS) and oseltamivir carboxylate (OSC) in human plasma was developed. Additionally, the stability of both substances in plasma was investigated under different conditions. The method involved protein precipitation (0.01 % HCl in acetonitrile), and then the supernatant was injected into the high-performance liquid chromatography (HPLC)-MS/MS. The chromatographic separation was achieved on a YMC-Triart C18 (100 × 2.0 mm, 5 μm) column using acetonitrile/water (30:70, v/v) containing 0.1 % formic acid as the mobile phase. Sample volume was 5 μl. The linearity of the method was established in the concentration range of 0.5-100 ng/mL for OS and 1.0-1000 ng/mL for OSC. The intra-day precision and accuracy for oseltamivir were 1.5-8.9 and 94.4-101.0 %, respectively. For oseltamivir carboxylate, the intra-day precision and accuracy were 3.2-12.7 and 92.8-108.8 %, respectively, whereas the inter-day precision and accuracy were 5.5-11.5 and 94.6-104.0 % for oseltamivir and 4.7-11.5 and 99.9-103.9 % for oseltamivir carboxylate, respectively. The application of this method was demonstrated by a bioequivalence study in 28 healthy humans with 75 mg oseltamivir phosphate capsules (Tamiflu®). Sodium fluoride (2.4 mg/mL) with potassium oxalate (3 mg/mL) was used as anticoagulant within sampling of trial. The assay reproducibility was established by reanalysis of 80 incurred samples. PMID:27002612

  10. Antiviral activity of luteolin against Japanese encephalitis virus.

    Science.gov (United States)

    Fan, Wenchun; Qian, Suhong; Qian, Ping; Li, Xiangmin

    2016-07-15

    Japanese encephalitis virus (JEV), a member of family Flaviviridae, is a neurotropic flavivirus that causes Japanese encephalitis (JE). JEV is one of the most important causative agents of viral encephalitis in humans, and this disease leads to high fatality rates. Although effective vaccines are available, no effective antiviral therapy for JE has been developed. Hence, identifying effective antiviral agents against JEV infection is important. In this study, we found that luteolin was an antiviral bioflavonoid with potent antiviral activity against JEV replication in A549 cells with IC50=4.56μg/mL. Luteolin also showed extracellular virucidal activity on JEV. With a time-of-drug addition assay revealing that JEV replication was inhibited by luteolin after the entry stage. Overall, our results suggested that luteolin can be used to develop an antiviral drug against JEV. PMID:27126774

  11. Laboratory-confirmed influenza B infection in immunized long-term care facility residents receiving oseltamivir prophylaxis in Ontario.

    Science.gov (United States)

    Winter, Anne-Luise; Peci, Adriana; Eshaghi, Alireza; Baird, Michelle; Memari, Nader; Kristjanson, Erik; Balogun, Elizabeth; Higgins, Rachel R; Li, Aimin; Farrell, David J; Gubbay, Jonathan B

    2013-11-01

    We report on an influenza B outbreak in an Ontario long-term care facility in which 2 immunized residents receiving oseltamivir prophylaxis for at least 5 days developed laboratory-confirmed influenza B infection. All isolates were tested for the most common oseltamivir resistance, and none of them had resistance identified. PMID:24113612

  12. Fate of three anti-influenza drugs during ozonation of wastewater effluents - degradation and formation of transformation products.

    Science.gov (United States)

    Fedorova, Ganna; Grabic, Roman; Nyhlen, Jonas; Järhult, Josef D; Söderström, Hanna

    2016-05-01

    Anti-influenza drugs constitute a key component of pandemic preparedness plans against influenza. However, the occurrence of such drugs in water environments, the potential of resistance development in the natural hosts, and the risk for transmission of antiviral resistance to humans call for measures to increase removal in wastewater treatment plants (WWTPs). In this study, removal of three anti-influenza drugs; amantadine (AM), oseltamivir carboxylate (OC) and zanamivir (ZA), and formation/removal of their transformation products during ozonation of wastewater effluents from two Swedish WWTPs in Uppsala and Stockholm were studied. The removal profile of target antivirals and formation/removal of their transformation products were studied by liquid chromatography/high resolution mass spectrometry. 3.5 h of ozone exposure (total dose of ozone 5.95 g) led to complete removal of the three anti-influenza drugs with a degradation in the following order ZA > OC > AM. Two, five and one transformation products were identified and semi-quantified for AM, OC and ZA, respectively. Increasing and later decreasing transformation products concentration followed the decrease in concentration of target compounds. All transformation products detected, except one of AM in wastewater from Stockholm WWTP, were removed at the end of the experiment. The removal efficiency was higher for all studied compounds in wastewater from Uppsala WWTP, which had lower TOC and COD values, less phosphorus, and also higher pH in the water. Ozonation thus offers multiple benefits through its potential to degrade influenza antivirals, hence decrease the risk of environmental resistance development, in addition to degrading other pharmaceuticals and resistant microorganisms. PMID:26746418

  13. Detection of peramivir and laninamivir, new anti-influenza drugs, in sewage effluent and river waters in Japan

    OpenAIRE

    Azuma, Takashi; Ishiuchi, Hirotaka; Inoyama, Tomomi; Teranishi, Yusuke; Yamaoka, Misato; Sato, Takaji; Yamashita, Naoyuki; Tanaka, Hiroaki; Mino, Yoshiki

    2015-01-01

    This is the first report of the detection of two new anti-influenza drugs, peramivir (PER) and laninamivir (LAN), in Japanese sewage effluent and river waters. Over about 1 year from October 2013 to July 2014, including the influenza prevalence season in January and February 2014, we monitored for five anti-influenza drugs - oseltamivir (OS), oseltamivir carboxylate (OC), zanamivir (ZAN), PER, and LAN - in river waters and in sewage effluent flowing into urban rivers of the Yodo River system ...

  14. Oseltamivir-resistant pandemic A/H1N1 virus is as virulent as its wild-type counterpart in mice and ferrets.

    Directory of Open Access Journals (Sweden)

    Marie-Eve Hamelin

    Full Text Available The neuraminidase inhibitor oseltamivir is currently used for treatment of patients infected with the pandemic A/H1N1 (pH1N1 influenza virus, although drug-resistant mutants can emerge rapidly and possibly be transmitted. We describe the characteristics of a pair of oseltamivir-resistant and oseltamivir-susceptible pH1N1 clinical isolates that differed by a single change (H274Y in the neuraminidase protein. Viral fitness of pH1N1 isolates was assessed in vitro by determining replication kinetics in MDCK alpha2,6 cells and in vivo by performing experimental infections of BALB/c mice and ferrets. Despite slightly reduced propagation of the mutant isolate in vitro during the first 24 h, the wild-type (WT and mutant resistant viruses induced similar maximum weight loss in mice and ferrets with an identical pyrexic response in ferrets (AUC of 233.9 and 233.2, P = 0.5156. Similarly, comparable titers were obtained for the WT and the mutant strains on days 1, 3, 6 and 9 post-infection in mouse lungs and on days 1-7 in ferret nasal washes. A more important perivascular (day 6 and pleural (days 6 and 12 inflammation was noted in the lungs of mice infected with the H274Y mutant, which correlated with increased pulmonary levels of IL-6 and KC. Such increased levels of IL-6 were also observed in lymph nodes of ferrets infected with the mutant strain. Furthermore, the H274Y mutant strain was transmitted to ferrets. In conclusion, viral fitness of the H274Y pH1N1 isolate is not substantially altered and has the potential to induce severe disease and to disseminate.

  15. Anti-viral properties and mode of action of standardized Echinacea purpurea extract against highly pathogenic avian Influenza virus (H5N1, H7N7 and swine-origin H1N1 (S-OIV

    Directory of Open Access Journals (Sweden)

    Schoop Roland

    2009-11-01

    Full Text Available Abstract Background Influenza virus (IV infections are a major threat to human welfare and animal health worldwide. Anti-viral therapy includes vaccines and a few anti-viral drugs. However vaccines are not always available in time, as demonstrated by the emergence of the new 2009 H1N1-type pandemic strain of swine origin (S-OIV in April 2009, and the acquisition of resistance to neuraminidase inhibitors such as Tamiflu® (oseltamivir is a potential problem. Therefore the prospects for the control of IV by existing anti-viral drugs are limited. As an alternative approach to the common anti-virals we studied in more detail a commercial standardized extract of the widely used herb Echinacea purpurea (Echinaforce®, EF in order to elucidate the nature of its anti-IV activity. Results Human H1N1-type IV, highly pathogenic avian IV (HPAIV of the H5- and H7-types, as well as swine origin IV (S-OIV, H1N1, were all inactivated in cell culture assays by the EF preparation at concentrations ranging from the recommended dose for oral consumption to several orders of magnitude lower. Detailed studies with the H5N1 HPAIV strain indicated that direct contact between EF and virus was required, prior to infection, in order to obtain maximum inhibition in virus replication. Hemagglutination assays showed that the extract inhibited the receptor binding activity of the virus, suggesting that the extract interferes with the viral entry into cells. In sequential passage studies under treatment in cell culture with the H5N1 virus no EF-resistant variants emerged, in contrast to Tamiflu®, which produced resistant viruses upon passaging. Furthermore, the Tamiflu®-resistant virus was just as susceptible to EF as the wild type virus. Conclusion As a result of these investigations, we believe that this standard Echinacea preparation, used at the recommended dose for oral consumption, could be a useful, readily available and affordable addition to existing control options

  16. Antiviral effects of Glycyrrhiza species.

    Science.gov (United States)

    Fiore, Cristina; Eisenhut, Michael; Krausse, Rea; Ragazzi, Eugenio; Pellati, Donatella; Armanini, Decio; Bielenberg, Jens

    2008-02-01

    Historical sources for the use of Glycyrrhiza species include ancient manuscripts from China, India and Greece. They all mention its use for symptoms of viral respiratory tract infections and hepatitis. Randomized controlled trials confirmed that the Glycyrrhiza glabra derived compound glycyrrhizin and its derivatives reduced hepatocellular damage in chronic hepatitis B and C. In hepatitis C virus-induced cirrhosis the risk of hepatocellular carcinoma was reduced. Animal studies demonstrated a reduction of mortality and viral activity in herpes simplex virus encephalitis and influenza A virus pneumonia. In vitro studies revealed antiviral activity against HIV-1, SARS related coronavirus, respiratory syncytial virus, arboviruses, vaccinia virus and vesicular stomatitis virus. Mechanisms for antiviral activity of Glycyrrhiza spp. include reduced transport to the membrane and sialylation of hepatitis B virus surface antigen, reduction of membrane fluidity leading to inhibition of fusion of the viral membrane of HIV-1 with the cell, induction of interferon gamma in T-cells, inhibition of phosphorylating enzymes in vesicular stomatitis virus infection and reduction of viral latency. Future research needs to explore the potency of compounds derived from licorice in prevention and treatment of influenza A virus pneumonia and as an adjuvant treatment in patients infected with HIV resistant to antiretroviral drugs. PMID:17886224

  17. Antiviral targets of human noroviruses.

    Science.gov (United States)

    Prasad, Bv Venkataram; Shanker, Sreejesh; Muhaxhiri, Zana; Deng, Lisheng; Choi, Jae-Mun; Estes, Mary K; Song, Yongcheng; Palzkill, Timothy; Atmar, Robert L

    2016-06-01

    Human noroviruses are major causative agents of sporadic and epidemic gastroenteritis both in children and adults. Currently there are no licensed therapeutic intervention measures either in terms of vaccines or drugs available for these highly contagious human pathogens. Genetic and antigenic diversity of these viruses, rapid emergence of new strains, and their ability to infect a broad population by using polymorphic histo-blood group antigens for cell attachment, pose significant challenges for the development of effective antiviral agents. Despite these impediments, there is progress in the design and development of therapeutic agents. These include capsid-based candidate vaccines, and potential antivirals either in the form of glycomimetics or designer antibodies that block HBGA binding, as well as those that target essential non-structural proteins such as the viral protease and RNA-dependent RNA polymerase. In addition to these classical approaches, recent studies suggest the possibility of interferons and targeting host cell factors as viable approaches to counter norovirus infection. This review provides a brief overview of this progress. PMID:27318434

  18. Antiviral lead compounds from marine sponges

    KAUST Repository

    Sagar, Sunil

    2010-10-11

    Marine sponges are currently one of the richest sources of pharmacologically active compounds found in the marine environment. These bioactive molecules are often secondary metabolites, whose main function is to enable and/or modulate cellular communication and defense. They are usually produced by functional enzyme clusters in sponges and/or their associated symbiotic microorganisms. Natural product lead compounds from sponges have often been found to be promising pharmaceutical agents. Several of them have successfully been approved as antiviral agents for clinical use or have been advanced to the late stages of clinical trials. Most of these drugs are used for the treatment of human immunodeficiency virus (HIV) and herpes simplex virus (HSV). The most important antiviral lead of marine origin reported thus far is nucleoside Ara-A (vidarabine) isolated from sponge Tethya crypta. It inhibits viral DNA polymerase and DNA synthesis of herpes, vaccinica and varicella zoster viruses. However due to the discovery of new types of viruses and emergence of drug resistant strains, it is necessary to develop new antiviral lead compounds continuously. Several sponge derived antiviral lead compounds which are hopedto be developed as future drugs are discussed in this review. Supply problems are usually the major bottleneck to the development of these compounds as drugs during clinical trials. However advances in the field of metagenomics and high throughput microbial cultivation has raised the possibility that these techniques could lead to the cost-effective large scale production of such compounds. Perspectives on biotechnological methods with respect to marine drug development are also discussed. 2010 by the authors; licensee MDPI.

  19. Antiviral Lead Compounds from Marine Sponges

    Directory of Open Access Journals (Sweden)

    Kenneth P. Minneman

    2010-10-01

    Full Text Available Marine sponges are currently one of the richest sources of pharmacologically active compounds found in the marine environment. These bioactive molecules are often secondary metabolites, whose main function is to enable and/or modulate cellular communication and defense. They are usually produced by functional enzyme clusters in sponges and/or their associated symbiotic microorganisms. Natural product lead compounds from sponges have often been found to be promising pharmaceutical agents. Several of them have successfully been approved as antiviral agents for clinical use or have been advanced to the late stages of clinical trials. Most of these drugs are used for the treatment of human immunodeficiency virus (HIV and herpes simplex virus (HSV. The most important antiviral lead of marine origin reported thus far is nucleoside Ara-A (vidarabine isolated from sponge Tethya crypta. It inhibits viral DNA polymerase and DNA synthesis of herpes, vaccinica and varicella zoster viruses. However due to the discovery of new types of viruses and emergence of drug resistant strains, it is necessary to develop new antiviral lead compounds continuously. Several sponge derived antiviral lead compounds which are hopedto be developed as future drugs are discussed in this review. Supply problems are usually the major bottleneck to the development of these compounds as drugs during clinical trials. However advances in the field of metagenomics and high throughput microbial cultivation has raised the possibility that these techniques could lead to the cost-effective large scale production of such compounds. Perspectives on biotechnological methods with respect to marine drug development are also discussed.

  20. Effects of solubilizing surfactants and loading of antiviral, antimicrobial, and antifungal drugs on their release rates from ethylene vinyl acetate copolymer

    Science.gov (United States)

    Tallury, Padmavathy; Randall, Marcus K; Thaw, Khin L; Preisser, John S.; Kalachandra, Sid

    2013-01-01

    Objectives This study investigates the effects of surfactants and drug loading on the drug release rate from ethylene vinyl acetate (EVA) copolymer. The release rate of nystatin from EVA was studied with addition of non-ionic surfactants Tween 60 and Cremophor RH 40. In addition, the effect of increasing drug load on the release rates of nystatin, chlorhexidine diacetate and acyclovir is also presented. Method Polymer casting solutions were prepared by stirring EVA copolymer and nystatin (2.5 wt %) in dichloromethane. Nystatin and surfactants were added in ratios of (1:1), (1:2) and (1:3). Drug loading was studied with 2.5, 5.0, 7.5, and 10.0% wt. proportions of nystatin, chlorhexidine diacetate and acyclovir incorporated into a separate polymer. Three drug loaded polymer square films (3cm × 3cm × 0.08 cm) were cut from dry films to follow the kinetics of drug release at 37°C. 10 ml of either distilled water or PBS was used as the extracting medium that was replaced daily. PBS was used for nystatin release with addition of surfactants and water was used for the study on drug loading and surfactant release. The rate of drug release was measured by UV-spectrophotometer. The amount of surfactant released was determined by HPLC. Results The release of nystatin was low in PBS and its release rate increased with the addition of surfactants. Also, increasing surfactant concentrations resulted in increased drug release rates. The release rates of chlorhexidine diacetate (p<0.0001), acyclovir (p<0.0003) and nystatin (p<0.0017) linearly increased with increasing drug loads. The amount of surfactants released was above the CMC. Significance This study demonstrates that the three therapeutic agents show a sustained rate of drug release from EVA copolymer over extended periods of time. Nystatin release in PBS is low owing to its poor solubility. Its release rate is enhanced by addition of surfactants and increasing the drug load as well. PMID:17049593

  1. Application of coamplification at lower denaturation temperature-PCR sequencing for early detection of antiviral drug resistance mutations of hepatitis B virus

    OpenAIRE

    Wong, Danny Ka-Ho; Tsoi, Ottilia; Huang, Fung-Yu; Seto, Wai-Kay; Fung, James; Lai, Ching-Lung; YUEN, MAN-FUNG

    2014-01-01

    Nucleoside/nucleotide analogue for the treatment of chronic hepatitis B virus (HBV) infection is hampered by the emergence of drug resistance mutations. Conventional PCR sequencing cannot detect minor variants of

  2. A Near-Fatal Infection with Oseltamivir-Resistant Seasonal Influenza A in a Previously Healthy Child: Case Report

    Directory of Open Access Journals (Sweden)

    Jesse Papenburg

    2009-01-01

    Full Text Available A case of near-fatal oseltamivir-resistant seasonal influenza A infection in a previously healthy four-year-old boy is reported. This case highlights three important points for physicians: oseltamivir-resistant influenza A (H1N1 has recently emerged in North America; contrary to previously held beliefs, such strains are capable of causing severe disease in healthy children; and given this change in epidemiology, clinicians caring for children with severe seasonal influenza A infection should consider empiric dual therapy with oseltamivir and amantadine.

  3. Oseltamivir-Resistant Pandemic (H1N1) 2009 Virus Infection in England and Scotland, 2009–2010

    OpenAIRE

    Calatayud, Laurence; Lackenby, Angie; Reynolds, Arlene; McMenamin, Jim; Phin, Nick F.; Zambon, Maria C.; Pebody, Richard

    2011-01-01

    Oseltamivir has been widely used for pandemic (H1N1) 2009 virus infection, and by April 30, 2010, a total of 285 resistant cases were reported worldwide, including 45 in the United Kingdom. To determine risk factors for emergence of oseltamivir resistance and severe infection, a case–control study was conducted in the United Kingdom. Study participants were hospitalized in England or Scotland during January 4, 2009–April 30, 2010. Controls had confirmed oseltamivir-sensitive pandemic (H1N1) 2...

  4. L-Valine Ester of Cyclopropavir - a New Antiviral Prodrug

    OpenAIRE

    Wu, Zhimeng; Drach, John C.; Prichard, Mark N.; Yanachkova, Milka; Yanachkov, Ivan; Bowlin, Terry L.; Zemlicka, Jiri

    2009-01-01

    The L-Valine ester of antiviral agent cyclopropavir, valcyclopropavir (6), was synthesized and evaluated for antiviral properties. Prodrug (6) inhibited replication of HCMV virus (Towne and AD169 strain) in HFF cells to approximately the same extent as the parent drug cyclopropavir (5). Stability of 6 toward hydrolysis at pH 7.0 roughly corresponds to that of valganciclovir (2). Pharmacokinetic studies in mice established that the oral bioavailability of valcyclopropavir (6) was 95%.

  5. ANTIVIRAL POTENTIAL OF MEDICINAL PLANTS: AN OVERVIEW

    OpenAIRE

    Ruwali Pushpa; Rai Nishant; Kumar Navin; Gautam Pankaj

    2013-01-01

    The term ‘Antiviral agents’ has been defined in very broad terms as substances other than a virus or virus containing vaccine or specific antibody which can produce either a protective or therapeutic effect to the clear detectable advantage of the virus infected host. The herbal medicine has a long traditional use and the major advantage over other medicines is their wide therapeutic window with rare side effects. There are some disadvantages of synthetic drugs like narrow therapeutic window...

  6. Antiviral therapy and outcomes of patients with pneumonia caused by influenza A pandemic (H1N1 virus.

    Directory of Open Access Journals (Sweden)

    Shi-gui Yang

    Full Text Available BACKGROUND: There is limited data on the clinical outcome of patients with pandemic H1N1 (pH1N1 pneumonia who received oseltamivir treatment, especially when the treatment was administered more than 48 hours after symptom onset. METHODS: During the pandemic in 2009, a cohort of pH1N1 influenza pneumonia was built in China, and their clinical information was collected systematically, and analyzed with Cox models. RESULTS: 920 adults and 541 children with pneumonia who didn't receive corticosteroids were analyzed. In-hospital mortality was higher in adults who did not receive antiviral therapy (18.2% than those with who received oseltamivir ≤ 2 days (2.9%, between 2-5 days (4.6% and >5 days after illness onset (4.9%, p5 days, respectively. For males patients, aged ≥ 14 years and baseline PaO(2/FiO(23.8 mg/kg/d did not improve clinical outcome (mortality, higher dose 2.5% vs standard dose 2.8%, p>0.05. CONCLUSIONS: Antiviral therapy might reduce mortality of patients with pH1N1 pneumonia, even when initiated more than 48 hours after onset of illness. Greater protective effects might be in males, patients aged 14-60 years, and patients with PaO(2/FiO(2<200.

  7. Antiviral immunity in marine molluscs.

    Science.gov (United States)

    Green, Timothy J; Raftos, David; Speck, Peter; Montagnani, Caroline

    2015-09-01

    Marine molluscs, like all living organisms, are constantly exposed to viruses and have evolved efficient antiviral defences. We review here recent developments in molluscan antiviral immunity against viruses belonging to the order Herpesvirales. Emerging results suggest an interferon-like response and autophagy are involved in the antiviral defence of bivalves to viral infection. Multi-functional plasma proteins from gastropods and bivalves have been identified to have broad-spectrum antiviral activity against mammalian viruses. The antiviral defences present in molluscs can be enhanced by genetic selection, as shown by the presence of oyster strains specifically resistant to ostreid herpesvirus type 1. Whether varying amounts or different isoforms of these antiviral plasma proteins contributes to genetic resistance is worthy of further research. Other evolutionarily conserved antiviral mechanisms, such as RNA interference and apoptosis, still need further characterization. PMID:26297577

  8. 奥司他韦治疗儿童流行性感冒的临床效果观察%The Clinical Effects of Oseltamivir Treatment of Influenza in Children are Observed

    Institute of Scientific and Technical Information of China (English)

    罗顺

    2015-01-01

    Objective To explore the clinical efects of oseltamivir treatment of influenza in children.Methods Select children 80 cases of pandemic flu admitted to our hospital in recent years, according to the duration of treatment were randomly divided into two groups, each 40 cases.In traditional oral anti-viral flu treat control group and use oseltamivir treatment observation group for comparison,Viewed from the receiving treatment to rehabilitation of cough, fever, stuffy nose disappearance time recorded.Results Using oseltamivir treatment of children in the treatment of pandemic flu total eficiency significantly higher than the control group, the diference was statisticaly significant (P<0.05),observation group in shortening their cough, fever and nasal congestion time was significantly better than the control group, the diference was statisticaly significant (P<0.05).Conclusion Oseltamivir treat the influenza in children, unique efects.%目的:探讨奥司他韦治疗儿童流行性感冒的临床效果。方法选取我院近年来收治的流行感冒的儿童80例,根据其治疗时间随机分为两组,每组各40例。以常规的抗病毒口服液治疗流行感冒的对照组与以选用奥司他韦治疗的观察组进行比较,观察从接受治疗至康复的咳嗽、发热、鼻塞消失的时间,进行记录。结果采用奥司他韦治疗的患儿在治疗流行感冒方面的总有效率方面明显高与对照组,其差异具有统计学意义(P<0.05),观察组在缩短其咳嗽、发热以及鼻塞的时间显著优于对照组,差异具有统计学意义(P<0.05)。结论奥司他韦治疗儿童流行性感冒效果独特。

  9. Role of combination antiviral therapy in pandemic influenza and stockpiling implications

    OpenAIRE

    Tsiodras, Sotirios; Mooney, John D; Hatzakis, Angelos

    2007-01-01

    It is impossible to predict which drugs will be effective against a new pandemic strain of influenza. Sotirios Tsiodras and colleagues argue that failure to stockpile both major classes of antiviral drugs could prove costly

  10. Drug: D02267 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available D02267 Drug Foscarnet sodium hydrate (JAN); Trisodium phosphonoformate hexahydrate;...Chemotherapeutics 625 Antivirals 6250 Antivirals D02267 Foscarnet sodium hydrate (JAN) Anatomical Therapeuti...SE J05A DIRECT ACTING ANTIVIRALS J05AD Phosphonic acid derivatives J05AD01 Foscarnet D02267 Foscar...net sodium hydrate (JAN) USP drug classification [BR:br08302] Antivirals Anti-cytomegalovirus (CMV) Agents Foscar...net D02267 Foscarnet sodium hydrate (JAN) Antiherpetic Agents Foscarnet D02267 Foscarn

  11. The Antiviral Activity of Approved and Novel Drugs against HIV-1 Mutations Evaluated under the Consideration of Dose-Response Curve Slope.

    Directory of Open Access Journals (Sweden)

    Shuai Chang

    Full Text Available This study was designed to identify common HIV-1 mutation complexes affecting the slope of inhibition curve, and to propose a new parameter incorporating both the IC50 and the slope to evaluate phenotypic resistance.Utilizing site-directed mutagenesis, we constructed 22 HIV-1 common mutation complexes. IC50 and slope of 10 representative approved drugs and a novel agent against these mutations were measured to determine the resistance phenotypes. The values of new parameter incorporating both the IC50 and the slope of the inhibition curve were calculated, and the correlations between parameters were assessed.Depending on the class of drug, there were intrinsic differences in how the resistance mutations affected the drug parameters. All of the mutations resulted in large increases in the IC50s of nucleoside reverse transcriptase inhibitors. The effects of the mutations on the slope were the most apparent when examining their effects on the inhibition of non-nucleoside reverse transcriptase inhibitors and protease inhibitors. For example, some mutations, such as V82A, had no effect on IC50, but reduced the slope. We proposed a new concept, termed IIPatoxic, on the basis of IC50, slope and the maximum limiting concentrations of the drug. The IIPatoxic values of 10 approved drugs and 1 novel agent were calculated, and were closely related to the IIPmax values (r > 0.95, p < 0.001.This study confirms that resistance mutations cannot be accurately assessed by IC50 alone, because it tends to underestimate the degree of resistance. The slope parameter is of very importance in the measurement of drug resistance and the effect can be applied to more complex patterns of resistance. This is the most apparent when testing the effects of the mutations on protease inhibitors activity. We also propose a new index, IIPatoxic, which incorporates both the IC50 and the slope. This new index could complement current IIP indices, thereby enabling predict the

  12. Evaluation of the in vitro skin permeation of antiviral drugs from penciclovir 1% cream and acyclovir 5% cream used to treat herpes simplex virus infection

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    Bader Marlene

    2009-04-01

    Full Text Available Abstract Background Herpes simplex virus infection (HSV is a common and ubiquitous infection of the skin which causes mucocutaneous lesions called cold sores (herpes labialis or fever blisters. It is estimated that approximately 80% of the population worldwide are carriers of the Herpes simplex virus, approximately 40% suffer from recurrent recurrent infections. This study evaluates the in vitro skin permeation and penetration of penciclovir and acyclovir from commercialized creams for the treatment of herpes labialis (cold sores, using non viable excised human abdominal skin samples, which were exposed to 5 mg/cm2 of acyclovir 5% cream or penciclovir 1% cream. Methods After 24 h of cream application, excess cream was washed off and layers of stratum corneum were removed by successive tape stripping. Amounts of active ingredients having penetrated through the skin were measured, as well as the amounts in the washed-off cream, in skin strips and creams remaining in the skin. Molecular modelling was used to evaluate physico-chemical differences between the drugs. Western blot analysis enabled to determine whether the marker of basal cells keratin 5 could be detected in the various tape strips. Results Application of penciclovir 1% cream yielded higher concentration of drug in the deeper layers of the epidermis as well as a higher drug flux through the skin. Molecular modelling showed two higher hydrophobic moieties for acyclovir. Presence of the basal cell marker keratin 5 was underscored in the deeper tape strips from the skin, giving evidence that both drugs can reach their target cells. Conclusion Penciclovir 1% cream has the tendency to facilitate the diffusion of the drug through the stratum corneum into the deeper epidermis layers, in which it could reach the target basal cells at effective therapeutical concentration. The small difference in the surface properties between both molecules might also contribute to favour the passage of

  13. Evolution and Spread of Influenza Virus and Progress on Antiviral Drugs and Vaccines%流感病毒的演变传播及抗病毒药物和疫苗的研究进展

    Institute of Scientific and Technical Information of China (English)

    陈执中

    2009-01-01

    The influenza virus is an infectious virus in mankind. After the storm of influenza across the world in 1918, that is nightmare incessantly now. In this article, the evolution and spread of itinerary map of influenza virus are reviewed. Additionally, the progress on unique 'cap-snatching' mechanism, antiviral drugs and vaccines are also introduced. The applications of neuraminidase inhibitors and the developments of new influenza vaccines will open up broad prospects for the prevention and therapy of influenza.%流感病毒是引起人类流感的传染性病毒.1918年流感风暴席卷全球,至今仍为挥之不去的梦魇.本文综述了流感病毒的演变,在世界的传播路线和流感病毒"劫持"人体细胞的新机制,以及抗流感病毒新药和新型流感疫苗的研究进展.神经氨酸苷酶抑制剂的应用和新型流感疫苗的研制成功将为预防和治疗流感开拓广阔的前景.

  14. Dancing with chemical formulae of antivirals: A panoramic view (Part 2).

    Science.gov (United States)

    De Clercq, Erik

    2013-11-15

    In this second part of "Dancing with antivirals as chemical formulae" I will focus on a number of chemical compounds that in the last few years have elicited more than common attraction from a commercial viewpoint: (i) favipiravir (T-705), as it is active against influenza, but also several other RNA viruses; (ii) neuraminidase inhibitors such as zanamivir and oseltamivir; (iii) peramivir and laninamivir octanoate, which might be effective against influenza virus following a single (intravenous or inhalation) administration; (iv) sofosbuvir, the (anticipated) cornerstone for the interferon-free therapy of HCV infections; (v) combinations of DAAs (direct antiviral agents) to achieve, in no time, a sustained virus response (SVR) against HCV infection; (vi) HIV protease inhibitors, the latest and most promising being darunavir; (vii) the integrase inhibitors (INIs) (raltegravir, elvitegravir, dolutegravir), representing a new dimension in the anti-HIV armamentarium; (viii), a new class of helicase primase inhibitors (HPIs) that may exceed acyclovir and the other anti-herpes compounds in both potency and safety; (ix) CMX-001, as the latest of Dr. Antonín Holý's legacy for its activity against poxviruses and CMV infections, and (x) noroviruses for which the ideal antiviral compounds are still awaited for. PMID:24070654

  15. Perspective of Use of Antiviral Peptides against Influenza Virus.

    Science.gov (United States)

    Skalickova, Sylvie; Heger, Zbynek; Krejcova, Ludmila; Pekarik, Vladimir; Bastl, Karel; Janda, Jozef; Kostolansky, Frantisek; Vareckova, Eva; Zitka, Ondrej; Adam, Vojtech; Kizek, Rene

    2015-10-01

    The threat of a worldwide influenza pandemic has greatly increased over the past decade with the emergence of highly virulent avian influenza strains. The increased frequency of drug-resistant influenza strains against currently available antiviral drugs requires urgent development of new strategies for antiviral therapy, too. The research in the field of therapeutic peptides began to develop extensively in the second half of the 20(th) century. Since then, the mechanisms of action for several peptides and their antiviral prospect received large attention due to the global threat posed by viruses. Here, we discussed the therapeutic properties of peptides used in influenza treatment. Peptides with antiviral activity against influenza can be divided into three main groups. First, entry blocker peptides such as a Flupep that interact with influenza hemagglutinin, block its binding to host cells and prevent viral fusion. Second, several peptides display virucidal activity, disrupting viral envelopes, e.g., Melittin. Finally, a third set of peptides interacts with the viral polymerase complex and act as viral replication inhibitors such as PB1 derived peptides. Here, we present a review of the current literature describing the antiviral activity, mechanism and future therapeutic potential of these influenza antiviral peptides. PMID:26492266

  16. Perspective of Use of Antiviral Peptides against Influenza Virus

    Directory of Open Access Journals (Sweden)

    Sylvie Skalickova

    2015-10-01

    Full Text Available The threat of a worldwide influenza pandemic has greatly increased over the past decade with the emergence of highly virulent avian influenza strains. The increased frequency of drug-resistant influenza strains against currently available antiviral drugs requires urgent development of new strategies for antiviral therapy, too. The research in the field of therapeutic peptides began to develop extensively in the second half of the 20th century. Since then, the mechanisms of action for several peptides and their antiviral prospect received large attention due to the global threat posed by viruses. Here, we discussed the therapeutic properties of peptides used in influenza treatment. Peptides with antiviral activity against influenza can be divided into three main groups. First, entry blocker peptides such as a Flupep that interact with influenza hemagglutinin, block its binding to host cells and prevent viral fusion. Second, several peptides display virucidal activity, disrupting viral envelopes, e.g., Melittin. Finally, a third set of peptides interacts with the viral polymerase complex and act as viral replication inhibitors such as PB1 derived peptides. Here, we present a review of the current literature describing the antiviral activity, mechanism and future therapeutic potential of these influenza antiviral peptides.

  17. Triple Combination of Oseltamivir, Amantadine, and Ribavirin Displays Synergistic Activity against Multiple Influenza Virus Strains In Vitro ▿

    OpenAIRE

    Nguyen, Jack T.; Justin D Hoopes; Smee, Donald F.; Prichard, Mark N.; Driebe, Elizabeth M; Engelthaler, David M.; Le, Minh H.; Keim, Paul S; Spence, R. Paul; Went, Gregory T.

    2009-01-01

    The recurring emergence of influenza virus strains that are resistant to available antiviral medications has become a global health concern, especially in light of the potential for a new influenza virus pandemic. Currently, virtually all circulating strains of influenza A virus in the United States are resistant to either of the two major classes of anti-influenza drugs (adamantanes and neuraminidase inhibitors). Thus, new therapeutic approaches that can be rapidly deployed and that will add...

  18. [Antiviral properties of basidiomycetes metabolites].

    Science.gov (United States)

    Avtonomova, A V; Krasnopolskaya, L M

    2014-01-01

    The data on the antiviral action of the Ganoderma lucidum, Lentinus edodes, Grifola frondosa, Agaricus brasiliensis and other basidiomycetes metabolites are summurized. The metabolites of these species of basidiomycetes exhibit a direct antiviral effect on herpes simplex virus types I and II, human immunodeficiency virus (HIV), hepatitis B virus, vesicular stomatitis virus, influenza virus, Epstein-Barr virus, and others. Moreover, metabolites of basidiomycetes increased antiviral immunity. PMID:25975107

  19. Antiviral agents against equid alphaherpesviruses: Current status and perspectives.

    Science.gov (United States)

    Vissani, María A; Thiry, Etienne; Dal Pozzo, Fabiana; Barrandeguy, María

    2016-01-01

    Equid herpesvirus infections cause respiratory, neurological and reproductive syndromes. Despite preventive and control measures and the availability of vaccines and immunostimulants, herpesvirus infections still constitute a major threat to equine health and for the equine industry worldwide. Antiviral drugs, particularly nucleoside analogues and foscarnet, are successfully used for the treatment of human alphaherpesvirus infections. In equine medicine, the use of antiviral medications in alphaherpesvirus infections would decrease the excretion of virus and diminish the risk of contagion and the convalescent time in affected horses, and would also improve the clinical outcome of equine herpesvirus myeloencephalopathy. The combined use of antiviral compounds, along with vaccines, immune modulators, and effective preventive and control measures, might be beneficial in diminishing the negative impact of alphaherpesvirus infections in horses. The purpose of this review is to analyse the available information regarding the use of antiviral agents against alphaherpesviruses, with particular emphasis on equine alphaherpesvirus infections. PMID:26654843

  20. Oseltamivir (Tamiflu-induced bilateral acute angle closure glaucoma and transient myopia

    Directory of Open Access Journals (Sweden)

    Ji Woong Lee

    2014-01-01

    Full Text Available A 27-year-old woman developed bilateral acute angle closure glaucoma (AACG and transient myopia after taking oseltamivir for four days. On the fourth day, she received systemic and topical intraocular pressure (IOP-lowering agents, and IOP decreased in both eyes. However, her visual acuity was unchanged. A myopic shift of -5.25 D OD and -5.0 D OS was estimated to have occurred in the acute phase. A-scan ultrasonography and Pentacam showed markedly shallow anterior chambers and increased lens thickness. Ultrasound biomicroscopy revealed an annular ciliochoroidal effusion with forward displacement of the lens-iris diaphragm. Ciliochoroidal effusion and transient myopia were resolved after discontinuation of oseltamivir.

  1. Is Minocycline an Antiviral Agent? A Review of Current Literature.

    Science.gov (United States)

    Nagarakanti, Sandhya; Bishburg, Eliahu

    2016-01-01

    Minocycline is a second-generation semi-synthetic derivative of tetracycline and has well-known anti-bacterial effects. The drug possesses anti-inflammatory, anti-oxidant, anti-apoptotic and immunomodulatory effects. The drug is widely used in bacterial infections and non-infectious conditions such as acne, dermatitis, periodontitis and neurodegenerative conditions. Minocycline was shown to have antiviral activity in vitro and also against different viruses in some animal models. Some studies have been done on human patients infected with Human Immunodeficiency Virus. We have review the available data regarding minocycline activity as an antiviral agent. PMID:26177421

  2. Severe human influenza infections in Thailand: oseltamivir treatment and risk factors for fatal outcome.

    Directory of Open Access Journals (Sweden)

    Wanna Hanshaoworakul

    Full Text Available BACKGROUND: Influenza is often not recognized as an important cause of severe or fatal disease in tropical and subtropical countries in Southeast Asia. The extent to which Oseltamivir treatment may protect against a fatal outcome in severe influenza infections is not known. Thailand's National Avian Influenza Surveillance (NAIS system affords a unique opportunity to describe the epidemiology of laboratory-confirmed severe and fatal human influenza infections. METHODOLOGY/PRINCIPAL FINDINGS: During January 2004 through December 2006, 11,641 notifications to the NAIS were investigated in 73 of 76 Thai provinces. Clinical and demographic data and respiratory swab specimens were collected and tested by PCR for influenza. Using the NAIS database, we identified all patients with laboratory confirmed human influenza (A/H3N2, A/H1N1 and Type B infection. A retrospective medical record review was conducted on all fatal cases with laboratory confirmed influenza and from a sample of hospitalized cases in 28 provinces. The association of underlying risk factors, Oseltamivir treatment and risk of a fatal outcome were examined. Human influenza infections were identified in 2,075 (18% cases. Twenty-two (1% deaths occurred including seven deaths in children less than ten years of age. Thirty-five percent of hospitalized human influenza infections had chest X-ray confirmed pneumonia. Current or former smoking; advanced age, hypertension and underlying cardiovascular, pulmonary or endocrine disease were associated with a fatal outcome from human influenza infection. Treatment with Oseltamivir was statistically associated with survival with a crude OR of .11 (95% CI: 0.04-0.30 and .13 (95% CI: 0.04-0.40 after controlling for age. CONCLUSIONS: Severe and fatal human influenza infections were commonly identified in the NAIS designed to identify avian A/H5N1 cases. Treatment with Oseltamivir is associated with survival in hospitalized human influenza pneumonia

  3. The study of bioavailability and bioequivalence of oseltamivir in Chinese health volunteers

    Institute of Scientific and Technical Information of China (English)

    LI Jing-lai; CUI Meng-cun; WANG Xiao-ying; QIAO Jian-zhong; YUAN Su-lan; ZHANG Zhen-qing; RUAN Jin-xiu; ZHONG Wu; LI Song

    2008-01-01

    Objective To evaluate the bioavailability and bioequivalence of oseltamivir capsule in Chinese health male volunteers. Methods A randomized, two period, two treatment, two sequence crossover bioequivalence trial was designed, 24 Chinese health volunteers were randomly divided into two groups, each group was orally given single dose oseltamivir phosphate (tamifla) or AMMS 607 capsule. The active metabolite oseltamivir carboxylate of oseltamivir in the plasma were determined by liquid chromatographic-tandem mass spectrometric (LC-MS/MS) method. The pharmacokinetics parameters and relative bioavailability were calculated to evaluate the bioequivalence of AMMS 607 and tamifla. Results Cmax of the AMMS 607 and tamifla were 602.07±153.27 ng·mL-1 and 620.09±132.39 ng·mL-1 respectively; tmax were 4.2± 1.1 h and 4.8±1.0 h; t1/2β were 6.60±0.87 h and 6.61±0.83 h;MRT were 10.00±1.77 h and 10.40 ±1.62 h; AUC0-24 were 6285.88±1083.66 ng·h·mL-1 and 6546.01±1199.32 ng·h·mL-1; Compared with the reference of tamifla capsule, the bioavailability F0-tn of AMMS 607 capsule was 99.5±27.7 %. The main pharmacokinetics parameters of AUC0-24, Cmax and Tmax showed no statistically significant difference between the two capsules. Conclusions The AMMS 607 capsule and tamifla capsule are bioequivalent.

  4. Influenza A(H1N1)pdm09 virus exhibiting enhanced cross-resistance to oseltamivir and peramivir due to a dual H275Y/G147R substitution, Japan, March 2016.

    Science.gov (United States)

    Takashita, Emi; Fujisaki, Seiichiro; Shirakura, Masayuki; Nakamura, Kazuya; Kishida, Noriko; Kuwahara, Tomoko; Shimazu, Yukie; Shimomura, Takeshi; Watanabe, Shinji; Odagiri, Takato

    2016-06-16

    An influenza A(H1N1)pdm09 virus carrying a G147R substitution in combination with an H275Y substitution in the neuraminidase protein, which confers cross-resistance to oseltamivir and peramivir, was detected from an immunocompromised inpatient in Japan, March 2016. This dual H275Y/G147R mutant virus exhibited enhanced cross-resistance to both drugs compared with the single H275Y mutant virus and reduced susceptibility to zanamivir, although it showed normal inhibition by laninamivir. PMID:27336226

  5. Neuropsychiatric Effects of HIV Antiviral Medications.

    Science.gov (United States)

    Treisman, Glenn J; Soudry, Olivia

    2016-10-01

    The development of antiretroviral therapy (ART) has dramatically increased the lifespan of HIV patients but treatment is complicated by numerous adverse effects and toxicities. ART complications include neuropsychiatric, metabolic, gastrointestinal, cardiac, and numerous other toxicities, and clinicians often have to choose one toxicity over another to offer the best medication regimen for a patient. Some antiviral drugs cause significant neuropsychiatric complications, including depression, cognitive impairment, and sleep disturbance. Even in careful studies, it may be difficult to determine which effects are related to the virus, the immune system, or the treatment. Of the six currently marketed classes of antiviral drugs, the nucleoside reverse transcriptase inhibitors and the non-nucleoside reverse transcriptase inhibitors have been most commonly associated with neuropsychiatric complications. Within these classes, certain drugs are more likely to cause difficulty than others. We review the contention regarding the central nervous system (CNS) complications of efavirenz, as well as debate about the role of CNS penetration in drug effectiveness and toxicity. A thorough working knowledge of the neuropsychiatric consequences of ART allows clinicians to tailor treatment more successfully to individual patients as well as to identify ART more quickly as the source of a problem or symptom. PMID:27534750

  6. Drug: D10469 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available 9 D10469.gif Treatment of hepatitis C [DS:H00413] Therapeutic category: 6250 Macrocyclic antivirus Direct-ac...tics 625 Antivirals 6250 Antivirals D10469 Simeprevir sodium (JAN) USP drug classification [BR:br08302] Antivirals Anti-hepatitis

  7. Age-prioritized use of antivirals during an influenza pandemic

    Directory of Open Access Journals (Sweden)

    Ajelli Marco

    2009-07-01

    Full Text Available Abstract Background The WHO suggested that governments stockpile, as part of preparations for the next influenza pandemic, sufficient influenza antiviral drugs to treat approximately 25% of their populations. Our aim is two-fold: first, since in many countries the antiviral stockpile is well below this level, we search for suboptimal strategies based on treatment provided only to an age-dependent fraction of cases. Second, since in some countries the stockpile exceeds the suggested minimum level, we search for optimal strategies for post-exposure prophylactic treatment of close contacts of cases. Methods We used a stochastic, spatially structured individual-based model, considering explicit transmission in households, schools and workplaces, to simulate the spatiotemporal spread of an influenza pandemic in Italy and to evaluate the efficacy of interventions based on age-prioritized use of antivirals. Results Our results show that the antiviral stockpile required for treatment of cases ranges from 10% to 35% of the population for R0 in 1.4 – 3. No suboptimal strategies, based on treatment provided to an age-dependent fraction of cases, were found able to remarkably reduce both clinical attack rate and antiviral drugs needs, though they can contribute to largely reduce the excess mortality. Treatment of all cases coupled with prophylaxis provided to younger individuals is the only intervention resulting in a significant reduction of the clinical attack rate and requiring a relatively small stockpile of antivirals. Conclusion Our results strongly suggest that governments stockpile sufficient influenza antiviral drugs to treat approximately 25% of their populations, under the assumption that R0 is not much larger than 2. In countries where the number of antiviral stockpiled exceeds the suggested minimum level, providing prophylaxis to younger individuals is an option that could be taken into account in preparedness plans. In countries where the

  8. Emerging trends, confront and scenario in healthcare and antiviral development for infectious diseases

    Directory of Open Access Journals (Sweden)

    Mishra N

    2011-09-01

    Full Text Available Health defines the state of being free from illness, infection or injury and healthcare performs the diagnosis, treatment and prevention of such anomalies. Infectious diseases are well known since ancient time to human civilization and put heavy toll on social health as well as healthcare system. Among different infections agents viruses are the most notorious ones. Even in 21st century word, virus creates a panic in well educated society and among healthcare professionals. This causes unnecessary havoc, limited help to the patients and malfunctioning of healthcare system. The scuffle between the viruses and the humans is unremitting process and both are continuously changing their combating strategies to succeed. Our increasing knowledge about viruses, mechanism of their infections and the rapid involvement of novel antiviral strategies and techniques has enabled us to develop various antivirals. Development of antiviral is very costly, complex, risky, tedious, time consuming and multistage process. Inspite of recent development in technology, identification of novel antivirals and stern regulation in quality control measures; till date there is no fool proof treatment (vaccines and drugs available against viruses and due to viral resistance and/or drug toxicity, the rate of antiviral drugs coming to the market for human application is very low probably. Therefore, this review is mainly based on global view of antiviral discovery including classification of antiviral, its developmental stages, current advancements in upcoming technologies and limitations of the antiviral drug development in last five decades as well as future challenges and briefly on emerging problems in healthcare.

  9. The significance of naturally occurring neuraminidase quasispecies of H5N1 avian influenza virus on resistance to oseltamivir: a point of concern.

    Science.gov (United States)

    Schaduangrat, Nalini; Phanich, Jiraphorn; Rungrotmongkol, Thanyada; Lerdsamran, Hatairat; Puthavathana, Pilaipan; Ubol, Sukathida

    2016-06-01

    Viral adaptability and survival arise due to the presence of quasispecies populations that are able to escape the immune response or produce drug-resistant variants. However, the presence of H5N1 virus with natural mutations acquired without any drug selection pressure poses a great threat. Cloacal samples collected from the 2004-2005 epidemics in Thailand from Asian open-billed storks revealed one major and several minor quasispecies populations with mutations on the oseltamivir (OTV)-binding site of the neuraminidase gene (NA) without prior exposure to a drug. Therefore, this study investigated the binding between the NA-containing novel mutations and OTV drug using molecular dynamic simulations and plaque inhibition assay. The results revealed that the mutant populations, S236F mutant, S236F/C278Y mutant, A250V/V266A/P271H/G285S mutant and C278Y mutant, had a lower binding affinity with OTV as compared with the WT virus due to rearrangement of amino acid residues and increased flexibility in the 150-loop. This result was further emphasized through the IC50 values obtained for the major population and WT virus, 104.74 nM and 18.30 nM, respectively. Taken together, these data suggest that H5N1 viruses isolated from wild birds have already acquired OTV-resistant point mutations without any exposure to a drug. PMID:26935590

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

    Directory of Open Access Journals (Sweden)

    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.

  11. Glucosidase inhibitors as antiviral agents for hepatitis B and C.

    Science.gov (United States)

    Durantel, David; Alotte, Christine; Zoulim, Fabien

    2007-02-01

    HBV and HCV infections are a major public health concern. New antiviral drugs are urgently needed with improved efficacy. Compounds that specifically target viral enzymes are the most attractive in terms of drug development and are therefore the most studied. However, antiviral strategies based entirely on this class of compounds encounter problems caused by the emergence of viral escape mutants, as already widely described for HIV. One way to prevent or delay viral resistance is to combine antiviral agents that target different steps of the virus life cycle. Future therapy may also combine such virus-specific antivirals with compounds targeting host proteins or functions. In this respect, viral morphogenesis and infectivity represent interesting, and still unexploited, novel molecular targets. Endoplasmic reticulum glucosidase inhibitors have demonstrated anti-HBV and anti-HCV properties by inhibiting viral morphogenesis and infectivity. One such compound, celgosivir, is currently being evaluated in clinical trials against HCV infection, and encouraging phase IIa data have been disclosed. This review will discuss HBV and HCV morphogenesis, with a particular focus on the role of N-glycosylation for viral protein folding and assembly, and will present the antiviral properties of glucosidase inhibitors. PMID:17328228

  12. Screening for antiviral activities of isolated compounds from essential oils.

    Science.gov (United States)

    Astani, Akram; Reichling, Jürgen; Schnitzler, Paul

    2011-01-01

    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. PMID:20008902

  13. In silico analysis to compare the effectiveness of assorted drugs prescribed for swine flu in diverse medicine systems

    Directory of Open Access Journals (Sweden)

    Kalpana Raja

    2014-01-01

    Full Text Available The genome of the virus H1N1 2009 consists of eight segments but maximum number of mutations occurs at segments 1 and 4, coding for PB2 subunit of hemagglutinin. Comparatively less number of mutations occur at segment 6, coding for neuraminidase. Two antiviral drugs, oseltamivir and zanamivir are commonly prescribed for treating H1N1 infection. Alternate medical systems do compete equally; andrographolide in Siddha and gelsemine in Homeopathy. Recent studies confirm the efficacy of eugenol from Tulsi and vitamins C and E against H1N1. As the protein structures are unavailable, we modeled them using Modeller by identifying suitable templates, 1RUY and 3BEQ, for hemagglutinin and neuraminidase, respectively. Prior to docking simulations using AutoDock, the drug likeness properties of the ligands were screened using in silico techniques. Docking results showed interaction between the proteins individually into selected ligands, except for gelsemine and vitamin E no interactions were shown. The best docking simulation was reported by vitamin C interacting through six hydrogen bonds into proteins hemagglutinin and neuraminidase with binding energies -4.28 and -4.56 kcal/mol, respectively. Furthermore, vitamin C showed hydrophobic interactions with both proteins, two bonds with Arg119, Glu120 of HA, and one bond with Arg74 of NA. In silico docking studies thus recommend vitamin C to be more effective against H1N1.

  14. In Silico Analysis to Compare the Effectiveness of Assorted Drugs Prescribed for Swine flu in Diverse Medicine Systems

    Science.gov (United States)

    Raja, Kalpana; Prabahar, Archana; Selvakumar, Suganya; Raja, T. K.

    2014-01-01

    The genome of the virus H1N1 2009 consists of eight segments but maximum number of mutations occurs at segments 1 and 4, coding for PB2 subunit of hemagglutinin. Comparatively less number of mutations occur at segment 6, coding for neuraminidase. Two antiviral drugs, oseltamivir and zanamivir are commonly prescribed for treating H1N1 infection. Alternate medical systems do compete equally; andrographolide in Siddha and gelsemine in Homeopathy. Recent studies confirm the efficacy of eugenol from Tulsi and vitamins C and E against H1N1. As the protein structures are unavailable, we modeled them using Modeller by identifying suitable templates, 1RUY and 3BEQ, for hemagglutinin and neuraminidase, respectively. Prior to docking simulations using AutoDock, the drug likeness properties of the ligands were screened using in silico techniques. Docking results showed interaction between the proteins individually into selected ligands, except for gelsemine and vitamin E no interactions were shown. The best docking simulation was reported by vitamin C interacting through six hydrogen bonds into proteins hemagglutinin and neuraminidase with binding energies -4.28 and -4.56 kcal/mol, respectively. Furthermore, vitamin C showed hydrophobic interactions with both proteins, two bonds with Arg119, Glu120 of HA, and one bond with Arg74 of NA. In silico docking studies thus recommend vitamin C to be more effective against H1N1. PMID:24799734

  15. Antiviral medication in sexually transmitted diseases. Part I: HSV, HPV.

    Science.gov (United States)

    Mlynarczyk-Bonikowska, Beata; Majewska, Anna; Malejczyk, Magdalena; Mlynarczyk, Grazyna; Majewski, Slawomir

    2013-11-01

    Sexually transmitted diseases (STD) are one of the most prevalent infectious diseases in the world and important cause of morbidity and mortality. Especially STDs of viral etiology are difficult to cure. In many cases the antiviral therapy can relieve the symptoms but not eliminate the virus. During the past decades, considerable progress has been made in the development of antiviral drugs. One of the oldest antiviral medications is acyclovir (ACV). It is approved to treat initial and recurrent genital herpes and as a suppressive therapy in severe recurrent genital infections as well. Drug resistance to ACV and related drugs is seen among immunocompromised hosts, including human immunodeficiency virus HIV-infected patients. Resistant infections can be managed by second-line drugs - foscarnet or cidofovir- but they are more toxic than ACV. In case of HPV there is not known specific target for the medication and that is why the substances used in human papilloma virus HPV infection therapy are either antimitotics or immunomodulators. The Part I review focuses on mechanisms of actions and mechanisms of resistance to antiviral agents used in a treatment of the genital herpes and genital HPV infection. In Part II we will show the therapeutic options in other sexually transmitted infections: hepatitis B, C and HIV. PMID:24032509

  16. 6-azacytidine--compound with wide spectrum of antiviral activity.

    Science.gov (United States)

    Alexeeva, I; Dyachenko, N; Nosach, L; Zhovnovataya, V; Rybalko, S; Lozitskaya, R; Fedchuk, A; Lozitsky, V; Gridina, T; Shalamay, A; Palchikovskaja, L; Povnitsa, O

    2001-01-01

    6-azacytidine demonstrates activity against adenoviruses types 1, 2, 5. It inhibit synthesis of viral DNA and proteins. 6-AC shows antiherpetic and antiinfluenza action during experimental infection in mice. 6-AC is prospective for drug development as an antiviral substance with a wide spectrum of activity. PMID:11562975

  17. Antiviral therapy: a perspective

    Directory of Open Access Journals (Sweden)

    Shahidi Bonjar AH

    2016-02-01

    s recovery to a large extent depends on their general health status. EVAC would be for single use and appropriately disposed of after each detoxification procedure. When sufficient research has yielded positive results in animal models, EVAC could be used as a supportive treatment in humans along with conventional antiviral therapies. EVAC would not be suitable for all viral infections, but could be expected to decrease the casualties resulting from blood-borne viral infections. The EVAC approach would be efficient in terms of time, effort, and expenditure in the research and treatment of blood-borne viral infections. Keywords: blood, virus, infection, antiviral, sepsis, HIV, Ebola

  18. 抗流感病毒药物神经氨酸酶抑制剂奥司他韦研究进展%Research progress on oseltamivir-one of influenza neuraminidase inhibitors

    Institute of Scientific and Technical Information of China (English)

    张玲; 魏绍静

    2011-01-01

    The outbreak of highly pathogenic avian influenza H5N1 in Asia and the global spread of new type 2009 H1N1,implies that to design and explore new anti-influenza drugs is quite urgent.Neuraminidase(NA) plays an important role in influenza virus reproduction and dissemination,furthermore the active center of NA is highly conservative,so the research on influenza NA inhibitors has been greatly concerned.This article reviews the research progress on pharmacodynamics,pharmacokinetics and drug resistance of oseltamivir,providing advices for its future application in clinic.%高致病性禽流感H 5N1病毒在亚州的爆发和2009新型H1N1病毒的全球性传播,提示设计与研发新型的抗流感药物尤为迫切.神经氨酸酶在病毒复制和传播中发挥重要作用,且活性中心高度保守,其抑制剂成为抗流感药物研发的热点.该文回顾了临床广泛使用的奥司他韦(oseltamivir)药动学、药效学及耐药性方面的研究进展,为此药今后的临床应用提出建议.

  19. Development of antiviral agents toward enterovirus 71 infection.

    Science.gov (United States)

    Pourianfar, Hamid Reza; Grollo, Lara

    2015-02-01

    Enterovirus 71 (EV71) infection remains a public health problem at a global level, particularly in the Asia-Pacific region. The infection normally manifests as hand-foot-mouth disease; however, it is capable of developing into potentially fatal neurological complications. There is currently no approved vaccine or antiviral substance available for the prevention or treatment of EV71 infection. This paper, thus, reviews efforts to develop or discover synthetic as well as naturally occurring compounds directed against EV71 infection. The recent achievements in cellular receptors of EV71 are also highlighted, and their contribution to the development of antiviral drugs against EV71 is discussed in this article. PMID:24560700

  20. Novel four-drug salvage treatment regimens after failure of a human immunodeficiency virus type 1 protease inhibitor-containing regimen: antiviral activity and correlation of baseline phenotypic drug susceptibility with virologic outcome.

    Science.gov (United States)

    Deeks, S G; Hellmann, N S; Grant, R M; Parkin, N T; Petropoulos, C J; Becker, M; Symonds, W; Chesney, M; Volberding, P A

    1999-06-01

    Twenty human immunodeficiency virus-infected patients experiencing virologic failure of an indinavir- or ritonavir-containing treatment regimen were evaluated in a prospective, open-label study. Subjects received nelfinavir, saquinavir, abacavir, and either another nucleoside analog (n=10) or nevirapine (n=10). Patients treated with the nevirapine-containing regimen experienced significantly greater virologic suppression at week 24 than those not treated with nevirapine (P=.04). Baseline phenotypic drug susceptibility was strongly correlated with outcome in both treatment arms. Subjects with baseline virus phenotypically sensitive to 2 or 3 drugs in the salvage regimen experienced significantly greater virus load suppression than those with baseline virus sensitive to 0 or 1 drug (median week-24 change=-2.24 log and -0.35 log, respectively; P=.01). In conclusion, non-nucleoside reverse transcriptase inhibitors may represent a potent drug in salvage therapy regimens after failure of an indinavir or ritonavir regimen. Phenotypic resistance testing may provide a useful tool for selecting more effective salvage regimens. PMID:10228057

  1. Exploiting Genetic Interference for Antiviral Therapy

    Science.gov (United States)

    Kirkegaard, Karla A.; Weinberger, Leor S.

    2016-01-01

    Rapidly evolving viruses are a major threat to human health. Such viruses are often highly pathogenic (e.g., influenza virus, HIV, Ebola virus) and routinely circumvent therapeutic intervention through mutational escape. Error-prone genome replication generates heterogeneous viral populations that rapidly adapt to new selection pressures, leading to resistance that emerges with treatment. However, population heterogeneity bears a cost: when multiple viral variants replicate within a cell, they can potentially interfere with each other, lowering viral fitness. This genetic interference can be exploited for antiviral strategies, either by taking advantage of a virus’s inherent genetic diversity or through generating de novo interference by engineering a competing genome. Here, we discuss two such antiviral strategies, dominant drug targeting and therapeutic interfering particles. Both strategies harness the power of genetic interference to surmount two particularly vexing obstacles—the evolution of drug resistance and targeting therapy to high-risk populations—both of which impede treatment in resource-poor settings. PMID:27149616

  2. Exploiting Genetic Interference for Antiviral Therapy.

    Science.gov (United States)

    Tanner, Elizabeth J; Kirkegaard, Karla A; Weinberger, Leor S

    2016-05-01

    Rapidly evolving viruses are a major threat to human health. Such viruses are often highly pathogenic (e.g., influenza virus, HIV, Ebola virus) and routinely circumvent therapeutic intervention through mutational escape. Error-prone genome replication generates heterogeneous viral populations that rapidly adapt to new selection pressures, leading to resistance that emerges with treatment. However, population heterogeneity bears a cost: when multiple viral variants replicate within a cell, they can potentially interfere with each other, lowering viral fitness. This genetic interference can be exploited for antiviral strategies, either by taking advantage of a virus's inherent genetic diversity or through generating de novo interference by engineering a competing genome. Here, we discuss two such antiviral strategies, dominant drug targeting and therapeutic interfering particles. Both strategies harness the power of genetic interference to surmount two particularly vexing obstacles-the evolution of drug resistance and targeting therapy to high-risk populations-both of which impede treatment in resource-poor settings. PMID:27149616

  3. Exploiting Genetic Interference for Antiviral Therapy.

    Directory of Open Access Journals (Sweden)

    Elizabeth J Tanner

    2016-05-01

    Full Text Available Rapidly evolving viruses are a major threat to human health. Such viruses are often highly pathogenic (e.g., influenza virus, HIV, Ebola virus and routinely circumvent therapeutic intervention through mutational escape. Error-prone genome replication generates heterogeneous viral populations that rapidly adapt to new selection pressures, leading to resistance that emerges with treatment. However, population heterogeneity bears a cost: when multiple viral variants replicate within a cell, they can potentially interfere with each other, lowering viral fitness. This genetic interference can be exploited for antiviral strategies, either by taking advantage of a virus's inherent genetic diversity or through generating de novo interference by engineering a competing genome. Here, we discuss two such antiviral strategies, dominant drug targeting and therapeutic interfering particles. Both strategies harness the power of genetic interference to surmount two particularly vexing obstacles-the evolution of drug resistance and targeting therapy to high-risk populations-both of which impede treatment in resource-poor settings.

  4. [Antiviral activity of aqueous extracts of the birch fungus Inonotus obliquus on the human immunodeficiency virus].

    Science.gov (United States)

    Shibnev, V A; Garaev, T M; Finogenova, M P; Kalnina, L B; Nosik, D N

    2015-01-01

    Fractions of aqueous and water-alcohol extracts of the birch fungus Inonotus obliquus have antiviral effect against the human immunodeficiency virus type 1 (HIV-1). Antiviral properties of low toxic extracts were manifested in the concentration of 5.0 μg/ml upon simultaneous application with the virus in the lymphoblastoid cells culture MT-4. The extract of the birch fungus can be used for development of new antiviral drugs, inhibitors of HIV-replication when used both in the form of individual drugs and as a part of complex therapy. PMID:26182655

  5. Oseltamivir-resistant influenza A(H1N1pdm09 virus in southern Brazil

    Directory of Open Access Journals (Sweden)

    Camila Marx

    2013-05-01

    Full Text Available The neuraminidase (NA genes of A(H1N1pdm09 influenza virus isolates from 306 infected patients were analysed. The circulation of oseltamivir-resistant viruses in Brazil has not been reported previously. Clinical samples were collected in the state of Rio Grande do Sul (RS from 2009-2011 and two NA inhibitor-resistant mutants were identified, one in 2009 (H275Y and the other in 2011 (S247N. This study revealed a low prevalence of resistant viruses (0.8% with no spread of the resistant mutants throughout RS.

  6. Liposomal Systems as Nanocarriers for the Antiviral Agent Ivermectin

    Science.gov (United States)

    Croci, Romina; Bottaro, Elisabetta; Chan, Kitti Wing Ki; Watanabe, Satoru; Pezzullo, Margherita; Mastrangelo, Eloise; Nastruzzi, Claudio

    2016-01-01

    RNA virus infections can lead to the onset of severe diseases such as fever with haemorrhage, multiorgan failure, and mortality. The emergence and reemergence of RNA viruses continue to pose a significant public health threat worldwide with particular attention to the increasing incidence of flaviviruses, among others Dengue, West Nile Virus, and Yellow Fever viruses. Development of new and potent antivirals is thus urgently needed. Ivermectin, an already known antihelminthic drug, has shown potent effects in vitro on Flavivirus helicase, with EC50 values in the subnanomolar range for Yellow Fever and submicromolar EC50 for Dengue Fever, Japanese encephalitis, and tick-borne encephalitis viruses. However ivermectin is hampered in its application by pharmacokinetic problems (little solubility and high cytotoxicity). To overcome such problems we engineered different compositions of liposomes as ivermectin carriers characterizing and testing them on several cell lines for cytotoxicity. The engineered liposomes were less cytotoxic than ivermectin alone and they showed a significant increase of the antiviral activity in all the Dengue stains tested (1, 2, and S221). In the current study ivermectin is confirmed to be an effective potential antiviral and liposomes, as drug carriers, are shown to modulate the drug activity. All together the results represent a promising starting point for future improvement of ivermectin as antiviral and its delivery. PMID:27242902

  7. Small molecules with antiviral activity against the Ebola virus.

    Science.gov (United States)

    Litterman, Nadia; Lipinski, Christopher; Ekins, Sean

    2015-01-01

    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. PMID:25713700

  8. Liposomal Systems as Nanocarriers for the Antiviral Agent Ivermectin.

    Science.gov (United States)

    Croci, Romina; Bottaro, Elisabetta; Chan, Kitti Wing Ki; Watanabe, Satoru; Pezzullo, Margherita; Mastrangelo, Eloise; Nastruzzi, Claudio

    2016-01-01

    RNA virus infections can lead to the onset of severe diseases such as fever with haemorrhage, multiorgan failure, and mortality. The emergence and reemergence of RNA viruses continue to pose a significant public health threat worldwide with particular attention to the increasing incidence of flaviviruses, among others Dengue, West Nile Virus, and Yellow Fever viruses. Development of new and potent antivirals is thus urgently needed. Ivermectin, an already known antihelminthic drug, has shown potent effects in vitro on Flavivirus helicase, with EC50 values in the subnanomolar range for Yellow Fever and submicromolar EC50 for Dengue Fever, Japanese encephalitis, and tick-borne encephalitis viruses. However ivermectin is hampered in its application by pharmacokinetic problems (little solubility and high cytotoxicity). To overcome such problems we engineered different compositions of liposomes as ivermectin carriers characterizing and testing them on several cell lines for cytotoxicity. The engineered liposomes were less cytotoxic than ivermectin alone and they showed a significant increase of the antiviral activity in all the Dengue stains tested (1, 2, and S221). In the current study ivermectin is confirmed to be an effective potential antiviral and liposomes, as drug carriers, are shown to modulate the drug activity. All together the results represent a promising starting point for future improvement of ivermectin as antiviral and its delivery. PMID:27242902

  9. Liposomal Systems as Nanocarriers for the Antiviral Agent Ivermectin

    Directory of Open Access Journals (Sweden)

    Romina Croci

    2016-01-01

    Full Text Available RNA virus infections can lead to the onset of severe diseases such as fever with haemorrhage, multiorgan failure, and mortality. The emergence and reemergence of RNA viruses continue to pose a significant public health threat worldwide with particular attention to the increasing incidence of flaviviruses, among others Dengue, West Nile Virus, and Yellow Fever viruses. Development of new and potent antivirals is thus urgently needed. Ivermectin, an already known antihelminthic drug, has shown potent effects in vitro on Flavivirus helicase, with EC50 values in the subnanomolar range for Yellow Fever and submicromolar EC50 for Dengue Fever, Japanese encephalitis, and tick-borne encephalitis viruses. However ivermectin is hampered in its application by pharmacokinetic problems (little solubility and high cytotoxicity. To overcome such problems we engineered different compositions of liposomes as ivermectin carriers characterizing and testing them on several cell lines for cytotoxicity. The engineered liposomes were less cytotoxic than ivermectin alone and they showed a significant increase of the antiviral activity in all the Dengue stains tested (1, 2, and S221. In the current study ivermectin is confirmed to be an effective potential antiviral and liposomes, as drug carriers, are shown to modulate the drug activity. All together the results represent a promising starting point for future improvement of ivermectin as antiviral and its delivery.

  10. Antiviral activity of monoterpenes beta-pinene and limonene against herpes simplex virus in vitro.

    Directory of Open Access Journals (Sweden)

    Akram Astani

    2014-06-01

    Full Text Available Essential oils are complex mixtures containing compounds of several different functional- group classes. Depending on the structure, we can distinguish monoterpenes, phenylpropanes, and other components. Here in this study two monoterpene compounds of essential oils, i.e. β-pinene and limonene were examined for their antiviral activity against herpes simplex virus type 1 (HSV-1 in vitro.All antiviral assays were performed using RC-37 cells. Cytotoxicity was determined in a neutral red assay, antiviral assays were performed with HSV-1 strain KOS. The mode of antiviral action was evaluated at different periods during the viral replication cycle. Acyclovir was used as positive antiviral control.Beta-pinenene and limonenen reduced viral infectivity by 100 %. The mode of antiviral action has been determined, only moderate antiviral effects were revealed by monoterpenes when these drugs were added to host cells prior infection or after entry of HSV into cells. However, both monoterpenes exhibited high anti-HSV-1 activity by direct interaction with free virus particles. Both tested drugs interacted with HSV-1 in a dose-dependent manner thereby inactivating viral infection.These results suggest that monoterpenes in essential oils exhibit antiherpetic activity in the early phase of viral multiplication and might be used as potential antiviral agents.

  11. Drug: D07441 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available D07441 Drug Amantadine (INN) C10H17N 151.1361 151.2487 D07441.gif Antiviral, Antiparkinson...synapse Transporter: SLC22A2 [HSA:6582] map07044 Antiviral agents map07057 Antiparkinson...inson Agents Antiparkinson Agents, Other Amantadine D07441 Amantadine (INN) Antivir...ntane derivatives N04BB01 Amantadine D07441 Amantadine (INN) USP drug classification [BR:br08302] Antipark

  12. Antiviral therapy: a perspective.

    Science.gov (United States)

    Shahidi Bonjar, Amir Hashem

    2016-01-01

    research has yielded positive results in animal models, EVAC could be used as a supportive treatment in humans along with conventional antiviral therapies. EVAC would not be suitable for all viral infections, but could be expected to decrease the casualties resulting from blood-borne viral infections. The EVAC approach would be efficient in terms of time, effort, and expenditure in the research and treatment of blood-borne viral infections. PMID:26893542

  13. Dried blood spot UHPLC-MS/MS analysis of oseltamivir and oseltamivircarboxylate-a validated assay for the clinic

    NARCIS (Netherlands)

    G.P. Hooff (Gero); R.J.W. Meesters (Roland); J.J.A. van Kampen (Jeroen); N.A. van Huizen (Nick); B. Koch (Birgit); A.F.Y. Al Hadithy (Asmar); T. van Gelder (Teun); A.D.M.E. Osterhaus (Albert); R.A. Gruters (Rob); T.M. Luider (Theo)

    2011-01-01

    textabstractThe neuraminidase inhibitor oseltamivir (Tamiflu®) is currently the first-line therapy for patients with influenza virus infection. Common analysis of the prodrug and its active metabolite oseltamivircarboxylate is determined via extraction from plasma. Compared with these assays, dried

  14. Continued emergence and changing epidemiology of oseltamivir-resistant influenza A(H1N1)2009 virus, United Kingdom, winter 2010/11.

    Science.gov (United States)

    Lackenby, A; Moran Gilad, J; Pebody, R; Miah, S; Calatayud, L; Bolotin, S; Vipond, I; Muir, P; Guiver, M; McMenamin, J; Reynolds, A; Moore, C; Gunson, R; Thompson, C; Galiano, M; Bermingham, A; Ellis, J; Zambon, M

    2011-01-01

    During the winter period 2010/11 27 epidemiologically unlinked, confirmed cases of oseltamivir-resistant influenza A(H1N1)2009 virus infection have been detected in multiple, geographically dispersed settings. Three of these cases were in community settings, with no known exposure to oseltamivir. This suggests possible onward transmission of resistant strains and could be an indication of a possibility of changing epidemiology of oseltamivir-resistant influenza A(H1N1)2009 virus. PMID:21315056

  15. Viral Ancestors of Antiviral Systems

    Directory of Open Access Journals (Sweden)

    Luis P. Villarreal

    2011-10-01

    Full Text Available All life must survive their corresponding viruses. Thus antiviral systems are essential in all living organisms. Remnants of virus derived information are also found in all life forms but have historically been considered mostly as junk DNA. However, such virus derived information can strongly affect host susceptibility to viruses. In this review, I evaluate the role viruses have had in the origin and evolution of host antiviral systems. From Archaea through bacteria and from simple to complex eukaryotes I trace the viral components that became essential elements of antiviral immunity. I conclude with a reexamination of the ‘Big Bang’ theory for the emergence of the adaptive immune system in vertebrates by horizontal transfer and note how viruses could have and did provide crucial and coordinated features.

  16. Viral ancestors of antiviral systems.

    Science.gov (United States)

    Villarreal, Luis P

    2011-10-01

    All life must survive their corresponding viruses. Thus antiviral systems are essential in all living organisms. Remnants of virus derived information are also found in all life forms but have historically been considered mostly as junk DNA. However, such virus derived information can strongly affect host susceptibility to viruses. In this review, I evaluate the role viruses have had in the origin and evolution of host antiviral systems. From Archaea through bacteria and from simple to complex eukaryotes I trace the viral components that became essential elements of antiviral immunity. I conclude with a reexamination of the 'Big Bang' theory for the emergence of the adaptive immune system in vertebrates by horizontal transfer and note how viruses could have and did provide crucial and coordinated features. PMID:22069523

  17. Antiviral Effect Assay of Aqueous Extract of Echium Amoenum-L against HSV-1

    Directory of Open Access Journals (Sweden)

    Malihe Farahani

    2013-08-01

    Full Text Available Background: Medicinal plants have been used for different diseases in past. There is an increasing need for substances with antiviral activity since the treatment of viral infections with the available antiviral drugs often leads to the problem of viral resistance. Therefore in the present study Echium amoenum L plant with ethnomedical background was screened for antiviral activity against HSV-1 in different times. Materials and Methods: Flower part of Echium amoenum L plant collected from Iran was extracted with different methods to obtain crude aqueous extract. This extract was screened for its cytotoxicity against Hep II cell line by CPE assay. Antiviral properties of the plant extract were determined by cytopathic effect inhibition assay.Results: Echium amoenum L extract exhibited significant antiviral activity at non toxic concentrations to the cell line used. Findings indicated that plant extract has the most antiviral activity when it used an hour after virus inoculation.Conclusion: Echium amoenum L plant had not toxic effect at highest concentrations to the cell lines used and showed the most antiviral activity when it used an hour after virus inoculation. Further research is needed to elucidate the active constituents of this plant which may be useful in the development of new and effective antiviral agents.

  18. Detection of Peramivir and Laninamivir, New Anti-Influenza Drugs, in Sewage Effluent and River Waters in Japan

    OpenAIRE

    Takashi Azuma; Hirotaka Ishiuchi; Tomomi Inoyama; Yusuke Teranishi; Misato Yamaoka; Takaji Sato; Naoyuki Yamashita; Hiroaki Tanaka; Yoshiki Mino

    2015-01-01

    This is the first report of the detection of two new anti-influenza drugs, peramivir (PER) and laninamivir (LAN), in Japanese sewage effluent and river waters. Over about 1 year from October 2013 to July 2014, including the influenza prevalence season in January and February 2014, we monitored for five anti-influenza drugs-oseltamivir (OS), oseltamivir carboxylate (OC), zanamivir (ZAN), PER, and LAN-in river waters and in sewage effluent flowing into urban rivers of the Yodo River system in J...

  19. Drug: D03256 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available D03256 Drug Valganciclovir hydrochloride (JAN/USAN); Valcyte (TN) C14H22N6O5. HCl 3...90.1418 390.8226 D03256.gif Antiviral [DS:H00368] Therapeutic category: 6250 ATC code: J05AB14 prodrug, active substance: Ganciclov...ms and parasites 62 Chemotherapeutics 625 Antivirals 6250 Antivirals D03256 Valganciclovir hydrochloride (JA...nd nucleotides excl. reverse transcriptase inhibitors J05AB14 Valganciclovir D03256 Valganciclovir hydrochlo...ride (JAN/USAN) USP drug classification [BR:br08302] Antivirals Anti-cytomegalovirus (CMV) Agents Valganciclovir D03256 Valganciclov

  20. Drug: D00333 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available D00333 Drug Ganciclovir (JAN/USP/INN); Cytovene (TN); Vitrasert (TN) C9H13N5O4 255....ic organisms and parasites 62 Chemotherapeutics 625 Antivirals 6250 Antivirals D00333 Ganciclovir (JAN/USP/I...ucleotides excl. reverse transcriptase inhibitors J05AB06 Ganciclovir D00333 Ganciclovir (JAN/USP/INN) S SEN...SORY ORGANS S01 OPHTHALMOLOGICALS S01A ANTIINFECTIVES S01AD Antivirals S01AD09 Ganciclovir D00333 Ganciclovi...r (JAN/USP/INN) USP drug classification [BR:br08302] Antivirals Anti-cytomegalovirus (CMV) Agents Ganciclo

  1. Antiviral effect of lithium chloride on infection of cells by canine parvovirus.

    Science.gov (United States)

    Zhou, Pei; Fu, Xinliang; Yan, Zhongshan; Fang, Bo; Huang, San; Fu, Cheng; Hong, Malin; Li, Shoujun

    2015-11-01

    Canine parvovirus type 2 causes significant viral disease in dogs, with high morbidity, high infectivity, and high mortality. Lithium chloride is a potential antiviral drug for viruses. We determined the antiviral effect of Lithium Chloride on canine parvovirus type 2 in feline kidney cells. The viral DNA and proteins of canine parvovirus were suppressed in a dose-dependent manner by lithium chloride. Further investigation verified that viral entry into cells was inhibited in a dose-dependent manner by lithium chloride. These results indicated that lithium chloride could be a potential antiviral drug for curing dogs with canine parvovirus infection. The specific steps of canine parvovirus entry into cells that are affected by lithium chloride and its antiviral effect in vivo should be explored in future studies. PMID:26315688

  2. Inhibition of MAO-A and stimulation of behavioural activities in mice by the inactive prodrug form of the anti-influenza agent oseltamivir

    OpenAIRE

    Hiasa, Miki; Isoda, Yumiko; Kishimoto, Yasushi; Saitoh, Kenta; Kimura, Yasuaki; Kanai, Motomu; Shibasaki, Masakatsu; Hatakeyama, Dai; Kirino, Yutaka; Kuzuhara, Takashi

    2013-01-01

    Background and Purpose Oseltamivir is the most widely prescribed anti-influenza medication. However, in rare instances, it has been reported to stimulate behavioural activities in adolescents. The goal of this study was to determine the molecular mechanism responsible for these behavioural activities. Experimental Approach We performed an in vitro assay of MAO-A, the enzyme responsible for neurotransmitter degradation, using either the active form – oseltamivir carboxylate (OC) or the inactiv...

  3. Effect of double dose oseltamivir on clinical and virological outcomes in children and adults admitted to hospital with severe influenza: double blind randomised controlled trial

    OpenAIRE

    ,

    2013-01-01

    Objective To investigate the validity of recommendations in treatment guidelines to use higher than approved doses of oseltamivir in patients with severe influenza. Design Double blind randomised trial. Setting Thirteen hospitals in Indonesia, Singapore, Thailand, and Vietnam. Participants Patients aged ≥1 year admitted to hospital with confirmed severe influenza. Interventions Oral oseltamivir at double dose (150 mg twice a day/paediatric equivalent) versus standard dose (75 mg twice a day/p...

  4. Antiviral therapies against Ebola and other emerging viral diseases using existing medicines that block virus entry

    OpenAIRE

    Long, Jason; Wright, Edward; Molesti, Eleonora; Temperton, Nigel J.; Barclay, Wendy

    2015-01-01

    Emerging viral diseases pose a threat to the global population as intervention strategies are mainly limited to basic containment due to the lack of efficacious and approved vaccines and antiviral drugs. The former was the only available intervention when the current unprecedented Ebolavirus (EBOV) outbreak in West Africa began. Prior to this, the development of EBOV vaccines and anti-viral therapies required time and resources that were not available. Therefore, focus has turned to re-purpos...

  5. Liposomal Systems as Nanocarriers for the Antiviral Agent Ivermectin

    OpenAIRE

    Romina Croci; Elisabetta Bottaro; Kitti Wing Ki Chan; Satoru Watanabe; Margherita Pezzullo; Eloise Mastrangelo; Claudio Nastruzzi

    2016-01-01

    RNA virus infections can lead to the onset of severe diseases such as fever with haemorrhage, multiorgan failure, and mortality. The emergence and reemergence of RNA viruses continue to pose a significant public health threat worldwide with particular attention to the increasing incidence of flaviviruses, among others Dengue, West Nile Virus, and Yellow Fever viruses. Development of new and potent antivirals is thus urgently needed. Ivermectin, an already known antihelminthic drug, has shown ...

  6. Drug: D00317 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available D00317 Drug Famciclovir (JAN/USAN/INN); Famvir (TN) C14H19N5O4 321.1437 321.3318 D0...0317.gif Antiviral [DS:H00365] Therapeutic category: 6250 ATC code: J05AB09 S01AD07 Prodrug, active substance: Penciclov...otherapeutics 625 Antivirals 6250 Antivirals D00317 Famciclovir (JAN/USAN/INN) Anatomical Therapeutic Chemic...ptase inhibitors J05AB09 Famciclovir D00317 Famciclovir (JAN/USAN/INN) S SENSORY ORGANS S01 OPHTHALMOLOGICAL...S S01A ANTIINFECTIVES S01AD Antivirals S01AD07 Famciclovir D00317 Famciclovir (JAN/USAN/INN) USP drug classification [BR:br08302] Antivirals Antiherpetic Agents Famciclovir D00317 Famciclovir (JAN/USAN/INN) Antiinfectives [BR:br08307] Antivirals Anti-HSV agent DNA polym

  7. In vitro antiviral effect of germacrone on feline calicivirus.

    Science.gov (United States)

    Wu, Hongxia; Liu, Yongxiang; Zu, Shaopo; Sun, Xue; Liu, Chunguo; Liu, Dafei; Zhang, Xiaozhan; Tian, Jin; Qu, Liandong

    2016-06-01

    Feline calicivirus (FCV) often causes respiratory tract and oral disease in cats and is a highly contagious virus. Widespread vaccination does not prevent the spread of FCV. Furthermore, the low fidelity of the RNA-dependent RNA polymerase of FCV leads to the emergence of new variants, some of which show increased virulence. Currently, few effective anti-FCV drugs are available. Here, we found that germacrone, one of the main constituents of volatile oil from rhizoma curcuma, was able to effectively reduce the growth of FCV strain F9 in vitro. This compound exhibited a strong anti-FCV effect mainly in the early phase of the viral life cycle. The antiviral effect depended on the concentration of the drug. In addition, germacrone treatment had a significant inhibitory effect against two other reference strains, 2280 and Bolin, and resulted in a significant reduction in the replication of strains WZ-1 and HRB-SS, which were recently isolated in China. This is the first report of antiviral effects of germacrone against a calicivirus, and extensive in vivo research is needed to evaluate this drug as an antiviral therapeutic agent for FCV. PMID:26997613

  8. Drug: D10518 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available D10518 Drug Valaciclovir hydrochloride hydrate (JAN); Valaciclovir (TN) C13H20N6O4.... HCl. xH2O D10518.gif Antiviral [DS:H00365] Therapeutic category: 6250 ATC code: J05AB11 prodrug, active substance: Aciclov...ganisms and parasites 62 Chemotherapeutics 625 Antivirals 6250 Antivirals D10518 Valaciclovir hydrochloride ...ides and nucleotides excl. reverse transcriptase inhibitors J05AB11 Valaciclovir D10518 Valaciclovir hydroch

  9. Antiviral treatment for the control of pandemic influenza: some logistical constraints

    OpenAIRE

    Arinaminpathy, N.; McLean, A. R.

    2007-01-01

    Disease control programmes for an influenza pandemic will rely initially on the deployment of antiviral drugs such as Tamiflu, until a vaccine becomes available. However, such control programmes may be severely hampered by logistical constraints such as a finite stockpile of drugs and a limit on the distribution rate. We study the effects of such constraints using a compartmental modelling approach.

  10. Escape Mutations in NS4B Render Dengue Virus Insensitive to the Antiviral Activity of the Paracetamol Metabolite AM404.

    Science.gov (United States)

    van Cleef, Koen W R; Overheul, Gijs J; Thomassen, Michael C; Marjakangas, Jenni M; van Rij, Ronald P

    2016-04-01

    Despite the enormous disease burden associated with dengue virus infections, a licensed antiviral drug is lacking. Here, we show that the paracetamol (acetaminophen) metabolite AM404 inhibits dengue virus replication. Moreover, we find that mutations in NS4B that were previously found to confer resistance to the antiviral compounds NITD-618 and SDM25N also render dengue virus insensitive to AM404. Our work provides further support for NS4B as a direct or indirect target for antiviral drug development. PMID:26856827

  11. Antifungal and antiviral products of marine organisms.

    Science.gov (United States)

    Cheung, Randy Chi Fai; Wong, Jack Ho; Pan, Wen Liang; Chan, Yau Sang; Yin, Cui Ming; Dan, Xiu Li; Wang, He Xiang; Fang, Evandro Fei; Lam, Sze Kwan; Ngai, Patrick Hung Kui; Xia, Li Xin; Liu, Fang; Ye, Xiu Yun; Zhang, Guo Qing; Liu, Qing Hong; Sha, Ou; Lin, Peng; Ki, Chan; Bekhit, Adnan A; Bekhit, Alaa El-Din; Wan, David Chi Cheong; Ye, Xiu Juan; Xia, Jiang; Ng, Tzi Bun

    2014-04-01

    Marine organisms including bacteria, fungi, algae, sponges, echinoderms, mollusks, and cephalochordates produce a variety of products with antifungal activity including bacterial chitinases, lipopeptides, and lactones; fungal (-)-sclerotiorin and peptaibols, purpurides B and C, berkedrimane B and purpuride; algal gambieric acids A and B, phlorotannins; 3,5-dibromo-2-(3,5-dibromo-2-methoxyphenoxy)phenol, spongistatin 1, eurysterols A and B, nortetillapyrone, bromotyrosine alkaloids, bis-indole alkaloid, ageloxime B and (-)-ageloxime D, haliscosamine, hamigeran G, hippolachnin A from sponges; echinoderm triterpene glycosides and alkene sulfates; molluscan kahalalide F and a 1485-Da peptide with a sequence SRSELIVHQR; and cepalochordate chitotriosidase and a 5026.9-Da antifungal peptide. The antiviral compounds from marine organisms include bacterial polysaccharide and furan-2-yl acetate; fungal macrolide, purpurester A, purpurquinone B, isoindolone derivatives, alterporriol Q, tetrahydroaltersolanol C and asperterrestide A, algal diterpenes, xylogalactofucan, alginic acid, glycolipid sulfoquinovosyldiacylglycerol, sulfated polysaccharide p-KG03, meroditerpenoids, methyl ester derivative of vatomaric acid, lectins, polysaccharides, tannins, cnidarian zoanthoxanthin alkaloids, norditerpenoid and capilloquinol; crustacean antilipopolysaccharide factors, molluscan hemocyanin; echinoderm triterpenoid glycosides; tunicate didemnin B, tamandarins A and B and; tilapia hepcidin 1-5 (TH 1-5), seabream SauMx1, SauMx2, and SauMx3, and orange-spotted grouper β-defensin. Although the mechanisms of antifungal and antiviral activities of only some of the aforementioned compounds have been elucidated, the possibility to use those known to have distinctly different mechanisms, good bioavailability, and minimal toxicity in combination therapy remains to be investigated. It is also worthwhile to test the marine antimicrobials for possible synergism with existing drugs. The prospects of

  12. ANTIVIRAL POTENTIAL OF MEDICINAL PLANTS: AN OVERVIEW

    Directory of Open Access Journals (Sweden)

    Ruwali Pushpa

    2013-06-01

    Full Text Available The term ‘Antiviral agents’ has been defined in very broad terms as substances other than a virus or virus containing vaccine or specific antibody which can produce either a protective or therapeutic effect to the clear detectable advantage of the virus infected host. The herbal medicine has a long traditional use and the major advantage over other medicines is their wide therapeutic window with rare side effects. There are some disadvantages of synthetic drugs like narrow therapeutic window and more importantly the various adverse side effects which occur quite frequently. Due to these disadvantages and other limitations, there is an increasing trend in the field of research for discovering new and noble drugs based on various herbal formulations. This review attempts to address the importance of developing therapeutic herbal formulations from various medicinal plants using the knowledge based on traditional system of medicines, the Ayurveda. Although natural products have been used by civilization since ancient times, only in recent decades has there been growing research into alternative therapies and the therapeutics use of natural products, especially those derived from plants. Plants synthesize and preserve a variety of biochemical products, many of which are extractable and used for various scientific investigations. Therefore, medicinal plants proved to be a major resort for the treatment of diseases and sicknesses by traditional healers in many societies.

  13. Meeting report: 26th International Conference on Antiviral Research.

    Science.gov (United States)

    Vere Hodge, R Anthony

    2013-10-01

    The 26th International Conference on Antiviral Research (ICAR) was held in San Francisco, California from May 11 to 15, 2013. This article summarizes the principal invited lectures at the meeting. The opening symposium on the legacy of the late Antonín Holý included presentations on his pioneering work with nucleotide analogs, which led to the development of several antiviral drugs including tenofovir. This drug has transformed the treatment of HIV infection and has recently become the first-line therapy for chronic hepatitis B. The Gertrude Elion Award lecturer described the anti-HIV activities of the CCR5 inhibitor cenicriviroc and the reverse transcriptase inhibitor festinavir®, and also reviewed the evaluation of biodegradable nanoparticles with adjuvant activity. The William Prusoff Award winner reported on the creation of NAOMI, a computer model with 21 enzymes to predict the activity of nucleoside analogs against hepatitis C virus (HCV). Other invited lecturers discussed the development of countermeasures against severe dengue and the potential of RNA virus capping and repair enzymes as drug targets. Topics in the clinical symposium included the current status of the anti-HCV compounds sovaprevir, ACH-3102, miravirsen and ALS-2200; the evaluation of single-tablet regimens for HIV infection; and the investigation of cytomegalovirus resistance to CMX001. Two chemistry minisymposia examined strategies and tactics in drug design and the use of in drug discovery. PMID:23973733

  14. Genetic Consequences of Antiviral Therapy on HIV-1

    Directory of Open Access Journals (Sweden)

    Miguel Arenas

    2015-01-01

    Full Text Available A variety of enzyme inhibitors have been developed in combating HIV-1, however the fast evolutionary rate of this virus commonly leads to the emergence of resistance mutations that finally allows the mutant virus to survive. This review explores the main genetic consequences of HIV-1 molecular evolution during antiviral therapies, including the viral genetic diversity and molecular adaptation. The role of recombination in the generation of drug resistance is also analyzed. Besides the investigation and discussion of published works, an evolutionary analysis of protease-coding genes collected from patients before and after treatment with different protease inhibitors was included to validate previous studies. Finally, the review discusses the importance of considering genetic consequences of antiviral therapies in models of HIV-1 evolution that could improve current genotypic resistance testing and treatments design.

  15. Drug: D03690 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available D03690 Drug Desciclovir (USAN/INN) C8H11N5O2 209.0913 209.2052 D03690.gif Antiviral...08307] Antivirals Anti-HSV agent DNA polymerase inhibitor Purine analogue Desciclovir D03690 Desciclovir (US

  16. Drug: D04008 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available 2O 295.1281 295.2945 D04008.gif Antiviral used in the treatment of hepatitis B infections [DS:H00412] Therap...ntecavir D04008 Entecavir hydrate (JAN); Entecavir (USAN) USP drug classification [BR:br08302] Antivirals Anti-hepatitis

  17. Drug: D01937 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available D01937 Drug Zanamivir hydrate (JAN); Relenza (TN) C12H20N4O7. xH2O D01937.gif Antiviral; Inhibit ... or [influenza virus neuraminidase] [DS:H00398] Therapeutic catego ... ry: 6250 ATC code: J05AH01 influenza virus A, B neuraminidase inhibitor map07044 Antivir ...

  18. Drug: D08775 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available D08775 Mixture, Drug Abacavir sulfate - lamivudine mixt; Epzicom (TN) Abacavir sulf...emotherapeutics 625 Antivirals 6250 Antivirals D08775 Abacavir sulfate - lamivudi...ns, combinations J05AR02 Lamivudine and abacavir D08775 Abacavir sulfate - lamivu... Transcriptase Inhibitors (NRTI)v Abacavir and Lamivudine D08775 Abacavir sulfate - lamivudine mixt PubChem: 96025458 ...

  19. Drug: D02764 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available OTHERAPEUTICS FOR DERMATOLOGICAL USE D06B CHEMOTHERAPEUTICS FOR TOPICAL USE D06BB Antivirals D06BB03 Aciclov...NTIINFECTIVES S01AD Antivirals S01AD03 Aciclovir D02764 Acyclovir sodium (USAN) USP drug classification [BR:...Antiinfectives [BR:br08307] Antivirals Anti-HSV agent DNA polymerase inhibitor Purine analogue Aciclovir [AT...se inhibitors J05AB01 Aciclovir D02764 Acyclovir sodium (USAN) S SENSORY ORGANS S01 OPHTHALMOLOGICALS S01A A...ECT ACTING ANTIVIRALS J05AB Nucleosides and nucleotides excl. reverse transcripta

  20. Systematic review of influenza resistance to the neuraminidase inhibitors

    Directory of Open Access Journals (Sweden)

    Boivin Guy

    2011-05-01

    Full Text Available Abstract Background Antivirals play a critical role in the prevention and the management of influenza. One class of antivirals, neuraminidase inhibitors (NAIs, is effective against all human influenza viruses. Currently there are two NAI drugs which are licensed worldwide: oseltamivir (Tamiflu® and zanamivir (Relenza®; and two drugs which have received recent approval in Japan: peramivir and laninamivir. Until recently, the prevalence of antiviral resistance has been relatively low. However, almost all seasonal H1N1 strains that circulated in 2008-09 were resistant to oseltamivir whereas about 1% of tested 2009 pandemic H1N1 viruses were found to be resistant to oseltamivir. To date, no studies have demonstrated widespread resistance to zanamivir. It seems likely that the literature on antiviral resistance associated with oseltamivir as well as zanamivir is now sufficiently comprehensive to warrant a systematic review. The primary objectives were to systematically review the literature to determine the incidence of resistance to oseltamivir, zanamivir, and peramivir in different population groups as well as assess the clinical consequences of antiviral resistance. Methods We searched MEDLINE and EMBASE without language restrictions in September 2010 to identify studies reporting incidence of resistance to oseltamivir, zanamivir, and peramivir. We used forest plots and meta-analysis of incidence of antiviral resistance associated with the three NAIs. Subgroup analyses were done across a number of population groups. Meta-analysis was also performed to evaluate associations between antiviral resistance and clinical complications and symptoms. Results We identified 19 studies reporting incidence of antiviral resistance. Meta-analysis of 15 studies yielded a pooled incidence rate for oseltamivir resistance of 2.6% (95%CI 0.7% to 5.5%. The incidence rate for all zanamivir resistance studies was 0%. Only one study measured incidence of antiviral

  1. Сost-effectiveness of the second wave of protease inhibitors in the treatment of chronic hepatitis C (genotype 1 in patients not previously treated with antiviral drugs, and for relapsed disease

    Directory of Open Access Journals (Sweden)

    A. V. Rudakova

    2016-01-01

    Full Text Available The protease inhibitors (PI actively using for the treatment of chronic hepatitis C (CHC.The aim of this analysis was to evaluate the cost-effectiveness of narlaprevir and simeprevir in the CHC (genotype 1 therapy in treatment-naïve patients and relapses.Material and methods. Analysis of the cost-effectiveness of simeprevir and narlaprevir was conducted from the perspective of the health care system and base on QUEST-1, QUEST-2, ASPIRE and PIONEER clinical trials. The relative risk of achieving SVR 24 compared to the peg-INF + RBV therapy was used in the model. Treatment discontinuation in patients receiving narlaprevir assumed in the absence of a SVR after 12 weeks and in patients receiving simeprevir in the SVR absence after 4 weeks. The cost of narlaprevir was calculate based on estimated registration price in case of EDL (essential pharmaceutical list approved by MOH inclusion, including VAT (10% and 10% as trade margin. Costs of other antiviral products were in line with the results of 2015 average auctions prices.Results. In the base case costs on antiviral products with narlaprevir as first-line therapy are lower compared with simeprevir by 12,2% (950,6 and 1083,0 thousand RUR, respectively, and the cost per patient with SVR 24 by 7,8%. In patients group after relapse costs on antiviral products with narlaprevir as first-line therapy will decrease compared with simeprevir by 4,3% (971,3 and 1014,7 thousand RUR, respectively, and the cost per patient with SVR 24 by 25,0%. The sensitivity analysis demonstrated a high reliability of obtained results. Thus, assuming equal clinical effectiveness of narlaprevir and simeprevir, costs of treatment naive patients will be 10.6% lower for narlaprevir group compared to simeprevir group (953,0 and 1066,0 thousand rur, respectively, and by 12,9% for the treatment of relapses (957,9 and 1100,0 thousand RUR, respectively.Conclusions. With comparable clinical efficacy and

  2. Population-wide emergence of antiviral resistance during pandemic influenza.

    Directory of Open Access Journals (Sweden)

    Seyed M Moghadas

    Full Text Available BACKGROUND: The emergence of neuraminidase inhibitor resistance has raised concerns about the prudent use of antiviral drugs in response to the next influenza pandemic. While resistant strains may initially emerge with compromised viral fitness, mutations that largely compensate for this impaired fitness can arise. Understanding the extent to which these mutations affect the spread of disease in the population can have important implications for developing pandemic plans. METHODOLOGY/PRINCIPAL FINDINGS: By employing a deterministic mathematical model, we investigate possible scenarios for the emergence of population-wide resistance in the presence of antiviral drugs. The results show that if the treatment level (the fraction of clinical infections which receives treatment is maintained constant during the course of the outbreak, there is an optimal level that minimizes the final size of the pandemic. However, aggressive treatment above the optimal level can substantially promote the spread of highly transmissible resistant mutants and increase the total number of infections. We demonstrate that resistant outbreaks can occur more readily when the spread of disease is further delayed by applying other curtailing measures, even if treatment levels are kept modest. However, by changing treatment levels over the course of the pandemic, it is possible to reduce the final size of the pandemic below the minimum achieved at the optimal constant level. This reduction can occur with low treatment levels during the early stages of the pandemic, followed by a sharp increase in drug-use before the virus becomes widely spread. CONCLUSIONS/SIGNIFICANCE: Our findings suggest that an adaptive antiviral strategy with conservative initial treatment levels, followed by a timely increase in the scale of drug-use, can minimize the final size of a pandemic while preventing large outbreaks of resistant infections.

  3. A new antiviral screening method that simultaneously detects viral replication, cell viability, and cell toxicity.

    Science.gov (United States)

    Matza-Porges, Sigal; Eisen, Kobi; Ibrahim, Hadeel; Haberman, Adva; Fridlender, Bertold; Joseph, Gili

    2014-11-01

    Viruses cause a variety of illnesses in humans, yet only a few antiviral drugs have been developed; thus, new antiviral drugs are urgently needed. Plants could be a good source of antiviral drugs, they do not have mobility and can only defend themselves by producing compounds against pathogens such as viruses in their own fix environment. These compounds may have the potential to inhibit animal and human viruses as well. In this study, a fast and reliable method for screening plant extracts for specific antiviral activity against Herpes simplex virus type-1 (HSV-1) was developed. This method distinguishes between host cell death due to infectivity and multiplicity of the virus versus toxicity of the plant extract. Extracts from 80 plant and plant organs were screened using this approach. Six plant extracts showed potential to exert specific HSV-1 growth inhibition activity. In two cases, different organs from the same plant showed similar active results. With this method it is possible to screen a large number of extracts in a rapid and accurate way to detect antiviral substances against HSV-I and other viruses. PMID:25152527

  4. 重症病毒性肺炎的抗病毒治疗%Antiviral therapy for severe viral pneumonia

    Institute of Scientific and Technical Information of China (English)

    缪惠洁; 张育才

    2015-01-01

    儿童重症病毒性肺炎病因主要包括腺病毒、呼吸道合胞病毒、流感病毒A和B型、巨细胞病毒等.新型病毒如甲型H1N1流感病毒、禽流感病毒(H5N1、H7N9)等也可能引起流行.利巴韦林是治疗呼吸道合胞病毒、腺病毒肺炎等的有效药物.阿昔洛韦或更昔洛韦常用于EB病毒或免疫缺陷和免疫抑制患者的巨细胞病毒肺炎.目前认为流感和季节性流感尽早使用神经氨酸酶抑制剂(neuraminidase inhibitor,NAI)奥司他韦,可减轻流感样症状、缩短发热时间,减少流感合并症.耐药或口服困难时使用扎那米韦和帕拉米韦.某些中药制剂如麻杏石甘汤-银翘散等治疗流感病毒感染可以获得类似于奥司他韦的效果.%Adenovirus,respiratory syncytial virus,influenza virus type A and B,cytomegalovirus and EB virus are the mainly etiology of severe pneumonia in children.New type of virus,such as influenza-H1N1 virus,avian influenza virus(H5N1 or H7N9) can also be epidemic in pediatric population.Ribavirin is effective drugs in the treatment of respiratory syncytial virus and adenovirus pneumonia.Acyclovir or ganciclovir is used for EB virus or immune deficiency and irnmunosuppressive patients with CMV pneumonia.Current opinin strongly recommend treatment with oral oseltamivir as soon as possible in influenza and seasonal influenza.Oseltamivir reduces the severity,duration of the symptoms of influenza,and reduces the frequency of secondary illnesses and exacerbation of underlying conditions.Zanamivir and peramivir may be effective in patients infected with influenza virus,including oseltamivir-resistant virus.Some Chinese medicine such as maxingshigan-yinqiaosan can obtain similar effect of oseltamivir in treatment of influenza virus infection.

  5. Antiviral Activities of Several Oral Traditional Chinese Medicines against Influenza Viruses

    OpenAIRE

    Lin-Lin Ma; Miao Ge; Hui-Qiang Wang; Jin-Qiu Yin; Jian-Dong Jiang; Yu-Huan Li

    2015-01-01

    Influenza is still a serious threat to human health with significant morbidity and mortality. The emergence of drug-resistant influenza viruses poses a great challenge to existing antiviral drugs. Traditional Chinese medicines (TCMs) may be an alternative to overcome the challenge. Here, 10 oral proprietary Chinese medicines were selected to evaluate their anti-influenza activities. These drugs exhibit potent inhibitory effects against influenza A H1N1, influenza A H3N2, and influenza B virus...

  6. Update On Emerging Antivirals For The Management Of Herpes Simplex Virus Infections: A Patenting Perspective

    OpenAIRE

    Vadlapudi, Aswani D.; Vadlapatla, Ramya K.; Ashim K. Mitra

    2013-01-01

    Herpes simplex virus (HSV) infections can be treated efficiently by the application of antiviral drugs. The herpes family of viruses is responsible for causing a wide variety of diseases in humans. The standard therapy for the management of such infections includes acyclovir (ACV) and penciclovir (PCV) with their respective prodrugs valaciclovir and famciclovir. Though effective, long term prophylaxis with the current drugs leads to development of drug-resistant viral isolates, particularly i...

  7. The RNA Template Channel of the RNA-Dependent RNA Polymerase as a Target for Development of Antiviral Therapy of Multiple Genera within a Virus Family

    NARCIS (Netherlands)

    van der Linden, Lonneke; Vives-Adrián, Laia; Selisko, Barbara; Ferrer-Orta, Cristina; Liu, Xinran; Lanke, Kjerstin; Ulferts, Rachel; De Palma, Armando M; Tanchis, Federica; Goris, Nesya; Lefebvre, David; De Clercq, Kris; Leyssen, Pieter; Lacroix, Céline; Pürstinger, Gerhard; Coutard, Bruno; Canard, Bruno; Boehr, David D; Arnold, Jamie J; Cameron, Craig E; Verdaguer, Nuria; Neyts, Johan; van Kuppeveld, Frank J M

    2015-01-01

    The genus Enterovirus of the family Picornaviridae contains many important human pathogens (e.g., poliovirus, coxsackievirus, rhinovirus, and enterovirus 71) for which no antiviral drugs are available. The viral RNA-dependent RNA polymerase is an attractive target for antiviral therapy. Nucleoside-b

  8. Drug: D06478 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available D06478 Drug Darunavir ethanolate (JAN); Prezista (TN) C27H37N3O7S. C2H6O 593.2771 5...BR:br08301] 6 Agents against pathologic organisms and parasites 62 Chemotherapeutics 625 Antivirals 6250 Antivirals D06478 Daruna...ING ANTIVIRALS J05AE Protease inhibitors J05AE10 Darunavir D06478 Darunavir ethanolate (JAN) USP drug classification [BR:br08302] Antivirals Anti-HIV Agents, Protease Inhibitors Darunavir D06478 Darunavir ethanolate ...08307] Antivirals Anti-HIV agent Protease inhibitor (PIs) Nonpeptidic Daruna...vir [ATC:J05AE10] D06478 Darunavir ethanolate (JAN) CAS: 635728-49-3 PubChem: 47208134

  9. Using the Ferret as an Animal Model for Investigating Influenza Antiviral Effectiveness.

    Science.gov (United States)

    Oh, Ding Y; Hurt, Aeron C

    2016-01-01

    The concern of the emergence of a pandemic influenza virus has sparked an increased effort toward the development and testing of novel influenza antivirals. Central to this is the animal model of influenza infection, which has played an important role in understanding treatment effectiveness and the effect of antivirals on host immune responses. Among the different animal models of influenza, ferrets can be considered the most suitable for antiviral studies as they display most of the human-like symptoms following influenza infections, they can be infected with human influenza virus without prior viral adaptation and have the ability to transmit influenza virus efficiently between one another. However, an accurate assessment of the effectiveness of an antiviral treatment in ferrets is dependent on three major experimental considerations encompassing firstly, the volume and titer of virus, and the route of viral inoculation. Secondly, the route and dose of drug administration, and lastly, the different methods used to assess clinical symptoms, viral shedding kinetics and host immune responses in the ferrets. A good understanding of these areas is necessary to achieve data that can accurately inform the human use of influenza antivirals. In this review, we discuss the current progress and the challenges faced in these three major areas when using the ferret model to measure influenza antiviral effectiveness. PMID:26870031

  10. Using the ferret as an animal model for investigating influenza antiviral effectiveness

    Directory of Open Access Journals (Sweden)

    Ding Yuan Oh

    2016-02-01

    Full Text Available The concern of the emergence of a pandemic influenza virus has sparked an increased effort towards the development and testing of novel influenza antivirals. Central to this is the animal model of influenza infection, which has played an important role in understanding treatment effectiveness and the effect of antivirals on host immune responses. Among the different animal models of influenza, ferrets can be considered the most suitable for antiviral studies as they display most of the human-like symptoms following influenza infections, they can be infected with human influenza virus without prior viral adaptation and have the ability to transmit influenza virus efficiently between one another. However, an accurate assessment of the effectiveness of an antiviral treatment in ferrets is dependent on three major experimental considerations encompassing firstly, the volume and titre of virus, and the route of viral inoculation. Secondly, the route and dose of drug administration, and lastly, the different methods used to assess clinical symptoms, viral shedding kinetics and host immune responses in the ferrets. A good understanding of these areas is necessary to achieve data that can accurately inform the human use of influenza antivirals. In this review, we discuss the current progress and the challenges faced in these three major areas when using the ferret model to measure influenza antiviral effectiveness.

  11. Antiviral active peptide from oyster

    Science.gov (United States)

    Zeng, Mingyong; Cui, Wenxuan; Zhao, Yuanhui; Liu, Zunying; Dong, Shiyuan; Guo, Yao

    2008-08-01

    An active peptide against herpes virus was isolated from the enzymic hydrolysate of oyster ( Crassostrea gigas) and purified with the definite direction hydrolysis technique in the order of alcalase and bromelin. The hydrolysate was fractioned into four ranges of molecular weight (>10 kDa, 10 5 kDa, 5 1 kDa and <1 kDa) using ultrafiltration membranes and dialysis. The fraction of 10 5 kDa was purified using consecutive chromatographic methods including DEAE Sephadex A-25 column, Sephadex G-25 column, and high performance liquid chromatogram (HPLC) by activity-guided isolation. The antiviral effect of the obtained peptide on herpetic virus was investigated in Vero cells by observing cytopathic effect (CPE). The result shows that the peptide has high inhibitory activity on herpetic virus.

  12. Antiviral active peptide from oyster

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    An active peptide against herpes virus was isolated from the enzymic hydrolysate of oyster (Crassostrea gigas) and purified with the definite direction hydrolysis technique in the order of alcalase and bromelin. The hydrolysate was fractioned into four ranges of molecular weight (>10 kDa, 10-5 kDa, 5-1 kDa and <1 kDa) using ultrafiltration membranes and dialysis. The fraction of 10?5 kDa was purified using consecutive chromatographic methods including DEAE Sephadex A-25 column, Sephadex G-25 column, and high performance liquid chromatogram (HPLC) by activity-guided isolation. The antiviral effect of the obtained peptide on herpetic virus was investigated in Vero cells by observing cytopathic effect (CPE). The result shows that the peptide has high inhibitory activity on herpetic virus.

  13. Drug: D02748 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available (generical recombination) (JAN); Peginterferon alfa-2b (INN) USP drug classification [BR:br08302] Antivirals Anti-hepatitis...(JAN); Peginterferon alfa-2b (INN) Anti-hepatitis C (HCV) Agents Peginterferon Al

  14. Antiviral and anti-inflammatory activity of arbidol hydrochloride in influenza A (H1N1) virus infection

    Institute of Scientific and Technical Information of China (English)

    Qiang LIU; Hai-rong XIONG; Li LU; Yuan-yuan LIU; Fan LUO; Wei HOU; Zhan-qiu YANG

    2013-01-01

    Aim:To investigate the effects of arbidol hydrochloride (ARB),a widely used antiviral agent,on the inflammation induced by influenza virus.Methods:MDCK cells were infected with seasonal influenza A/FM/1/47 (H1N1) or pandemic influenza A/Hubei/71/2009 (H1N1).In vitro cytotoxicity and antiviral activity of ARB was determined using MTT assay.BALB/c mice were infected with A/FM/1/47 (H1N1).Four hours later the mice were administered ARB (45,90,and 180 mg·kg-1·d-1) or the neuraminidase inhibitor oseltamivir (22.5mg·kg-1·d-1) via oral gavage once a day for 5 d.Body-weight,median survival time,viral titer,and lung index of the mice were measured.The levels of inflammatory cytokines were examined using real-time RT-PCR and ELISA.Results:Both H1N1 stains were equally sensitive to ARB as tested in vitro.In the infected mice,ARB (90 and 180 mg·kg-1·d-1)significantly decreased the mortality,alleviated virus-induced lung lesions and viral titers.Furthermore,ARB suppressed the levels of IL-1β,IL-6,IL-12,and TNF-α,and elevated the level of IL-10 in the bronchoalveolar lavage fluids and lung tissues.However,ARB did not significantly affect the levels of IFN-α and IFN-γ,but reduced the level of IFN-β1 in lung tissues at 5 dpi.In peritoneal macrophages challenged with A/FM/1/47 (H1N1) or poly I∶C,ARB (20 μmol/L) suppressed the levels of IL-1β,IL-6,IL-12,and TNF-α,and elevated the level of IL-10.Oseltamivir produced comparable alleviation of virus-induced lung lesions with more reduction in the viral titers,but less effective modulation of the inflammatory cytokines.Conclusion:ARB efficiently inhibits both H1N1 stains and diminishes both viral replication and acute inflammation through modulating the expression of inflammatory cytokines.

  15. Drug: D02297 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available n [BR:br08301] 6 Agents against pathologic organisms and parasites 62 Chemotherapeutics 625 Antivirals 6250 Ant...D02297 Mixture, Drug Emtricitabine - tenofovir disoproxil fumarate mixt; Truvada (T...N) Emtricitabine [DR:D01199], Tenofovir disoproxil fumarate [DR:D01982] Antiviral [DS:H00406] Therapeutic cate...ivirals D02297 Emtricitabine - tenofovir disoproxil fumarate mixt Anatomical Therapeutic Chemical (ATC) classificat...ofovir disoproxil and emtricitabine D02297 Emtricitabine - tenofovir disoproxil fumarate mixt USP drug classificat

  16. Drug: D07896 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available nhibitors J05AF10 Entecavir D07896 Entecavir (INN) USP drug classification [BR:br08302] Antivirals Anti-hepatitis...atitis B infection [DS:H00412] ATC code: J05AF10 Nucleoside reverse transcriptase i...D07896 Drug Entecavir (INN) C12H15N5O3 277.1175 277.2792 D07896.gif Antiviral agent used in treatment of hep

  17. Drug: D10081 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available ease inhibitor [CPD:C18290 C18291] ko05160 Hepatitis C USP drug classification [BR:br08302] Antivirals Anti-hepatitis...D10081 Drug Simeprevir (JAN/USAN); Olysio (TN) C38H47N5O7S2 749.2917 749.9391 D10081.gif Treatment of hepati...tis C [DS:H00413] Macrocyclic antivirus Direct-acting antiviral (DAA) NS3/NS4A prot

  18. Drug: D08483 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available D08483 Drug Rimantadine (INN) C12H21N 179.1674 179.3018 D08483.gif Antiviral [DS:H00398] Same as ... : C07236 ATC code: J05AC02 Adamantane derivative influenza ... A M2 proton channel blocker [VG:NC_004907_1 NC_002 ... P drug classification [BR:br08302] Antivirals Anti-influenza ... Agents Rimantadine D08483 Rimantadine (INN) Antiin ...

  19. Drug: D02737 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available D02737 Drug Palivizumab (genetical recombination) (JAN); Palivizumab (INN); Synagis... parasites 62 Chemotherapeutics 625 Antivirals 6250 Antivirals D02737 Palivizumab (genetica...pecific immunoglobulins J06BB16 Palivizumab D02737 Palivizumab (genetical recombi...tein monoclonal antibody Palivizumab [ATC:J06BB16] D02737 Palivizumab (genetical recombination) (JAN); Palivizumab (INN) CAS: 188039-54-5 PubChem: 47205815 DrugBank: DB00110 ...

  20. Drug: D05407 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available D05407 Drug Penciclovir (USAN/INN); Denavir (TN) C10H15N5O3 253.1175 253.2578 D0540...TICS FOR TOPICAL USE D06BB Antivirals D06BB06 Penciclovir D05407 Penciclovir (USAN/INN) J ANTIINFECTIVES FOR...s excl. reverse transcriptase inhibitors J05AB13 Penciclovir D05407 Penciclovir (...USAN/INN) USP drug classification [BR:br08302] Antivirals Antiherpetic Agents Penciclovir D05407 Penciclovir... (USAN/INN) Antiinfectives [BR:br08307] Antivirals Anti-HSV agent DNA polymerase inhibitor Purine analogue Penciclov

  1. Drug: D02124 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available D02124 Drug Penciclovir sodium (USAN); Denavir (TN) C10H14N5O3. Na 275.0994 275.239...LOGICAL USE D06B CHEMOTHERAPEUTICS FOR TOPICAL USE D06BB Antivirals D06BB06 Penciclovir D02124 Penciclovir s... J05AB Nucleosides and nucleotides excl. reverse transcriptase inhibitors J05AB13 Penciclov...ir D02124 Penciclovir sodium (USAN) USP drug classification [BR:br08302] Antivirals Antiherpetic Agents Penciclov...ir D02124 Penciclovir sodium (USAN) Antiinfectives [BR:br08307] Antivirals Anti-HSV agent DNA

  2. Drug: D04301 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available D04301 Drug Ganciclovir sodium (USAN); Cytovene IV (TN) C9H12N5O4. Na 277.0787 277....DIRECT ACTING ANTIVIRALS J05AB Nucleosides and nucleotides excl. reverse transcriptase inhibitors J05AB06 Ganciclovir D04301 Ganciclo...lovir D04301 Ganciclovir sodium (USAN) USP drug classifi...cation [BR:br08302] Antivirals Anti-cytomegalovirus (CMV) Agents Ganciclovir D04301 Ganciclovir sodium (USAN...) Antiinfectives [BR:br08307] Antivirals Anti-CMV agent DNA polymerase inhibitor Purine analogue Ganciclovir

  3. Drug: D02495 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available D02495 Drug Valganciclovir (INN) C14H22N6O5 354.1652 354.3617 D02495.gif Antiviral ...[DS:H00368] ATC code: J05AB14 prodrug, active substance: Ganciclovir [DR:D00333] DNA polymerase inhibitor [E...NTIVIRALS J05AB Nucleosides and nucleotides excl. reverse transcriptase inhibitors J05AB14 Valganciclovir D02495 Valganciclov...ir (INN) USP drug classification [BR:br08302] Antivirals Anti-cytomegalovirus (CMV) Agents Valganciclov...ir D02495 Valganciclovir (INN) Antiinfectives [BR:br08307] Antivirals

  4. Drug: D00579 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available D00579 Drug Foscarnet sodium (USAN/INN); Foscavir (TN) CO5P. 3Na 191.9176 191.9508 ...d derivatives J05AD01 Foscarnet D00579 Foscarnet sodium (USAN/INN) USP drug classification [BR:br08302] Anti...virals Anti-cytomegalovirus (CMV) Agents Foscarnet D00579 Foscarnet sodium (USAN/INN) Antiherpetic Agents Foscarnet D00579 Foscar... Anti-CMV agent DNA polymerase inhibitor Phosphonic acid derivatives Foscarnet [ATC:J05AD01] D00579 Foscarne...05 ANTIVIRALS FOR SYSTEMIC USE J05A DIRECT ACTING ANTIVIRALS J05AD Phosphonic aci

  5. 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.

  6. Transdermal Delivery and Cutaneous Targeting of Antivirals using a Penetration Enhancer and Lysolipid Prodrugs

    Czech Academy of Sciences Publication Activity Database

    Diblíková, D.; Kopečná, M.; Školová, B.; Krečmerová, Marcela; Roh, J.; Hrabálek, A.; Vávrová, K.

    2014-01-01

    Roč. 31, č. 4 (2014), s. 1071-1081. ISSN 0724-8741 Grant ostatní: GA ČR(CZ) GAP207/11/0365 Institutional support: RVO:61388963 Keywords : acyclic nucleoside phosphonate antivirals * lysolipid prodrug * penetration enhancer * skin absorption * transdermal drug delivery Subject RIV: FR - Pharmacology ; Medidal Chemistry Impact factor: 3.420, year: 2014

  7. In silico modification of oseltamivir as neuraminidase inhibitor of influenza A virus subtype H1N1

    Institute of Scientific and Technical Information of China (English)

    Usman Sumo Friend Tambunan; Rizky Archintya Rachmania; Arli Aditya Parikesit

    2015-01-01

    This research focused on the modification of the functional groups of oseltamivir as neuraminidase inhibitor against influenza A virus subtype H1N1.Interactions of three of the best ligands were evaluated in the hydrated state using molecular dynamics simulation at two different temperatures.The docking result showed that AD3BF2D ligand (N-[(1S,6R)-5-amino-5-{[(2R,3S,4S)-3,4-dihydroxy-4-(hydroxymethyl) tetrahydrofuran-2-yl]oxy}-4-formylcyclohex-3-en-l-yl]acetamide-3-(1-ethylpropoxy)-1-cyclohexene-1-carboxylate) had better binding energy values than standard oseltamivir.AD3BF2D had several interactions,including hydrogen bonds,with the residues in the catalytic site of neuraminidase as identified by molecular dynamics simulation.The results showed that AD3BF2D ligand can be used as a good candidate for neuraminidase inhibitor to cope with influenza A virus subtype H1N1.

  8. Antiviral activities of whey proteins.

    Science.gov (United States)

    Ng, Tzi Bun; Cheung, Randy Chi Fai; Wong, Jack Ho; Wang, Yan; Ip, Denis Tsz Ming; Wan, David Chi Cheong; Xia, Jiang

    2015-09-01

    Milk contains an array of proteins with useful bioactivities. Many milk proteins encompassing native or chemically modified casein, lactoferrin, alpha-lactalbumin, and beta-lactoglobulin demonstrated antiviral activities. Casein and alpha-lactalbumin gained anti-HIV activity after modification with 3-hydroxyphthalic anhydride. Many milk proteins inhibited HIV reverse transcriptase. Bovine glycolactin, angiogenin-1, lactogenin, casein, alpha-lactalbumin, beta-lactoglobulin, bovine lactoferrampin, and human lactoferrampin inhibited HIV-1 protease and integrase. Several mammalian lactoferrins prevented hepatitis C infection. Lactoferrin, methylated alpha-lactalbumin and methylated beta-lactoglobulin inhibited human cytomegalovirus. Chemically modified alpha-lactalbumin, beta-lactoglobulin and lysozyme, lactoferrin and lactoferricin, methylated alpha-lactalbumin, methylated and ethylated beta-lactoglobulins inhibited HSV. Chemically modified bovine beta-lactoglobulin had antihuman papillomavirus activity. Beta-lactoglobulin, lactoferrin, esterified beta-lactoglobulin, and esterified lactoferrindisplayed anti-avian influenza A (H5N1) activity. Lactoferrin inhibited respiratory syncytial virus, hepatitis B virus, adenovirus, poliovirus, hantavirus, sindbis virus, semliki forest virus, echovirus, and enterovirus. Milk mucin, apolactoferrin, Fe(3+)-lactoferrin, beta-lactoglobulin, human lactadherin, bovine IgG, and bovine kappa-casein demonstrated antihuman rotavirus activity. PMID:26198883

  9. Identification of a series of compounds with potent antiviral activity for the treatment of enterovirus infections.

    Science.gov (United States)

    MacLeod, Angus M; Mitchell, Dale R; Palmer, Nicholas J; Van de Poël, Hervé; Conrath, Katja; Andrews, Martin; Leyssen, Pieter; Neyts, Johan

    2013-07-11

    Rhinovirus (genus enterovirus) infections are responsible for many of the severe exacerbations of asthma and chronic obstructive pulmonary disease. Other members of the genus can cause life-threatening acute neurological infections. There is currently no antiviral drug approved for the treatment of such infections. We have identified a series of potent, broad-spectrum antiviral compounds that inhibit the replication of the human rhinovirus, Coxsackie virus, poliovirus, and enterovirus-71. The mechanism of action of the compounds has been established as inhibition of a lipid kinase, PI4KIIIβ. Inhibition of hepatitis C replication in a replicon assay correlated with enterovirus inhibition. PMID:24900715

  10. Antiviral activity of viro care gz-08 against newcastle disease virus in poultry and its in-vitro cytotoxicity assay

    International Nuclear Information System (INIS)

    Newcastle disease (ND), one of the most important disease of poultry throughout the World is caused by Newcastle Disease Virus (NDV). It is causing huge economic losses in poultry industry of Pakistan. Regardless of vaccination, other prevention and control measures are necessary to prevent ND outbreaks. Natural resources have been exploited to obtain antiviral compounds in several latest studies. In this study, the antiviral activity of Viro Care GZ-081 was checked up in-vitro, in-ovo and in-vivo. The cytotoxicity assay of the product was performed using Vero cell line. All the trials revealed that the stock solution and 1:2 dilution of GZ-08 had some antiviral activity as well as were cytotoxic. As the concentration decreased, cytotoxicity as well as antiviral activities were lost. Based on these findings, it was concluded that GZ-08 sanitizer or spray can be used as antiviral agent to clean or disinfect some non-living surfaces against different viruses in general and NDV in particular. However, in-vivo use of GZ-08 in poultry against NDV is recommended only as pre-treatment with ND vaccines as it significantly reduced morbidity and mortality as compared to the use of vaccines alone. However, further work is recommended in future on GZ-08 for its use as post-treatment of ND as well as on other antiviral compounds of natural origin to develop a novel antiviral drug against NDV in poultry. (author)

  11. Antiviral effect of ranpirnase against Ebola virus.

    Science.gov (United States)

    Hodge, Thomas; Draper, Ken; Brasel, Trevor; Freiberg, Alexander; Squiquera, Luis; Sidransky, David; Sulley, Jamie; Taxman, Debra J

    2016-08-01

    The recent epidemic of Ebola has intensified the need for the development of novel antiviral therapeutics that prolong and improve survival against deadly viral diseases. We sought to determine whether ranpirnase, an endoribonuclease from Rana pipiens with a demonstrated human safety profile in phase III oncology trials, can reduce titers of Ebola virus (EBOV) in infected cells, protect mice against mouse-adapted EBOV challenge, and reduce virus levels in infected mice. Our results demonstrate that 0.50 μg/ml ranpirnase is potently effective at reducing EBOV Zaire Kikwit infection in cultured Vero E6 cells (Selectivity Index 47.8-70.2). In a prophylactic study, a single intravenous dose of 0.1 mg/kg ranpirnase protected 70% of mice from progressive infection. Additionally, in a post-exposure prophylactic study, 100% of female mice survived infection after intraperitoneal administration of 0.1 mg/kg ranpirnase for ten days beginning 1 h post challenge. Most of the male counterparts were sacrificed due to weight loss by Study Day 8 or 9; however, the Clinical Activity/Behavior scores of these mice remained low and no significant microscopic pathologies could be detected in the kidneys, livers or spleens. Furthermore, live virus could not be detected in the sera of ranpirnase-treated mice by Study Day 8 or in the kidneys, livers or spleens by Study Day 12, and viral RNA levels declined exponentially by Study Day 12. Because ranpirnase is exceptionally stable and has a long track record of safe intravenous administration to humans, this drug provides a promising new candidate for clinical consideration in the treatment of Ebola virus disease alone or in combination with other therapeutics. PMID:27350309

  12. Repurposing Kinase Inhibitors as Antiviral Agents to Control Influenza A Virus Replication.

    Science.gov (United States)

    Perwitasari, Olivia; Yan, Xiuzhen; O'Donnell, Jason; Johnson, Scott; Tripp, Ralph A

    2015-12-01

    Influenza A virus (IAV) infection causes seasonal epidemics of contagious respiratory illness that causes substantial morbidity and some mortality. Regular vaccination is the principal strategy for controlling influenza virus, although vaccine efficacy is variable. IAV antiviral drugs are available; however, substantial drug resistance has developed to two of the four currently FDA-approved antiviral drugs. Thus, new therapeutic approaches are being sought to reduce the burden of influenza-related disease. A high-throughput screen using a human kinase inhibitor library was performed targeting an emerging IAV strain (H7N9) in A549 cells. The inhibitor library contained 273 structurally diverse, active cell permeable kinase inhibitors with known bioactivity and safety profiles, many of which are at advanced stages of clinical development. The current study shows that treatment of human A549 cells with kinase inhibitors dinaciclib, flavopiridol, or PIK-75 exhibits potent antiviral activity against H7N9 IAV as well as other IAV strains. Thus, targeting host kinases can provide a broad-spectrum therapeutic approach against IAV. These findings provide a path forward for repurposing existing kinase inhibitors safely as potential antivirals, particularly those that can be tested in vivo and ultimately for clinical use. PMID:26192013

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

    Science.gov (United States)

    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. In the current study, the antiviral activity of hederasaponin B against EV71 C3 and C4a was determined by cytopathic effect (CPE) reduction method and western blot assay. Our results demonstrated that hederasaponin B and 30% ethanol extract of Hedera helix containing hederasaponin B showed significant antiviral activity against EV71 subgenotypes C3 and C4a by reducing the formation of a visible CPE. Hederasaponin B also inhibited the viral VP2 protein expression, suggesting the inhibition of viral capsid protein synthesis.These results suggest that hederasaponin B and Hedera helix extract containing hederasaponin B can be novel drug candidates with broad-spectrum antiviral activity against various subgenotypes of EV71. PMID:24596620

  14. NaVirCept - Nucleic Acid-Based Anti-Viral Project

    International Nuclear Information System (INIS)

    Vaccines are generally considered to be the most effective countermeasures to bacterial and viral diseases, however, licensed vaccines against many disease agents are either not available or their efficacies have not been demonstrated. Vaccines are generally agent specific in terms of treatment spectrum and are subject to defeat through natural mutation or through directed efforts. With respect to viral therapeutics, one of the major limitations associated with antiviral drugs is acquired drug resistance caused by antigenic shift or drift. A number of next-generation prophylactic and/or therapeutic measures are on the horizon. Of these, nucleic acid-based drugs are showing great antiviral potential. These drugs elicit long-lasting, broad spectrum protective immune responses, especially to respiratory viral pathogens. The Nucleic Acid-Based Antiviral (NaVirCept) project provides the opportunity to demonstrate the effectiveness of novel medical countermeasures against military-significant endemic and other viral threat agents. This project expands existing DRDC drug delivery capability development, in the form of proprietary liposome intellectual property, by coupling it with leading-edge nucleic acid-based technology to deliver effective medical countermeasures that will protect deployed personnel and the warfighter against a spectrum of viral disease agents. The technology pathway will offer a means to combat emerging viral diseases or modified threat agents such as the bird flu or reconstructed Spanish flu without going down the laborious, time-consuming and expensive paths to develop countermeasures for each new and/or emerging viral disease organism.(author)

  15. Update on emerging antivirals for the management of herpes simplex virus infections: a patenting perspective.

    Science.gov (United States)

    Vadlapudi, Aswani D; Vadlapatla, Ramya K; Mitra, Ashim K

    2013-04-01

    Herpes simplex virus (HSV) infections can be treated efficiently by the application of antiviral drugs. The herpes family of viruses is responsible for causing a wide variety of diseases in humans. The standard therapy for the management of such infections includes acyclovir (ACV) and penciclovir (PCV) with their respective prodrugs valaciclovir and famciclovir. Though effective, long term prophylaxis with the current drugs leads to development of drug-resistant viral isolates, particularly in immunocompromised patients. Moreover, some drugs are associated with dose-limiting toxicities which limit their further utility. Therefore, there is a need to develop new antiherpetic compounds with different mechanisms of action which will be safe and effective against emerging drug resistant viral isolates. Significant advances have been made towards the design and development of novel antiviral therapeutics during the last decade. As evident by their excellent antiviral activities, pharmaceutical companies are moving forward with several new compounds into various phases of clinical trials. This review provides an overview of structure and life cycle of HSV, progress in the development of new therapies, update on the advances in emerging therapeutics under clinical development and related recent patents for the treatment of Herpes simplex virus infections. PMID:23331181

  16. A fresh look at an antiviral helicase

    Institute of Scientific and Technical Information of China (English)

    Leonid Gitlin; Marco Colonna

    2007-01-01

    @@ In order to survive,all organlsms must guard against viral infections.Recognition of viruses is accomplished via multiple sensors.Many mammalian proteins can recognize viral products,such as double-stranded RNA(dsRNA),yet feW of them are known to induce interferon,the central antiviral messenger.Since interferon is indispensable for Successful antiviral defense [1],the interferon-inducing sensors have been of particular interest.However,a clear understanding of such sensors has been elusive,and the first well-established sensor family,the toll-like receptors (TLRs),was described relatively recently[2].Antiviral TLRS are positioned in the endosomes,where they report the appearance of viral genetic material(DNA,single-and double-stranded RNA).

  17. Report of the first Asia-Pacific Forum on antiviral treatment of influenza, Asia-Pacific Alliance for the Control of Influenza, Bangkok, 14 June 2012.

    Science.gov (United States)

    Jennings, Lance C; Smith, David W; Chan, Paul K S

    2013-11-01

    On 14 June 2012, the Asia-Pacific Alliance for the Control of Influenza (APACI) convened the first Antiviral Forum jointly with the Influenza Foundation of Thailand and the Thailand Department of Disease Control. The goals of the meeting were to improve pandemic planning in the region from lessons learned during the 2009 pandemic, particularly with regard to the safety and efficacy of antiviral use; gain a better understanding of the therapeutic use of antivirals in seasonal influenza; review and analyse the official influenza control policies of Asia-Pacific countries and evidence gaps to support policy development; and to establish collaborative relationships to promote best practices in the use of antivirals for the treatment of influenza. The urgent need for education highlighting the importance of influenza and the benefits of antiviral drug use in the Asia-Pacific region was identified. PMID:23756551

  18. Drug: D00222 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available D00222 Drug Aciclovir (JP16/INN); Acyclovir (USP); Sitavig (TN); Zovirax (TN) C8H11...Ophthalmic agents 1319 Others D00222 Aciclovir (JP16/INN); Acyclovir (USP) 6 Agents against pathologic organ...isms and parasites 62 Chemotherapeutics 625 Antivirals 6250 Antivirals D00222 Aciclov...SE D06BB Antivirals D06BB03 Aciclovir D00222 Aciclovir (JP16/INN); Acyclovir (USP...eosides and nucleotides excl. reverse transcriptase inhibitors J05AB01 Aciclovir D00222 Aciclovir (JP16/INN)

  19. Comparative study on the antiviral activity of selected monoterpenes derived from essential oils.

    Science.gov (United States)

    Astani, Akram; Reichling, Jürgen; Schnitzler, Paul

    2010-05-01

    Essential oils are complex natural mixtures, their main constituents, e.g. terpenes and phenylpropanoids, being responsible for their biological properties. Essential oils from eucalyptus, tea tree and thyme and their major monoterpene compounds alpha-terpinene, gamma-terpinene, alpha-pinene, p-cymene, terpinen-4-ol, alpha-terpineol, thymol, citral and 1,8-cineole were examined for their antiviral activity against herpes simplex virus type 1 (HSV-1) in vitro. These essential oils were able to reduce viral infectivity by >96%, the monoterpenes inhibited HSV by about >80%. The mode of antiviral action has been determined, only moderate antiviral effects were revealed by essential oils and monoterpenes when these drugs were added to host cells prior to infection or after entry of HSV into cells. However, both essential oils and monoterpenes exhibited high anti-HSV-1 activity by direct inactivation of free virus particles. All tested drugs interacted in a dose-dependent manner with herpesvirus particles thereby inactivating viral infection. Among the analysed compounds, monoterpene hydrocarbons were slightly superior to monoterpene alcohols in their antiviral activity, alpha-pinene and alpha-terpineol revealed the highest selectivity index. However, mixtures of different monoterpenes present in natural tea tree essential oil revealed a ten-fold higher selectivity index and a lower toxicity than its isolated single monoterpenes. PMID:19653195

  20. Antiviral activity of constituents of Tamus communis.

    Science.gov (United States)

    Aquino, R; Conti, C; De Simone, F; Orsi, N; Pizza, C; Stein, M L

    1991-10-01

    The antiviral activity of the phenanthrene derivatives 1-6, of the spyrostane triglycosides dioscin (7) and gracillin (8), of the furostanol tetraglycosides methylprotodioscin (9), its (25S) epimer methylprotoneodioscin (10), and methylprotogracillin 11, have been tested towards two RNA viruses: vesicular stomatitis virus and human rhinovirus type 1B. All these products were extracted from the rizomes of Tamus communis L; compound 11 was isolated also from Asparagus cochinchinesis, together with pseudoprotodioscin (12), a 20 (22)-unsaturated furostanoside, which was also investigated for antiviral activity. The results were of some interest mainly for the phenanthrene derivatives. PMID:1667189

  1. Drug: D00398 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available D00398 Drug Valaciclovir hydrochloride (JAN); Valacyclovir hydrochloride (USAN); Va...tegory: 6250 ATC code: J05AB11 prodrug, active substance: Aciclovir [DR:D00222] DNA polymerase inhibitor Tra...erapeutics 625 Antivirals 6250 Antivirals D00398 Valaciclovir hydrochloride (JAN); Valacyclovir hydrochlorid...and nucleotides excl. reverse transcriptase inhibitors J05AB11 Valaciclovir D00398 Valaciclovir hydrochlorid...ntivirals Antiherpetic Agents Valacyclovir D00398 Valaciclovir hydrochloride (JAN); Valacyclovir hydrochlori

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

    Directory of Open Access Journals (Sweden)

    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.

  3. Viral genome imaging of hepatitis C virus to probe heterogeneous viral infection and responses to antiviral therapies.

    Science.gov (United States)

    Ramanan, Vyas; Trehan, Kartik; Ong, Mei-Lyn; Luna, Joseph M; Hoffmann, Hans-Heinrich; Espiritu, Christine; Sheahan, Timothy P; Chandrasekar, Hamsika; Schwartz, Robert E; Christine, Kathleen S; Rice, Charles M; van Oudenaarden, Alexander; Bhatia, Sangeeta N

    2016-07-01

    Hepatitis C virus (HCV) is a positive single-stranded RNA virus of enormous global health importance, with direct-acting antiviral therapies replacing an immunostimulatory interferon-based regimen. The dynamics of HCV positive and negative-strand viral RNAs (vRNAs) under antiviral perturbations have not been studied at the single-cell level, leaving a gap in our understanding of antiviral kinetics and host-virus interactions. Here, we demonstrate quantitative imaging of HCV genomes in multiple infection models, and multiplexing of positive and negative strand vRNAs and host antiviral RNAs. We capture the varying kinetics with which antiviral drugs with different mechanisms of action clear HCV infection, finding the NS5A inhibitor daclatasvir to induce a rapid decline in negative-strand viral RNAs. We also find that the induction of host antiviral genes upon interferon treatment is positively correlated with viral load in single cells. This study adds smFISH to the toolbox available for analyzing the treatment of RNA virus infections. PMID:27128351

  4. Drug: D08664 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available D08664 Drug Valaciclovir (INN); Valacyclovir; Valtrex (TN) C13H20N6O4 324.1546 324....3357 D08664.gif Antiviral [DS:H00365] ATC code: J05AB11 prodrug, active substance: Aciclovir [DR:D00222] DNA...xcl. reverse transcriptase inhibitors J05AB11 Valaciclovir D08664 Valaciclovir (INN) USP drug classification... [BR:br08302] Antivirals Antiherpetic Agents Valacyclovir D08664 Valaciclovir (IN...ir [ATC:J05AB11] D08664 Valaciclovir (INN) CAS: 124832-26-4 PubChem: 96025347 DrugBank: DB00577 LigandBox: D

  5. IFN-gamma: Novel antiviral cytokines

    DEFF Research Database (Denmark)

    Ank, Nina; West, Hans; Paludan, Søren Riis

    2006-01-01

    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 the...

  6. The IKK Kinases: Operators of Antiviral Signaling

    Directory of Open Access Journals (Sweden)

    Alissa M. Pham

    2010-01-01

    Full Text Available The ability of a cell to combat an intracellular pathogen requires a mechanism to recognize the threat and elicit a transcriptional response against it. In the context of virus infection, the cell must take measures to inhibit viral replication, meanwhile, convey warning signals to neighboring cells of the imminent threat. This immune response is predominantly mediated by the production of cytokines, notably, interferon beta (IFNβ. IFNβ signaling results in the transcriptional induction of over one hundred antiviral gene products whose timely expression renders infected cells more capable of inhibiting virus replication, while providing the uninfected cells with the reinforcements to generate a less permissive cellular environment. Induction of IFNβ and many aspects of the antiviral response pivot on the function of the IKK and IKK-related kinases. Despite sharing high levels of homology and some degree of functional redundancy, the classic IKK kinases: IKKα and IKKβ, and the IKK-related kinases: TBK1 and IKKε, perform distinct roles in regulating the host antiviral defense. These kinases serve as molecular operators in their cooperative ability to integrate incoming cellular cues and act on a range of essential antiviral transcription factors to reshape the cellular transcriptome during infection.

  7. Anti-viral Responses in Insects

    Science.gov (United States)

    Although the study of anti-viral responses in insects has lagged behind studies of responses to other types of pathogens, progress has begun to rapidly accelerate over the past few years. Insects are subject to infection by many different kinds of DNA and RNA viruses. These include viruses that ar...

  8. Antiviral Prophylaxis and H1N1

    Centers for Disease Control (CDC) Podcasts

    2011-07-14

    Dr. Richard Pebody, a consultant epidemiologist at the Health Protection Agency in London, UK, discusses the use of antiviral post-exposure prophylaxis and pandemic H1N1.  Created: 7/14/2011 by National Center for Emerging Zoonotic and Infectious Diseases (NCEZID).   Date Released: 7/18/2011.

  9. Evidence of person-to-person transmission of oseltamivir-resistant pandemic influenza A(H1N1) 2009 virus in a hematology unit.

    Science.gov (United States)

    Moore, Catherine; Galiano, Monica; Lackenby, Angie; Abdelrahman, Tamer; Barnes, Rosemary; Evans, Meirion R; Fegan, Christopher; Froude, Susannah; Hastings, Mark; Knapper, Steven; Litt, Emma; Price, Nicola; Salmon, Roland; Temple, Mark; Davies, Eleri

    2011-01-01

    We describe the first confirmed person-to-person transmission of oseltamivir-resistant pandemic influenza A(H1N1) 2009 virus that occurred in a hematology unit in the United Kingdom. Eleven cases of (H1N1) 2009 virus infection were identified, of which, ten were related as shown by sequence analysis of the hemagglutinin and neuraminidase genes. H275Y analysis demonstrated that 8 of 10 case patients had oseltamivir-resistant virus, with 4 of 8 case patients infected by direct transmission of resistant virus. Zanamivir should be considered as first-line therapy for influenza in patients with lymphopenic hematological conditions and uptake of influenza vaccination encouraged to further reduce the number of susceptible individuals. PMID:21148492

  10. Polymyxin-B-immobilized-fiber column hemoperfusion with oseltamivir treatment for ARDS due to influenza H1N1/09

    Science.gov (United States)

    Binh, Nguyen Gia; Manabe, Toshie; Co, Dao Xuan; Tuan, Nguyen Dang; Thach, Pham The; Kudo, Koichiro

    2015-01-01

    Acute respiratory distress syndrome (ARDS) is one of the severe complications of influenza H1N1/09 infection, resulting in high mortality. Effective treatment strategies for ARDS are needed. This report presents two cases of ARDS due to influenza in Vietnam. Both cases were similar in terms of starting symptoms, the rapid progression to ARDS, and the treatment strategy, direct hemoperfusion with a polymyxin-B-immobilized fiber column (PMX-DHP) and oseltamivir. However, the clinical course of disease and the outcomes were different. For case 1, treatment was initiated on day 4 following the onset of hypoxemia due to ARDS. Symptoms improved rapidly after treatment and the patient was discharged on day 12. For case 2, treatment was initiated on day 9 after the onset of symptoms. Despite intensive therapy, the patient died on day 18. In conclusion, treatment with PMX-DHP and oseltamivir is effective on ARDS due to influenza but only if initiated early. PMID:26090112

  11. Antiviral treatment in patients with cytomegalovirus positive ulcerative colitis

    Institute of Scientific and Technical Information of China (English)

    Kadir; Ozturk

    2014-01-01

    Cytomegalovirus(CMV) is a common virus in patients with ulcerative colitis receiving immunosuppressive drugs. Many studies suggested that CMV infection is an exacerbating factor in patients with ulcerative colitis. The role of CMV in exacerbations of ulcerative colitis has been discussed. One of studies starting this discussion is an article entitled "CMV positive ulcerative colitis: A single center experience and literature review" by Kopylov et al. However, we think that there are some points that should be emphasized about the study. Especially, the small number of patients in the study has led to meaningless results. Large controlled prospective trials are needed to clarify the benefit of antiviral therapy for active ulcerative colitis patients.

  12. Effect of an Echinacea-Based Hot Drink Versus Oseltamivir in Influenza Treatment: A Randomized, Double-Blind, Double-Dummy, Multicenter, Noninferiority Clinical Trial

    Directory of Open Access Journals (Sweden)

    Karel Rauš

    2015-12-01

    Conclusions: Echinaforce Hotdrink is as effective as oseltamivir in the early treatment of clinically diagnosed and virologically confirmed influenza virus infections with a reduced risk of complications and adverse events. It appears to be an attractive treatment option, particularly suitable for self-care. Clinical trial identifier: Eudra-CT: 2010-021571-88. (Curr Ther Res Clin Exp. 2015; 77:66–72

  13. Drug: D00901 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available D00901 Drug Rimantadine hydrochloride (USAN); Flumadine (TN) C12H21N. HCl 215.1441 215.7628 D009 ... TC code: J05AC02 Adamantane derivative Indication: Influenza ... A influenza ... A M2 proton channel blocker [VG:NC_004 ... P drug classification [BR:br08302] Antivirals Anti-influenza ... Agents Rimantadine D00901 Rimantadine hydrochlorid ...

  14. Drug: D06806 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available D06806 Drug Measles virus vaccine live (USP) Immunizing agent [active] Component of... M-M-Vax (TN) map07044 Antiviral agents USP drug classification [BR:br08302] Immunological Agents Vaccines Measles... virus vaccine live D06806 Measles virus vaccine live (USP) PubChem: 47208457 ...

  15. Determination of Appropriate Dosing of Influenza Drugs in Pediatric Patients

    OpenAIRE

    Acosta, EP; Kimberlin, DW

    2010-01-01

    Dose-finding studies of influenza antiviral drugs are challenging because it is difficult to enroll subjects in pediatric interventional studies and also because of the lack of concentration (or toxicity)–response relationships, the short duration of antiviral therapy, and the continually developing metabolic profiles of infants and young children. The evaluation of influenza antiviral agents in premature infants adds even more complexity. Recent advances in exposure-targeted study designs an...

  16. The promise and progress of RNA-interference-based antiviral therapy for respiratory syncytial virus.

    OpenAIRE

    V. V. Vysochinskayа; E. V. Esaulenko; Bogdanov, A A; D. N. Ghorab; N. A. Кnyazev; Dubina, M. V.

    2014-01-01

    Respiratory syncytial virus (RSV) is a major cause of morbidity in infants, young children, and the elderly worldwide. Presently, there are no explicit recommendations for RSV treatment apart from supportive care. Recent progress in studies of the mechanism of RNA interference suggests the formation of a new class of antiviral drugs in the treatment of RSV infection and related respiratory diseases.

  17. The promise and progress of RNA-interference-based antiviral therapy for respiratory syncytial virus.

    Directory of Open Access Journals (Sweden)

    V. V. Vysochinskayа

    2012-01-01

    Full Text Available Respiratory syncytial virus (RSV is a major cause of morbidity in infants, young children, and the elderly worldwide. Presently, there are no explicit recommendations for RSV treatment apart from supportive care. Recent progress in studies of the mechanism of RNA interference suggests the formation of a new class of antiviral drugs in the treatment of RSV infection and related respiratory diseases.

  18. Design, synthesis, and antiviral properties of 2-aryl-lH-benzimidazole-4-carboxamide derivatives

    Institute of Scientific and Technical Information of China (English)

    Xianjin LUO; Zhonglü ZHANG; Yutian YANG; Fei XUE; Naiyun XIU; Yuanbin SHE

    2009-01-01

    A series of new benzimidazole derivatives were designed and synthesized. Their chemical structures were testified by 1H NMR, infrared spectroscopy (IR), mass spectrography (MS), and elemental analysis. Their potent antiviral properties indicated the prospect of new drugs. Compound 13, 16, 18, 19, 21, 22, and 23 were identified as novel antivirus with much better selective activity and inhibitory activity than the comparable ribavirin against Coxsackie virus B3 in VERO cells.

  19. Treatment of norovirus infections: Moving antivirals from the bench to the bedside

    OpenAIRE

    Kaufman, Stuart S.; Green, Kim Y.; Korba, Brent E.

    2014-01-01

    Noroviruses (NV) are the most common cause of acute gastrointestinal illness in the United States and worldwide. The development of specific antiviral countermeasures has lagged behind that of other viral pathogens, primarily because norovirus disease has been perceived as brief and self-limiting and robust assays suitable for drug discovery have been lacking. The increasing recognition that NV illness can be life-threatening, especially in immunocompromised patients who often require prolong...

  20. Genetic diversity of the hepatitis C virus: Impact and issues in the antiviral therapy

    Institute of Scientific and Technical Information of China (English)

    H Le Guillou-Guillemette; S Vallet; C Gaudy-Graffin; C Payan; A Pivert; A Goudeau; F Lunel-Fabiani

    2007-01-01

    The hepatitis C Virus (HCV) presents a high degree of genetic variability which is explained by the combination of a lack of proof reading by the RNA dependant RNA polymerase and a high level of viral replication. The resuiting genetic polymorphism defines a classification in clades, genotypes, subtypes, isolates and quasispecies.This diversity is known to reflect the range of responses to Interferon therapy. The genotype is one of the predictive parameters currently used to define the antiviral treatment strategy and the chance of therapeutic success. Studies have also reported the potential impact of the viral genetic polymorphism in the outcome of antiviral therapy in patients infected by the same HCV genotype. Both structural and non structural genomic regions of HCV have been suggested to be involved in the Interferon pathway and the resistance to antiviral therapy. In this review, we first detail the viral basis of HCV diversity.Then, the HCV genetic regions that may be implicated in resistance to therapy are described, with a focus on the structural region encoded by the E2 gene and the non-structural genes NS3, NS5A and NS5B. Both mechanisms of the Interferon resistance and of the new antiviral drugs are described in this review.

  1. A High Throughput Assay for Screening Host Restriction Factors and Antivirals Targeting Influenza A Virus.

    Science.gov (United States)

    Wang, Lingyan; Li, Wenjun; Li, Shitao

    2016-01-01

    Influenza A virus (IAV) is a human respiratory pathogen that causes seasonal epidemics and occasional global pandemics with devastating levels of morbidity and mortality. Currently approved treatments against influenza are losing effectiveness, as new viral strains are often refractory to conventional treatments. Thus, there is an urgent need to find new therapeutic targets with which to develop novel antiviral drugs. The common strategy to discover new drug targets and antivirals is high throughput screening. However, most current screenings for IAV rely on the engineered virus carrying a reporter, which prevents the application to newly emerging wild type flu viruses, such as 2009 pandemic H1N1 flu. Here we developed a simple and sensitive screening assay for wild type IAV by quantitatively analyzing viral protein levels using a Dot Blot Assay in combination with the LI-COR Imaging System (DBALIS). We first validated DBALIS in overexpression and RNAi assays, which are suitable methods for screening host factors regulating viral infection. More importantly, we also validated and initiated drug screening using DBALIS. A pilot compound screening identified a small molecule that inhibited IAV infection. Taken together, our method represents a reliable and convenient high throughput assay for screening novel host factors and antiviral compounds. PMID:27375580

  2. A High Throughput Assay for Screening Host Restriction Factors and Antivirals Targeting Influenza A Virus

    Science.gov (United States)

    Wang, Lingyan; Li, Wenjun; Li, Shitao

    2016-01-01

    Influenza A virus (IAV) is a human respiratory pathogen that causes seasonal epidemics and occasional global pandemics with devastating levels of morbidity and mortality. Currently approved treatments against influenza are losing effectiveness, as new viral strains are often refractory to conventional treatments. Thus, there is an urgent need to find new therapeutic targets with which to develop novel antiviral drugs. The common strategy to discover new drug targets and antivirals is high throughput screening. However, most current screenings for IAV rely on the engineered virus carrying a reporter, which prevents the application to newly emerging wild type flu viruses, such as 2009 pandemic H1N1 flu. Here we developed a simple and sensitive screening assay for wild type IAV by quantitatively analyzing viral protein levels using a Dot Blot Assay in combination with the LI-COR Imaging System (DBALIS). We first validated DBALIS in overexpression and RNAi assays, which are suitable methods for screening host factors regulating viral infection. More importantly, we also validated and initiated drug screening using DBALIS. A pilot compound screening identified a small molecule that inhibited IAV infection. Taken together, our method represents a reliable and convenient high throughput assay for screening novel host factors and antiviral compounds. PMID:27375580

  3. Indian marine bivalves: Potential source of antiviral drugs

    Digital Repository Service at National Institute of Oceanography (India)

    Chatterji, A.; Ansari, Z.A.; Ingole, B.S.; Bichurina, M.A.; Sovetova, M.; Boikov, Y.A.

    ( Crassostrea gryphoides ) and clam (Meretrix casta , M. meretrix , Paphia malabarica , Villorita cypr i noides ) . Recent investigations conducted jointly by Russian and Indian scientists showed that Indian green mussels ( P. viridis... prophyla c tic effect has been observed in mice when a dose of mussel extract was given 5 h before inoculation of v i rus 3 and the mice showed 100% survival. Marine bivalves are filter - feeding animals, and while feeding they accumulate...

  4. Pandemic influenza: overview of vaccines and antiviral drugs.

    OpenAIRE

    Cox, Manon M. J.

    2005-01-01

    Pandemic influenza has become a high priority item for all public health authorities. An influenza pandemic is believed to be imminent, and scientists agree that it will be a matter of when, where, and what will be the causative agent. Recently, most attention has been directed to human cases of avian influenza caused by a H5N1 avian influenza virus. An effective vaccine will be needed to substantially reduce the impact of an influenza pandemic. Current influenza vaccine manufacturing technol...

  5. Acyclic nucleoside phosphonates: A key class of antiviral drugs

    Czech Academy of Sciences Publication Activity Database

    De Clercq, E.; Holý, Antonín

    2005-01-01

    Roč. 4, č. 13 (2005), 928-940. ISSN 1474-1776 Institutional research plan: CEZ:AV0Z4055905 Keywords : tenofovir * adefovir * cidofovir Subject RIV: CC - Organic Chemistry Impact factor: 18.775, year: 2005

  6. 78 FR 57166 - Antiviral Drugs Advisory Committee; Notice of Meeting

    Science.gov (United States)

    2013-09-17

    ... the treatment of chronic hepatitis C genotype 1 infection, in combination with peginterferon alfa and... disease (including cirrhosis) who are treatment- na ve or who have failed previous interferon...

  7. An antiviral furanoquinone from Paulownia tomentosa Steud.

    Science.gov (United States)

    Kang, K H; Huh, H; Kim, B K; Lee, C K

    1999-11-01

    A methanol extract of the stem bark of Paulownia tomentosa showed antiviral activity against poliovirus types 1 and 3. Sequential liquid-liquid extraction with n-hexane, chloroform and water, and a silicagel column chromatography resulted in the purification of a compound. The compound was identified as methyl-5-hydroxy-dinaphthol[1,2-2',3']furan-7,12-dione-6-carbox yla te on the basis of spectroscopic data. The component caused a significant reduction of viral cytopathic effect when it was subjected to a standard antiviral assay by using HeLa cells. The EC(50) of the compound against poliovirus type 1 strain Brunhilde, and type 3 strain Leon were 0.3 microg/mL and 0.6 microg/mL, respectively. PMID:10548761

  8. RNAi: antiviral therapy against dengue virus

    OpenAIRE

    Idrees, Sobia; Ashfaq, Usman A

    2013-01-01

    Dengue virus infection has become a global threat affecting around 100 countries in the world. Currently, there is no licensed antiviral agent available against dengue. Thus, there is a strong need to develop therapeutic strategies that can tackle this life threatening disease. RNA interference is an important and effective gene silencing process which degrades targeted RNA by a sequence specific process. Several studies have been conducted during the last decade to evaluate the efficiency of...

  9. Strategies to develop antivirals against enterovirus 71

    OpenAIRE

    Kuo, Rei-Lin; Shih, Shin-Ru

    2013-01-01

    Enterovirus 71 (EV71) is an important human pathogen which may cause severe neurological complications and death in children. The virus caused several outbreaks in the Asia-Pacific region during the past two decades and has been considered a significant public health problem in the post-poliovirus eradication era. Unlike poliovirus, there is no effective vaccine or approved antivirals against EV71. To explore anti-EV71 agents therefore is of vital importance. Several strategies have been empl...

  10. Antiviral and Immunostimulant Activities of Andrographis paniculata

    OpenAIRE

    Churiyah; Olivia Bunga Pongtuluran; Elrade Rofaani; Tarwadi,

    2015-01-01

    Andrographis paniculata (Burm. f.) Nees is a medicinal plant which was reported to have anti HIV, anti pathogenic bacteria and immunoregulatory activities. The research purpose was to investigate the activity of Andrographis paniculata ethanol extract as antiviral and immunostimulant. A. paniculata leaves oven-dried, then grinded and macerated with ethanol 90%, and the extract then analyzed using High Performance Liquid Chromatography (HPLC) to determine the content of active compounds androg...

  11. TDP1 repairs nuclear and mitochondrial DNA damage induced by chain-terminating anticancer and antiviral nucleoside analogs

    OpenAIRE

    Huang, Shar-yin N.; Murai, Junko; Dalla Rosa, Ilaria; Dexheimer, Thomas S.; Naumova, Alena; Gmeiner, William H.; Pommier, Yves

    2013-01-01

    Chain-terminating nucleoside analogs (CTNAs) that cause stalling or premature termination of DNA replication forks are widely used as anticancer and antiviral drugs. However, it is not well understood how cells repair the DNA damage induced by these drugs. Here, we reveal the importance of tyrosyl–DNA phosphodiesterase 1 (TDP1) in the repair of nuclear and mitochondrial DNA damage induced by CTNAs. On investigating the effects of four CTNAs—acyclovir (ACV), cytarabine (Ara-C), zidovudine (AZT...

  12. Study of oseltamivir and zanamivir resistance-related mutations in influenza viruses isolated from wild mallards in Sweden.

    Directory of Open Access Journals (Sweden)

    Goran Orozovic

    Full Text Available Resistance to neuraminidase inhibitors (NAIs is a growing problem in battle against influenza A virus. However, little is known about the resistance of viruses isolated from dabbling ducks, the natural reservoir of the influenza virus. To our knowledge, no low-pathogenic avian influenza (LPAI virus resistant to NAIs has been detected. The aim of this study was to investigate mallard isolates of influenza A virus previously identified to carry oseltamivir carboxylate (OC or zanamivir (ZA resistance-related mutations. In this work, 21 viruses belonging to the N1, N3, N6 and N9 subtypes were analyzed using a colorimetric NA inhibition assay. The results of assay showed no NAIs-resistant phenotype for any of the viruses. The R118K mutation was the most recurrent, as it was observed in all subtypes except for N6. IC50 values confirmed the differences in sensitivity to OC or ZA observed in the N1 and N2 groups of NAs. Furthermore, both wild types (WTs in the N6 and one WT in the N9 subtype were less sensitive to ZA than were genotypically related mutants with R152K and R118K change in the respective subtypes. This may indicate that these and probably even other NAIs resistance-related mutations found in our virus collection were not induced by NAIs residuals in the environment and that the impact of such mutations in an avian influenza could be dependent on subtype, strain and host species.

  13. In Vitro Antiviral Effect of "Nanosilver" on Influenza Virus

    Directory of Open Access Journals (Sweden)

    P Mehrbod

    2009-08-01

    Full Text Available Introduction: Influenza is a viral infectious disease with frequent seasonal epidemics causing world-wide economical and social effects. Due to antigenic shifts and drifts of influenza virus, long-lasting vaccine has not been developed so far. The current annual vaccines and effective antiviral drugs are not available sufficiently. Therefore in order to prevent spread of infectious agents including viruses, antiseptics are considered by world health authorities. Small particles of silver have a long history as general antiseptic and disinfectant. Silver does not induce resistance in microorganisms and this ability in Nano-size is stronger. Materials and methods: The aim of this study was to determine antiviral effects of Nanosilver against influenza virus. TCID50 (50% Tissue Culture Infectious Dose of the virus as well as CC50 (50% Cytotoxic Concentration of Nanosilver was obtained by MTT (3- [4, 5-dimethylthiazol-2-yl]-2, 5-diphenyl-tetrazolium bromide, Sigma method. This compound was non-toxic to MDCK (Madin-Darbey Canin Kidney cells at concentration up to 1 µg/ml.  Effective minimal cytotoxic concentration and 100 TCID50 of the virus were added to the confluent cells.  Inhibitory effects of Nanosilver on the virus and its cytotoxicity were assessed at different temperatures using Hemagglutination (HA assay, RT-PCR (Reverse Transcriptase-Polymerase Chain Reaction, and DIF (Direct Immunofluorescent. RT-PCR and free band densitometry software were used to compare the volume of the PCR product bands on the gel. Results and Discussion:  In this study it was found that Nanosilver has destructive effect on the virus membrane glycoprotein knobs as well as the cells.

  14. Drug: D02734 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available D02734 Drug Abacavir succinate (USAN) C14H18N6O. C4H6O4 404.1808 404.4204 D02734.gi...ry the HLA-B*5701 allele are at high risk for experiencing a hypersensitivity reaction to Abacavir RNA-direc...scriptase inhibitors J05AF06 Abacavir D02734 Abacavir succinate (USAN) USP drug c...lassification [BR:br08302] Antivirals Anti-HIV Agents, Nucleoside and Nucleotide Reverse Transcriptase Inhibitors (NRTI)v Abacavir... D02734 Abacavir succinate (USAN) Antiinfectives [BR:br08307] Antivirals Anti-HIV agen

  15. Drug: D07057 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available D07057 Drug Abacavir (INN) C14H18N6O 286.1542 286.3323 D07057.gif Antiviral [DS:H00...the HLA-B*5701 allele are at high risk for experiencing a hypersensitivity reaction to Abacavir RNA-directed...iptase inhibitors J05AF06 Abacavir D07057 Abacavir (INN) USP drug classification ...[BR:br08302] Antivirals Anti-HIV Agents, Nucleoside and Nucleotide Reverse Transcriptase Inhibitors (NRTI)v Abacavir D07057 Abacavir...nhibitor (RTI) Nucleoside and nucleotide reverse transcriptase inhibitors (NRTIs) Abacavir

  16. Drug: D03656 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available D03656 Drug Darunavir (USAN/INN) C27H37N3O7S 547.2352 547.6636 D03656.gif Treatment...tease inhibitors J05AE10 Darunavir D03656 Darunavir (USAN/INN) USP drug classification [BR:br08302] Antivira...ls Anti-HIV Agents, Protease Inhibitors Darunavir D03656 Darunavir (USAN/INN) Ant...iinfectives [BR:br08307] Antivirals Anti-HIV agent Protease inhibitor (PIs) Nonpeptidic Darunavir [ATC:J05AE10] D03656 Daruna

  17. Modulation of alpha-interferon's antiviral and clinical effects by aspirin, acetaminophen, and prednisone in healthy volunteers.

    Science.gov (United States)

    Hendrix, C W; Petty, B G; Woods, A; Kuwahara, S K; Witter, F R; Soo, W; Griffin, D E; Lietman, P S

    1995-10-01

    The magnitude and duration of the antiviral and clinical effect of alpha-interferon was measured in healthy volunteers. A single 3 million unit intramuscular dose of interferon was given either alone (controls) or after 72 h of concomitant medications. These medications included either aspirin (650 mg every 4 h), acetaminophen (650 mg every 4 h), or prednisone (40 mg per day). Peripheral blood mononuclear cells were assayed for resistance to vesicular stomatitis virus infection and induction of 2'-5'-oligoadenylate synthetase activity as evidence of interferon's antiviral effect. Co-administration of acetaminophen increased both antiviral parameters by more than 70% (P acetaminophen, aspirin, and prednisone reduced the clinical symptoms by 47% compared to controls (P = 0.03) after interferon dosing, although individual drug comparisons failed to reach statistical significance. Independent of treatment group, the changes in antiviral markers after interferon dosing correlated closely with each other (r = 0.72, P 0.05). Acetaminophen enhances the antiviral effects of a single intramuscular dose of alpha-interferon, considering the parameters measured in these healthy volunteers. PMID:8585766

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

    Science.gov (United States)

    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

  19. Anti-viral RNA silencing: do we look like plants ?

    OpenAIRE

    Lecellier Charles-Henri; Saumet Anne

    2006-01-01

    Abstract The anti-viral function of RNA silencing was first discovered in plants as a natural manifestation of the artificial 'co-suppression', which refers to the extinction of endogenous gene induced by homologous transgene. Because silencing components are conserved among most, if not all, eukaryotes, the question rapidly arose as to determine whether this process fulfils anti-viral functions in animals, such as insects and mammals. It appears that, whereas the anti-viral process seems to ...

  20. Antiviral therapy for hepatitis C: Has anything changed for pregnant/lactating women?

    Science.gov (United States)

    Spera, Anna Maria; Eldin, Tarek Kamal; Tosone, Grazia; Orlando, Raffaele

    2016-04-28

    Hepatitis C virus (HCV) affects about 3% of the world's population, with the highest prevalence in individuals under 40. The prevalence in pregnant women varies with geographical distribution (highest in developing countries). Prevalence also increases in sub-populations of women at high risk for blood-transmitted infections. HCV infection in pregnancy represents a non-negligible problem. However, most of the past antiviral regimens cannot be routinely offered to pregnant or breastfeeding women because of their side effects. We briefly reviewed the issue of treatment of HCV infection in pregnant/breastfeeding women focusing on the effects of the new direct-acting antivirals on fertility, pregnancy and lactation in animal studies and on the potential risk for humans based on the pharmacokinetic properties of each drug. Currently, all new therapy regimens are contraindicated in this setting because of lack of sufficient safety information and adequate measures of contraception are still routinely recommended for female patients of childbearing potential. PMID:27134703

  1. Antiviral effect of lithium chloride on infection of cells by porcine parvovirus.

    Science.gov (United States)

    Chen, Ye; Yan, Huichao; Zheng, Hao; Shi, Yuzhen; Sun, Lingsuang; Wang, Chong; Sun, Jingchen

    2015-04-01

    Porcine parvovirus (PPV) causes reproductive failure in pigs, which leads to economic losses to the industry. As reported previously, LiCl efficiently impairs the replication of a variety of viruses, including the coronavirus infectious bronchitis virus (IBV), transmissible gastroenteritis virus (TGEV), and pseudorabies herpesvirus. We demonstrate for the first time that inhibition of PPV replication in swine testis (ST) cells by LiCl is dose-dependent, and that the antiviral effect of LiCl occurred in the early phase of PPV replication. These results indicate that LiCl might be an effective anti-PPV drug to control PPV disease. Further studies are required to explore the mechanism of the antiviral effect of LiCl on PPV infection in vivo. PMID:25663217

  2. NEW SPECTROPHOTOMETRIC METHODS DEVELOPMENT FOR THE DETERMINATION OF OSELTAMIVIR PHOSPHATE IN CAPSULES BASED ON THE OXIDATION REACTIONS OF THE OLEFENIC DOUBLE BOND

    OpenAIRE

    B. KALYANA RAMU, M. SYAM BAB U. VIPLAVA PRASAD

    2013-01-01

    Simple, sensitive and selective spectrophotometric methods (M1 and M2) for the assay of oseltamivir phosphate (OP) through the olefenic double bond are proposed. Method M1 is based on the reaction of potassium permanganate to the olefenic double bond in OP and estimating the unreacted permanganate with fast green FCF (FGFCF). Method M2 involves the treatment of the olefenic double bond in OP with a Lemieux reagent (mixture of KMnO4 and NaIO4) and estimating the aldehyde formed with 3-methyl-2...

  3. Antiviral Activity of Euphorbia helioscopia Extract

    Directory of Open Access Journals (Sweden)

    M. Ramezani

    2008-01-01

    Full Text Available In the present study, the antiviral effects of Euphorbia helioscopia extracts were investigated using plaque reduction assay. Plant extracts were prepared using Soxhlet apparatus or by maceration in methanol. After applying several enriching stages of phage CP51, phage titration was performed to determine the phage concentration in phage lysate for specifying the dilution factor of the phage to be used as negative control for the next working stages. Then IC50 of trifluridine, as a positive control, for phage CP51 was determined. The MIC of the extracts for Bacillus cereus was determined as 1.25 and 0.5 mg mL-1 for Soxhlet and maceration extracts, respectively. To determine whether the extracts have the ability to inhibit the adsorption of virus to host cell, it was pre-incubated with phage CP51 for 30 min at 25°C. The growth and reproduction of phage was inhibited by more than 50% at concentration of 1 and 0.25 mg mL-1, respectively. In order to test the effects of extract on transcription process, Bacillus cereus, phage CP51 and extract were incubated together. The growth and reproduction of phage was inhibited by more than 50% at concentration of 0.75 and 0.125 mg mL-1 or Soxhlet and macerated extracts, respectively. These results indicated that both extracts of E. helioscopia have considerable antiviral activity.

  4. Antiviral and Immunostimulant Activities of Andrographis paniculata

    Directory of Open Access Journals (Sweden)

    Churiyah

    2015-04-01

    Full Text Available Andrographis paniculata (Burm. f. Nees is a medicinal plant which was reported to have anti HIV, anti pathogenic bacteria and immunoregulatory activities. The research purpose was to investigate the activity of Andrographis paniculata ethanol extract as antiviral and immunostimulant. A. paniculata leaves oven-dried, then grinded and macerated with ethanol 90%, and the extract then analyzed using High Performance Liquid Chromatography (HPLC to determine the content of active compounds andrographolide. The antiviral activity of the extract was determined by observing its ability on inhibiting virus load in A549 cells transfected with Simian Retro Virus (SRV by Real Time – Polymerase Chain Reaction (RT-PCR analysis. The immunostimulant activity of extract was determined by its ability to induce lymphocytes cell proliferation using 3-(4,5-dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide (MTT assay. Our result indicated that the A. paniculata ethanol extract inhibited the SRV virus titer similar to the positive control Lamivudine, and it was not toxic to the A459 cell line. Furthermore, low concentration (1 μg/mL of A. paniculata extract could stimulated lymphocyte cell proliferation about 38% compared to the control lymphocyte cell without any treatment.

  5. An innate antiviral pathway acting before interferons at epithelial surfaces

    DEFF Research Database (Denmark)

    Iversen, Marie B; Reinert, Line S; Thomsen, Martin K;

    2015-01-01

    we identify an innate antiviral pathway that works at epithelial surfaces before the IFNs. The pathway is activated independently of known innate sensors of viral infections through a mechanism dependent on viral O-linked glycans, which induce CXCR3 chemokines and stimulate antiviral activity in a...

  6. An initial assessment of correlations between host- and virus-related factors affecting analogues antiviral therapy in HBV chronically infected patients

    OpenAIRE

    Stalke, Piotr; Rybicka, Magda; Wróblewska, Anna; Dreczewski, Marcin; Stracewska, Ewa; Smiatacz, Tomasz; Bielawski, Krzysztof Piotr

    2014-01-01

    Background Success in treating hepatitis B virus (HBV) infection with nucleoside analogues drugs is limited by the emergence of drug-resistant viral strains upon prolonged therapy. In addition to mutation patterns in the viral polymerase gene, host factors are assumed to contribute to failure of treatment in chronic HBV infections. The aim of this study was to analyze the correlation between efficacy of antiviral therapy and the prevalence of HBV pretreatment drug-resistant variants. We also ...

  7. EVA copolymer matrix for intra-oral delivery of antimicrobial and antiviral agents.

    Science.gov (United States)

    Ramadevi, A; Padmavathy, T; Stigall, G; Paquette, D; Kalachandra, S

    2008-02-01

    Biocompatible ethylene vinyl acetate copolymer (EVA) was utilized to study the release of an antiviral drug (acyclovir (ACY)) and an antimicrobial drug (doxycycline hyclate (DOH)). Release of both drugs from EVA was measured individually and in combination. The effect of drug combination of DOH and ACY is presented. Additionally, the release rate of DOH after coating of the matrix with a different copolymer, in drug-loading with increasing loads of DOH, and with increases in temperature are also presented. The drugs incorporated in EVA films were prepared from the dry sheet obtained by solvent evaporation of polymer casting solutions with drugs. Drug release from the films was examined for about 12 days in distilled water at 37 degrees C. Changes in optical density were followed spectrophotometrically. The combination of ACY and DOH resulted in an increased release of ACY by about three times (P < 0.001) while DOH showed a decrease in rate of about two times compared to the individual release rates (P = 0.008). Increases in drug levels of DOH resulted in increases in drug release rates (P = 0.001). The release rate of DOH increased with temperature (P = .001; 27, 32, 37 and 42 degrees C were studied) and the energy of activation (DeltaE ( not equal) = 56.69 kJ/mol) was calculated using the Arrhenius equation for the diffusion of DOH molecules. Thus, the release rates of drugs were influenced by many factors: drug combination, coating the device, drug-loading, and temperature variation. Therefore it is proposed that controlling these variables should make it possible to obtain therapeutic levels of drugs released from drug loaded polymer, which may be beneficial in treating oral infections. PMID:17619973

  8. Drug: D03001 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available D03001 Drug Atevirdine mesylate (USAN) C21H25N5O2. CH4SO3 475.1889 475.5612 D03001.gif Antiviral nonnucleosi...de reverse transcriptase inhibitor (NNRTI) RNA-directed DNA polymerase inhibitor [K

  9. Drug: D09012 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available 7 679.8493 D09012.gif Treatment of hepatitis [DS:H00413] Therapeutic category: 6250 ATC code: J05AE11 hepatitis...vir D09012 Telaprevir (JAN/USAN/INN) USP drug classification [BR:br08302] Antivirals Anti-hepatitis C (HCV)

  10. Drug: D04553 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available sponse modifier [DS:H00004 H00021 H00034 H00038 H00045] USP drug classification [BR:br08302] Antivirals Anti-hepatitis... B (HBV) Agents Interferon Alfa-n3 D04553 Interferon alfa-n3 (USAN) Anti-hepatitis C (HCV) Agents

  11. Drug: D00423 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available bavirin (JAN/USP/INN) USP drug classification [BR:br08302] Antivirals Anti-hepatitis B (HBV) Agents Ribaviri...n D00423 Ribavirin (JAN/USP/INN) Anti-hepatitis C (HCV) Agents Ribavirin D00423 Ribavirin (JAN/USP/INN) Anti

  12. Drug: D02747 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available te: 31; 121; 131; 134) Peptide Treatment of hepatitis C Therapeutic category: 6399 ATC code: L03AB11 R: Inte...ation) (JAN); Peginterferon alfa-2a (USAN/INN) USP drug classification [BR:br08302] Antivirals Anti-hepatitis...rferon alfa-2a (USAN/INN) Anti-hepatitis C (HCV) Agents Peginterferon Alfa-2a D02

  13. Drug: D06676 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available D06676 Drug Raltegravir (USAN/INN); MK-0518 C20H21FN6O5 444.1557 444.4163 D06676.gif Antivirals ... [DS:H00406] ATC code: J05AX08 HIV -1 integrase inhibitor Enzyme: UGT1A1 [HSA:54658] m ... ap07053 Anti-HIV ... agents Anatomical Therapeutic Chemical (ATC) class ...

  14. Drug: D08605 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available D08605 Drug Tipranavir (INN); Aptivus (TN) C31H33F3N2O5S 602.2062 602.6643 D08605.gif Antiviral; ... HIV ... protease inhibitor; Nonpeptidic [DS:H00406] ATC co ... de: J05AE09 HIV ... protease inhibitor [CPD:C19849] Enzyme: CYP3A [HSA ...

  15. Drug: D03837 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available D03837 Drug Fosamprenavir sodium (USAN) C25H34N3O9PS. 2Na 629.1549 629.5705 D03837.gif Antiviral ... [HIV ... protease inhibitor] [DS:H00406] ATC code: J05AE07 ... prodrug, active substance: Amprenavir [DR:D00894] HIV ... protease inhibitor [CPD:C19849] Enzyme: CYP3A4 [HS ...

  16. Drug: D00902 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available D00902 Drug Zanamivir (USAN/INN); Relenza (TN) C12H20N4O7 332.1332 332.3098 D00902.gif Antiviral ... ; Inhibitor [influenza ... virus neuraminidase] [DS:H00398] Same as: C08095 A ... TC code: J05AH01 Indication: Influenza ... A and B influenza virus A, B neuraminidase inhibito ...

  17. Drug: D03829 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available D03829 Drug Peramivir hydrate (JAN); Peramivir (USAN/INN) C15H28N4O4. 3H2O 382.2427 382.4531 D03 ... 829.gif Treatment and prevention of influenza ... A and B viruses [neuraminidase inhibitor] [DS:H003 ... 98] Therapeutic category: 6250 influenza virus A, B neuraminidase inhibitor map07044 Antivir ...

  18. Drug: D07989 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available D07989 Drug Fomivirsen (INN) C204H243N63O114P20S20 6657.4321 6662.2412 Antisense antiviral used in the thera...py of cytomegalovirus retinitis [DS:H00368] ATC code: S01AD08 Antisense oligonucleo

  19. Targeting dengue virus NS4B protein for drug discovery.

    Science.gov (United States)

    Xie, Xuping; Zou, Jing; Wang, Qing-Yin; Shi, Pei-Yong

    2015-06-01

    The flavivirus nonstructural 4B protein (NS4B) has recently emerged as a valid antiviral target for drug discovery. Here we review (i) the current understanding of the structure and function of DENV NS4B, (ii) the approaches that have been taken to identify NS4B inhibitors, and (iii) the known inhibitors of flavivirus NS4B protein. This article forms part of a symposium in Antiviral Research on flavivirus drug discovery. PMID:25796970

  20. Hepatitis C virus cell-cell transmission and resistance to direct-acting antiviral agents.

    Directory of Open Access Journals (Sweden)

    Fei Xiao

    2014-05-01

    Full Text Available Hepatitis C virus (HCV is transmitted between hepatocytes via classical cell entry but also uses direct cell-cell transfer to infect neighboring hepatocytes. Viral cell-cell transmission has been shown to play an important role in viral persistence allowing evasion from neutralizing antibodies. In contrast, the role of HCV cell-cell transmission for antiviral resistance is unknown. Aiming to address this question we investigated the phenotype of HCV strains exhibiting resistance to direct-acting antivirals (DAAs in state-of-the-art model systems for cell-cell transmission and spread. Using HCV genotype 2 as a model virus, we show that cell-cell transmission is the main route of viral spread of DAA-resistant HCV. Cell-cell transmission of DAA-resistant viruses results in viral persistence and thus hampers viral eradication. We also show that blocking cell-cell transmission using host-targeting entry inhibitors (HTEIs was highly effective in inhibiting viral dissemination of resistant genotype 2 viruses. Combining HTEIs with DAAs prevented antiviral resistance and led to rapid elimination of the virus in cell culture model. In conclusion, our work provides evidence that cell-cell transmission plays an important role in dissemination and maintenance of resistant variants in cell culture models. Blocking virus cell-cell transmission prevents emergence of drug resistance in persistent viral infection including resistance to HCV DAAs.

  1. Antiviral Ability of Kalanchoe gracilis Leaf Extract against Enterovirus 71 and Coxsackievirus A16

    Directory of Open Access Journals (Sweden)

    Ching-Ying Wang

    2012-01-01

    Full Text Available Pandemic infection or reemergence of Enterovirus 71 (EV71 and coxsackievirus A16 (CVA16 occurs in tropical and subtropical regions, being associated with hand-foot-and-mouth disease, herpangina, aseptic meningitis, brain stem encephalitis, pulmonary edema, and paralysis. However, effective therapeutic drugs against EV71 and CVA16 are rare. Kalanchoe gracilis (L. DC is used for the treatment of injuries, pain, and inflammation. This study investigated antiviral effects of K. gracilis leaf extract on EV71 and CVA16 replications. HPLC analysis with a C-18 reverse phase column showed fingerprint profiles of K. gracilis leaf extract had 15 chromatographic peaks. UV/vis absorption spectra revealed peaks 5, 12, and 15 as ferulic acid, quercetin, and kaempferol, respectively. K. gracilis leaf extract showed little cytotoxicity, but exhibited concentration-dependent antiviral activities including cytopathic effect, plaque, and virus yield reductions. K. gracilis leaf extract was shown to be more potent in antiviral activity than ferulic acid, quercetin, and kaempferol, significantly inhibiting in vitro replication of EV71 (IC50=35.88 μg/mL and CVA16 (IC50=42.91 μg/mL. Moreover, K. gracilis leaf extract is a safe antienteroviral agent with the inactivation of viral 2A protease and reduction of IL-6 and RANTES expressions.

  2. Antiviral activity of 3,4'-dihydroxyflavone on influenza a virus.

    Science.gov (United States)

    Hossain, Mohammed Kawser; Choi, Hye Yeon; Hwang, Jae-Seon; Dayem, Ahmed Abdal; Kim, Jung-Hyun; Kim, Young Bong; Poo, Haryoung; Cho, Ssang-Goo

    2014-06-01

    Influenza virus infection causes thousands of deaths and millions of hospitalizations worldwide every year and the emergence of resistance to anti-influenza drugs has prompted scientists to seek new natural antiviral materials. In this study, we screened 13 different flavonoids from various flavonoid groups to identify the most potent antiviral flavonoid against human influenza A/PR/8/34 (H1N1). The 3-hydroxyl group flavonoids, including 3,2᾿dihydroxyflavone (3,2᾿DHF) and 3,4᾿dihydroxyflavone (3,4᾿DHF), showed potent anti-influenza activity. They inhibited viral neuraminidase activity and viral adsorption onto cells. To confirm the anti-influenza activity of these flavonoids, we used an in vivo mouse model. In mice infected with human influenza, oral administration of 3,4᾿DHF significantly decreased virus titers and pathological changes in the lung and reduced body weight loss and death. Our data suggest that 3-hydroxyl group flavonoids, particularly 3,4᾿DHF, have potent antiviral activity against human influenza A/PR/8/34 (H1N1) in vitro and in vivo. Further clinical studies are needed to investigate the therapeutic and prophylactic potential of the 3-hydroxyl group flavonoids in treating influenza pandemics. PMID:24871979

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

    Directory of Open Access Journals (Sweden)

    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.

  4. 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. PMID:27234554

  5. Novel concept on antiviral strategies to dengue.

    Science.gov (United States)

    Lo, Yu-Chih; Perng, Guey Chuen

    2016-06-01

    Recent evidence has revealed that asymptomatic and/or persistent dengue virus (DENV) infections play a role in the cycling pattern of dengue outbreaks. These findings add a new dimension to the continually evolving search for effective prevention strategies in dengue. Disappointing outcomes of clinical trials in anti-dengue modalities have become commonplace. These failures may result from confounding variables and/or unresolved scientific issues that surround dengue, including the replication cycle of DENV in a natural setting, the target cells and reservoir for viral replication in vivo, and the effect of asymptomatic/persistent carriers in the dissemination of dengue. This article sets forth to address these issues using the most updated information available in the literature and to propose a novel antiviral strategy for the prevention and control of dengue. PMID:27284691

  6. RNAi:antiviral therapy against dengue virus

    Institute of Scientific and Technical Information of China (English)

    Sobia Idrees; Usman A Ashfaq

    2013-01-01

    Dengue virus infection has become a global threat affecting around 100 countries in the world. Currently, there is no licensed antiviral agent available against dengue. Thus, there is a strong need to develop therapeutic strategies that can tackle this life threatening disease. RNA interference is an important and effective gene silencing process which degrades targeted RNA by a sequence specific process. Several studies have been conducted during the last decade to evaluate the efficiency of siRNA in inhibiting dengue virus replication. This review summarizes siRNAs as a therapeutic approach against dengue virus serotypes and concludes that siRNAs against virus and host genes can be next generation treatment of dengue virus infection.

  7. Atividade antiviral de Musa acuminata Colla, Musaceae Antiviral activity of Musa acuminata Colla, Musaceae

    Directory of Open Access Journals (Sweden)

    Fernanda Otaviano Martins

    2009-09-01

    Full Text Available O presente trabalho avalia a atividade antiviral de extratos e frações de Musa acuminata Colla, Musaceae, coletada em duas regiões do Estado do Rio de Janeiro (Petrópolis e Santo Antônio de Pádua. As inflorescências de M. acuminata apresentaram excelente atividade para os dois vírus avaliados: herpesvírus simples humano tipo 1 e herpesvírus simples humano tipo 2, ambos resistentes ao Aciclovir. Os resultados indicam que os extratos de M. acuminata testados podem constituir alvo potencial para uso em terapias antivirais.This study evaluates the antiviral activity of extracts and fractions of Musa acuminata Colla collected in two regions of Rio de Janeiro State (Petrópolis and Santo Antônio de Pádua. The inflorescences of M. acuminata showed excellent activity for the two virus evaluated: simple human herpesvirus type 1 and simple human herpesvirus type 2, both resistant to Acyclovir. The results indicate that the tested extracts of M. acuminata can be potential target for use in antiviral therapy.

  8. Drug: D00891 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available D00891 Drug Abacavir sulfate (JAN/USAN); Ziagen (TN) (C14H18N6O)2. H2SO4 670.2758 6...ersensitivity reaction to Abacavir RNA-directed DNA polymerase inhibitor Genomic ...ls 6250 Antivirals D00891 Abacavir sulfate (JAN/USAN) Anatomical Therapeutic Chem...A DIRECT ACTING ANTIVIRALS J05AF Nucleoside and nucleotide reverse transcriptase inhibitors J05AF06 Abacavir D00891 Abacavir...ls Anti-HIV Agents, Nucleoside and Nucleotide Reverse Transcriptase Inhibitors (NRTI)v Abacavir D00891 Abacavir

  9. Drug: D00777 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available 28 187.7096 D00777.gif Antiviral, Antiparkinsonian [DS:H00057 H00398] Same as: C07939 Therapeutic category: ...ansporter: SLC22A2 [HSA:6582] map07044 Antiviral agents map07057 Antiparkinsonian agents map07235 N-Metyl-D-...rvous system and sensory organs 11 Agents affecting central nervous system 116 Antiparkinson...ation [BR:br08302] Antiparkinson Agents Antiparkinson Agents, Other Amantadine D0...04BB Adamantane derivatives N04BB01 Amantadine D00777 Amantadine hydrochloride (JP16/USP) USP drug classific

  10. Antiviral Activity of Chloroquine against Human Coronavirus OC43 Infection in Newborn Mice▿

    OpenAIRE

    Keyaerts, Els; Li, Sandra; Vijgen, Leen; Rysman, Evelien; Verbeeck, Jannick; Van Ranst, Marc; Maes, Piet

    2009-01-01

    Until recently, human coronaviruses (HCoVs), such as HCoV strain OC43 (HCoV-OC43), were mainly known to cause 15 to 30% of mild upper respiratory tract infections. In recent years, the identification of new HCoVs, including severe acute respiratory syndrome coronavirus, revealed that HCoVs can be highly pathogenic and can cause more severe upper and lower respiratory tract infections, including bronchiolitis and pneumonia. To date, no specific antiviral drugs to prevent or treat HCoV infectio...

  11. Molecular Sleds and More: Novel Antiviral Agents via Single-Molecule Biology (441st Brookhaven Lecture)

    Energy Technology Data Exchange (ETDEWEB)

    Mangel, Wally (Ph.D., Biology Department)

    2008-10-15

    Vaccines are effective against viruses such as polio and measles, but vaccines against other important viruses, such as HIV and flu viruses, may be impossible to obtain. These viruses change their genetic makeup each time they replicate so that the immune system cannot recognize all their variations. Hence it is important to develop new antiviral agents that inhibit virus replication. During this lecture, Dr. Mangel will discuss his group's work with a model system, the human adenovirus, which causes, among other ailments, pink eye, blindness and obesity. Mangel's team has developed a promising drug candidate that works by inihibiting adenovirus proteinase, an enzyme necessary for viral replication.

  12. Characterization of Antiviral Activity of Benzamide Derivative AH0109 against HIV-1 Infection

    OpenAIRE

    Chen, Liyu; Ao, Zhujun; Jayappa, Kallesh Danappa; Kobinger, Gary; Liu, ShuiPing; Wu, Guojun; Wainberg, Mark A.; Yao, Xiaojian

    2013-01-01

    In the absence of an effective vaccine against HIV-1 infection, anti-HIV-1 strategies play a major role in disease control. However, the rapid emergence of drug resistance against all currently used anti-HIV-1 molecules necessitates the development of new antiviral molecules and/or strategies against HIV-1 infection. In this study, we have identified a benzamide derivative named AH0109 that exhibits potent anti-HIV-1 activity at an 50% effective concentration of 0.7 μM in HIV-1-susceptible CD...

  13. Drug: D02499 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available D02499 Drug Enfuvirtide (USAN/INN); Fuzeon (TN) C204H301N51O64 4489.1866 4491.876 Ac-Tyr Thr Ser ... on] [DS:H00406] ATC code: J05AX07 fusion inhibitor HIV ... glycoprotein 41 (gp41) map07053 Anti-HIV ... agents An ... P drug classification [BR:br08302] Antivirals Anti-HIV ... Agents, Other Enfuvirtide D02499 Enfuvirtide (USAN ...

  14. Drug: D10066 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available D10066 Drug Dolutegravir (USAN) C20H19F2N3O5 419.1293 419.3788 D10066.gif Treatment of HIV ... infec ... tion [DS:H00406] ATC code: J05AX12 HIV -1 integrase inhibitor map07053 Anti-HIV ... agents Ana ... P drug classification [BR:br08302] Antivirals Anti-HIV ... Agents, Integrase Inhibitors (INSTI) Dolutegravir ...

  15. HIV-1 Antiretroviral Drug Therapy

    OpenAIRE

    Arts, Eric J.; Hazuda, Daria J.

    2012-01-01

    The most significant advance in the medical management of HIV-1 infection has been the treatment of patients with antiviral drugs, which can suppress HIV-1 replication to undetectable levels. The discovery of HIV-1 as the causative agent of AIDS together with an ever-increasing understanding of the virus replication cycle have been instrumental in this effort by providing researchers with the knowledge and tools required to prosecute drug discovery efforts focused on targeted inhibition with ...

  16. Evaluation antiviral effect of leaf extract of Rosmarinus officinalis against Herpes simplex virus type 1 in cell cultur

    OpenAIRE

    G Yousefi Kordestani; M Parsania

    2015-01-01

    Introduction Herpes simplex virus type I belongs to herpesviridae. Several studies are ongoing for achieve a drug with good effectiveness and lower side effects, because the incidence of infections caused by this virus is increasing and there is some HSV resistance in the world. In this study, anti-viral effects of rosemary extract against of HSV was evaluated in cell culture. Material and methods: At first the rosemary extract toxicity on Hela cells with trypan blue and MTT methods has been ...

  17. 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.

  18. Genetically Engineered Protein Modules: Development and Applications in Anti-Viral Agent Screening and Cancer Marker Detection

    OpenAIRE

    Biswas, Payal

    2010-01-01

    ABSTRACT OF THE DISSERTATION Genetically Engineered Protein Modules: Development and Applications in Anti-Viral Agent Screening and Cancer Marker Detection byPayal BiswasDoctor of Philosophy Cell Molecular and Developmental Biology Graduate ProgramUniversity of California, Riverside, August 2010Dr. Wilfred Chen, ChairpersonOne of the most critical aspects in drug discovery is the bioactivity screening assay, by which compounds that most effectively inhibit the target are identified. During t...

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

    International Nuclear Information System (INIS)

    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 IC50 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

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

    OpenAIRE

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

    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 bro...

  1. Antiviral effect of HPMPC (Cidofovir (R)), entrapped in cationic liposomes: In vitro study on MDBK cell and BHV-1 virus

    Czech Academy of Sciences Publication Activity Database

    Korvasová, Z.; Drašar, L.; Mašek, J.; Turánek Knotigová, P.; Kulich, P.; Matiašovic, J.; Kovařčík, K.; Bartheldyová, E.; Koudelka, Š.; Škrabalová, M.; Miller, A. D.; Holý, Antonín; Ledvina, Miroslav; Turánek, J.

    2012-01-01

    Roč. 160, č. 2 (2012), s. 330-338. ISSN 0168-3659 R&D Projects: GA ČR(CZ) GAP304/10/1951; GA AV ČR(CZ) KAN200520703; GA AV ČR KAN200100801 Institutional research plan: CEZ:AV0Z40550506 Keywords : cationic lipids * BHV-1 virus * Cidofovir * HPMC * antiviral drugs Subject RIV: CC - Organic Chemistry Impact factor: 7.633, year: 2012

  2. Clinical Effectiveness of Peramivir in Comparison with Other Neuraminidase Inhibitors in Pediatric Influenza Patients

    OpenAIRE

    Toshiyuki Hikita; Hiroyuki Hikita; Fusako Hikita; Naoko Hikita; Shizue Hikita

    2012-01-01

    The currently used antivirals in the treatment of influenza in Japan include amantadine, oseltamivir, zanamivir, laninamivir, and peramivir. We compared the efficacy of intravenous peramivir with that of other neuraminidase inhibitors for treating pediatric influenza. The present study included 223 influenza patients (≤18 years) who presented at the Hikita Pediatric Clinic between February and April 2011. We compared fever duration after starting treatment with antiviral drugs. Because inhala...

  3. Antiviral therapy with nucleotide/nucleoside analogues in chronic hepatitis B: A meta-analysis of prospective randomized trials.

    Science.gov (United States)

    Bedre, Renesh H; Raj, Utkarsh; Misra, Sri Prakash; Varadwaj, Pritish Kumar

    2016-03-01

    Nucleotide/nucleoside analogues (antiviral therapy) are used in the therapy of HBeAg positive and HBeAg negative chronic hepatitis B. We analyzed ten selected randomized controlled with 2557 patients to estimate the effect of antiviral drugs in chronic hepatitis B with compared to placebo. Virological response, biochemical response, histological response, seroconversion of HBeAg, and loss of HBeAg were estimated as primary efficacy measures. The included studies were subjected for heterogeneity and publication bias. The heterogeneity was assessed with χ2 and I(2) statistics. Publication bias was assessed by funnel plot. Greater rates of improvement obtained in antiviral group for virological response [43.96 % vs. 3.15 %, RR = 0.57, 95 % CI = 0.54-0.61, p-value pharyngitis [22.22 % vs. 18.23 %, OR = 1.12, 95 % CI = 0.86-1.45, p-value = 0.40]. Excluding adverse events, all primary efficacy measures shown statistical significant result for chronic hepatitis treatment (p-value <0.05). Antiviral therapy provided significant benefit for the treatment of chronic hepatitis B with no measurable adverse effects. PMID:27083430

  4. Multiplex Liquid Chromatography-Tandem Mass Spectrometry Assay for Simultaneous Therapeutic Drug Monitoring of Ribavirin, Boceprevir, and Telaprevir

    OpenAIRE

    Aouri, Manel; Moradpour, Darius; Cavassini, Matthias; Mercier, Thomas; Buclin, Thierry; Csajka, Chantal; Telenti, Amalio; Rauch, Andri; Decosterd, Laurent A.

    2013-01-01

    New directly acting antivirals (DAAs) that inhibit hepatitis C virus (HCV) replication are increasingly used for the treatment of chronic hepatitis C. A marked pharmacokinetic variability and a high potential for drug-drug interactions between DAAs and numerous drug classes have been identified. In addition, ribavirin (RBV), commonly associated with hemolytic anemia, often requires dose adjustment, advocating for therapeutic drug monitoring (TDM) in patients under combined antiviral therapy. ...

  5. Detection of peramivir and laninamivir, new anti-influenza drugs, in sewage effluent and river waters in Japan.

    Directory of Open Access Journals (Sweden)

    Takashi Azuma

    Full Text Available This is the first report of the detection of two new anti-influenza drugs, peramivir (PER and laninamivir (LAN, in Japanese sewage effluent and river waters. Over about 1 year from October 2013 to July 2014, including the influenza prevalence season in January and February 2014, we monitored for five anti-influenza drugs-oseltamivir (OS, oseltamivir carboxylate (OC, zanamivir (ZAN, PER, and LAN-in river waters and in sewage effluent flowing into urban rivers of the Yodo River system in Japan. The dynamic profiles of these anti-influenza drugs were synchronized well with that of the numbers of influenza patients treated with the drugs. The highest levels in sewage effluents and river waters were, respectively, 82 and 41 ng/L (OS, 347 and 125 ng/L (OC, 110 and 35 ng/L (ZAN, 64 and 11 ng/L (PER, and 21 and 9 ng/L (LAN. However, application of ozone treatment before discharge from sewage treatment plants was effective in reducing the levels of these anti-influenza drugs in effluent. The effectiveness of the ozone treatment and the drug dependent difference in susceptibility against ozone were further evidenced by ozonation of a STP effluent in a batch reactor. These findings should help to promote further environmental risk assessment of the generation of drug-resistant influenza viruses in aquatic environments.

  6. Detection of peramivir and laninamivir, new anti-influenza drugs, in sewage effluent and river waters in Japan.

    Science.gov (United States)

    Azuma, Takashi; Ishiuchi, Hirotaka; Inoyama, Tomomi; Teranishi, Yusuke; Yamaoka, Misato; Sato, Takaji; Yamashita, Naoyuki; Tanaka, Hiroaki; Mino, Yoshiki

    2015-01-01

    This is the first report of the detection of two new anti-influenza drugs, peramivir (PER) and laninamivir (LAN), in Japanese sewage effluent and river waters. Over about 1 year from October 2013 to July 2014, including the influenza prevalence season in January and February 2014, we monitored for five anti-influenza drugs-oseltamivir (OS), oseltamivir carboxylate (OC), zanamivir (ZAN), PER, and LAN-in river waters and in sewage effluent flowing into urban rivers of the Yodo River system in Japan. The dynamic profiles of these anti-influenza drugs were synchronized well with that of the numbers of influenza patients treated with the drugs. The highest levels in sewage effluents and river waters were, respectively, 82 and 41 ng/L (OS), 347 and 125 ng/L (OC), 110 and 35 ng/L (ZAN), 64 and 11 ng/L (PER), and 21 and 9 ng/L (LAN). However, application of ozone treatment before discharge from sewage treatment plants was effective in reducing the levels of these anti-influenza drugs in effluent. The effectiveness of the ozone treatment and the drug dependent difference in susceptibility against ozone were further evidenced by ozonation of a STP effluent in a batch reactor. These findings should help to promote further environmental risk assessment of the generation of drug-resistant influenza viruses in aquatic environments. PMID:26110817

  7. Dendrimers in drug research

    DEFF Research Database (Denmark)

    Boas, Ulrik; Heegaard, Peter M. H.

    2004-01-01

    and in vivo cytotoxicity, as well as biopermeability, biostability and immunogenicity. The review deals with numerous applications of dendrimers as tools for efficient multivalent presentation of biological ligands in biospecific recognition, inhibition and targeting. Dendrimers may be used as drugs...... for antibacterial and antiviral treatment and have found use as antitumor agents. The review highlights the use of dendrimers as drug or gene delivery devices in e.g. anticancer therapy, and the design of different host-guest binding motifs directed towards medical applications is described. Other specific examples...

  8. Brote de gripe A H1N1 en la base española de Camp "Arena" (Herat, Afganistán durante julio y agosto de 2009. Parte I: Características clínicas y reducción de la duración de la fiebre con el uso de oseltamivir Outbreak of new influenza a H1N1 in Spanish base Camp "Arena" (Herat, Afghanistan during july and august 2009. Part I: Clinical features and reducing the duration of fever with the use of oseltamivir during the outbreak of new influenza A H1N1 in Spanish forces in Afghanistan

    Directory of Open Access Journals (Sweden)

    F. Maimir Jané

    2011-03-01

    Full Text Available Introducción: Desde la declaración de alerta fase 6 por la OMS se han presentado brotes de gripe A H1N1 en todo el mundo. Presentamos los resultados del estudio realizado en el brote de nueva gripe A H1N1 en la Base Militar de Camp Arena en Herat (Afganistán. Método: Estudio prospectivo de serie de casos, de pacientes controlados por el Servicio de Sanidad del Role 2, valorando la edad, síntomas al ingreso, duración de la fiebre, test de despistaje rápido, complicaciones, intolerancia al oseltamivir. En el grupo inicial de paciente se valoró RT-PCR. Se compararon los grupos con y sin tratamiento con oseltamivir para la duración de la fiebre. Resultados: Estudio de 106 pacientes, con edad media 27,17 años, los síntomas más frecuentes fueron la tos seca y mal estado general. Los pacientes tratados sin oseltamivir presentaron una duración media de la fiebre de 3,71 días, y con oseltamivir de 2,54 días (pIntroduction: Since the warning statement of Phase 6 by WHO, the world has presented Influenza A H1N1 outbreaks. We present the results of the study of a new Influenza A H1N1 outbreak in the Military Base Camp Arena, in Heart (Afghanistan. Methods: Prospective case series of patients monitored by the Health Service of the Role 2, assessing the age, symptoms at admission, duration of fever, rapid screening test, complications, intolerance to oseltamivir. The initial group of patients was evaluated RT-PCR. We compared groups with and without treatment with oseltamivir for the duration of fever. Results: Study of 106 patients, mean age 27.17 years, the most common symptoms were dry cough and general disrepair. Patients without oseltamivir showed an average of 3.71 days of fever and with oseltamivir of 2.54 days (p <0.001. There were a total of 13 complications, the most frequent bronchitis. Intolerance to oseltamivir was presented in 11.29% of patients. Conclusions: Oseltamivir reduces the duration of fever significantly, with onset of

  9. The SARS-coronavirus papain-like protease: structure, function and inhibition by designed antiviral compounds.

    Science.gov (United States)

    Báez-Santos, Yahira M; St John, Sarah E; Mesecar, Andrew D

    2015-03-01

    Over 10 years have passed since the deadly human coronavirus that causes severe acute respiratory syndrome (SARS-CoV) emerged from the Guangdong Province of China. Despite the fact that the SARS-CoV pandemic infected over 8500 individuals, claimed over 800 lives and cost billions of dollars in economic loss worldwide, there still are no clinically approved antiviral drugs, vaccines or monoclonal antibody therapies to treat SARS-CoV infections. The recent emergence of the deadly human coronavirus that causes Middle East respiratory syndrome (MERS-CoV) is a sobering reminder that new and deadly coronaviruses can emerge at any time with the potential to become pandemics. Therefore, the continued development of therapeutic and prophylactic countermeasures to potentially deadly coronaviruses is warranted. The coronaviral proteases, papain-like protease (PLpro) and 3C-like protease (3CLpro), are attractive antiviral drug targets because they are essential for coronaviral replication. Although the primary function of PLpro and 3CLpro are to process the viral polyprotein in a coordinated manner, PLpro has the additional function of stripping ubiquitin and ISG15 from host-cell proteins to aid coronaviruses in their evasion of the host innate immune responses. Therefore, targeting PLpro with antiviral drugs may have an advantage in not only inhibiting viral replication but also inhibiting the dysregulation of signaling cascades in infected cells that may lead to cell death in surrounding, uninfected cells. This review provides an up-to-date discussion on the SARS-CoV papain-like protease including a brief overview of the SARS-CoV genome and replication followed by a more in-depth discussion on the structure and catalytic mechanism of SARS-CoV PLpro, the multiple cellular functions of SARS-CoV PLpro, the inhibition of SARS-CoV PLpro by small molecule inhibitors, and the prospect of inhibiting papain-like protease from other coronaviruses. This paper forms part of a series of

  10. Dengue Virus Entry as Target for Antiviral Therapy

    Directory of Open Access Journals (Sweden)

    Marijke M. F. Alen

    2012-01-01

    Full Text Available Dengue virus (DENV infections are expanding worldwide and, because of the lack of a vaccine, the search for antiviral products is imperative. Four serotypes of DENV are described and they all cause a similar disease outcome. It would be interesting to develop an antiviral product that can interact with all four serotypes, prevent host cell infection and subsequent immune activation. DENV entry is thus an interesting target for antiviral therapy. DENV enters the host cell through receptor-mediated endocytosis. Several cellular receptors have been proposed, and DC-SIGN, present on dendritic cells, is considered as the most important DENV receptor until now. Because DENV entry is a target for antiviral therapy, various classes of compounds have been investigated to inhibit this process. In this paper, an overview is given of all the putative DENV receptors, and the most promising DENV entry inhibitors are discussed.

  11. Regulation of antiviral innate immunity by deubiquitinase CYLD

    Institute of Scientific and Technical Information of China (English)

    Minying Zhang; Andrew J Lee; Xuefeng Wu; Shao-Cong Sun

    2011-01-01

    An antiviral innate immune response involves induction of type Ⅰ interferons (IFNs) and their subsequent autocrine and paracrine actions,but the underlying regulatory mechanisms are incompletely understood.Here we report that CYLD,a deubiquitinase that specifically digests lysine 63-1inked ubiquitin chains,is required for antiviral host defense.Loss of CYLD renders mice considerably more susceptible to infection by vesicular stomatitis virus (VSV).Consistently,CYLD-deficient dendritic cells are more sensitive to VSV infection.This functional defect was not due to lack of type I IFN production but rather because of attenuated IFN receptor signaling.In the absence of CYLD,IFN-β is ineffective in the induction of antiviral genes and protection of cells from viral infection.These findings establish CYLD as a novel regulator of antiviral innate immunity and suggest a role for CYLD in regulating IFN receptor signaling.

  12. STUDY OF ANTIVIRAL ACTIVITY OF SOME HYDRAZONE PINOSTROBIN DERIVATIVES

    Directory of Open Access Journals (Sweden)

    G. K. Mukusheva

    2014-01-01

    Full Text Available New derivatives on the basis of hydrazone pinostrobin molecule were synthesized. Significant antiviral activity of received samples of new hydrazone pinstrobin derivatives was identified.

  13. Development of Small-Molecule Antivirals for Ebola

    Czech Academy of Sciences Publication Activity Database

    Janeba, Zlatko

    2015-01-01

    Roč. 35, č. 6 (2015), s. 1175-1194. ISSN 0198-6325 Institutional support: RVO:61388963 Keywords : antiviral * filovirus * Ebola virus * Marburg virus * hemorrhagic fever Subject RIV: CC - Organic Chemistry Impact factor: 8.431, year: 2014

  14. Budesonide and formoterol reduce early innate anti-viral immune responses in vitro.

    Directory of Open Access Journals (Sweden)

    Janet M Davies

    Full Text Available Asthma is a chronic inflammatory airways disease in which respiratory viral infections frequently trigger exacerbations. Current treatment of asthma with combinations of inhaled corticosteroids and long acting beta2 agonists improves asthma control and reduces exacerbations but what impact this might have on innate anti-viral immunity is unclear. We investigated the in vitro effects of asthma drugs on innate anti-viral immunity. Peripheral blood mononuclear cells (PBMC from healthy and asthmatic donors were cultured for 24 hours with the Toll-like receptor 7 agonist, imiquimod, or rhinovirus 16 (RV16 in the presence of budesonide and/or formoterol. Production of proinflammatory cytokines and expression of anti-viral intracellular signalling molecules were measured by ELISA and RT-PCR respectively. In PBMC from healthy donors, budesonide alone inhibited IP-10 and IL-6 production induced by imiquimod in a concentration-dependent manner and the degree of inhibition was amplified when budesonide and formoterol were used in combination. Formoterol alone had little effect on these parameters, except at high concentrations (10⁻⁶ M when IL-6 production increased. In RV16 stimulated PBMC, the combination of budesonide and formoterol inhibited IFNα and IP-10 production in asthmatic as well as healthy donors. Combination of budesonide and formoterol also inhibited RV16-stimulated expression of the type I IFN induced genes myxovirus protein A and 2', 5' oligoadenylate synthetise. Notably, RV16 stimulated lower levels of type Myxovirus A and oligoadenylate synthase in PBMC of asthmatics than control donors. These in vitro studies demonstrate that combinations of drugs commonly used in asthma therapy inhibit both early pro-inflammatory cytokines and key aspects of the type I IFN pathway. These findings suggest that budesonide and formoterol curtail excessive inflammation induced by rhinovirus infections in patients with asthma, but whether this inhibits

  15. Diagnosis and antiviral intervention strategies for mitigating an influenza epidemic.

    Directory of Open Access Journals (Sweden)

    Robert Moss

    Full Text Available BACKGROUND: Many countries have amassed antiviral stockpiles for pandemic preparedness. Despite extensive trial data and modelling studies, it remains unclear how to make optimal use of antiviral stockpiles within the constraints of healthcare infrastructure. Modelling studies informed recommendations for liberal antiviral distribution in the pandemic phase, primarily to prevent infection, but failed to account for logistical constraints clearly evident during the 2009 H1N1 outbreaks. Here we identify optimal delivery strategies for antiviral interventions accounting for logistical constraints, and so determine how to improve a strategy's impact. METHODS AND FINDINGS: We extend an existing SEIR model to incorporate finite diagnostic and antiviral distribution capacities. We evaluate the impact of using different diagnostic strategies to decide to whom antivirals are delivered. We then determine what additional capacity is required to achieve optimal impact. We identify the importance of sensitive and specific case ascertainment in the early phase of a pandemic response, when the proportion of false-positive presentations may be high. Once a substantial percentage of ILI presentations are caused by the pandemic strain, identification of cases for treatment on syndromic grounds alone results in a greater potential impact than a laboratory-dependent strategy. Our findings reinforce the need for a decentralised system capable of providing timely prophylaxis. CONCLUSIONS: We address specific real-world issues that must be considered in order to improve pandemic preparedness policy in a practical and methodologically sound way. Provision of antivirals on the scale proposed for an effective response is infeasible using traditional public health outbreak management and contact tracing approaches. The results indicate to change the transmission dynamics of an influenza epidemic with an antiviral intervention, a decentralised system is required for

  16. Small creatures use small RNAs to direct antiviral defenses

    OpenAIRE

    Sabin, Leah R.; Cherry, Sara

    2013-01-01

    Antiviral RNA silencing has been recognized as an important defense mechanism in arthropods against RNA viruses. However, the role of this pathway in DNA virus infection remains largely unexplored. A report in this issue of the European Journal of Immunology [Eur J Immunol 2012. XXXX] provides new insight into the role of RNA silencing in antiviral defense against DNA viruses. Huang and Zhang found that the dsDNA virus White Spot Syndrome virus, an agriculturally important pathogen of shrimp,...

  17. Antiviral properties of two trimeric recombinant gp41 proteins

    Directory of Open Access Journals (Sweden)

    Nisole Sébastien

    2006-03-01

    Full Text Available Abstract Background As it is the very first step of the HIV replication cycle, HIV entry represents an attractive target for the development of new antiviral drugs. In this context, fusion inhibitors are the third class of anti-HIV drugs to be used for treatment, in combination with nucleoside analogues and antiproteases. But the precise mechanism of HIV fusion mechanism is still unclear. Gp41 ectodomain-derived synthetic peptides represent ideal tools for clarifying this mechanism, in order to design more potent anti-HIV drugs. Results Two soluble trimeric recombinant gp41 proteins, termed Rgp41B and Rgp41A were designed. Both comprise the N- and C-terminal heptad repeat regions of the ectodomain of HIV-1 gp41, connected by a 7-residue hydrophilic linker, in order to mimic the trimeric fusogenic state of the transmembrane glycoprotein. Both recombinant proteins were found to inhibit HIV-1 entry into target cells in a dose-dependent manner. Rgp41A, the most potent inhibitor, was able to inhibit both X4 and R5 isolates into HeLa cells and primary T lymphocytes. X4 viruses were found to be more susceptible than R5 isolates to inhibition by Rgp41A. In order to elucidate how the trimeric recombinant gp41 protein can interfere with HIV-1 entry into target cells, we further investigated its mode of action. Rgp41A was able to bind gp120 but did not induce gp120-gp41 dissociation. Furthermore, this inhibitor could also interfere with a late step of the fusion process, following the mixing of lipids. Conclusion Taken together, our results suggest that Rgp41A can bind to gp120 and also interfere with a late event of the fusion process. Interestingly, Rgp41A can block membrane fusion without preventing lipid mixing. Although further work will be required to fully understand its mode of action, our results already suggest that Rgp41A can interfere with multiple steps of the HIV entry process.

  18. RNA interference: Antiviral weapon and beyond

    Institute of Scientific and Technical Information of China (English)

    Quan-Chu Wang; Qing-He Nie; Zhi-Hua Feng

    2003-01-01

    RNA interference (RNAi) is a remarkable type of gene regulation based on sequence-specific targeting and degradation of RNA. The term encompasses related pathways found in a broad range of eukaryotic organisms, including fungi, plants, and animals. RNA interference is part of a sophisticated network of interconnected pathways for cellular defense, RNA surveillance, and development and it may become a powerful tool to manipulate gene expression experimentally. RNAi technology is currently being evaluated not only as an extremely powerful instrument for functional genomic analyses, but also as a potentially useful method to develop specific dsRNA based gene-silencing therapeutics.Several laboratories have been interested in using RNAi to control viral infection and many reports in Nature and in Cell show that short interfering (si) RNAs can inhibit infection by HIV-1, polio and hepatitis C viruses in a sequence-specific manner. RNA-based strategies for gene inhibition in mammalian cells have recently been described, which offer the promise of antiviral therapy.

  19. Antiviral Warrior-APOBEC3G

    Institute of Scientific and Technical Information of China (English)

    WU Xiao-xia; MA Yi-cai

    2005-01-01

    This paper is to further understand how APOBEC3G can defend the retroviruses and to find new approaches to AIDs (acquired immure deficiency syndrome).The viral infectivity factor (Vif) induces rapid degradation of APOBEC3G by ubiquitination, which is a proteosome-dependent pathway. Precisely speaking, only in the virus-producing cell Vif expression is necessary; in its absence, infection of a subsequent target cell terminates at a postentry step through the action of the human APOBEC3G antiviral mechanism. Vif protein has two domains: one binds to APOBEC3G and the other regulates the degradation of APOBEC3G by a conserved sequence, SLQ (Y/F) LA motif. Recently, the research on Vif has also revealed APOBEC3G is a novel component of innate immune system. In fact, APOBEC3G not only acts in DNA editing to block the replication of retroviruses such as HIV-1, but also is able to defend a wide spectrum of distantly related retroviruses and interferes with HBV through a different mechanism from HIV.

  20. [Study of the antiviral action of gentamicin].

    Science.gov (United States)

    Novokhatskiĭ, A S; Gerasimova, S S

    1975-05-01

    Experimental data on the effect of various concentrations of gentamycin on reproduction of VEE and Sindbis viruses in tissue culture are presented. It was found that gentamycin had no cytotoxic effect on the primary tripsinized chick embryon fibroblasts (CEF) when used in doses of 10, 20 or 30 mg/ml and only when used in a dose of 50 mg/ml it induced 50 percent destruction of the cell layer. Multiplication of the VEE and Sindbis viruses in the culture of CEF was inhibited in the presence of gentamycin by 1.5--3.5 lg PFU/ml. Two stages in the virus inhibiting effect of gentamycin were determined on the model of VEE, i. e. the stage of inhibition in the absence of visible damages of the cells and the stage associated with their destruction. The doses of gentamycin higher than 3 mg/ml inhibited in parallel the virus specific synthesis and synthesis of the cell proteins and nucleic acids. At the same time, when gentamycin was used in a dose of 10 mg/ml, no impairement of the cell viability was observed and the cell capacity to produce high titers of the model virus was reduced after incubation without the antibiotic for 24 hours. The antiviral activity of gentamycin were therefore determined by revers inhibition of the cell metabolic activity. PMID:1225192

  1. Antiviral therapies against Ebola and other emerging viral diseases using existing medicines that block virus entry.

    Science.gov (United States)

    Long, Jason; Wright, Edward; Molesti, Eleonora; Temperton, Nigel; Barclay, Wendy

    2015-01-01

    Emerging viral diseases pose a threat to the global population as intervention strategies are mainly limited to basic containment due to the lack of efficacious and approved vaccines and antiviral drugs. The former was the only available intervention when the current unprecedented Ebolavirus (EBOV) outbreak in West Africa began. Prior to this, the development of EBOV vaccines and anti-viral therapies required time and resources that were not available. Therefore, focus has turned to re-purposing of existing, licenced medicines that may limit the morbidity and mortality rates of EBOV and could be used immediately. Here we test three such medicines and measure their ability to inhibit pseudotype viruses (PVs) of two EBOV species, Marburg virus (MARV) and avian influenza H5 (FLU-H5). We confirm the ability of chloroquine (CQ) to inhibit viral entry in a pH specific manner. The commonly used proton pump inhibitors, Omeprazole and Esomeprazole were also able to inhibit entry of all PVs tested but at higher drug concentrations than may be achieved in vivo. We propose CQ as a priority candidate to consider for treatment of EBOV. PMID:26069727

  2. Antiviral activity of glycyrrhizin against hepatitis C virus in vitro.

    Directory of Open Access Journals (Sweden)

    Yoshihiro Matsumoto

    Full Text Available Glycyrrhizin (GL has been used in Japan to treat patients with chronic viral hepatitis, as an anti-inflammatory drug to reduce serum alanine aminotransferase levels. GL is also known to exhibit various biological activities, including anti-viral effects, but the anti-hepatitis C virus (HCV effect of GL remains to be clarified. In this study, we demonstrated that GL treatment of HCV-infected Huh7 cells caused a reduction of infectious HCV production using cell culture-produced HCV (HCVcc. To determine the target step in the HCV lifecycle of GL, we used HCV pseudoparticles (HCVpp, replicon, and HCVcc systems. Significant suppressions of viral entry and replication steps were not observed. Interestingly, extracellular infectivity was decreased, and intracellular infectivity was increased. By immunofluorescence and electron microscopic analysis of GL treated cells, HCV core antigens and electron-dense particles had accumulated on endoplasmic reticulum attached to lipid droplet (LD, respectively, which is thought to act as platforms for HCV assembly. Furthermore, the amount of HCV core antigen in LD fraction increased. Taken together, these results suggest that GL inhibits release of infectious HCV particles. GL is known to have an inhibitory effect on phospholipase A2 (PLA2. We found that group 1B PLA2 (PLA2G1B inhibitor also decreased HCV release, suggesting that suppression of virus release by GL treatment may be due to its inhibitory effect on PLA2G1B. Finally, we demonstrated that combination treatment with GL augmented IFN-induced reduction of virus in the HCVcc system. GL is identified as a novel anti-HCV agent that targets infectious virus particle release.

  3. LIVER SPECIFIC DRUG TARGETING STRATEGIES: A REVIEW

    OpenAIRE

    Ramesh S. Gorad*, Satish K. Mandlik and Kishore N. Gujar

    2013-01-01

    Drug delivery to liver is one of the most challenging research areas in pharmaceutical sciences. The some physiological barrier such as opsonization, mechanical entrapment by pulmonary vascular bed, uptake by RES represents an insurmountable obstacle for a large number of proteins and drugs, including antibiotics, antineoplastic agents and antiviral agents to target liver disorders. Therefore, various strategies have been proposed to improve the delivery of different drugs to liver and hepato...

  4. 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.

  5. Antiviral macrophage responses in flavivirus encephalitis.

    Science.gov (United States)

    Ashhurst, Thomas Myles; Vreden, Caryn van; Munoz-Erazo, Luis; Niewold, Paula; Watabe, Kanami; Terry, Rachael L; Deffrasnes, Celine; Getts, Daniel R; Cole King, Nicholas Jonathan

    2013-11-01

    Mosquito-borne flaviviruses are a major current and emerging threat, affecting millions of people worldwide. Global climate change, combined with increasing proximity of humans to animals and mosquito vectors by expansion into natural habitats, coupled with the increase in international travel, have resulted in significant spread and concomitant increase in the incidence of infection and severe disease. Although neuroinvasive disease has been well described for some viral infections such as Japanese Encephalitis virus (JEV) and West Nile virus (WNV), others such as dengue virus (DENV) have recently displayed an emerging pattern of neuroinvasive disease, distinct from the previously observed, systemically-induced encephalomyelopathy. In this setting, the immune response is a crucial component of host defence, in preventing viral dissemination and invasion of the central nervous system (CNS). However, subversion of the anti-viral activities of macrophages by flaviviruses can facilitate viral replication and spread, enhancing the intensity of immune responses, leading to severe immune-mediated disease which may be further exacerbated during the subsequent infection with some flaviviruses. Furthermore, in the CNS myeloid cells may be responsible for inducing specific inflammatory changes, which can lead to significant pathological damage during encephalitis. The interaction of virus and cells of the myeloid lineage is complex, and this interaction is likely responsible at least in part, for crucial differences between viral clearance and pathology. Recent studies on the role of myeloid cells in innate immunity and viral control, and the mechanisms of evasion and subversion used by flaviviruses are rapidly advancing our understanding of the immunopathological mechanisms involved in flavivirus encephalitis and will lead to the development of therapeutic strategies previously not considered. PMID:24434318

  6. Research on expulsion law of influenza A(H1N1) virus and antiviral therapy%甲型H1N1流感患者排毒规律及抗病毒治疗研究

    Institute of Scientific and Technical Information of China (English)

    刘映霞; 杨桂林; 陈心春; 周伯平; 杨大国; 李慧涓; 高雪; 刘艳; 谢靖婧; 李建民; 刘水腾; 张明霞

    2010-01-01

    目的 研究2009年深圳市收治的甲型H1N1流感确诊病例排毒规律和抗病毒治疗疗效.方法 75例患者均经两次鼻咽拭子甲型H1N1流感病毒核酸检测阳性(RT-PCR),此后每天检测病毒核酸直至连续两天均阴性.第1次病毒检测阳性后立即随机分三组抗病毒治疗,分别为奥司他韦(Oseltamivir)(组Ⅰ)、中药(组Ⅱ)和奥司他韦联合中药(组Ⅲ)抗病毒治疗,5 d为一疗程.应用流式细胞仪检测T细胞亚群和IL-17表达.结果 75例患者中,78.7%(59/75)在起病后甲型H1N1流感病毒核酸阳性持续≤7 d,平均年龄为(22.25±10.38)岁;21.3%(16/75)病毒持续>7 d,年龄为(17.16±13.66)岁.对其中56例患者细胞与体液免疫功能进行分析,发现其IL-17表达明显低于季节性流感和健康人(P<0.01).进一步研究发现,10例病毒持续>7 d的患者IL-17表达值(1.91±0.80)明显低于46例病毒持续≤7 d者IL-17表达(3.05±1.59)(P<0.05),也明显低于季节性流感(P<0.01)和正常对照组(P<0.001).比较三治疗组抗病毒治疗5 d疗程结束时病毒核酸转阴率,分别为组Ⅲ92.86%,组Ⅰ71.43%,组Ⅱ46.15%,组Ⅱ明显低于前两组(分别为P<0.01,P<0.05).组Ⅲ经治疗后体温恢复正常时间较组Ⅰ、组Ⅱ缩短(P<0.05).结论 IL-17和年龄与甲型H1N1流感病毒感染及排毒时间长短可能存在一定关系.奥司他韦联合中药治疗在抗病毒疗效和减轻症状方面均有其独特优势.%Objective To investigate the A (H1N1 ) influenza patients whose viral expulsion law and antiviral effecacy in Shenzhen city in 2009. Methods A (H1N1) flu virus nucleic acid positive by reverse transcription-polymerasechain reaction (RT-PCR) with nose swabs pharynx swabs two times were showed in 75 patients. Thereafter, to detect the virus nucleic acid once per day until negative for two days in a row. Begin the antiviral therapy with Oseltamivir (Ⅰ) or the Chinese medicine (Ⅱ) or Oseltamivir combined the Chinese

  7. Modeling Viral Infectious Diseases and Development of Antiviral Therapies Using Human Induced Pluripotent Stem Cell-Derived Systems

    Directory of Open Access Journals (Sweden)

    Marta Trevisan

    2015-07-01

    Full Text Available The recent biotechnology breakthrough of cell reprogramming and generation of induced pluripotent stem cells (iPSCs, which has revolutionized the approaches to study the mechanisms of human diseases and to test new drugs, can be exploited to generate patient-specific models for the investigation of host–pathogen interactions and to develop new antimicrobial and antiviral therapies. Applications of iPSC technology to the study of viral infections in humans have included in vitro modeling of viral infections of neural, liver, and cardiac cells; modeling of human genetic susceptibility to severe viral infectious diseases, such as encephalitis and severe influenza; genetic engineering and genome editing of patient-specific iPSC-derived cells to confer antiviral resistance.

  8. Metabolic syndrome in chronic hepatitis C infection: does it still matter in the era of directly acting antiviral therapy?

    Directory of Open Access Journals (Sweden)

    Lim TR

    2014-12-01

    Full Text Available TR Lim Centre for Liver Research and NIHR Biomedical Research Unit in Liver Disease, University of Birmingham and Liver and Hepatobiliary Unit, Queen Elizabeth Hospital Birmingham, UK Abstract: Metabolic syndrome is prevalent in patients with hepatitis C virus (HCV infection. Given the pandemic spread of HCV infection and metabolic syndrome, the burden of their interaction is a major public health issue. The presence of metabolic syndrome accelerates the progression of liver disease in patients with HCV infection. New drug development in HCV has seen an unprecedented rise in the last year, which resulted in better efficacy, better tolerance, and a shorter treatment duration. This review describes the underlying mechanisms and clinical effects of metabolic syndrome in HCV infection, as well as their importance in the era of new directly acting antiviral therapy. Keywords: HCV, genotype 3, metabolic syndrome, steatosis, directly acting antiviral agents

  9. Autoimmune disease: A role for new anti-viral therapies?

    Science.gov (United States)

    Dreyfus, David H

    2011-12-01

    Many chronic human diseases may have an underlying autoimmune mechanism. In this review, the author presents a case of autoimmune CIU (chronic idiopathic urticaria) in stable remission after therapy with a retroviral integrase inhibitor, raltegravir (Isentress). Previous reports located using the search terms "autoimmunity" and "anti-viral" and related topics in the pubmed data-base are reviewed suggesting that novel anti-viral agents such as retroviral integrase inhibitors, gene silencing therapies and eventually vaccines may provide new options for anti-viral therapy of autoimmune diseases. Cited epidemiologic and experimental evidence suggests that increased replication of epigenomic viral pathogens such as Epstein-Barr Virus (EBV) in chronic human autoimmune diseases such as rheumatoid arthritis (RA), systemic lupus Erythematosus (SLE), and multiple sclerosis (MS) may activate endogenous human retroviruses (HERV) as a pathologic mechanism. Memory B cells are the reservoir of infection of EBV and also express endogenous retroviruses, thus depletion of memory b-lymphocytes by monoclonal antibodies (Rituximab) may have therapeutic anti-viral effects in addition to effects on B-lymphocyte presentation of both EBV and HERV superantigens. Other novel anti-viral therapies of chronic autoimmune diseases, such as retroviral integrase inhibitors, could be effective, although not without risk. PMID:21871974

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

    Directory of Open Access Journals (Sweden)

    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.

  11. Antiviral responses of arthropod vectors: an update on recent advances.

    Science.gov (United States)

    Rückert, Claudia; Bell-Sakyi, Lesley; Fazakerley, John K; Fragkoudis, Rennos

    2014-01-01

    Arthropod vectors, such as mosquitoes, ticks, biting midges and sand flies, transmit many viruses that can cause outbreaks of disease in humans and animals around the world. Arthropod vector species are invading new areas due to globalisation and environmental changes, and contact between exotic animal species, humans and arthropod vectors is increasing, bringing with it the regular emergence of new arboviruses. For future strategies to control arbovirus transmission, it is important to improve our understanding of virus-vector interactions. In the last decade knowledge of arthropod antiviral immunity has increased rapidly. RNAi has been proposed as the most important antiviral response in mosquitoes and it is likely to be the most important antiviral response in all arthropods. However, other newly-discovered antiviral strategies such as melanisation and the link between RNAi and the JAK/STAT pathway via the cytokine Vago have been characterised in the last few years. This review aims to summarise the most important and most recent advances made in arthropod antiviral immunity. PMID:25674592

  12. Bioprospecting of Red Sea Sponges for Novel Antiviral Pharmacophores

    KAUST Repository

    O'Rourke, Aubrie

    2015-05-01

    Natural products offer many possibilities for the treatment of disease. More than 70% of the Earth’s surface is ocean, and recent exploration and access has allowed for new additions to this catalog of natural treasures. The Central Red Sea off the coast of Saudi Arabia serves as a newly accessible location, which provides the opportunity to bioprospect marine sponges with the purpose of identifying novel antiviral scaffolds. Antivirals are underrepresented in present day clinical trials, as well as in the academic screens of marine natural product libraries. Here a high-throughput pipeline was initiated by prefacing the antiviral screen with an Image-based High-Content Screening (HCS) technique in order to identify candidates with antiviral potential. Prospective candidates were tested in a biochemical or cell-based assay for the ability to inhibit the NS3 protease of the West Nile Virus (WNV NS protease) as well as replication and reverse transcription of the Human Immunodeficiency Virus 1 (HIV-1). The analytical chemistry techniques of High-Performance Liquid Chromatograpy (HPLC), Liquid Chromatography-Mass Spectrometry (LC-MS), and Nuclear Magnetic Resonance (NMR) where used in order to identify the compounds responsible for the characteristic antiviral activity of the selected sponge fractions. We have identified a 3-alkyl pyridinium from Amphimedon chloros as the causative agent of the observed WNV NS3 protease inhibition in vitro. Additionally, we identified debromohymenialdisine, hymenialdisine, and oroidin from Stylissa carteri as prospective scaffolds capable of HIV-1 inhibition.

  13. Liposome-incorporated santolina insularis essential oil: preparation, characterization and in vitro antiviral activity.

    Science.gov (United States)

    Valenti, D; De Logu, A; Loy, G; Sinico, C; Bonsignore, L; Cottiglia, F; Garau, D; Fadda, A M

    2001-01-01

    The effect of liposomal inclusion on the stability and in vitro antiherpetic activity of Santolina insularis essential oil was investigated. In order to study the influence of vesicle structure on the liposome properties, multilamellar and unilamellar vesicles were prepared by the film method and sonication, respectively. Vesicles were obtained from hydrogenated soya phosphatydilcholine and cholesterol. Formulations were examined for their stability for over one year monitoring the drug leakage from vesicles and the average size distribution. The stability of the incorporated oil was verified by studying its quali-quantitative composition. The antiviral activity was studied against Herpes simplex virus type 1 (HSV-1) by plaque reduction and yield reduction assays. Results showed that Santolina insularis essential oil can be incorporated in high amounts in the prepared liposomes, which successfully prevented its degradation. Moreover, stability studies pointed out that vesicle dispersions were stable for at least one year and neither oil leakage nor vesicle size alteration occurred during this period. Antiviral activity assays demonstrated that Santolina insularis essential oil is effective in inactivating HSV-1 and that the activity is principally due to direct virucidal effects. Free essential oil proved to be more effective than liposomal oil and a different activity was discovered which related to the vesicular structure. The ED(50) values, significantly lower when cells were pre-incubated with the essential oil before the virus adsorption, indicate an intracellular mechanism in the antiviral activity of Santolina insularis. Moreover, liposomal Santolina essential oil is non toxic in the range of the concentration tested. PMID:19530920

  14. Drug: D06512 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available D06512 Drug Freeze-dried live attenuated rubella vaccine (JP16) Rubella vaccine [DS...:H00395] Therapeutic category: 6313 ATC code: J07BJ01 map07044 Antiviral agents Therapeutic category of drug...accines 6313 Viral vaccines D06512 Freeze-dried live attenuated rubella vaccine (...7 VACCINES J07B VIRAL VACCINES J07BJ Rubella vaccines J07BJ01 Rubella, live attenuated D06512 Freeze-dried l...ive attenuated rubella vaccine (JP16) USP drug classification [BR:br08302] Immuno

  15. Interaction Characteristics of Viral Protease Targets and Inhibitors : Perspectives for drug discovery and development of model systems

    OpenAIRE

    Shuman, Cynthia F

    2003-01-01

    Viral proteases are important targets for anti-viral drugs. Discovery of protease inhibitors as anti-viral drugs is aided by an understanding of the interactions between viral protease and inhibitors. This thesis addresses the characterization of protease-inhibitor interactions for application to drug discovery and model system development. The choice of a relevant target is essential to molecular interaction studies. Therefore, full-length NS3 protein of hepatitis C virus (HCV) was obtained,...

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

    Directory of Open Access Journals (Sweden)

    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

  17. 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.

  18. The Antiviral Effect of Baicalin on Enterovirus 71 In Vitro

    Directory of Open Access Journals (Sweden)

    Xiang Li

    2015-08-01

    Full Text Available Baicalin is a flavonoid compound extracted from Scutellaria roots that has been reported to possess antibacterial, anti-inflammatory, and antiviral activities. However, the antiviral effect of baicalin on enterovirus 71 (EV71 is still unknown. In this study, we found that baicalin showed inhibitory activity on EV71 infection and was independent of direct virucidal or prophylactic effect and inhibitory viral absorption. The expressions of EV71/3D mRNA and polymerase were significantly blocked by baicalin treatment at early stages of EV71 infection. In addition, baicalin could decrease the expressions of FasL and caspase-3, as well as inhibit the apoptosis of EV71-infected human embryonal rhabdomyosarcoma (RD cells. Altogether, these results indicate that baicalin exhibits potent antiviral effect on EV71 infection, probably through inhibiting EV71/3D polymerase expression and Fas/FasL signaling pathways.

  19. Oxysterols: An emerging class of broad spectrum antiviral effectors.

    Science.gov (United States)

    Lembo, David; Cagno, Valeria; Civra, Andrea; Poli, Giuseppe

    2016-06-01

    Oxysterols are a family of cholesterol oxidation derivatives that contain an additional hydroxyl, epoxide or ketone group in the sterol nucleus and/or a hydroxyl group in the side chain. The majority of oxysterols in the blood are of endogenous origin, derived from cholesterol via either enzymatic or non-enzymatic mechanisms. A large number of reports demonstrate multiple physiological roles of specific oxysterols. One such role is the inhibition of viral replication. This biochemical/biological property was first characterised against a number of viruses endowed with an external lipid membrane (enveloped viruses), although antiviral activity has since been observed in relation to several non-enveloped viruses. In the present paper, we review the recent findings about the broad antiviral activity of oxysterols against enveloped and non-enveloped human viral pathogens, and provide an overview of their putative antiviral mechnism(s). PMID:27086126

  20. Drug Discovery of Host CLK1 Inhibitors for Influenza Treatment

    OpenAIRE

    Mian Zu; Chao Li; Jian-Song Fang; Wen-Wen Lian; Ai-Lin Liu; Li-Shu Zheng; Guan-Hua Du

    2015-01-01

    The rapid evolution of influenza virus makes antiviral drugs less effective, which is considered to be a major bottleneck in antiviral therapy. The key proteins in the host cells, which are related with the replication cycle of influenza virus, are regarded as potential drug targets due to their distinct advantage of lack of evolution and drug resistance. Cdc2-like kinase 1 (CLK1) in the host cells is responsible for alternative splicing of the M2 gene of influenza virus during influenza infe...

  1. Antiviral Effect of Matrine against Human Enterovirus 71

    OpenAIRE

    Jiangning Liu; Chuan Qin; Kai Yan; Liangfeng Zhang; Xu Zhang; Jinghui Xiu; Yajun Yang

    2012-01-01

    Human enterovirus 71, a member of the Picornaviridae family, is one of the major causative agent of hand, foot and mouth disease in children less than six years old. This illness has caused mortalities in large-scale outbreaks in the Asia-Pacific region in recent years. No vaccine or antiviral therapy is available. In this study, antiviral effect of matrine against enterovirus 71 were evaluated in vitro and in vivo. Matrine could ...

  2. A screen of approved drugs and molecular probes identifies therapeutics with anti-Ebola virus activity.

    Science.gov (United States)

    Johansen, Lisa M; DeWald, Lisa Evans; Shoemaker, Charles J; Hoffstrom, Benjamin G; Lear-Rooney, Calli M; Stossel, Andrea; Nelson, Elizabeth; Delos, Sue E; Simmons, James A; Grenier, Jill M; Pierce, Laura T; Pajouhesh, Hassan; Lehár, Joseph; Hensley, Lisa E; Glass, Pamela J; White, Judith M; Olinger, Gene G

    2015-06-01

    Currently, no approved therapeutics exist to treat or prevent infections induced by Ebola viruses, and recent events have demonstrated an urgent need for rapid discovery of new treatments. Repurposing approved drugs for emerging infections remains a critical resource for potential antiviral therapies. We tested ~2600 approved drugs and molecular probes in an in vitro infection assay using the type species, Zaire ebolavirus. Selective antiviral activity was found for 80 U.S. Food and Drug Administration-approved drugs spanning multiple mechanistic classes, including selective estrogen receptor modulators, antihistamines, calcium channel blockers, and antidepressants. Results using an in vivo murine Ebola virus infection model confirmed the protective ability of several drugs, such as bepridil and sertraline. Viral entry assays indicated that most of these antiviral drugs block a late stage of viral entry. By nature of their approved status, these drugs have the potential to be rapidly advanced to clinical settings and used as therapeutic countermeasures for Ebola virus infections. PMID:26041706

  3. Synthetic strategy and antiviral evaluation of diamide containing heterocycles targeting dengue and yellow fever virus.

    Science.gov (United States)

    Saudi, Milind; Zmurko, Joanna; Kaptein, Suzanne; Rozenski, Jef; Gadakh, Bharat; Chaltin, Patrick; Marchand, Arnaud; Neyts, Johan; Van Aerschot, Arthur

    2016-10-01

    High-throughput screening of a subset of the CD3 chemical library (Centre for Drug Design and Discovery; KU Leuven) provided us with a lead compound 1, displaying low micromolar potency against dengue virus and yellow fever virus. Within a project aimed at discovering new inhibitors of flaviviruses, substitution of its central imidazole ring led to synthesis of variably substituted pyrazine dicarboxylamides and phthalic diamides, which were evaluated in cell-based assays for cytotoxicity and antiviral activity against the dengue virus (DENV) and yellow fever virus (YFV). Fourteen compounds inhibited DENV replication (EC50 ranging between 0.5 and 3.4 μM), with compounds 6b and 6d being the most potent inhibitors (EC50 0.5 μM) with selectivity indices (SI) > 235. Compound 7a likewise exhibited anti-DENV activity with an EC50 of 0.5 μM and an SI of >235. In addition, good antiviral activity of seven compounds in the series was also noted against the YFV with EC50 values ranging between 0.4 and 3.3 μM, with compound 6n being the most potent for this series with an EC50 0.4 μM and a selectivity index of >34. Finally, reversal of one of the central amide bonds as in series 13 proved deleterious to the inhibitory activity. PMID:27240271

  4. Antiviral Effects of Black Raspberry (Rubus coreanus) Seed and Its Gallic Acid against Influenza Virus Infection.

    Science.gov (United States)

    Lee, Ji-Hye; Oh, Mi; Seok, Jong Hyeon; Kim, Sella; Lee, Dan Bi; Bae, Garam; Bae, Hae-In; Bae, Seon Young; Hong, Young-Min; Kwon, Sang-Oh; Lee, Dong-Hun; Song, Chang-Seon; Mun, Ji Young; Chung, Mi Sook; Kim, Kyung Hyun

    2016-01-01

    Influenza is a serious public health concern worldwide, as it causes significant morbidity and mortality. The emergence of drug-resistant viral strains requires new approaches for the treatment of influenza. In this study, Rubus coreanus seed (RCS) that is left over from the production of wine or juice was found to show antiviral activities against influenza type A and B viruses. Using the time-of-addition plaque assay, viral replication was almost completely abolished by simultaneous treatment with the RCS fraction of less than a 1-kDa molecular weight (RCSF1). One of the polyphenols derived from RCSF1, gallic acid (GA), identified by liquid chromatography-tandem mass spectrometry, showed inhibitory effects against both influenza type A and B viruses, albeit at relatively high concentrations. RCSF1 was bound to hemagglutinin protein, inhibited hemagglutination significantly and disrupted viral particles, whereas GA was found to only disrupt the viral particles by using transmission electron microscopy. In BALB/c mice infected with influenza virus, oral administration of RCSF1 significantly improved the survival rate and reduced the viral titers in the lungs. Our results demonstrate that RCSF1 and GA show potent and broad antiviral activity against influenza A and B type viruses and are promising sources of agents that target virus particles. PMID:27275830

  5. Resolute efforts to cure hepatitis C: Understanding patients' reasons for completing antiviral treatment.

    Science.gov (United States)

    Clark, Jack A; Gifford, Allen L

    2015-09-01

    Antiviral treatment for hepatitis C is usually difficult, demanding, and debilitating and has long offered modest prospects of successful cure. Most people who may need treatment have faced stigma of an illness associated with drug and alcohol misuse and thus may be deemed poor candidates for treatment, while completing a course of treatment typically calls for resolve and responsibility. Patients' efforts and their reasons for completing treatment have received scant attention in hepatitis C clinical policy discourse that instead focuses on problems of adherence and patients' expected failures. Thus, we conducted qualitative interviews with patients who had recently undertaken treatment to explore their reasons for completing antiviral treatment. Analysis of their narrative accounts identified four principal reasons: cure the infection, avoid a bad end, demonstrate the virtue of perseverance through a personal trial, and achieve personal rehabilitation. Their reasons reflect moral rationales that mark the social discredit ascribed to the infection and may represent efforts to restore creditable social membership. Their reasons may also reflect the selection processes that render some of the infected as good candidates for treatment, while excluding others. Explication of the moral context of treatment may identify opportunities to support patients' efforts in completing treatment, as well as illuminate the choices people with hepatitis C make about engaging in care. PMID:25377666

  6. Antibacterial/Antiviral Property and Mechanism of Dual-Functional Quaternized Pyridinium-type Copolymer

    Directory of Open Access Journals (Sweden)

    Yan Xue

    2015-11-01

    Full Text Available Due to the massive outbreaks of pathogen-caused diseases and the increase of drug-resistant pathogens, there is a particular interest in the development of novel disinfection agents with broad-spectrum antipathogenic activity. In the present study, water-soluble pyridinium-type polyvinylpyrrolidones with different counter anions were prepared. Structural characterization was conducted via 13C–1H heteronuclear single quantum coherence spectroscopy, static light scattering, UV spectrometry and apparent charge density. The influence of counter anion and polymer compositions on the antibacterial activity was studied against Staphylococcus aureus and Escherichia coli. Atomic force microscopy (AFM was applied for tracking the morphological alterations in bacterial cells induced by prepared polycations. It was found that the exposure of bacteria to the polycations resulted in the destruction of cell membranes and the leakage of cytoplasm. The antiviral activity of pyridinium-type polycations against enveloped influenza virus was evaluated via a plaque assay. The action mode against enveloped virus was depicted to rationalize the antiviral mechanism.

  7. Design, synthesis, optimization and antiviral activity of a class of hybrid dengue virus E protein inhibitors.

    Science.gov (United States)

    Jadav, Surender Singh; Kaptein, Suzanne; Timiri, Ajaykumar; De Burghgraeve, Tine; Badavath, Vishnu Nayak; Ganesan, Ramesh; Sinha, Barij Nayan; Neyts, Johan; Leyssen, Pieter; Jayaprakash, Venkatesan

    2015-04-15

    The β-OG pocket is a cavity in the flavivirus envelope (E) protein that was identified by Proc. Natl. Acad. Sci. U.S.A.2003, 100, 6986 as a promising site for the design of antiviral agents that interfere with virus entry into the host cell. The availability of the X-ray crystal structure of the dengue virus (DENV) E protein provided an opportunity for in silico drug design efforts to identify candidate inhibitors. The present study was set up to explore whether it is possible to generate a novel class of molecules that are hybrids between two hit compounds that have been reported previously by ACS. Chem. Biol.2008, 3, 765 following an in silico screening effort against the DENV E protein. First, a library of twenty hybrid molecules were designed and synthesized to explore the feasibility of this strategy. Antiviral evaluation in a virus-cell-based assay for DENV proved this approach to be successful, after which another twenty-four molecules were produced to further explore and optimize the potency of this novel class of hybrid inhibitors. In the end, a molecule was obtained with an EC50 against dengue virus serotype 2 in the low micromolar range (23, 1.32±0.41μM). PMID:25791449

  8. Human DDX3 protein is a valuable target to develop broad spectrum antiviral agents.

    Science.gov (United States)

    Brai, Annalaura; Fazi, Roberta; Tintori, Cristina; Zamperini, Claudio; Bugli, Francesca; Sanguinetti, Maurizio; Stigliano, Egidio; Esté, José; Badia, Roger; Franco, Sandra; Martinez, Miguel A; Martinez, Javier P; Meyerhans, Andreas; Saladini, Francesco; Zazzi, Maurizio; Garbelli, Anna; Maga, Giovanni; Botta, Maurizio

    2016-05-10

    Targeting a host factor essential for the replication of different viruses but not for the cells offers a higher genetic barrier to the development of resistance, may simplify therapy regimens for coinfections, and facilitates management of emerging viral diseases. DEAD-box polypeptide 3 (DDX3) is a human host factor required for the replication of several DNA and RNA viruses, including some of the most challenging human pathogens currently circulating, such as HIV-1, Hepatitis C virus, Dengue virus, and West Nile virus. Herein, we showed for the first time, to our knowledge, that the inhibition of DDX3 by a small molecule could be successfully exploited for the development of a broad spectrum antiviral agent. In addition to the multiple antiviral activities, hit compound 16d retained full activity against drug-resistant HIV-1 strains in the absence of cellular toxicity. Pharmacokinetics and toxicity studies in rats confirmed a good safety profile and bioavailability of 16d. Thus, DDX3 is here validated as a valuable therapeutic target. PMID:27118832

  9. Deep sequencing analysis of HBV genotype shift and correlation with antiviral efficiency during adefovir dipivoxil therapy.

    Directory of Open Access Journals (Sweden)

    Yuwei Wang

    Full Text Available Viral genotype shift in chronic hepatitis B (CHB patients during antiviral therapy has been reported, but the underlying mechanism remains elusive.38 CHB patients treated with ADV for one year were selected for studying genotype shift by both deep sequencing and Sanger sequencing method.Sanger sequencing method found that 7.9% patients showed mixed genotype before ADV therapy. In contrast, all 38 patients showed mixed genotype before ADV treatment by deep sequencing. 95.5% mixed genotype rate was also obtained from additional 200 treatment-naïve CHB patients. Of the 13 patients with genotype shift, the fraction of the minor genotype in 5 patients (38% increased gradually during the course of ADV treatment. Furthermore, responses to ADV and HBeAg seroconversion were associated with the high rate of genotype shift, suggesting drug and immune pressure may be key factors to induce genotype shift. Interestingly, patients with genotype C had a significantly higher rate of genotype shift than genotype B. In genotype shift group, ADV treatment induced a marked enhancement of genotype B ratio accompanied by a reduction of genotype C ratio, suggesting genotype C may be more sensitive to ADV than genotype B. Moreover, patients with dominant genotype C may have a better therapeutic effect. Finally, genotype shifts was correlated with clinical improvement in terms of ALT.Our findings provided a rational explanation for genotype shift among ADV-treated CHB patients. The genotype and genotype shift might be associated with antiviral efficiency.

  10. Antiviral activity of Ellagic Acid against envelope proteins from Dengue Virus through Insilico Docking

    Directory of Open Access Journals (Sweden)

    Giridharan Bupesh

    2014-06-01

    Full Text Available Arbo viral infection such as dengue, chikungunya, japanese encephalitis, west nile viruses and other flaviviruses have transmemberane envelope proteins. These proteins (glycoproteins form spike-like projections responsible for virus attachment to target cells and acid-activated membrane fusion. Further it targets numerous serologic reactions and tests including neutralization and hemagglutination inhibition. These viruses showed wide range of antigenic cross reactions and caused by seven antigenic complexes from 30 species, huge subtypes and varieties. This protein is the chief site for most neutralizing epitopes, highly conserved with cross-reactive epitopes. In the present study, the ellagic acid (4,4,5,5,6,6-Hexahydroxydiphenic acid 2,6,2,6-dilactone was evaluated for the antiviral activity through Insilico docking against drug target envelope proteins from dengue viruses. Ellagic acid showed good docking score with all the four glycoproteins from dengue 1-4 viruses. Among the glycoprotein receptors the glycoprotein-1 and 4 demonstrates the highest docking score with energy minimization. This highlights that the ellagic acid have potent antiviral activity against the dengue viruses.

  11. Antiviral Effects of Black Raspberry (Rubus coreanus) Seed and Its Gallic Acid against Influenza Virus Infection

    Science.gov (United States)

    Lee, Ji-Hye; Oh, Mi; Seok, Jong Hyeon; Kim, Sella; Lee, Dan Bi; Bae, Garam; Bae, Hae-In; Bae, Seon Young; Hong, Young-Min; Kwon, Sang-Oh; Lee, Dong-Hun; Song, Chang-Seon; Mun, Ji Young; Chung, Mi Sook; Kim, Kyung Hyun

    2016-01-01

    Influenza is a serious public health concern worldwide, as it causes significant morbidity and mortality. The emergence of drug-resistant viral strains requires new approaches for the treatment of influenza. In this study, Rubus coreanus seed (RCS) that is left over from the production of wine or juice was found to show antiviral activities against influenza type A and B viruses. Using the time-of-addition plaque assay, viral replication was almost completely abolished by simultaneous treatment with the RCS fraction of less than a 1-kDa molecular weight (RCSF1). One of the polyphenols derived from RCSF1, gallic acid (GA), identified by liquid chromatography-tandem mass spectrometry, showed inhibitory effects against both influenza type A and B viruses, albeit at relatively high concentrations. RCSF1 was bound to hemagglutinin protein, inhibited hemagglutination significantly and disrupted viral particles, whereas GA was found to only disrupt the viral particles by using transmission electron microscopy. In BALB/c mice infected with influenza virus, oral administration of RCSF1 significantly improved the survival rate and reduced the viral titers in the lungs. Our results demonstrate that RCSF1 and GA show potent and broad antiviral activity against influenza A and B type viruses and are promising sources of agents that target virus particles. PMID:27275830

  12. Drug: D08876 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available itis C infection [DS:H00413] ATC code: J05AE12 Indication: Chronic hepatitis C geno...ion [BR:br08302] Antivirals Anti-hepatitis C (HCV) Agents Boceprevir D08876 Bocep...D08876 Drug Boceprevir (INN/USAN); Victrelis (TN) C27H45N5O5 519.3421 519.6767 D08876.gif Treatment of hepat

  13. Drug: D03835 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available D03835 Drug Fosamprenavir calcium (USAN); Lexiva (TN) C25H34N3O9PS. Ca 623.1379 623.6689 D03835. ... gif Antiviral [HIV ... protease inhibitor] [DS:H00406] ATC code: J05AE07 ... prodrug, active substance: Amprenavir [DR:D00894] HIV ... protease inhibitor [CPD:C19849] Enzyme: CYP3A4 [HS ...

  14. Drug: D02497 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available D02497 Drug Fosamprenavir (INN) C25H36N3O9PS 585.191 585.6068 D02497.gif Antiviral [HIV ... protease ... prodrug, active substance: Amprenavir [DR:D00894] HIV ... protease inhibitor [CPD:C19849] Enzyme: CYP3A4 [HS ... CYP3A inhibitor [HSA:1576 1577 1551] map07053 Anti-HIV ... agents map07218 HIV ... protease inhibitors Anatomical ...

  15. Drug: D08259 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available D08259 Drug Nelfinavir (INN); Viracept (TN) C32H45N3O4S 567.3131 567.7824 D08259.gif Antiviral, ... itor [DS:H00406] Same as: C07257 ATC code: J05AE04 HIV ... protease inhibitor [CPD:C19849] Enzyme: CYP3A4 [HS ... sporter inhibition: ABCB1 [HSA:5243] map07053 Anti-HIV ... agents map07218 HIV ... protease inhibitors map04976 B ...

  16. Drug: D10165 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available D10165 Drug Setrobuvir (USAN) C25H25FN4O6S2 560.12 560.6176 D10165.gif Treatment of...Hepatitis C Antiinfectives [BR:br08307] Antivirals Anti-HCV agent Polymerase inhibitor NS5B polymerase inhibitor Setrobuvir D101...65 Setrobuvir (USAN) CAS: 1071517-39-9 PubChem: 135626883 LigandBox: D101

  17. Aktivitas Antiviral Minyak Atsiri Jahe Merah terhadap Virus Flu Burung (ANTIVIRAL ACTIVITY OF ESSENSIAL OIL RED GINGER ON AVIAN INFLUENZA

    Directory of Open Access Journals (Sweden)

    Tri Untari

    2013-07-01

    Full Text Available The studies have reported that ginger have many activities such as antiemesis, anti-inflammatory,anti-bacterial and anti-parasites. Therefore, this study was conducted to evaluate antiviral effect of essentialred ginger oil againts Avian Influenza (AI in ovo using hemagglutination test (HA. Avian Influenzaviruses were treated with 0,01%, 0,1% and 1% of essential red ginger oil, and then inoculated in chickenembryonated egg via allantoic sac. Allantoic fluid was harvested using for HA test . Result of this studyshows that application of 1% of essential red ginger oil results in the reduction of titer HA . Interestingly,essential oil shows antiviral activity revealed HA titre 20 whereas the titre HA AI which AI virus treatedwith 0,01% and 0,1% essential red ginger oil, the HA titer was 25. The conclution of this study proved thatessensial oil 1% of the red gingger is the best concentration as antiviral activity .

  18. Antiviral therapies for chronic hepatitis C virus infectionwith cirrhosis

    Institute of Scientific and Technical Information of China (English)

    2015-01-01

    Patients who are infected with hepatitis C virus (HCV)and also have advanced fibrosis or cirrhosis have beenrecognized as "difficult-to-treat" patients during an erawhen peginterferon and ribavirin combination therapy isthe standard of care. Recent guidelines have clearly statedthat treatment should be prioritized in this populationto prevent complications such as decompensationand hepatocellular carcinoma. Recent advances in thetreatment of chronic hepatitis C have been achievedthrough the development of direct-acting antiviral agents(DAAs). Boceprevir and telaprevir are first-generationDAAs that inhibit the HCV NS3/4A protease. Bocepreviror telaprevir, in combination with peginterferon andribavirin, improved the sustained virological responserates compared with peginterferon and ribavirin alone andwere tolerated in patients with HCV genotype 1 infectionwithout cirrhosis or compensated cirrhosis. However, theefficacy is lower especially in prior non-responders withor without cirrhosis. Furthermore, a high incidence ofadverse events was observed in patients with advancedliver disease, including cirrhosis, in real-life settings.Current guidelines in the United States and in someEuropean countries no longer recommend these regimensfor the treatment of HCV. Next-generation DAAs includesecond-generation HCV NS3/4A protease inhibitors, HCVNS5A inhibitors and HCV NS5B inhibitors, which have ahigh efficacy and a lower toxicity. These drugs are usedin interferon-free or in interferon-based regimens withor without ribavirin in combination with different classesof DAAs. Interferon-based regimens, such as simeprevirin combination with peginterferon and ribavirin, are welltolerated and are highly effective especially in treatmentna?vepatients and in patients who received treatmentbut who relapsed. The efficacy is less pronounced in nullrespondersand in patients with cirrhosis. Interferonfreeregimens in combination with ribavirin and/ortwo or more DAAs could be

  19. Predicting the emergence of drug-resistant HSV-2: new predictions

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    Darby Graham

    2003-03-01

    Full Text Available Abstract Background Mathematical models can be used to predict the emergence and transmission of antiviral resistance. Previously it has been predicted that high usage of antivirals (in immunocompetent populations to treat Herpes Simplex Virus type 2 (HSV-2 would only lead to fairly low levels of antiviral resistance. The HSV-2 predictions were based upon the assumption that drug-resistant strains of HSV-2 would be less infectious than drug-sensitive strains but that the drug-resistant strains would not be impaired in their ability to reactivate. Recent data suggest that some drug-resistant strains of HSV-2 are likely to be impaired in their ability to reactivate. Objectives: (1 To predict the effect of a high usage of antivirals on the prevalence of drug-resistant HSV-2 under the assumption that drug-resistant strains will be less infectious than drug-sensitive strains of HSV-2 and also have an impaired ability to reactivate. (2 To compare predictions with previous published predictions. Methods We generated theoretical drug-resistant HSV-2 strains that were attenuated (in comparison with drug-sensitive strains in both infectivity and ability to reactivate. We then used a transmission model to predict the emergence and transmission of drug-resistant HSV-2 in the immunocompetent population assuming a high usage of antivirals. Results Our predictions are an order of magnitude lower than previous predictions; we predict that even after 25 years of high antiviral usage only 5 out of 10,000 immunocompetent individuals will be shedding drug-resistant virus. Furthermore, after 25 years, 52 cases of HSV-2 would have been prevented for each prevalent case of drug-resistant HSV-2. Conclusions The predicted levels of drug-resistant HSV-2 for the immunocompetent population are so low that it seems unlikely that cases of drug-resistant HSV-2 will be detected.

  20. Using high-throughput sequencing to leverage surveillance of genetic diversity and oseltamivir resistance: a pilot study during the 2009 influenza A(H1N1 pandemic.

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    Juan Téllez-Sosa

    Full Text Available BACKGROUND: Influenza viruses display a high mutation rate and complex evolutionary patterns. Next-generation sequencing (NGS has been widely used for qualitative and semi-quantitative assessment of genetic diversity in complex biological samples. The "deep sequencing" approach, enabled by the enormous throughput of current NGS platforms, allows the identification of rare genetic viral variants in targeted genetic regions, but is usually limited to a small number of samples. METHODOLOGY AND PRINCIPAL FINDINGS: We designed a proof-of-principle study to test whether redistributing sequencing throughput from a high depth-small sample number towards a low depth-large sample number approach is feasible and contributes to influenza epidemiological surveillance. Using 454-Roche sequencing, we sequenced at a rather low depth, a 307 bp amplicon of the neuraminidase gene of the Influenza A(H1N1 pandemic (A(H1N1pdm virus from cDNA amplicons pooled in 48 barcoded libraries obtained from nasal swab samples of infected patients (n  =  299 taken from May to November, 2009 pandemic period in Mexico. This approach revealed that during the transition from the first (May-July to second wave (September-November of the pandemic, the initial genetic variants were replaced by the N248D mutation in the NA gene, and enabled the establishment of temporal and geographic associations with genetic diversity and the identification of mutations associated with oseltamivir resistance. CONCLUSIONS: NGS sequencing of a short amplicon from the NA gene at low sequencing depth allowed genetic screening of a large number of samples, providing insights to viral genetic diversity dynamics and the identification of genetic variants associated with oseltamivir resistance. Further research is needed to explain the observed replacement of the genetic variants seen during the second wave. As sequencing throughput rises and library multiplexing and automation improves, we foresee that

  1. Polyethylenimine combined with liposomes and with decreased numbers of primary amine residues strongly enhanced therapeutic antiviral efficiency against herpes simplex virus type 2 in a mouse model.

    Science.gov (United States)

    Maitani, Yoshie; Ishigaki, Kenji; Nakazawa, Yuta; Aragane, Daisuke; Akimoto, Tomoya; Iwamizu, Masatoshi; Kai, Takashi; Hayashi, Kyoko

    2013-03-10

    The development of antiviral agents that have novel mechanisms of action is urgently required in the topical therapy of herpes simplex virus type 2 (HSV-2) infections. We reported previously that topical application of branched 3610-Da polyethylenimine (PEI) exhibited preventative antiviral activity. In this study, to develop therapeutic anti-HSV-2 agents, the most potent PEI combined with ~200 nm-sized liposomes with or without oleic acid (liposomes/PEI) was selected in vitro and further evaluated using in vivo studies. The mechanism of action in vivo was elucidated using PEIs with decreased numbers of primary amine residues, resulting from ethylene carbonate treatment, and polyallylamine, a linear polyamine consisting of primary amines. Cytotoxicity and antiviral activity in vitro, and the appearance of acute herpetic disease and virus yields in mice intravaginally administered with liposomes/PEI were evaluated in cell culture assays and a mouse genital herpes model, respectively. In addition, the cellular association of liposome/PEI was examined by flow cytometry and confocal microscopy. PEI showed higher antiviral activity postinfection than preinfection in vivo. Liposome/PEI and PEI with decreased numbers of primary amine residues at a dose of 0.2 mg PEI/mouse exhibited more potent therapeutic antiviral activity than acyclovir and PEI alone without acute lesion appearance or toxicity pre- or postinfection, but polyallylamine was moderately effective only preinfection. Liposome concentrations were important for the effectiveness of liposome/PEI. This finding suggests that PEI combined with liposomes and with slightly decreased numbers of primary amines may be an effective vaginally administrated antiviral drug, and secondary and tertiary amine residues of PEI may contribute to the inhibitory efficiency against viral infection. PMID:23298614

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

    Directory of Open Access Journals (Sweden)

    OliverPlanz

    2014-04-01

    Full Text Available 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 - 1mg/ml the extract showed no cytotoxic effect on three cell lines and a CC50 of 0.5 ± 0.3 mg/ml, on PBMCs. 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.

  3. Structures of mammalian ER α-glucosidase II capture the binding modes of broad-spectrum iminosugar antivirals.

    Science.gov (United States)

    Caputo, Alessandro T; Alonzi, Dominic S; Marti, Lucia; Reca, Ida-Barbara; Kiappes, J L; Struwe, Weston B; Cross, Alice; Basu, Souradeep; Lowe, Edward D; Darlot, Benoit; Santino, Angelo; Roversi, Pietro; Zitzmann, Nicole

    2016-08-01

    The biosynthesis of enveloped viruses depends heavily on the host cell endoplasmic reticulum (ER) glycoprotein quality control (QC) machinery. This dependency exceeds the dependency of host glycoproteins, offering a window for the targeting of ERQC for the development of broad-spectrum antivirals. We determined small-angle X-ray scattering (SAXS) and crystal structures of the main ERQC enzyme, ER α-glucosidase II (α-GluII; from mouse), alone and in complex with key ligands of its catalytic cycle and antiviral iminosugars, including two that are in clinical trials for the treatment of dengue fever. The SAXS data capture the enzyme's quaternary structure and suggest a conformational rearrangement is needed for the simultaneous binding of a monoglucosylated glycan to both subunits. The X-ray structures with key catalytic cycle intermediates highlight that an insertion between the +1 and +2 subsites contributes to the enzyme's activity and substrate specificity, and reveal that the presence of d-mannose at the +1 subsite renders the acid catalyst less efficient during the cleavage of the monoglucosylated substrate. The complexes with iminosugar antivirals suggest that inhibitors targeting a conserved ring of aromatic residues between the α-GluII +1 and +2 subsites would have increased potency and selectivity, thus providing a template for further rational drug design. PMID:27462106

  4. Novel norbornane-based nucleoside and nucleotide analogues and their antiviral activities

    Czech Academy of Sciences Publication Activity Database

    Dejmek, Milan; Šála, Michal; Hřebabecký, Hubert; Andrei, G.; Balzarini, J.; Naesens, L.; Neyts, J.; Nencka, Radim

    San Francisco: International Society for Antiviral Research (ISAR), 2013. s. 48-48. [International Conference on Antiviral Research /26./. 11.05.2013-15.05.2013, San Francisco] Grant ostatní: European Social Fund(XE) CZ.1.07/2.2.00/28.0184 Institutional support: RVO:61388963 Keywords : HIV * antiviral activity * norbornane-based derivatives Subject RIV: CC - Organic Chemistry

  5. DMPD: What is disrupting IFN-alpha's antiviral activity? [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 15283983 What is disrupting IFN-alpha's antiviral activity? Mbow ML, Sarisky RT. Tr...ends Biotechnol. 2004 Aug;22(8):395-9. (.png) (.svg) (.html) (.csml) Show What is disrupting IFN-alpha's antiviral activity...? PubmedID 15283983 Title What is disrupting IFN-alpha's antiviral activity? Authors Mbow ML,

  6. DMPD: Regulation of mitochondrial antiviral signaling pathways. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 18549796 Regulation of mitochondrial antiviral signaling pathways. Moore CB, Ting J...P. Immunity. 2008 Jun;28(6):735-9. (.png) (.svg) (.html) (.csml) Show Regulation of mitochondrial antiviral ...signaling pathways. PubmedID 18549796 Title Regulation of mitochondrial antiviral signaling pathways. Author

  7. DMPD: TLR3 in antiviral immunity: key player or bystander? [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 16027039 TLR3 in antiviral immunity: key player or bystander? Schroder M, Bowie AG.... Trends Immunol. 2005 Sep;26(9):462-8. (.png) (.svg) (.html) (.csml) Show TLR3 in antiviral immunity: key pl...ayer or bystander? PubmedID 16027039 Title TLR3 in antiviral immunity: key player or bystander? Authors Schr

  8. Investigation of Anticancer and Antiviral Properties of Selected Aroma Samples

    Czech Academy of Sciences Publication Activity Database

    Ryabchenko, B.; Tulupová, Elena; Schmidt, E.; Wlcek, K.; Buchbauer, G.; Jirovetz, L.

    2008-01-01

    Roč. 3, č. 7 (2008), s. 1085-1088. ISSN 1934-578X Institutional research plan: CEZ:AV0Z50390703 Keywords : Antiviral * Anticancer * Cytotoxicity Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 0.766, year: 2008

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

    Directory of Open Access Journals (Sweden)

    CesareMancuso

    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.

  10. Antiviral phenolics from the leaves of Cleistocalyx operculatus.

    Science.gov (United States)

    Ha, Thi Kim Quy; Dao, Trong Tuan; Nguyen, Ngoc Hieu; Kim, Jiwon; Kim, Eunhee; Cho, Tae Oh; Oh, Won Keun

    2016-04-01

    During the screening program for anti-influenza agents from medicinal plants, the ethanolic extract of Cleistocalyx operculatus leaves was found to exhibit potential neuraminidase (NA) inhibitory activity. Bioassay-directed fractionation led to the isolation of two new acetophenones (1 and 2) and one new flavanone (3), along with six known compounds (4-9). The structures of all isolated compounds were elucidated using various spectroscopic methods and through comparison with the previous literature. Compounds 6 and 8 exhibited strong enzymatic inhibition on various neuraminidases from different influenza viruses, including H1N1, H9N2, novel H1N1, and oseltamivir-resistant novel H1N1 (H274Y mutation) expressed in HEK293 cells (IC50 values ranging from 5.07 ± 0.94 μM to 9.34 ± 2.52 μM, respectively). Kinetic experiments revealed the non-competitive inhibitory mode of both compounds 6 and 8. Furthermore, these flavonoids reduced the cytopathic effect of the H1N1 virus in MDCK cells. The present study suggests the potential of two flavonoids (6 and 8) as new lead compounds for the development of novel NA inhibitors in the future. PMID:26972228

  11. NS3 protease from flavivirus as a target for designing antiviral inhibitors against dengue virus

    Directory of Open Access Journals (Sweden)

    Satheesh Natarajan

    2010-01-01

    Full Text Available The development of novel therapeutic agents is essential for combating the increasing number of cases of dengue fever in endemic countries and among a large number of travelers from non-endemic countries. The dengue virus has three structural proteins and seven non-structural (NS proteins. NS3 is a multifunctional protein with an N-terminal protease domain (NS3pro that is responsible for proteolytic processing of the viral polyprotein, and a C-terminal region that contains an RNA triphosphatase, RNA helicase and RNA-stimulated NTPase domain that are essential for RNA replication. The serine protease domain of NS3 plays a central role in the replicative cycle of dengue virus. This review discusses the recent structural and biological studies on the NS2B-NS3 protease-helicase and considers the prospects for the development of small molecules as antiviral drugs to target this fascinating, multifunctional protein.

  12. Era of direct acting antivirals in chronic hepatitis C: Who will benefit?

    Institute of Scientific and Technical Information of China (English)

    James; Fung

    2015-01-01

    In the era of highly effective direct acting antiviral(DAA) drugs for the treatment of chronic hepatitis C(CHC) infection, where eradication is almost ensured with minimal side effects, all hepatitis C carriers should benefit theoretically. In the real world setting however, only a small proportion will benefit at this time point due to the multiple barriers to accessing therapy. Given that universal treatment is unlikely, treatment with DAAs will likely be restricted to those with the highest health benefits, and for those who can afford the high expense of a treatment course. Those with the highest unmet needs include those who have failed previous interferon-based therapy or who are interferon-ineligible with evidence of active disease, those with advance liver disease, and those with recurrence of hepatitis C after liver transplantation. In the future, the focus should be on increasing access to treatment for those infected with CHC.

  13. Influenza virus surveillance in Argentina during the 2012 season: antigenic characterization, genetic analysis and antiviral susceptibility.

    Science.gov (United States)

    Benedetti, E; Daniels, R S; Pontoriero, A; Russo, M; Avaro, M; Czech, A; Campos, A; Periolo, N; Gregory, V; McCauley, J W; Baumeister, E G

    2016-03-01

    The activity and circulation of influenza viruses in Argentina was studied during 2012 as part of the Argentinean Surveillance for Influenza and other Respiratory Viruses, in the context of Global Influenza Surveillance. The antigenicity and molecular characteristics of haemagglutinins (HA) of circulating influenza A and B viruses were analysed to assess the emergence of virus variants. Susceptibility to oseltamivir and zanamivir was evaluated by enzymatic assay and results were backed-up by sequencing of the neuraminidase (NA) genes. During the 2012 season, influenza virus circulation in Argentina was detected from weeks 24 to 51. The HA sequences of the studied A(H1N1)pdm09 subtype viruses segregated in a different genetic group compared to those identified during the 2009 pandemic, although they were still closely related antigenically to the vaccine virus A/California/07/2009. The HA sequences of the A(H3N2) viruses analysed fell into the A/Victoria/208/2009 clade, genetic group 3C. A mixed circulation of virus variants belonging to B/Victoria and B/Yamagata lineages was detected, with B/Victoria being dominant. All viruses tested were sensitive to oseltamivir and zanamivir except one. This isolate, an A(H1N1)pdm09 virus possessing the substitution NA-N295S, showed highly reduced inhibition by oseltamivir and reduced inhibition by zanamivir. Virological and epidemiological surveillance remains critical for detection of evolving influenza viruses. PMID:26345289

  14. Epimedium koreanum Nakai displays broad spectrum of antiviral activity in vitro and in vivo by inducing cellular antiviral state.

    Science.gov (United States)

    Cho, Won-Kyung; Weeratunga, Prasanna; Lee, Byeong-Hoon; Park, Jun-Seol; Kim, Chul-Joong; Ma, Jin Yeul; Lee, Jong-Soo

    2015-01-01

    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. PMID:25609307

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Science.gov (United States)

    Cho, Won-Kyung; Weeratunga, Prasanna; Lee, Byeong-Hoon; Park, Jun-Seol; Kim, Chul-Joong; Ma, Jin Yeul; Lee, Jong-Soo

    2015-01-01

    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 Nakaimarkedly 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. PMID:25609307

  17. Antiviral effects of two Ganoderma lucidum triterpenoids against enterovirus 71 infection

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Wenjing; Tao, Junyan; Yang, Xiaoping [State Key Laboratory of Virology and College of Life Sciences, Wuhan University, Wuhan 430072 (China); Yang, Zhuliang [Key Laboratory of Biodiversity and Biogeography, Kunming Institute of Botany, Chinese Academy of Science, Kunming 650201 (China); Zhang, Li; Liu, Hongsheng [Department of Academy of Sciences, Liaoning University, Shenyang 110036 (China); Wu, Kailang [State Key Laboratory of Virology and College of Life Sciences, Wuhan University, Wuhan 430072 (China); Wu, Jianguo, E-mail: jwu@whu.edu.cn [State Key Laboratory of Virology and College of Life Sciences, Wuhan University, Wuhan 430072 (China)

    2014-07-04

    Highlights: • Triterpenoids GLTA and GLTB display anti-EV71 activities without cytotoxicity. • The compounds prevent EV71 infection by blocking adsorption of the virus to the cells. • GLTA and GLTB bind to EV71 capsid at the hydrophobic pocket to block EV71 uncoating. • The two compounds significantly inhibit the replication of EV71 viral RNA. • GLTA and GLTB may be used as potential therapeutic agents to treat EV71 infection. - Abstract: Enterovirus 71 (EV71) is a major causative agent for hand, foot and mouth disease (HFMD), and fatal neurological and systemic complications in children. However, there is currently no clinical approved antiviral drug available for the prevention and treatment of the viral infection. Here, we evaluated the antiviral activities of two Ganoderma lucidum triterpenoids (GLTs), Lanosta-7,9(11),24-trien-3-one,15;26-dihydroxy (GLTA) and Ganoderic acid Y (GLTB), against EV71 infection. The results showed that the two natural compounds display significant anti-EV71 activities without cytotoxicity in human rhabdomyosarcoma (RD) cells as evaluated by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) cell proliferation assay. The mechanisms by which the two compounds affect EV71 infection were further elucidated by three action modes using Ribavirin, a common antiviral drug, as a positive control. The results suggested that GLTA and GLTB prevent EV71 infection through interacting with the viral particle to block the adsorption of virus to the cells. In addition, the interactions between EV71 virion and the compounds were predicated by computer molecular docking, which illustrated that GLTA and GLTB may bind to the viral capsid protein at a hydrophobic pocket (F site), and thus may block uncoating of EV71. Moreover, we demonstrated that GLTA and GLTB significantly inhibit the replication of the viral RNA (vRNA) of EV71 replication through blocking EV71 uncoating. Thus, GLTA and GLTB may represent two potential

  18. Antiviral effects of two Ganoderma lucidum triterpenoids against enterovirus 71 infection

    International Nuclear Information System (INIS)

    Highlights: • Triterpenoids GLTA and GLTB display anti-EV71 activities without cytotoxicity. • The compounds prevent EV71 infection by blocking adsorption of the virus to the cells. • GLTA and GLTB bind to EV71 capsid at the hydrophobic pocket to block EV71 uncoating. • The two compounds significantly inhibit the replication of EV71 viral RNA. • GLTA and GLTB may be used as potential therapeutic agents to treat EV71 infection. - Abstract: Enterovirus 71 (EV71) is a major causative agent for hand, foot and mouth disease (HFMD), and fatal neurological and systemic complications in children. However, there is currently no clinical approved antiviral drug available for the prevention and treatment of the viral infection. Here, we evaluated the antiviral activities of two Ganoderma lucidum triterpenoids (GLTs), Lanosta-7,9(11),24-trien-3-one,15;26-dihydroxy (GLTA) and Ganoderic acid Y (GLTB), against EV71 infection. The results showed that the two natural compounds display significant anti-EV71 activities without cytotoxicity in human rhabdomyosarcoma (RD) cells as evaluated by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) cell proliferation assay. The mechanisms by which the two compounds affect EV71 infection were further elucidated by three action modes using Ribavirin, a common antiviral drug, as a positive control. The results suggested that GLTA and GLTB prevent EV71 infection through interacting with the viral particle to block the adsorption of virus to the cells. In addition, the interactions between EV71 virion and the compounds were predicated by computer molecular docking, which illustrated that GLTA and GLTB may bind to the viral capsid protein at a hydrophobic pocket (F site), and thus may block uncoating of EV71. Moreover, we demonstrated that GLTA and GLTB significantly inhibit the replication of the viral RNA (vRNA) of EV71 replication through blocking EV71 uncoating. Thus, GLTA and GLTB may represent two potential

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

    OpenAIRE

    Lianfeng Zhang; Chuan Qin; Yanfeng Xu; Xiaoying Li; Li Zhang; Jiangning Liu; Jinghui Xiu; Yajun Yang

    2013-01-01

    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 e...

  20. Inhibition of Influenza A Virus Infection In Vitro by Peptides Designed In Silico

    OpenAIRE

    Rogelio López-Martínez; G Lizbeth Ramírez-Salinas; José Correa-Basurto; Barrón, Blanca L.

    2013-01-01

    Influenza A viruses are enveloped, segmented negative single-stranded RNA viruses, capable of causing severe human respiratory infections. Currently, only two types of drugs are used to treat influenza A infections, the M2 H(+) ion channel blockers (amantadine and rimantadine) and the neuraminidase inhibitors (NAI) (oseltamivir and zanamivir). Moreover, the emergence of drug-resistant influenza A virus strains has emphasized the need to develop new antiviral agents to complement or replace th...