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Sample records for reported decreased antiviral

  1. Prophylactic Antiviral Treatment in Recurrent Herpes Zoster: A Case Report

    Directory of Open Access Journals (Sweden)

    Hatice Gamze Bayram

    2011-06-01

    Full Text Available Herpes zoster (HZ occurs in older ages with activation of varicella-zoster virus (VZV which persists in a dormant phase within the dorsal root ganglia. The incidence of HZ in immunosuppressed patients is 20-100 times higher and the clinical progress is more severe than in immunocompetent individuals. A 48-year-old man who had been diagnosed with acute myelocytic leukemia type M3 and had been treated with immunosuppressive agents was admitted to our clinic. The patient was clinically diagnosed as having HZ. He was treated with acyclovir 800 mg five times daily for 7 days. In the consecutive three months, he attended our clinic again with similar complaints. The left cervical (C5, C6 dermatomes were involved at the fourth attack of HZ. Multinucleated giant cells were determined on the Tzanck smear. VZV DNA was detected by polymerase chain reaction (PCR. Treatment with valacyclovir 1 g three times daily for 14 days was prescribed and then, prophylactic treatment with valacyclovir 500 mg two times a day was administered. Although immunosuppressive treatment was continued, no new attacks of herpes zoster occurred. We think that prophylactic antiviral therapy should be initiated in immunosuppressive individuals who have recurrent herpes zoster attacks.

  2. Direct-acting antiviral therapy decreases hepatocellular carcinoma recurrence rate in cirrhotic patients with chronic hepatitis C.

    Science.gov (United States)

    Virlogeux, Victor; Pradat, Pierre; Hartig-Lavie, Kerstin; Bailly, François; Maynard, Marianne; Ouziel, Guillaume; Poinsot, Domitille; Lebossé, Fanny; Ecochard, Marie; Radenne, Sylvie; Benmakhlouf, Samir; Koffi, Joseph; Lack, Philippe; Scholtes, Caroline; Uhres, Anne-Claire; Ducerf, Christian; Mabrut, Jean-Yves; Rode, Agnès; Levrero, Massimo; Combet, Christophe; Merle, Philippe; Zoulim, Fabien

    2017-08-01

    Arrival of direct-acting antiviral agents against hepatitis C virus with high-sustained virological response rates and very few side effects has drastically changed the management of hepatitis C virus infection. The impact of direct-acting antiviral exposure on hepatocellular carcinoma recurrence after a first remission in patients with advanced fibrosis remains to be clarified. 68 consecutive hepatitis C virus patients with a first hepatocellular carcinoma diagnosis and under remission, subsequently treated or not with a direct-acting antiviral combination, were included. Clinical, biological and virological data were collected at first hepatocellular carcinoma diagnosis, at remission and during the surveillance period. All patients were cirrhotic. Median age was 62 years and 76% of patients were male. Twenty-three patients (34%) were treated with direct-acting antivirals and 96% of them achieved sustained virological response. Median time between hepatocellular carcinoma remission and direct-acting antivirals initiation was 7.2 months (IQR: 3.6-13.5; range: 0.3-71.4) and median time between direct-acting antivirals start and hepatocellular carcinoma recurrence was 13.0 months (IQR: 9.2-19.6; range: 3.0-24.7). Recurrence rate was 1.7/100 person-months among treated patients vs 4.2/100 person-months among untreated patients (P=.008). In multivariate survival analysis, the hazard ratio for hepatocellular carcinoma recurrence after direct-acting antivirals exposure was 0.24 (95% confidence interval: 0.10-0.55; PHepatocellular carcinoma recurrence rate was significantly lower among patients treated with direct-acting antivirals compared with untreated patients. Given the potential impact of our observation, large-scale prospective cohort studies are needed to confirm these results. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  3. Meeting report: 28th International Conference on Antiviral Research in Rome, Italy.

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    Vere Hodge, R Anthony

    2015-11-01

    The 28th International Conference on Antiviral Research (ICAR) was held in Rome, Italy from May 11 to 15, 2015. This article summarizes the principal invited lectures. Phillip Furman, the Elion award recipient, described the research leading to sofosbuvir. Dennis Liotta, who received the Holý award, described how an investigation into HIV entry inhibitors led to a new therapy for cancer patients. Erica Ollmann Saphire, winner of the Prusoff Young Investigator award, explored the world of viral proteins and how they remodel to perform different essential roles in viral replication. The keynote addresses, by Raffaele De Francesco and Michael Manns, reported on the remarkable progress made in the therapy of chronic HCV infections. A third keynote address, by Armand Sprecher, related the difficulties and successes of Médicins Sans Frontières in West Africa ravaged by the Ebola outbreak. There were three mini-symposia on RNA Viruses, Antiviral Chemistry and Emerging Viruses. There was a good collection of talks on RNA viruses (norovirus, rabies, dengue, HEV, HCV, and RSV). A highlight of the chemistry was the preparation of prodrugs for nucleotide triphosphates as this opens a door to new options. The third mini-symposium emphasized how research work in the antiviral area is continuing to expand and needs to do so with a sense of urgency. Although this meeting report covers only a few of the presentations, it aims to illustrate the great diversity of topics discussed at ICAR, bringing together knowledge and expertise from the whole spectrum of antiviral research. Copyright © 2015. Published by Elsevier B.V.

  4. The Denver Tube Combined with Antiviral Drugs In the Treatment of HBV-related Cirrhosis with Refractory Ascites: A Report of Three Cases

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    Wang Xiao-jin

    2014-03-01

    Full Text Available Treatment of nucleos(tide antiviral drugs for decompensated HBV-related cirrhosis can significantly improve the prognosis. But those patients with refractory ascites possibly deteriorate due to the complications of ascites before any benefit from anti-viral drugs could be observed. Therefore, it is important to find a way to help the patients with HBV-related cirrhosis and refractory ascites to receive the full benefits from antiviral therapy. Peritoneovenous shunt (PVS using Denver tube enables ascites to continuously bypass into systemic circulation, thereby reducing ascites and albumin input and improving quality of life. We report herein 3 cases of decompensated HBV-related cirrhosis with refractory ascites, PVS using Denver tube was combined with lamivudine for antiviral treatment before and after. Then, ascites was alleviated significantly or disapeared and viral responsed well. All patients achieved a satisfactory long-term survival from 6.7 to 14.7 years. It was suggested that the Denver shunt could be used as an adjuvant method to antiviral drugs for decompensated HBV-related cirrhosis with refractory ascites to help the patients reap the full benefits and maximize efficacy of antiviral treatment.

  5. Side effects of antiviral therapy in hepatitis C virus infection-sarcoidosis - case report.

    Science.gov (United States)

    Teodor, D; Teodor, Andra; Grigore, Lucia; Jugănariu, Gabriela; Dorobăţ, Carmen Mihaela; Miftode, Egidia; Azoicăi, Doina

    2012-01-01

    Standard therapy in chronic hepatitis C virus infection is still a combination of peginterferon alfa2a/2b and ribavirin for 48 weeks. As of side effects, there are organic side effects, such as hematologic disorders, and functional side effects, reflected in the quality of life of hepatitis C patients. Up to 30% of the patients develop specific side effects such as headache, fever, fatigue. Sarcoidosis, known as a granulomatous disease of uncertain cause, is an uncommon finding in this category of patients. This cause-effect relation is accounted for by the convergent action of peginterferon and ribavirin of stimulating type 1 T helper cells and reducing type 2 helper T cells activation. We present the case of male patient known with chronic hepatitis C who developed pulmonary sarcoidosis following antiviral therapy. The first manifestation of the disease was unexplained fever accompanied by pulmonary tract disease. The diagnosis was established by immunophenotyping in bronchial aspirate

  6. Antiviral therapy: a perspective

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    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

  7. The Antiviral Effect of Baicalin on Enterovirus 71 In Vitro

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    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.

  8. 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.

  9. Antiviral lead compounds from marine sponges

    KAUST Repository

    Sagar, Sunil; Kaur, Mandeep; Minneman, Kenneth P.

    2010-01-01

    ). 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

  10. Antiviral agents for infectious mononucleosis (glandular fever).

    Science.gov (United States)

    De Paor, Muireann; O'Brien, Kirsty; Fahey, Tom; Smith, Susan M

    2016-12-08

    Infectious mononucleosis (IM) is a clinical syndrome, usually caused by the Epstein Barr virus (EPV), characterised by lymphadenopathy, fever and sore throat. Most cases of symptomatic IM occur in older teenagers or young adults. Usually IM is a benign self-limiting illness and requires only symptomatic treatment. However, occasionally the disease course can be complicated or prolonged and lead to decreased productivity in terms of school or work. Antiviral medications have been used to treat IM, but the use of antivirals for IM is controversial. They may be effective by preventing viral replication which helps to keep the virus inactive. However, there are no guidelines for antivirals in IM. To assess the effects of antiviral therapy for infectious mononucleosis (IM). We searched the Cochrane Central Register of Controlled Trials (CENTRAL, Issue 3, March 2016), which contains the Cochrane Acute Respiratory Infections (ARI) Group's Specialised Register, MEDLINE (1946 to 15 April 2016), Embase (1974 to 15 April 2016), CINAHL (1981 to 15 April 2016), LILACS (1982 to 15 April 2016) and Web of Science (1955 to 15 April 2016). We searched the World Health Organization (WHO) International Clinical Trials Registry Platform and ClinicalTrials.gov for completed and ongoing trials. We included randomised controlled trials (RCTs) comparing antivirals versus placebo or no treatment in IM. We included trials of immunocompetent participants of any age or sex with clinical and laboratory-confirmed diagnosis of IM, who had symptoms for up to 14 days. Our primary outcomes were time to clinical recovery and adverse events and side effects of medication. Secondary outcomes included duration of abnormal clinical examination, complications, viral shedding, health-related quality of life, days missing from school or work and economic outcomes. Two review authors independently assessed studies for inclusion, assessed the included studies' risk of bias and extracted data using a

  11. Smallpox Antiviral Drug

    Science.gov (United States)

    2007-01-01

    Candida albicans] A G1L (590 aa) Flag VV(WR) 30/ENDIDEILGIAHLLEHLLISF/50 107/HIKELENEYYFRNEVFH/123 H41A 30/ENDIDEILGIAALLEHLLISF/50 107...RSV) (Table 1). Additional antiviral drug examples include the use of interferon for human papilloma virus ( HPV ) [Cantell, 1995]. Antivirals are most...low oral bioavailability, and quick elimination from plasma [Ghosn et al., 2004; Hostetler et al., 1994; Kempf et al., 1991; Matsumoto et al., 2001

  12. Evidence-based guideline update: steroids and antivirals for Bell palsy: report of the Guideline Development Subcommittee of the American Academy of Neurology.

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    Gronseth, Gary S; Paduga, Remia

    2012-11-27

    To review evidence published since the 2001 American Academy of Neurology (AAN) practice parameter regarding the effectiveness, safety, and tolerability of steroids and antiviral agents for Bell palsy. We searched Medline and the Cochrane Database of Controlled Clinical Trials for studies published since January 2000 that compared facial functional outcomes in patients with Bell palsy receiving steroids/antivirals with patients not receiving these medications. We graded each study (Class I-IV) using the AAN therapeutic classification of evidence scheme. We compared the proportion of patients recovering facial function in the treated group with the proportion of patients recovering facial function in the control group. Nine studies published since June 2000 on patients with Bell palsy receiving steroids/antiviral agents were identified. Two of these studies were rated Class I because of high methodologic quality. For patients with new-onset Bell palsy, steroids are highly likely to be effective and should be offered to increase the probability of recovery of facial nerve function (2 Class I studies, Level A) (risk difference 12.8%-15%). For patients with new-onset Bell palsy, antiviral agents in combination with steroids do not increase the probability of facial functional recovery by >7%. Because of the possibility of a modest increase in recovery, patients might be offered antivirals (in addition to steroids) (Level C). Patients offered antivirals should be counseled that a benefit from antivirals has not been established, and, if there is a benefit, it is likely that it is modest at best.

  13. Inhibition of enterovirus 71 (EV-71 infections by a novel antiviral peptide derived from EV-71 capsid protein VP1.

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    Chee Wah Tan

    Full Text Available Enterovirus 71 (EV-71 is the main causative agent of hand, foot and mouth disease (HFMD. In recent years, EV-71 infections were reported to cause high fatalities and severe neurological complications in Asia. Currently, no effective antiviral or vaccine is available to treat or prevent EV-71 infection. In this study, we have discovered a synthetic peptide which could be developed as a potential antiviral for inhibition of EV-71. Ninety five synthetic peptides (15-mers overlapping the entire EV-71 capsid protein, VP1, were chemically synthesized and tested for antiviral properties against EV-71 in human Rhabdomyosarcoma (RD cells. One peptide, SP40, was found to significantly reduce cytopathic effects of all representative EV-71 strains from genotypes A, B and C tested, with IC(50 values ranging from 6-9.3 µM in RD cells. The in vitro inhibitory effect of SP40 exhibited a dose dependent concentration corresponding to a decrease in infectious viral particles, total viral RNA and the levels of VP1 protein. The antiviral activity of SP40 peptide was not restricted to a specific cell line as inhibition of EV-71 was observed in RD, HeLa, HT-29 and Vero cells. Besides inhibition of EV-71, it also had antiviral activities against CV-A16 and poliovirus type 1 in cell culture. Mechanism of action studies suggested that the SP40 peptide was not virucidal but was able to block viral attachment to the RD cells. Substitutions of arginine and lysine residues with alanine in the SP40 peptide at positions R3A, R4A, K5A and R13A were found to significantly decrease antiviral activities, implying the importance of positively charged amino acids for the antiviral activities. The data demonstrated the potential and feasibility of SP40 as a broad spectrum antiviral agent against EV-71.

  14. Antiviral potential of a diterpenoid compound sugiol from Metasequoia glyptostroboides.

    Science.gov (United States)

    Bajpai, Vivek K; Kim, Na-Hyung; Kim, Kangmin; Kang, Sun Chul

    2016-05-01

    This research reports first time antiviral activity of sugiol, a diterpenoid isolated from Metasequoia glyptostroboides in terms of its ability to inhibit in vitro growth of H1N1 influenza virus. Antiviral potential of sugiol was evaluated through hcytopathogenic reduction assay using Madin-Darby canine kidney (MDCK) cell line. Sugiol (500 μg/ml) was found to exhibit considerable anti-cytopathic effect on MDCK cell line confirming its antiviral efficacy against H1N1 influenza virus. These findings strongly reinforce the suggestion that sugiol could be a candidate of choice in combinational regimen with potential antiviral efficacy.

  15. Ophthalmic antiviral chemotherapy : An overview

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    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.

  16. 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.

  17. Antiviral properties of photosensitizers

    International Nuclear Information System (INIS)

    Hudson, J.B.; Towers, G.H.N.

    1988-01-01

    We have studied the antiviral properties of three different groups of photo-sensitizers, viz. (i) various furyl compounds; (ii) β-carboline alkaloids; (iii) thiophenes and their acetylene derivatives. In general the antiviral potency of the furyl compounds correlated with their ability to produce DNA photoadducts. Among the naturally occurring β-carboline alkaloids, harmine was considerably more potent (in the presence of long wavelength UV radiation, UVA) than several other harmane-related compounds. Slight alterations in chemical structure had profound effects on their antiviral activities. Harmine was shown to inactivate the DNA-virus murine cytomegalovirus (MCMV) by inhibiting viral gene expression, although other targets may also exist. Several eudistomins, carboline derivatives isolated from a tunicate, were also photoactive against viruses. Various plant thiophenes and polyacetylenes were studied in detail. These compounds also required UVA for antiviral activity, and some of them were extremely potent against viruses with membranes, e.g. α-terthienyl, which showed significant activity at only 10 -5 μg/ml. When MCMV had been treated with α-terthienyl plus UVA, the virus retained its integrity and penetrated cells normally; but the virus did not replicate. (author)

  18. La respuesta inmune antiviral

    OpenAIRE

    Sánchez de la Rosa, Rainel; Sánchez de la Rosa, Ernesto; Rodríguez Hernández, Néstor

    1998-01-01

    Se expone que los virus son parásitos intracelulares obligados, puesto que no tienen metabolismo propio; esto obliga al sistema inmune a poner en marcha sus mecanismos más especializados para reconocer y eliminar, tanto a los virus libres, como a las células infectadas. Se señala que las células presentadoras de antígenos, los linfocitos B y los T unidos al complejo mayor de histocompatibilidad, forman parte de la organización de la respuesta inmune antiviral; la inducción de esta respuesta c...

  19. La respuesta inmune antiviral

    Directory of Open Access Journals (Sweden)

    Rainel Sánchez de la Rosa

    1998-02-01

    Full Text Available Se expone que los virus son parásitos intracelulares obligados, puesto que no tienen metabolismo propio; esto obliga al sistema inmune a poner en marcha sus mecanismos más especializados para reconocer y eliminar, tanto a los virus libres, como a las células infectadas. Se señala que las células presentadoras de antígenos, los linfocitos B y los T unidos al complejo mayor de histocompatibilidad, forman parte de la organización de la respuesta inmune antiviral; la inducción de esta respuesta con proteínas, péptidos y ADN desnudo, son alternativas actuales tanto en la prevención como en el tratamiento de las infecciones viralesIt is explained that viruses are compulsory intracellular parasites, since they don't have their own metabolism, which makes the immune system to start its mest specialized mechanisms to recognize and eliminate the free viruses and the infected cells. It is stated that the cells presenting antigens, and the B and T lymphocytes together with the major histocompatibility complex, are part of the organization of the immune antiviral response. The induction of this response with proteins, peptides and naked DNA are the present alternatives for the prevention and treatment of viral infections

  20. Aciclovir: nuevo antiviral

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    G. Repetto

    2017-05-01

    Full Text Available El aciclovir es un antiviral útil en infecciones graves causadas por el virus varicela-zoster. Es bien tolerado con escasas reacciones adversas. En pacientes deshidratados, en insuficiencia renal o si la infusión endovenosa es muy rápida, puede ocacionar una "nefropatía obstructiva" transitoria. Existen preparados de uso tópico, oftálmico, endovenoso y oral; esta última vía constituye una ventaja sobre la vidarabina con la que tiene en común el espectro de actividad. En razón de su selectividad, riesgo de resistencia y número reducido de antivirales, su prescripción debe restringirse a infecciones graves causadas por los agentes inmunodeprimidos; excluyendo por lo tanto las comunes y autolimitadas, frecuentes en el individuo normal.

  1. Antiviral Drug Research Proposal Activity

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    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.

  2. Weight loss decreases self-reported appetite and alters food preferences in overweight and obese adults

    DEFF Research Database (Denmark)

    Andriessen, Charlotte; Christensen, Pia; Nielsen, Lone Vestergaard

    2018-01-01

    consumption (p meal. An interaction effect (visit x time) was found for hunger ratings (p ... preferences were measured before and after the LCD, in response to a standardized meal test, using visual analogue rating scales (VAS) and the Leeds Food Choice Questionnaire (FCQ). After the LCD, participants reported increased fullness (p ....9%. Preference for low-energy products measured by the Food Preference Checklist (FPC) decreased by 1.9% before the test meal and by 13.5% after the test meal (p meal and by 17.4% and 22.7% after the meal (p 

  3. Use of Direct-Acting Antivirals for the Treatment of Hepatitis C Virus-Associated Oral Lichen Planus: A Case Report

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    Kenji Misaka

    2016-10-01

    Full Text Available Hepatitis C virus (HCV is frequently associated with various extrahepatic manifestations such as autoimmune features and immune complex deposit diseases. Oral lichen planus (OLP is one of the representative extrahepatic manifestations of HCV infection. Direct-acting antivirals (DAA are highly effective and safe for the eradication of HCV. However, there is a lack of information regarding the association between HCV-associated OLP and interferon (IFN-free DAA therapy. Herein, we present the case of a 60-year-old female who was diagnosed with OLP during routine periodontal treatment by a dentist. The patient was referred for hepatitis C treatment using IFN-free DAA, which resulted in the improvement of the symptoms of OLP. This case represents the safety and efficacy of IFN-free DAAs in patients with HCV-associated OLP. However, long-term follow-up studies are required to elucidate the therapeutic effects of this therapy in these patients.

  4. 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.

  5. Trainees May Add Value to Patient Care by Decreasing Addendum Utilization in Radiology Reports.

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    Balthazar, Patricia; Konstantopoulos, Christina; Wick, Carson A; DeSimone, Ariadne K; Tridandapani, Srini; Simoneaux, Stephen; Applegate, Kimberly E

    2017-11-01

    The purpose of this study was to evaluate the impact of trainee involvement and other factors on addendum rates in radiology reports. This retrospective study was performed in a tertiary care pediatric hospital. From the institutional radiology data repository, we extracted all radiology reports from January 1 to June 30, 2016, as well as trainee (resident or fellow) involvement, imaging modality, patient setting (emergency, inpatient, or outpatient), order status (routine vs immediate), time of interpretation (regular work hours vs off-hours), radiologist's years of experience, and sex. We grouped imaging modalities as advanced (CT, MRI, and PET) or nonadvanced (any modality that was not CT, MRI, or PET) and radiologist experience level as ≤ 20 years or > 20 years. Our outcome measure was the rate of addenda in radiology reports. Statistical analysis was performed using multivariate logistic regression. From 129,033 reports finalized during the study period, 418 (0.3%) had addenda. Reports generated without trainees were 12 times more likely than reports with trainee involvement to have addenda (odds ratio [OR] = 12.2, p use (OR = 4.7, p use than those in an inpatient setting (OR = 1.5, p = 0.04; and OR = 1.3, p = 0.04, respectively). Routine orders had a slightly higher likelihood of addendum use compared with immediate orders (OR = 1.3, p = 0.01). We found no difference in addendum use by radiologist's sex, radiologist's years of experience, emergency versus outpatient setting, or time of interpretation. Trainees may add value to patient care by decreasing addendum rates in radiology reports.

  6. Cannabidiol Oil for Decreasing Addictive Use of Marijuana: A Case Report.

    Science.gov (United States)

    Shannon, Scott; Opila-Lehman, Janet

    2015-12-01

    This case study illustrates the use of cannabidiol (CBD) oil to decrease the addictive use of marijuana and provide anxiolytic and sleep benefits. Addiction to marijuana is a chronic, relapsing disorder, which is becoming a prevalent condition in the United States. The most abundant compound in the marijuana, which is called tetrahydrocannabinol (THC), has been widely studied and known for its psychoactive properties. The second most abundant component-CBD-has been suggested to have the medicinal effects of decreasing anxiety, improving sleep, and other neuro-protective effects. The mechanism of action for CBD has been suggested to be antagonistic to the psychoactive properties of THC in many locations within the central nervous system. Such action raises the issue of whether it might be beneficial to use CBD in isolation to facilitate withdrawal of marijuana use. The specific use of CBD for marijuana reduction has not been widely studied. The patient was a 27-y-old male who presented with a long-standing diagnosis of bipolar disorder and a daily addiction to marijuana use. In the described intervention, the only change made to the patient's treatment was the addition of CBD oil with the dosage gradually decreasing from 24 to 18 mg. With use of the CBD oil, the patient reported being less anxious, as well as settling into a regular pattern of sleep. He also indicated that he had not used any marijuana since starting the CBD oil. With the decrease in the dosage to 18 mg, the patient was able to maintain his nonuse of marijuana.

  7. 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.

  8. 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.

  9. Decision Making with Regard to Antiviral Intervention during an Influenza Pandemic

    Science.gov (United States)

    Shim, Eunha; Chapman, Gretchen B.; Galvani, Alison P.

    2012-01-01

    Background Antiviral coverage is defined by the proportion of the population that takes antiviral prophylaxis or treatment. High coverage of an antiviral drug has epidemiological and evolutionary repercussions. Antivirals select for drug resistance within the population, and individuals may experience adverse effects. To determine optimal antiviral coverage in the context of an influenza outbreak, we compared 2 perspectives: 1) the individual level (the Nash perspective), and 2) the population level (utilitarian perspective). Methods We developed an epidemiological game-theoretic model of an influenza pandemic. The data sources were published literature and a national survey. The target population was the US population. The time horizon was 6 months. The perspective was individuals and the population overall. The interventions were antiviral prophylaxis and treatment. The outcome measures were the optimal coverage of antivirals in an influenza pandemic. Results At current antiviral pricing, the optimal Nash strategy is 0% coverage for prophylaxis and 30% coverage for treatment, whereas the optimal utilitarian strategy is 19% coverage for prophylaxis and 100% coverage for treatment. Subsidizing prophylaxis by $440 and treatment by $85 would bring the Nash and utilitarian strategies into alignment. For both prophylaxis and treatment, the optimal antiviral coverage decreases as pricing of antivirals increases. Our study does not incorporate the possibility of an effective vaccine and lacks probabilistic sensitivity analysis. Our survey also does not completely represent the US population. Because our model assumes a homogeneous population and homogeneous antiviral pricing, it does not incorporate heterogeneity of preference. Conclusions The optimal antiviral coverage from the population perspective and individual perspectives differs widely for both prophylaxis and treatment strategies. Optimal population and individual strategies for prophylaxis and treatment might

  10. Medically unexplained symptom reports are associated with a decreased response to the rubber hand illusion.

    Science.gov (United States)

    Miles, Eleanor; Poliakoff, Ellen; Brown, Richard J

    2011-10-01

    Medically unexplained symptoms (MUS) have been hypothesized to result from a distortion in perception, whereby top-down factors influence the process of body representation. Perceptual illusions provide a novel method of investigating this hypothesis. This study aimed to investigate whether self-reported unexplained symptoms are associated with altered experience of the rubber hand illusion (RHI). A non-clinical MUS group with high scores on the Somatoform Dissociation Questionnaire (SDQ), and a control group with low scores on this scale, were exposed to the RHI. Illusion experience was measured by self-reports and by proprioceptive alteration. After controlling for somatosensory amplification and trait anxiety, the low-SDQ group responded significantly more strongly to the RHI on both questionnaire and proprioceptive measures of the illusion. In contrast, the high-SDQ group scored significantly higher on the Perceptual Aberrations Scale, a measure of bodily distortions in daily life. These findings support the proposed link between MUS and disturbances in body representation, and suggest that a decreased reliance on current sensory inputs may contribute to symptom experience in susceptible individuals. Copyright © 2011 Elsevier Inc. All rights reserved.

  11. DECREASE Final Technical Report: Development of a Commercial Ready Enzyme Application System for Ethanol

    Energy Technology Data Exchange (ETDEWEB)

    Teter, Sarah A

    2012-04-18

    Conversion of biomass to sugars plays a central in reducing our dependence on petroleum, as it allows production of a wide range of biobased fuels and chemicals, through fermentation of those sugars. The DECREASE project delivers an effective enzyme cocktail for this conversion, enabling reduced costs for producing advanced biofuels such as cellulosic ethanol. Benefits to the public contributed by growth of the advanced biofuels industry include job creation, economic growth, and energy security. The DECREASE primary project objective was to develop a two-fold improved enzyme cocktail, relative to an advanced cocktail (CZP00005) that had been developed previously (from 2000- 2007). While the final milestone was delivery of all enzyme components as an experimental mixture, a secondary objective was to deploy an improved cocktail within 3 years following the close of the project. In February 2012, Novozymes launched Cellic CTec3, a multi-enzyme cocktail derived in part from components developed under DECREASE. The externally validated performance of CTec3 and an additional component under project benchmarking conditions indicated a 1.8-fold dose reduction in enzyme dose required for 90% conversion (based on all available glucose and xylose sources) of NREL dilute acid pretreated PCS, relative to the starting advanced enzyme cocktail. While the ability to achieve 90% conversion is impressive, targeting such high levels of biomass digestion is likely not the most cost effective strategy. Novozymes techno economic modeling showed that for NREL's dilute acid pretreated corn stover (PCS), 80% target conversion enables a lower total production cost for cellulosic ethanol than for 90% conversion, and this was also found to be the case when cost assumptions were based on the NREL 2002 Design Report. A 1.8X dose-reduction was observed for 80% conversion in the small scale (50 g) DECREASE benchmark assay for CTec3 and an additional component. An upscaled experiment (in 0

  12. The future of antiviral immunotoxins

    DEFF Research Database (Denmark)

    Spiess, K.; Høy Jakobsen, Mette; Kledal, Thomas N

    2016-01-01

    There is a constant need for new therapeutic interventions in a wide range of infectious diseases. Over the past few years, the immunotoxins have entered the stage as promising antiviral treatments. Immunotoxins have been extensively explored in cancer treatment and have achieved FDA approval in ...

  13. Antiviral effect of diammonium glycyrrhizinate on cell infection by porcine parvovirus

    Science.gov (United States)

    Porcine parvovirus (PPV) can cause reproductive failure in swine resulting in economic losses to the industry. Antiviral effects of diammonium glycyrrhizinate (DG) have been reported on several animal viruses; however, to date it has yet to be tested on PPV. In this study, the antiviral activity of ...

  14. Cannabidiol Oil for Decreasing Addictive Use of Marijuana: A Case Report

    OpenAIRE

    Shannon, Scott; Opila-Lehman, Janet

    2015-01-01

    This case study illustrates the use of cannabidiol (CBD) oil to decrease the addictive use of marijuana and provide anxiolytic and sleep benefits. Addiction to marijuana is a chronic, relapsing disorder, which is becoming a prevalent condition in the United States. The most abundant compound in the marijuana, which is called tetrahydrocannabinol (THC), has been widely studied and known for its psychoactive properties. The second most abundant component—CBD—has been suggested to have the medic...

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

    Directory of Open Access Journals (Sweden)

    Elaissi Ameur

    2012-06-01

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

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

    Science.gov (United States)

    2012-01-01

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

  17. Stockpiling anti-viral drugs for a pandemic: the role of Manufacturer Reserve Programs.

    Science.gov (United States)

    Harrington, Joseph E; Hsu, Edbert B

    2010-05-01

    To promote stockpiling of anti-viral drugs by non-government organizations such as hospitals, drug manufacturers have introduced Manufacturer Reserve Programs which, for an annual fee, provide the right to buy in the event of a severe outbreak of influenza. We show that these programs enhance drug manufacturer profits but could either increase or decrease the amount of pre-pandemic stockpiling of anti-viral drugs.

  18. Tacrolimus interaction with nafcillin resulting in significant decreases in tacrolimus concentrations: A case report.

    Science.gov (United States)

    Wungwattana, Minkey; Savic, Marizela

    2017-04-01

    Tacrolimus (TAC) is subject to many drug interactions as a result of its metabolism primarily via CYP450 isoenzyme 3A4. Numerous case reports of TAC and CYP3A4 inducers and inhibitors have been described including antimicrobials, calcium channel antagonists, and antiepileptic drugs. We present the case of a 13-year-old patient with cystic fibrosis and a history of liver transplantation, where subtherapeutic TAC concentrations were suspected to be a result of concomitant TAC and nafcillin (NAF) therapy. The observed drug interaction occurred on two separate hospital admissions, during both of which the patient exhibited therapeutic TAC concentrations prior to exposure to NAF, a CYP3A4 inducer. Upon discontinuation of NAF, TAC concentrations recovered in both instances. This case represents a drug-drug interaction between TAC and NAF that has not previously been reported to our knowledge. Despite the lack of existing reports of interaction between these two agents, this case highlights the importance of therapeutic drug monitoring and assessing for any potential drug-drug or drug-food interactions in patients receiving TAC therapy. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

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

    Directory of Open Access Journals (Sweden)

    Rosaria eSantangelo

    2012-03-01

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

  20. What You Should Know about Flu Antiviral Drugs

    Science.gov (United States)

    ... Other What You Should Know About Flu Antiviral Drugs Language: English (US) Español Recommend on Facebook Tweet ... used to treat flu illness. What are antiviral drugs? Antiviral drugs are prescription medicines (pills, liquid, an ...

  1. New pathogenic viruses and novel antiviral drugs

    NARCIS (Netherlands)

    Berkhout, Ben; Eggink, Dirk

    2011-01-01

    The journal Antiviral Research was conceived and born in 1980, and launched in 1981, a time when very few antiviral drugs were around. This 30-year celebration meeting was convened by the publisher Elsevier and chaired by Eric de Clercq (Leuven University), who has acted as editor-in-chief for the

  2. Decreased Daily Melatonin Levels in Women with Systemic Lupus Erythematosus - A Short Report

    Directory of Open Access Journals (Sweden)

    Ralitsa Robeva

    2013-09-01

    Full Text Available Background: The neuroendocrine system is known to influence immunity, but the precise interactions between different hormones and autoimmune disorders remain obscure. Aims: The present study aimed to investigate the role of daily serum melatonin concentrations in the development of systemic lupus erythematosus (SLE in women. Study Design: Case-control study Methods: One-hundred and eleven SLE female patients and 46 healthy women were included in the study. Daily serum melatonin levels were investigated in all participants. Results: SLE patients showed significantly lower daily melatonin levels in comparison to healthy women during the short photoperiod (17.75±7.13 pg/mL [16.05] vs. 21.63±6.60 pg/mL [20.10], p=0.012. Hormone concentrations were inversely related to the SLE activity index (SLEDAI (r= -0.268, p=0.004, but they did not correlate to any particular American College Rheumatology (ACR criterion (p>0.05 for all. Conclusion: Daily melatonin levels were decreased in women with systemic lupus erythematosus and correlated inversely to the activity of the autoimmune disease. Further studies are needed to clarify the importance of the pineal and extrapineal melatonin secretion in patients with systemic lupus erythematosus as well as the interrelations between hormones and autoimmunity.

  3. Hepatitis C Virus and Antiviral Drug Resistance.

    Science.gov (United States)

    Kim, Seungtaek; Han, Kwang-Hyub; Ahn, Sang Hoon

    2016-11-15

    Since its discovery in 1989, hepatitis C virus (HCV) has been intensively investigated to understand its biology and develop effective antiviral therapies. The efforts of the previous 25 years have resulted in a better understanding of the virus, and this was facilitated by the development of in vitro cell culture systems for HCV replication. Antiviral treatments and sustained virological responses have also improved from the early interferon monotherapy to the current all-oral regimens using direct-acting antivirals. However, antiviral resistance has become a critical issue in the treatment of chronic hepatitis C, similar to other chronic viral infections, and retreatment options following treatment failure have become important questions. Despite the clinical challenges in the management of chronic hepatitis C, substantial progress has been made in understanding HCV, which may facilitate the investigation of other closely related flaviviruses and lead to the development of antiviral agents against these human pathogens.

  4. Decreased hospital length of stay associated with presentation of cases at morning report with librarian support

    Science.gov (United States)

    Banks, Daniel E.; Shi, Runhua; Timm, Donna F.; Christopher, Kerri Ann; Duggar, David Charles; Comegys, Marianne; McLarty, Jerry

    2007-01-01

    Objective: The research sought to determine whether case discussion at residents' morning report (MR), accompanied by a computerized literature search and librarian support, affects hospital charges, length of stay (LOS), and thirty-day readmission rate. Methods: This case-control study, conducted from August 2004 to March 2005, compared outcomes for 105 cases presented at MR within 24 hours of admission to 19,210 potential matches, including cases presented at MR and cases not presented at MR. With matching criteria of patient age (± 5 years), identical primary diagnosis, and secondary diagnoses (within 3 additional diagnoses) using International Classification of Diseases (ICD-9) codes, 55 cases were matched to 136 controls. Statistical analyses included Student's t tests, chi-squared tests, and nonparametric methods. Results: LOS differed significantly between matched MR cases and controls (3 days vs. 5 days, P librarians, was an effective means for introducing evidence-based medicine into patient care practices. PMID:17971885

  5. Antimicrobial, antiviral and antioxidant activities of "água-mel" from Portugal.

    Science.gov (United States)

    Miguel, Maria G; Faleiro, Leonor; Antunes, Maria D; Aazza, Smail; Duarte, Joana; Silvério, Ana R

    2013-06-01

    "Água-mel" is a honey-based product produced in Portugal for ancient times. Several attributes have been reported to "água-mel" particularly in the alleviation of simple symptoms of upper respiratory tract. Samples of "água-mel" from diverse beekeepers from different regions of Portugal were studied in what concerns antimicrobial, antioxidant and antiviral properties. The amounts of phenol and brown pigment were also evaluated and correlated with the antioxidant activities. A great variability on the levels of these compounds was found among samples which were responsible for the variability detected also on the antioxidant activities, independent on the method used. Generally, antioxidant activity correlated better with brown pigments' amount than with phenols' content. The antimicrobial activity found for "água-mel" samples confirm the virtues reported by popular findings. In addition, this work also reveals the antiviral properties of "água-mel" evidenced by a decrease on the infectivity of the Qβ bacteriophage. Copyright © 2013 Elsevier Ltd. All rights reserved.

  6. Discovery of potent broad spectrum antivirals derived from marine actinobacteria.

    Directory of Open Access Journals (Sweden)

    Avi Raveh

    Full Text Available Natural products provide a vast array of chemical structures to explore in the discovery of new medicines. Although secondary metabolites produced by microbes have been developed to treat a variety of diseases, including bacterial and fungal infections, to date there has been limited investigation of natural products with antiviral activity. In this report, we used a phenotypic cell-based replicon assay coupled with an iterative biochemical fractionation process to identify, purify, and characterize antiviral compounds produced by marine microbes. We isolated a compound from Streptomyces kaviengensis, a novel actinomycetes isolated from marine sediments obtained off the coast of New Ireland, Papua New Guinea, which we identified as antimycin A1a. This compound displays potent activity against western equine encephalitis virus in cultured cells with half-maximal inhibitory concentrations of less than 4 nM and a selectivity index of greater than 550. Our efforts also revealed that several antimycin A analogues display antiviral activity, and mechanism of action studies confirmed that these Streptomyces-derived secondary metabolites function by inhibiting the cellular mitochondrial electron transport chain, thereby suppressing de novo pyrimidine synthesis. Furthermore, we found that antimycin A functions as a broad spectrum agent with activity against a wide range of RNA viruses in cultured cells, including members of the Togaviridae, Flaviviridae, Bunyaviridae, Picornaviridae, and Paramyxoviridae families. Finally, we demonstrate that antimycin A reduces central nervous system viral titers, improves clinical disease severity, and enhances survival in mice given a lethal challenge with western equine encephalitis virus. Our results provide conclusive validation for using natural product resources derived from marine microbes as source material for antiviral drug discovery, and they indicate that host mitochondrial electron transport is a viable

  7. Viruses and Antiviral Immunity in Drosophila

    Science.gov (United States)

    Xu, Jie; Cherry, Sara

    2013-01-01

    Viral pathogens present many challenges to organisms, driving the evolution of a myriad of antiviral strategies to combat infections. A wide variety of viruses infect invertebrates, including both natural pathogens that are insect-restricted, and viruses that are transmitted to vertebrates. Studies using the powerful tools available in the model organism Drosophila have expanded our understanding of antiviral defenses against diverse viruses. In this review, we will cover three major areas. First, we will describe the tools used to study viruses in Drosophila. Second, we will survey the major viruses that have been studied in Drosophila. And lastly, we will discuss the well-characterized mechanisms that are active against these diverse pathogens, focusing on non-RNAi mediated antiviral mechanisms. Antiviral RNAi is discussed in another paper in this issue. PMID:23680639

  8. Nanoparticulate delivery systems for antiviral drugs.

    Science.gov (United States)

    Lembo, David; Cavalli, Roberta

    2010-01-01

    Nanomedicine opens new therapeutic avenues for attacking viral diseases and for improving treatment success rates. Nanoparticulate-based systems might change the release kinetics of antivirals, increase their bioavailability, improve their efficacy, restrict adverse drug side effects and reduce treatment costs. Moreover, they could permit the delivery of antiviral drugs to specific target sites and viral reservoirs in the body. These features are particularly relevant in viral diseases where high drug doses are needed, drugs are expensive and the success of a therapy is associated with a patient's adherence to the administration protocol. This review presents the current status in the emerging area of nanoparticulate delivery systems in antiviral therapy, providing their definition and description, and highlighting some peculiar features. The paper closes with a discussion on the future challenges that must be addressed before the potential of nanotechnology can be translated into safe and effective antiviral formulations for clinical use.

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

    Directory of Open Access Journals (Sweden)

    Zandi Keivan

    2011-12-01

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

  10. Antiviral Potential of Algae Polysaccharides Isolated from Marine Sources: A Review

    Directory of Open Access Journals (Sweden)

    Azin Ahmadi

    2015-01-01

    Full Text Available From food to fertilizer, algal derived products are largely employed in assorted industries, including agricultural, biomedical, food, and pharmaceutical industries. Among different chemical compositions isolated from algae, polysaccharides are the most well-established compounds, which were subjected to a variety of studies due to extensive bioactivities. Over the past few decades, the promising results for antiviral potential of algae-derived polysaccharides have advocated them as inordinate candidates for pharmaceutical research. Numerous studies have isolated various algal polysaccharides possessing antiviral activities, including carrageenan, alginate, fucan, laminaran, and naviculan. In addition, different mechanisms of action have been reported for these polysaccharides, such as inhibiting the binding or internalization of virus into the host cells or suppressing DNA replication and protein synthesis. This review strives for compiling previous antiviral studies of algae-derived polysaccharides and their mechanism of action towards their development as natural antiviral agents for future investigations.

  11. Human and Mouse Eosinophils Have Antiviral Activity against Parainfluenza Virus.

    Science.gov (United States)

    Drake, Matthew G; Bivins-Smith, Elizabeth R; Proskocil, Becky J; Nie, Zhenying; Scott, Gregory D; Lee, James J; Lee, Nancy A; Fryer, Allison D; Jacoby, David B

    2016-09-01

    Respiratory viruses cause asthma exacerbations. Because eosinophils are the prominent leukocytes in the airways of 60-70% of patients with asthma, we evaluated the effects of eosinophils on a common respiratory virus, parainfluenza 1, in the lung. Eosinophils recruited to the airways of wild-type mice after ovalbumin sensitization and challenge significantly decreased parainfluenza virus RNA in the lungs 4 days after infection compared with nonsensitized animals. This antiviral effect was also seen in IL-5 transgenic mice with an abundance of airway eosinophils (NJ.1726) but was lost in transgenic eosinophil-deficient mice (PHIL) and in IL-5 transgenic mice crossed with eosinophil-deficient mice (NJ.1726-PHIL). Loss of the eosinophil granule protein eosinophil peroxidase, using eosinophil peroxidase-deficient transgenic mice, did not reduce eosinophils' antiviral effect. Eosinophil antiviral mechanisms were also explored in vitro. Isolated human eosinophils significantly reduced parainfluenza virus titers. This effect did not involve degradation of viral RNA by eosinophil granule RNases. However, eosinophils treated with a nitric oxide synthase inhibitor lost their antiviral activity, suggesting eosinophils attenuate viral infectivity through production of nitric oxide. Consequently, eosinophil nitric oxide production was measured with an intracellular fluorescent probe. Eosinophils produced nitric oxide in response to virus and to a synthetic agonist of the virus-sensing innate immune receptor, Toll-like receptor (TLR) 7. IFNγ increased expression of eosinophil TLR7 and potentiated TLR7-induced nitric oxide production. These results suggest that eosinophils promote viral clearance in the lung and contribute to innate immune responses against respiratory virus infections in humans.

  12. Does an elevated CO2 concentration decrease dark respiration in trees? Final technical report

    Energy Technology Data Exchange (ETDEWEB)

    Long, Stephen [Univ. of Illinois, Urbana-Champaign, IL (United States)

    2003-12-31

    Averaged across many previous investigations, doubling the CO2 concentration ([CO2]) has frequently been reported to cause an instantaneous reduction of leaf dark respiration measured as CO2 efflux. No known mechanism accounts for this effect. While four recent studies have shown that the measurement of respiratory CO2 efflux is prone to experimental artifacts that could account for the reported response, papers published since the start of the current research continue to report an instantaneous depression of respiratory CO2 efflux by elevation of [CO2]. Here, these artifacts are avoided by use of a high-resolution dual channel oxygen analyzer within an open gas exchange system to measure respiratory 02 uptake in normal air. Leaf 02 uptake was determined in response to instantaneous elevation of [CO2] in nine contrasting species and to long-term elevation in seven species from four of the DOE-sponsored long-term elevated [CO2] field experiments. Over one thousand separate measurements of respiration failed to reveal any decrease in respiratory 02 uptake with an instantaneous increase in [CO2]. Respiration was found insensitive not only to doubling [CO2], but also to a five-fold increase and to decrease to zero.

  13. Assessment of Inhibition of Ebola Virus Progeny Production by Antiviral Compounds.

    Science.gov (United States)

    Falzarano, Darryl

    2017-01-01

    Assessment of small molecule compounds against filoviruses, such as Ebola virus, has identified numerous compounds that appear to have antiviral activity and should presumably be further investigated in animal efficacy trials. However, despite the many compounds that are purported to have good antiviral activity in in vitro studies, there are few instances where any efficacy has been reported in nonhuman primate models. Many of the high-throughput screening assays use reporter systems that only recapitulate a portion of the virus life cycle, while other assays only assess antiviral activity at relatively early time points. Moreover, many assays do not assess virus progeny production. A more in-depth evaluation of small numbers of test compounds is useful to economize resources and to generate higher quality antiviral hits. Assessing virus progeny production as late as 5 days post-infection allows for the elimination of compounds that have initial antiviral effects that are not sustained or where the virus rapidly develops resistance. While this eliminates many potential lead compounds that may be worthy of further structure-activity relationship (SAR) development, it also quickly excludes compounds that in their current form are unlikely to be effective in animal models. In addition, the inclusion of multiple assays that assess both cell viability and cell cytotoxicity, via different mechanisms, provides a more thorough assessment to exclude compounds that are not direct-acting antivirals.

  14. Antithrombin deficiency and decreased protein C activity in a young man with venous thromboembolism: a case report.

    Science.gov (United States)

    Wang, Dong; Tian, Min; Cui, Guanglin; Wang, Dao Wen

    2018-06-01

    Antithrombin and protein C are two crucial members in the anticoagulant system and play important roles in hemostasis. Mutations in SERPINC1 and PROC lead to deficiency or dysfunction of the two proteins, which could result in venous thromboembolism (VTE). Here, we report a Chinese 22-year-old young man who developed recurrent and serious VTE in cerebral veins, visceral veins, and deep veins of the lower extremity. Laboratory tests and direct sequencing of PROC and SERPINC1 were conducted for the patient and his family members. Coagulation tests revealed that the patient presented type I antithrombin deficiency combined with decreased protein C activity resulting from a small insertion mutation c.848_849insGATGT in SERPINC1 and a short deletion variant c.572_574delAGA in PROC. This combination of the two mutations was absent in 400 healthy subjects each from southern and northern China. Then, we summarized all the mutations of the SERPINC1 and PROC gene reported in the Chinese Han population. This study demonstrates that the combination of antithrombin deficiency and decreased protein C activity can result in severe VTE and that the coexistence of different genetic factors may increase the risk of VTE.

  15. Niclosamide is a proton carrier and targets acidic endosomes with broad antiviral effects.

    Science.gov (United States)

    Jurgeit, Andreas; McDowell, Robert; Moese, Stefan; Meldrum, Eric; Schwendener, Reto; Greber, Urs F

    2012-01-01

    Viruses use a limited set of host pathways for infection. These pathways represent bona fide antiviral targets with low likelihood of viral resistance. We identified the salicylanilide niclosamide as a broad range antiviral agent targeting acidified endosomes. Niclosamide is approved for human use against helminthic infections, and has anti-neoplastic and antiviral effects. Its mode of action is unknown. Here, we show that niclosamide, which is a weak lipophilic acid inhibited infection with pH-dependent human rhinoviruses (HRV) and influenza virus. Structure-activity studies showed that antiviral efficacy and endolysosomal pH neutralization co-tracked, and acidification of the extracellular medium bypassed the virus entry block. Niclosamide did not affect the vacuolar H(+)-ATPase, but neutralized coated vesicles or synthetic liposomes, indicating a proton carrier mode-of-action independent of any protein target. This report demonstrates that physico-chemical interference with host pathways has broad range antiviral effects, and provides a proof of concept for the development of host-directed antivirals.

  16. Niclosamide is a proton carrier and targets acidic endosomes with broad antiviral effects.

    Directory of Open Access Journals (Sweden)

    Andreas Jurgeit

    Full Text Available Viruses use a limited set of host pathways for infection. These pathways represent bona fide antiviral targets with low likelihood of viral resistance. We identified the salicylanilide niclosamide as a broad range antiviral agent targeting acidified endosomes. Niclosamide is approved for human use against helminthic infections, and has anti-neoplastic and antiviral effects. Its mode of action is unknown. Here, we show that niclosamide, which is a weak lipophilic acid inhibited infection with pH-dependent human rhinoviruses (HRV and influenza virus. Structure-activity studies showed that antiviral efficacy and endolysosomal pH neutralization co-tracked, and acidification of the extracellular medium bypassed the virus entry block. Niclosamide did not affect the vacuolar H(+-ATPase, but neutralized coated vesicles or synthetic liposomes, indicating a proton carrier mode-of-action independent of any protein target. This report demonstrates that physico-chemical interference with host pathways has broad range antiviral effects, and provides a proof of concept for the development of host-directed antivirals.

  17. Resolving cognitive dissonance by acquisition of self-organizational skills may decrease drug-resistant seizures - A case report.

    Science.gov (United States)

    Michaelis, Rosa; Andrews, Donna J; Reiter, Joel M; von Schoen-Angerer, Tido

    2014-01-01

    A recent review of psychobehavioral therapy for epilepsy recommends case reports as a research design to explore specific psychological mediators of psychobehavioral interventions for epilepsy that address the bidirectional relationship between psychological states and seizures. The report was prepared according to the consensus-based CARE guidelines for standardized clinical case reporting. This is a case of a 16-year-old male individual with a diagnosed seizure disorder and learning disability who continued to have daytime and nighttime seizures on a regular basis despite exhausting of available conventional treatment options. A psychological assessment led to the working hypothesis that cognitive dissonance between fear of failure and high expectations of self had led to a "broken" self-image and active avoidance of responsibility that resulted in intense emotional distress which correlated with the occurrence of seizures. This working hypothesis resulted in a treatment plan that employed the acquisition of self-organizational skills and relaxation techniques as the main therapeutic strategy. Motivational strategies were employed to facilitate the regulation of lifestyle-related seizure precipitants. In this case, the acquisition of self-organizational skills and the development of seizure interruption techniques correlated with a clinically significant decrease of seizures. Methodological limitations of the interpretation of the presented data are discussed.

  18. Decreased HIV diversity after allogeneic stem cell transplantation of an HIV-1 infected patient: a case report

    Directory of Open Access Journals (Sweden)

    Thielen Alexander

    2010-03-01

    Full Text Available Abstract The human immunodeficiency virus type 1 (HIV-1 coreceptor use and viral evolution were analyzed in blood samples from an HIV-1 infected patient undergoing allogeneic stem cell transplantation (SCT. Coreceptor use was predicted in silico from sequence data obtained from the third variable loop region of the viral envelope gene with two software tools. Viral diversity and evolution was evaluated on the same samples by Bayesian inference and maximum likelihood methods. In addition, phenotypic analysis was done by comparison of viral growth in peripheral blood mononuclear cells and in a CCR5 (R5-deficient T-cell line which was controlled by a reporter assay confirming viral tropism. In silico coreceptor predictions did not match experimental determinations that showed a consistent R5 tropism. Anti-HIV directed antibodies could be detected before and after the SCT. These preexisting antibodies did not prevent viral rebound after the interruption of antiretroviral therapy during the SCT. Eventually, transplantation and readministration of anti-retroviral drugs lead to sustained increase in CD4 counts and decreased viral load to undetectable levels. Unexpectedly, viral diversity decreased after successful SCT. Our data evidence that only R5-tropic virus was found in the patient before and after transplantation. Therefore, blocking CCR5 receptor during stem cell transplantation might have had beneficial effects and this might apply to more patients undergoing allogeneic stem cell transplantation. Furthermore, we revealed a scenario of HIV-1 dynamic different from the commonly described ones. Analysis of viral evolution shows the decrease of viral diversity even during episodes with bursts in viral load.

  19. Antiviral Defense Mechanisms in Honey Bees

    Science.gov (United States)

    Brutscher, Laura M.; Daughenbaugh, Katie F.; Flenniken, Michelle L.

    2015-01-01

    Honey bees are significant pollinators of agricultural crops and other important plant species. High annual losses of honey bee colonies in North America and in some parts of Europe have profound ecological and economic implications. Colony losses have been attributed to multiple factors including RNA viruses, thus understanding bee antiviral defense mechanisms may result in the development of strategies that mitigate colony losses. Honey bee antiviral defense mechanisms include RNA-interference, pathogen-associated molecular pattern (PAMP) triggered signal transduction cascades, and reactive oxygen species generation. However, the relative importance of these and other pathways is largely uncharacterized. Herein we review the current understanding of honey bee antiviral defense mechanisms and suggest important avenues for future investigation. PMID:26273564

  20. Antiviral Activity of Polyacrylic and Polymethacrylic Acids

    Science.gov (United States)

    De Somer, P.; De Clercq, E.; Billiau, A.; Schonne, E.; Claesen, M.

    1968-01-01

    Polyacrylic acid (PAA) and polymethacrylic acid (PMAA) were investigated for their antiviral properties in tissue culture. Compared to other related polyanions, as dextran sulfate, polystyrene sulfonate, polyvinyl sulfate, and polyphloroglucinol phosphate, PAA and PMAA were found to be significantly more antivirally active and less cytotoxic. PMAA added 24 hr prior to virus inoculation inhibited viral growth most efficiently but it was still effective when added 3 hr after infection. Neither a direct irreversible action on the virus nor inhibition of virus penetration into the cell could explain the antiviral activity of PMAA. PMAA inhibited the adsorption of the virus to the host cell and suppressed the one-cycle viral synthesis in tissue cultures inoculated with infectious RNA. PMID:4302187

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

    International Nuclear Information System (INIS)

    Rasool, M.H.; Afzal, A.M.

    2014-01-01

    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)

  2. Bioprospecting of Red Sea Sponges for Novel Antiviral Pharmacophores

    KAUST Repository

    O'Rourke, Aubrie

    2015-01-01

    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

  3. 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.

  4. Generation of antiviral transgenic chicken using spermatogonial ...

    African Journals Online (AJOL)

    This study was conducted in order to generate anti-viral transgenic chickens through transfected spermatogonial stem cell with fusion gene EGFP-MMx. After injecting fusion gene EGFP-MMx into testes, tissues frozen section, polymerase chain reaction (PCR) and dot blot of testes was performed at 30, 40, 50, 60, 70 and 80 ...

  5. 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.

  6. Comparative analysis of the lambda-interferons IL-28A and IL-29 regarding their transcriptome and their antiviral properties against hepatitis C virus.

    Directory of Open Access Journals (Sweden)

    Julia Diegelmann

    Full Text Available BACKGROUND: Specific differences in signaling and antiviral properties between the different Lambda-interferons, a novel group of interferons composed of IL-28A, IL-28B and IL-29, are currently unknown. This is the first study comparatively investigating the transcriptome and the antiviral properties of the Lambda-interferons IL-28A and IL-29. METHODOLOGY/PRINCIPAL FINDINGS: Expression studies were performed by microarray analysis, quantitative PCR (qPCR, reporter gene assays and immunoluminometric assays. Signaling was analyzed by Western blot. HCV replication was measured in Huh-7 cells expressing subgenomic HCV replicon. All hepatic cell lines investigated as well as primary hepatocytes expressed both IFN-λ receptor subunits IL-10R2 and IFN-λR1. Both, IL-28A and IL-29 activated STAT1 signaling. As revealed by microarray analysis, similar genes were induced by both cytokines in Huh-7 cells (IL-28A: 117 genes; IL-29: 111 genes, many of them playing a role in antiviral immunity. However, only IL-28A was able to significantly down-regulate gene expression (n = 272 down-regulated genes. Both cytokines significantly decreased HCV replication in Huh-7 cells. In comparison to liver biopsies of patients with non-viral liver disease, liver biopsies of patients with HCV showed significantly increased mRNA expression of IL-28A and IL-29. Moreover, IL-28A serum protein levels were elevated in HCV patients. In a murine model of viral hepatitis, IL-28 expression was significantly increased. CONCLUSIONS/SIGNIFICANCE: IL-28A and IL-29 are up-regulated in HCV patients and are similarly effective in inducing antiviral genes and inhibiting HCV replication. In contrast to IL-29, IL-28A is a potent gene repressor. Both IFN-λs may have therapeutic potential in the treatment of chronic HCV.

  7. Nucleic acid-induced antiviral immunity in invertebrates: an evolutionary perspective.

    Science.gov (United States)

    Wang, Pei-Hui; Weng, Shao-Ping; He, Jian-Guo

    2015-02-01

    Nucleic acids derived from viral pathogens are typical pathogen associated molecular patterns (PAMPs). In mammals, the recognition of viral nucleic acids by pattern recognition receptors (PRRs), which include Toll-like receptors (TLRs) and retinoic acid-inducible gene (RIG)-I-like receptors (RLRs), induces the release of inflammatory cytokines and type I interferons (IFNs) through the activation of nuclear factor κB (NF-κB) and interferon regulatory factor (IRF) 3/7 pathways, triggering the host antiviral state. However, whether nucleic acids can induce similar antiviral immunity in invertebrates remains ambiguous. Several studies have reported that nucleic acid mimics, especially dsRNA mimic poly(I:C), can strongly induce non-specific antiviral immune responses in insects, shrimp, and oyster. This behavior shows multiple similarities to the hallmarks of mammalian IFN responses. In this review, we highlight the current understanding of nucleic acid-induced antiviral immunity in invertebrates. We also discuss the potential recognition and regulatory mechanisms that confer non-specific antiviral immunity on invertebrate hosts. Copyright © 2014 Elsevier Ltd. All rights reserved.

  8. Antiviral treatment of feline immunodeficiency virus-infected cats with (R)-9-(2-phosphonylmethoxypropyl)-2,6-diaminopurine.

    Science.gov (United States)

    Taffin, Elien; Paepe, Dominique; Goris, Nesya; Auwerx, Joeri; Debille, Mariella; Neyts, Johan; Van de Maele, Isabel; Daminet, Sylvie

    2015-02-01

    Feline immunodeficiency virus (FIV), the causative agent of an acquired immunodeficiency syndrome in cats (feline AIDS), is a ubiquitous health threat to the domestic and feral cat population, also triggering disease in wild animals. No registered antiviral compounds are currently available to treat FIV-infected cats. Several human antiviral drugs have been used experimentally in cats, but not without the development of serious adverse effects. Here we report on the treatment of six naturally FIV-infected cats, suffering from moderate to severe disease, with the antiretroviral compound (R)-9-(2-phosphonylmethoxypropyl)-2,6-diaminopurine ([R]-PMPDAP), a close analogue of tenofovir, a widely prescribed anti-HIV drug in human medicine. An improvement in the average Karnofsky score (pretreatment 33.2 ± 9.4%, post-treatment 65±12.3%), some laboratory parameters (ie, serum amyloid A and gammaglobulins) and a decrease of FIV viral load in plasma were noted in most cats. The role of concurrent medication in ameliorating the Karnofsky score, as well as the possible development of haematological side effects, are discussed. Side effects, when noted, appeared mild and reversible upon cessation of treatment. Although strong conclusions cannot be drawn owing to the small number of patients and lack of a placebo-treated control group, the activity of (R)-PMPDAP, as observed here, warrants further investigation. © ISFM and AAFP 2014.

  9. miR-194 Inhibits Innate Antiviral Immunity by Targeting FGF2 in Influenza H1N1 Virus Infection

    Directory of Open Access Journals (Sweden)

    Keyu Wang

    2017-11-01

    Full Text Available Fibroblast growth factor 2 (FGF2 or basic FGF regulates a wide range of cell biological functions including proliferation, angiogenesis, migration, differentiation, and injury repair. However, the roles of FGF2 and the underlying mechanisms of action in influenza A virus (IAV-induced lung injury remain largely unexplored. In this study, we report that microRNA-194-5p (miR-194 expression is significantly decreased in A549 alveolar epithelial cells (AECs following infection with IAV/Beijing/501/2009 (BJ501. We found that miR-194 can directly target FGF2, a novel antiviral regulator, to suppress FGF2 expression at the mRNA and protein levels. Overexpression of miR-194 facilitated IAV replication by negatively regulating type I interferon (IFN production, whereas reintroduction of FGF2 abrogated the miR-194-induced effects on IAV replication. Conversely, inhibition of miR-194 alleviated IAV-induced lung injury by promoting type I IFN antiviral activities in vivo. Importantly, FGF2 activated the retinoic acid-inducible gene I signaling pathway, whereas miR-194 suppressed the phosphorylation of tank binding kinase 1 and IFN regulatory factor 3. Our findings suggest that the miR-194-FGF2 axis plays a vital role in IAV-induced lung injury, and miR-194 antagonism might be a potential therapeutic target during IAV infection.

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

    Science.gov (United States)

    Visintini Jaime, María F; Redko, Flavia; Muschietti, Liliana V; Campos, Rodolfo H; Martino, Virginia S; Cavallaro, Lucia V

    2013-07-27

    Due to the high prevalence of viral infections having no specific treatment and the constant appearance of resistant viral strains, the development of novel antiviral agents is essential. The aim of this study was to evaluate the antiviral activity against bovine viral diarrhea virus, herpes simplex virus type 1 (HSV-1), poliovirus type 2 (PV-2) and vesicular stomatitis virus of organic (OE) and aqueous extracts (AE) from: Baccharis gaudichaudiana, B. spicata, Bidens subalternans, Pluchea sagittalis, Tagetes minuta and Tessaria absinthioides. A characterization of the antiviral activity of B. gaudichaudiana OE and AE and the bioassay-guided fractionation of the former and isolation of one active compound is also reported. The antiviral activity of the OE and AE of the selected plants was evaluated by reduction of the viral cytopathic effect. Active extracts were then assessed by plaque reduction assays. The antiviral activity of the most active extracts was characterized by evaluating their effect on the pretreatment, the virucidal activity and the effect on the adsorption or post-adsorption period of the viral cycle. The bioassay-guided fractionation of B. gaudichaudiana OE was carried out by column chromatography followed by semipreparative high performance liquid chromatography fractionation of the most active fraction and isolation of an active compound. The antiviral activity of this compound was also evaluated by plaque assay. B. gaudichaudiana and B. spicata OE were active against PV-2 and VSV. T. absinthioides OE was only active against PV-2. The corresponding three AE were active against HSV-1. B. gaudichaudiana extracts (OE and AE) were the most selective ones with selectivity index (SI) values of 10.9 (PV-2) and > 117 (HSV-1). For this reason, both extracts of B. gaudichaudiana were selected to characterize their antiviral effects. Further bioassay-guided fractionation of B. gaudichaudiana OE led to an active fraction, FC (EC50 = 3.1 μg/ml; SI = 37

  11. Antiviral Activity of Novel Quinoline Derivatives against Dengue Virus Serotype 2

    Directory of Open Access Journals (Sweden)

    Carolina de la Guardia

    2018-03-01

    Full Text Available Dengue virus causes dengue fever, a debilitating disease with an increasing incidence in many tropical and subtropical territories. So far, there are no effective antivirals licensed to treat this virus. Here we describe the synthesis and antiviral activity evaluation of two compounds based on the quinoline scaffold, which has shown potential for the development of molecules with various biological activities. Two of the tested compounds showed dose-dependent inhibition of dengue virus serotype 2 in the low and sub micromolar range. The compounds 1 and 2 were also able to impair the accumulation of the viral envelope glycoprotein in infected cells, while showing no sign of direct virucidal activity and acting possibly through a mechanism involving the early stages of the infection. The results are congruent with previously reported data showing the potential of quinoline derivatives as a promising scaffold for the development of new antivirals against this important virus.

  12. Antiviral activity and specific modes of action of bacterial prodigiosin against Bombyx mori nucleopolyhedrovirus in vitro.

    Science.gov (United States)

    Zhou, Wei; Zeng, Cheng; Liu, RenHua; Chen, Jie; Li, Ru; Wang, XinYan; Bai, WenWen; Liu, XiaoYuan; Xiang, TingTing; Zhang, Lin; Wan, YongJi

    2016-05-01

    Prodigiosin, the tripyrrole red pigment, is a bacterial secondary metabolite with multiple bioactivities; however, the antiviral activity has not been reported yet. In the present study, we found the antiviral activity of bacterial prodigiosin on Bombyx mori nucleopolyhedrovirus (BmNPV)-infected cells in vitro, with specific modes of action. Prodigiosin at nontoxic concentrations selectively killed virus-infected cells, inhibited viral gene transcription, especially viral early gene ie-1, and prevented virus-mediated membrane fusion. Under prodigiosin treatment, both progeny virus production and viral DNA replication were significantly inhibited. Fluorescent assays showed that prodigiosin predominantly located in cytoplasm which suggested it might interact with cytoplasm factors to inhibit virus replication. In conclusion, the present study clearly indicates that prodigiosin possesses significant antiviral activity against BmNPV.

  13. 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.

  14. Divergent antiviral effects of bioflavonoids on the hepatitis C virus life cycle

    Energy Technology Data Exchange (ETDEWEB)

    Khachatoorian, Ronik, E-mail: RnKhch@ucla.edu [Molecular Biology Interdepartmental Ph.D. Program (MBIDP), Molecular Biology Institute, David Geffen School of Medicine at University of California, Los Angeles, California, CA (United States); Molecular Biology Institute, David Geffen School of Medicine at University of California, Los Angeles, California, CA (United States); Arumugaswami, Vaithilingaraja, E-mail: VArumugaswami@mednet.ucla.edu [Department of Molecular and Medical Pharmacology, David Geffen School of Medicine at University of California, Los Angeles, California, CA (United States); Department of Surgery, Regenerative Medicine Institute at Cedars-Sinai Medical Center, Los Angeles, California, CA (United States); Raychaudhuri, Santanu, E-mail: SRaychau@ucla.edu [Department of Microbiology, Immunology, and Molecular Genetics, David Geffen School of Medicine at University of California, Los Angeles, California, CA (United States); Yeh, George K., E-mail: GgYeh@ucla.edu [Molecular Biology Interdepartmental Ph.D. Program (MBIDP), Molecular Biology Institute, David Geffen School of Medicine at University of California, Los Angeles, California, CA (United States); Molecular Biology Institute, David Geffen School of Medicine at University of California, Los Angeles, California, CA (United States); Maloney, Eden M., E-mail: EMaloney@ucla.edu [Department of Molecular, Cell, and Developmental Biology, University of California, Los Angeles, California, CA (United States); Wang, Julie, E-mail: JulieW1521@ucla.edu [Department of Microbiology, Immunology, and Molecular Genetics, David Geffen School of Medicine at University of California, Los Angeles, California, CA (United States); and others

    2012-11-25

    We have previously demonstrated that quercetin, a bioflavonoid, blocks hepatitis C virus (HCV) proliferation by inhibiting NS5A-driven internal ribosomal entry site (IRES)-mediated translation of the viral genome. Here, we investigate the mechanisms of antiviral activity of quercetin and six additional bioflavonoids. We demonstrate that catechin, naringenin, and quercetin possess significant antiviral activity, with no associated cytotoxicity. Infectious virion secretion was not significantly altered by these bioflavonoids. Catechin and naringenin demonstrated stronger inhibition of infectious virion assembly compared to quercetin. Quercetin markedly blocked viral translation whereas catechin and naringenin demonstrated mild activity. Similarly quercetin completely blocked NS5A-augmented IRES-mediated translation in an IRES reporter assay, whereas catechin and naringenin had only a mild effect. Moreover, quercetin differentially inhibited HSP70 induction compared to catechin and naringenin. Thus, the antiviral activity of these bioflavonoids is mediated through different mechanisms. Therefore combination of these bioflavonoids may act synergistically against HCV.

  15. Appetite - decreased

    Science.gov (United States)

    Loss of appetite; Decreased appetite; Anorexia ... Any illness can reduce appetite. If the illness is treatable, the appetite should return when the condition is cured. Loss of appetite can cause weight ...

  16. Broad-spectrum antiviral properties of andrographolide.

    Science.gov (United States)

    Gupta, Swati; Mishra, K P; Ganju, Lilly

    2017-03-01

    Andrographolide, a diterpenoid, is known for its anti-inflammatory effects. It can be isolated from various plants of the genus Andrographis, commonly known as 'creat'. This purified compound has been tested for its anti-inflammatory effects in various stressful conditions, such as ischemia, pyrogenesis, arthritis, hepatic or neural toxicity, carcinoma, and oxidative stress, Apart from its anti-inflammatory effects, andrographolide also exhibits immunomodulatory effects by effectively enhancing cytotoxic T cells, natural killer (NK) cells, phagocytosis, and antibody-dependent cell-mediated cytotoxicity (ADCC). All these properties of andrographolide form the foundation for the use of this miraculous compound to restrain virus replication and virus-induced pathogenesis. The present article covers antiviral properties of andrographolide in variety of viral infections, with the hope of developing of a new highly potent antiviral drug with multiple effects.

  17. A small effect of adding antiviral agents in treating patients with severe Bell palsy.

    NARCIS (Netherlands)

    Veen, E.L. van der; Rovers, M.M.; Ru, J.A. de; Heijden, G.J. van der

    2012-01-01

    In this evidence-based case report, the authors studied the following clinical question: What is the effect of adding antiviral agents to corticosteroids in the treatment of patients with severe or complete Bell palsy? The search yielded 250 original research articles. The 6 randomized trials of

  18. Antiviral Effects of Saffron and its Major Ingredients.

    Science.gov (United States)

    Soleymani, Sepehr; Zabihollahi, Rezvan; Shahbazi, Sepideh; Bolhassani, Azam

    2018-01-01

    The lack of an effective vaccine against viral infections, toxicity of the synthetic anti-viral drugs and the generation of resistant viral strains led to discover novel inhibitors. Recently, saffron and its compounds were used to treat different pathological conditions. In this study, we tested the anti-HSV-1 and anti-HIV-1 activities of Iranian saffron extract and its major ingredients including crocin and picrocrocin as well as cytotoxicity in vitro. The data showed that the aqueous saffron extract was not active against HIV-1 and HSV-1 virions at certain doses (i.e., a mild activity), but crocin and picrocrocin indicated significant anti-HSV-1 and also anti-HIV-1 activities. Crocin inhibited the HSV replication at before and after entry of virions into Vero cells. Indeed, crocin carotenoid suppressed HSV penetration in the target cells as well as disturbed virus replication after entry into the cells. Picrocrocin was also effective for inhibiting virus entry and also its replication. This monoterpen aldehyde showed higher anti-HSV effects after virus penetrating in the cells. Generally, these sugar-containing compounds extracted from saffron showed to be effective antiherpetic drug candidates. The recent study is the first report suggesting antiviral activities for saffron extract and its major ingredients. Crocin and picrocrocin could be a promising anti-HSV and anti-HIV agent for herbal therapy against viral infections. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

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

    Directory of Open Access Journals (Sweden)

    Elizondo-Gonzalez Regina

    2012-12-01

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

  20. Decreasing the dispatch time of medical reports sent from hospital to primary care with Lean Six Sigma.

    Science.gov (United States)

    Basta, Yara L; Zwetsloot, Inez M; Klinkenbijl, Jean H G; Rohof, Thomas; Monster, Mathijs M C; Fockens, Paul; Tytgat, Kristien M A J

    2016-10-01

    Timely communication is important to ensure high-quality health care. To facilitate this, the Gastro Intestinal Oncology Center Amsterdam (GIOCA) stipulated to dispatch medical reports on the day of the patient's visit. However, with the increasing number of patients, administrative processes at GIOCA were under pressure, and this standard was not met for the majority of patients. The aim and objective of this study was to dispatch 90% of medical reports on the day of the patient's visit by improving the logistic process. To assess the main causes for a prolonged dispatch time and to design improvements actions, the roadmap offered by Lean Six Sigma (LSS) was used, consisting of five phases: Define, Measure, Analyze, Improve and Control (DMAIC roadmap). Initially, 12.3% of the reports were dispatched on the day of the patient's visit. Three causes for a prolonged dispatch time were identified: (1) determining which doctors involved with treatment would compose the report; (2) the reports composed by a senior resident had to be reviewed by a medical specialist; and (3) a medical specialist had to authorize the administration to dispatch the reports. To circumvent these causes, a digital form was implemented in the electronic medical record that could be completed during the multidisciplinary team meeting. After implementation, 90.6% of the reports were dispatched on the day of the visit. The dispatch time of reports sent from hospital to primary care can be significantly reduced using Lean Six Sigma, improving the communication between hospital and primary care. © 2016 John Wiley & Sons, Ltd.

  1. A small effect of adding antiviral agents in treating patients with severe Bell palsy.

    Science.gov (United States)

    van der Veen, Erwin L; Rovers, Maroeska M; de Ru, J Alexander; van der Heijden, Geert J

    2012-03-01

    In this evidence-based case report, the authors studied the following clinical question: What is the effect of adding antiviral agents to corticosteroids in the treatment of patients with severe or complete Bell palsy? The search yielded 250 original research articles. The 6 randomized trials of these that could be used all reported low-quality data for answering the clinical question; apart from apparent flaws, they did not primarily include patients with severe or complete Bell palsy. Complete functional facial nerve recovery was seen in 75% of the patients receiving prednisolone only and in 83% with additional antiviral treatment. The pooled risk difference of 7% (95% confidence interval, -1% to 15%) results in a number needed to treat of 14 (ie, slightly favors adding an antiviral agent). The authors conclude that although a strong recommendation for adding antiviral agents to corticosteroids to further improve the recovery of patients with severe Bell palsy is precluded by the lack of robust evidence, it should be discussed with the patient.

  2. Atividade antiviral de Musa acuminata Colla, Musaceae

    Directory of Open Access Journals (Sweden)

    Fernanda Otaviano Martins

    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.

  3. Decreasing the dispatch time of medical reports sent from hospital to primary care with Lean Six Sigma

    NARCIS (Netherlands)

    Basta, Y.L.; Zwetsloot, I.M.; Klinkenbijl, J. H. G.; Rohof, T.; Monster, M.M.C.; Fockens, P.; Tytgat, K.M.A.J.

    2016-01-01

    Rationale, aims and objectives Timely communication is important to ensure high-quality health care. To facilitate this, the Gastro Intestinal Oncology Center Amsterdam (GIOCA) stipulated to dispatch medical reports on the day of the patient's visit. However, with the increasing number of patients,

  4. Decreasing the dispatch time of medical reports sent from hospital to primary care with Lean Six Sigma

    NARCIS (Netherlands)

    Basta, Yara L.; Zwetsloot, Inez M.; Klinkenbijl, Jean H. G.; Rohof, Thomas; Monster, Mathijs M. C.; Fockens, Paul; Tytgat, Kristien M. A. J.

    2016-01-01

    Timely communication is important to ensure high-quality health care. To facilitate this, the Gastro Intestinal Oncology Center Amsterdam (GIOCA) stipulated to dispatch medical reports on the day of the patient's visit. However, with the increasing number of patients, administrative processes at

  5. Is the apparent decrease in injury and illness rates in construction the result of changes in reporting?

    Science.gov (United States)

    Welch, Laura S; Dong, Xiuwen; Carre, Francoise; Ringen, Knut

    2007-01-01

    Injury rates in all industries and in construction in particular have been declining. Inconsistencies in the information suggest some of the apparent decrease may be due to changes in the ways injuries are treated, misclassification of employees, or underreporting. Lost-time injury rates for the largest construction employers declined by as much as 92% between 1988 and 1999. Yet the rate for cases with restricted work activity actually increased from 0.7 to 1.2 per 100 full-time workers between 1990 and 2000, and fatalities among construction workers remain high. In Massachusetts, at least 14% of construction employers misclassified workers as independent contractors, with the effect that injuries to these workers are not recordable. Studies that compare OSHA logs with other data sources find that the OSHA logs do not include a significant proportion of injuries and illnesses identified elsewhere.

  6. Identification and Analysis of Antiviral Compounds Against Poliovirus.

    Science.gov (United States)

    Leyssen, Pieter; Franco, David; Tijsma, Aloys; Lacroix, Céline; De Palma, Armando; Neyts, Johan

    2016-01-01

    The Global Polio Eradication Initiative, launched in 1988, had as its goal the eradication of polio worldwide by the year 2000 through large-scale vaccinations campaigns with the live attenuated oral PV vaccine (OPV) (Griffiths et al., Biologicals 34:73-74, 2006). Despite substantial progress, polio remains endemic in several countries and new imported cases are reported on a regular basis ( http://www.polioeradication.org/casecount.asp ).It was recognized by the poliovirus research community that developing antivirals against poliovirus would be invaluable in the post-OPV era. Here, we describe three methods essential for the identification of selective inhibitors of poliovirus replication and for determining their mode of action by time-of-drug-addition studies as well as by the isolation of compound-resistant poliovirus variants.

  7. Towards antiviral therapies for treating dengue virus infections.

    Science.gov (United States)

    Kaptein, Suzanne Jf; Neyts, Johan

    2016-10-01

    Dengue virus is an emerging human pathogen that poses a huge public health burden by infecting annually about 390 million individuals of which a quarter report with clinical manifestations. Although progress has been made in understanding dengue pathogenesis, a licensed vaccine or antiviral therapy against this virus is still lacking. Treatment of patients is confined to symptomatic alleviation and supportive care. The development of dengue therapeutics thus remains of utmost importance. This review focuses on the few molecules that were evaluated in dengue virus-infected patients: balapiravir, chloroquine, lovastatin, prednisolone and celgosivir. The lessons learned from these clinical trials can be very helpful for the design of future trials for the next generation of dengue virus inhibitors. Copyright © 2016 Elsevier Ltd. All rights reserved.

  8. Direct-acting antivirals for chronic hepatitis C

    DEFF Research Database (Denmark)

    Jakobsen, Janus C; Nielsen, Emil Eik; Feinberg, Joshua

    2017-01-01

    BACKGROUND: Millions of people worldwide suffer from hepatitis C, which can lead to severe liver disease, liver cancer, and death. Direct-acting antivirals (DAAs), e.g. sofosbuvir, are relatively new and expensive interventions for chronic hepatitis C, and preliminary results suggest that DAAs may...... eradicate hepatitis C virus (HCV) from the blood (sustained virological response). Sustained virological response (SVR) is used by investigators and regulatory agencies as a surrogate outcome for morbidity and mortality, based solely on observational evidence. However, there have been no randomised trials...... hepatitis C-related morbidity, serious adverse events, and health-related quality of life. Our secondary outcomes were all-cause mortality, ascites, variceal bleeding, hepato-renal syndrome, hepatic encephalopathy, hepatocellular carcinoma, non-serious adverse events (each reported separately), and SVR. We...

  9. Signing at the beginning makes ethics salient and decreases dishonest self-reports in comparison to signing at the end.

    Science.gov (United States)

    Shu, Lisa L; Mazar, Nina; Gino, Francesca; Ariely, Dan; Bazerman, Max H

    2012-09-18

    Many written forms required by businesses and governments rely on honest reporting. Proof of honest intent is typically provided through signature at the end of, e.g., tax returns or insurance policy forms. Still, people sometimes cheat to advance their financial self-interests-at great costs to society. We test an easy-to-implement method to discourage dishonesty: signing at the beginning rather than at the end of a self-report, thereby reversing the order of the current practice. Using laboratory and field experiments, we find that signing before-rather than after-the opportunity to cheat makes ethics salient when they are needed most and significantly reduces dishonesty.

  10. Signing at the beginning makes ethics salient and decreases dishonest self-reports in comparison to signing at the end

    Science.gov (United States)

    Shu, Lisa L.; Mazar, Nina; Gino, Francesca; Ariely, Dan; Bazerman, Max H.

    2012-01-01

    Many written forms required by businesses and governments rely on honest reporting. Proof of honest intent is typically provided through signature at the end of, e.g., tax returns or insurance policy forms. Still, people sometimes cheat to advance their financial self-interests—at great costs to society. We test an easy-to-implement method to discourage dishonesty: signing at the beginning rather than at the end of a self-report, thereby reversing the order of the current practice. Using laboratory and field experiments, we find that signing before—rather than after—the opportunity to cheat makes ethics salient when they are needed most and significantly reduces dishonesty. PMID:22927408

  11. Evidence of the innate antiviral and neuroprotective properties of progranulin.

    Directory of Open Access Journals (Sweden)

    Hyeon-Sook Suh

    Full Text Available Compelling data exist that show that normal levels of progranulin (PGRN are required for successful CNS aging. PGRN production is also modulated by inflammation and infection, but no data are available on the production and role of PGRN during CNS HIV infection.To determine the relationships between PGRN and HIV disease, neurocognition, and inflammation, we analyzed 107 matched CSF and plasma samples from CHARTER, a well-characterized HIV cohort. Levels of PGRN were determined by ELISA and compared to levels of several inflammatory mediators (IFNγ, IL-6, IL-10, IP-10, MCP-1, TNFα, IL-1β, IL-4 and IL-13, as well as clinical, virologic and demographic parameters. The relationship between HIV infection and PGRN was also examined in HIV-infected primary human microglial cultures.In plasma, PGRN levels correlated with the viral load (VL, p<0.001. In the CSF of subjects with undetectable VL, lower PGRN was associated with neurocognitive impairment (p = 0.046. CSF PGRN correlated with CSF IP-10, TNFα and IL-10, and plasma PGRN correlated with plasma IP-10. In vitro, microglial HIV infection increased PGRN production and PGRN knockdown increased HIV replication, demonstrating that PGRN is an innate antiviral protein.We propose that PGRN plays dual roles in people living with HIV disease. With active HIV replication, PGRN is induced in infected macrophages and microglia and functions as an antiviral protein. In individuals without active viral replication, decreased PGRN production contributes to neurocognitive dysfunction, probably through a diminution of its neurotrophic functions. Our results have implications for the pathogenesis, biomarker studies and therapy for HIV diseases including HIV-associated neurocognitive dysfunction (HAND.

  12. 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.

  13. How to Control HTLV-1-Associated Diseases: Preventing de Novo Cellular Infection Using Antiviral Therapy

    Directory of Open Access Journals (Sweden)

    Amandine Pasquier

    2018-03-01

    targeting HTLV-1 replication. We also tested a series of HIV-1 RT inhibitors in an in vitro anti-HTLV-1 screen, and report that bis-POM-PMEA (adefovir dipivoxil and bis-POC-PMPA (tenofovir disoproxil are much more efficient compared to AZT to decrease HTLV-1 cell-to-cell transmission in vitro. Our results suggest that revisiting already established antiviral drugs is an interesting approach to discover new anti-HTLV-1 drugs.

  14. Molecular Mechanisms of Foot-and-Mouth Disease Virus Targeting the Host Antiviral Response.

    Science.gov (United States)

    Rodríguez Pulido, Miguel; Sáiz, Margarita

    2017-01-01

    Foot-and-mouth disease virus (FMDV) is the causative agent of an acute vesicular disease affecting pigs, cattle and other domestic, and wild animals worldwide. The aim of the host interferon (IFN) response is to limit viral replication and spread. Detection of the viral genome and products by specialized cellular sensors initiates a signaling cascade that leads to a rapid antiviral response involving the secretion of type I- and type III-IFNs and other antiviral cytokines with antiproliferative and immunomodulatory functions. During co-evolution with their hosts, viruses have acquired strategies to actively counteract host antiviral responses and the balance between innate response and viral antagonism may determine the outcome of disease and pathogenesis. FMDV proteases Lpro and 3C have been found to antagonize the host IFN response by a repertoire of mechanisms. Moreover, the putative role of other viral proteins in IFN antagonism is being recently unveiled, uncovering sophisticated immune evasion strategies different to those reported to date for other members of the Picornaviridae family. Here, we review the interplay between antiviral responses induced by FMDV infection and viral countermeasures to block them. Research on strategies used by viruses to modulate immunity will provide insights into the function of host pathways involved in defense against pathogens and will also lead to development of new therapeutic strategies to fight virus infections.

  15. Drug-induced Sweet's syndrome secondary to hepatitis C antiviral therapy.

    Science.gov (United States)

    Gheorghe, Liana; Cotruta, Bogdan; Trifu, Viorel; Cotruta, Cristina; Becheanu, Gabriel; Gheorghe, Cristian

    2008-09-01

    Pegylated interferon-alpha in combination with ribavirin currently represents the therapeutic standard for the hepatitis C virus infection. Interferon based therapy may be responsible for many cutaneous side effects. We report a case of drug-induced Sweet's syndrome secondary to hepatitis C antiviral therapy. To our knowledge, this is the first reported case of Sweet's syndrome in association with pegylated interferon-alpha therapy.

  16. EXPRESSION OF ANTIVIRAL GENE ON TIGER SHRIMP Penaeus monodon AT DIFFERENT TISSUE AND BODY SIZE

    Directory of Open Access Journals (Sweden)

    Andi Parenrengi

    2012-12-01

    Full Text Available The role of tiger shrimp defense against invading pathogen on molecular level such antiviral gene expression is limited to be reported. Gene expression is a process which codes information of genes that is converted to the protein as a phenotype. Distribution of PmAV antivirus gene, that has been reported as an important gene on non-specific response immune, is needed to be observed to several organs/tissues and size of tiger shrimp. The aim of this study is to determine the distribution of gene antiviral expression at several organ/tissue and size of shrimp. The organs/tissues observed in this study were: gill, hepatopancres, muscle tissue, eyes, heart, stomach, gonad, and intestine. While the size of shrimp consisted of three groups, those are: (A 10-20 g/ind., (B 30-40 g/ind., and (C 60-70 g/ind. Analysis of antiviral gene expression was performed by RNA extraction, followed by the cDNA syntesis, and amplification of gene expression by semi-quantitative PCR. The result of PCR optimation showed the optimal concentration of cDNA and primer was 1 μL and 50 mol, respectively for PCR final volume of 25 μL. Antiviral gene was expressed on the hepatopancreas and stomach in percentage of 50.0% and 16.7%, respectively. While the highest percentage of individual expressing the antiviral gene was observed in the shrimp size of C (66.7%, followed by B (50.0% and A (16.7%. The result of study implied that the hepatopancreas has importantly involed in tiger shrimp defense mechanism on viral infection.

  17. Decreasing Complications of Quadricepsplasty for Knee Contracture after Femoral Fracture Treatment with an External Fixator: Report of Four Cases

    Directory of Open Access Journals (Sweden)

    Naoya Kashiwagi

    2013-01-01

    Full Text Available Introduction: In performing quadricepsplasty for contracture that develops after application of an external fixator for femoral fractures, surgeons must be aware of the potential risk for re-fracture and pin-related problems. The purpose of this report is to highlight these not well-detailed complications and to discuss specific findings and treatment suggestions.Case Report: 4 men (mean age, 40 years presenting with secondary to contracture that developed after application of an external fixator for femoral fractures were included in this study. The radiographs showed union across the fracture site however two of these patients couldn't stand on one leg raising suspicion about the union status. A computed tomographic image indeed demonstrated limited continuity of the cortex. Bone grafting was performed prior to quadricepsplasty. The mean extension and flexion before the quadricepsplasty were 0o and 570 , respectively. At the final follow-up examination, the mean active flexion of the knee had increased to 98o.Results: The incidence of re-fracture during and after quadricepsplasty has been reported to be between 10 and 25%. There are 2 preoperative features that may mislead surgeons into believing that complete union of the fractures has been attained: one is the patient's ability to stand on a single leg, and the other is the fact that plain radiographs may lend themselves to different interpretations. In such cases, computed tomography will provide evidence of the continuity of the cortical bone. Bone grafting in 2 of our patients is thought to have prevented the postoperative complications of re-fracture. Complications at pin sites induce contracture at surrounding structures. When extreme tightness of the skin is noted, a tension-releasing procedure such as a skin graft should be performed.Conclusion: In conclusion, re-fracture or pin-site contracture should be carefully managed before quadricepsplasty, because the patients who need a

  18. Plants as sources of antiviral agents | Abonyi | African Journal of ...

    African Journals Online (AJOL)

    Antivirals are 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 search for antiviral agents began in earnest in the 1950s but this was directed mainly by chance, with little or ...

  19. Self-interest versus group-interest in antiviral control

    NARCIS (Netherlands)

    Boven, M. van; Klinkenberg, D.; Pen, I.; Weissing, F.J.; Heesterbeek, J.A.P.

    2008-01-01

    Antiviral agents have been hailed to hold considerable promise for the treatment and prevention of emerging viral diseases like H5N1 avian influenza and SARS. However, antiviral drugs are not completely harmless, and the conditions under which individuals are willing to participate in a

  20. Anti-viral effect of herbal medicine Korean traditional Cynanchum ...

    African Journals Online (AJOL)

    Background: Pestiviruses in general, and Bovine Viral Diarrhea (BVD) in particular, present several potential targets for directed antiviral therapy. Material and Methods: The antiviral effect of Cynanchum paniculatum (Bge.) Kitag (Dog strangling vine: DS) extract on the bovine viral diarrhea (BVD) virus was tested. First ...

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

    African Journals Online (AJOL)

    Keywords: Hantavirus, Arbidol, Toll-like receptors, inducible nitric oxide synthase, Antiviral activity, ... hantavirus infection. Arbidol is a broad-spectrum antiviral compound that has been shown to have inhibitory effect on influenza virus [4,5], respiratory syncytial virus [6], ..... species in hantavirus cardiopulmonary syndrome.

  2. Atomoxetine treatment may decrease striatal dopaminergic transporter availability after 8 weeks: pilot SPECT report of three cases

    Directory of Open Access Journals (Sweden)

    Akay AP

    2015-11-01

    Full Text Available Aynur Pekcanlar Akay,1 Gamze Capa Kaya,2,3 Burak Baykara,1 Yusuf Demir,2,3 Handan Özek,1 Sevay Alsen,1 Mine Sencan Eren,2,3 Neslihan Inal Emiroglu,1 Turkan Ertay,2,3 Yesim Ozturk,4 Suha Miral,1 Hatice Durak,2,3 Evren Tufan4 1Department of Child and Adolescent Psychiatry, 2Department of Nuclear Medicine, 3Department of Pediatrics, Dokuz Eylul University Medical Faculty, Izmir, 4Department of Child and Adolescent Psychiatry, Abant İzzet Baysal University, Bolu, Turkey Abstract: Attention deficit/hyperactivity disorder is one of the most common neurodevelopmental disorders. The pathophysiology is thought to involve noradrenaline and dopamine. The role of dopamine transporter (DAT was evaluated in imaging studies using mostly dopamine reuptake inhibitors. Atomoxetine is a selective noradrenaline reuptake inhibitor. Here we report the results of a pilot study conducted to evaluate changes in striatal DAT after 8 weeks of atomoxetine treatment. Our results suggest that 8 weeks of atomoxetine treatment may change striatal DAT bioavailability as measured via SPECT but that change was not correlated with genotype or clinical improvement. Keywords: neuroimaging, dopamine, noradrenaline, SLC6A3 protein, human, pragmatic clinical trial, pilot study

  3. Production of transgenic pigs over-expressing the antiviral gene Mx1

    Directory of Open Access Journals (Sweden)

    Quanmei Yan

    2014-01-01

    Full Text Available The myxovirus resistance gene (Mx1 has a broad spectrum of antiviral activities. It is therefore an interesting candidate gene to improve disease resistance in farm animals. In this study, we report the use of somatic cell nuclear transfer (SCNT to produce transgenic pigs over-expressing the Mx1 gene. These transgenic pigs express approximately 15–25 times more Mx1 mRNA than non-transgenic pigs, and the protein level of Mx1 was also markedly enhanced. We challenged fibroblast cells isolated from the ear skin of transgenic and control pigs with influenza A virus and classical swine fever virus (CFSV. Indirect immunofluorescence assay (IFA revealed a profound decrease of influenza A proliferation in Mx1 transgenic cells. Growth kinetics showed an approximately 10-fold reduction of viral copies in the transgenic cells compared to non-transgenic controls. Additionally, we found that the Mx1 transgenic cells were more resistant to CSFV infection in comparison to non-transgenic cells. These results demonstrate that the Mx1 transgene can protect against viral infection in cells of transgenic pigs and indicate that the Mx1 transgene can be harnessed to develop disease-resistant pigs.

  4. Evasion of the Interferon-Mediated Antiviral Response by Filoviruses

    Directory of Open Access Journals (Sweden)

    Washington B. Cárdenas

    2010-01-01

    Full Text Available The members of the filoviruses are recognized as some of the most lethal viruses affecting human and non-human primates. The only two genera of the Filoviridae family, Marburg virus (MARV and Ebola virus (EBOV, comprise the main etiologic agents of severe hemorrhagic fever outbreaks in central Africa, with case fatality rates ranging from 25 to 90%. Fatal outcomes have been associated with a late and dysregulated immune response to infection, very likely due to the virus targeting key host immune cells, such as macrophages and dendritic cells (DCs that are necessary to mediate effective innate and adaptive immune responses. Despite major progress in the development of vaccine candidates for filovirus infections, a licensed vaccine or therapy for human use is still not available. During the last ten years, important progress has been made in understanding the molecular mechanisms of filovirus pathogenesis. Several lines of evidence implicate the impairment of the host interferon (IFN antiviral innate immune response by MARV or EBOV as an important determinant of virulence. In vitro and in vivo experimental infections with recombinant Zaire Ebola virus (ZEBOV, the best characterized filovirus, demonstrated that the viral protein VP35 plays a key role in inhibiting the production of IFN-α/β. Further, the action of VP35 is synergized by the inhibition of cellular responses to IFN-α/β by the minor matrix viral protein VP24. The dual action of these viral proteins may contribute to an efficient initial virus replication and dissemination in the host. Noticeably, the analogous function of these viral proteins in MARV has not been reported. Because the IFN response is a major component of the innate immune response to virus infection, this chapter reviews recent findings on the molecular mechanisms of IFN-mediated antiviral evasion by filovirus infection.

  5. RNAi: antiviral therapy against dengue virus.

    Science.gov (United States)

    Idrees, Sobia; Ashfaq, Usman A

    2013-03-01

    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.

  6. Innate and intrinsic antiviral immunity in skin.

    Science.gov (United States)

    Kawamura, Tatsuyoshi; Ogawa, Youichi; Aoki, Rui; Shimada, Shinji

    2014-09-01

    As the body's most exposed interface with the environment, the skin is constantly challenged by potentially pathogenic microbes, including viruses. To sense the invading viruses, various types of cells resident in the skin express many different pattern-recognition receptors (PRRs) such as C-type lectin receptors (CLRs), Toll-like receptors (TLRs), nucleotide-binding oligomerization domain (NOD)-like receptors (NLRs), retinoic acid-inducible gene I (RIG-I)-like receptors (RLRs) and cytosolic DNA sensors, that can detect the pathogen-associated molecular patterns (PAMPs) of the viruses. The detection of viral PAMPs initiates two major innate immune signaling cascades: the first involves the activation of the downstream transcription factors, such as interferon regulatory factors (IRFs), nuclear factor kappa B (NF-κB) and activator protein 1 (AP-1), which cooperate to induce the transcription of type I interferons and pro-inflammatory cytokines. The second signaling pathway involves the caspase-1-mediated processing of IL-1β and IL-18 through the formation of an inflammasome complex. Cutaneous innate immunity including the production of the innate cytokines constitutes the first line of host defence that limits the virus dissemination from the skin, and also plays an important role in the activation of adaptive immune response, which represents the second line of defence. More recently, the third immunity "intrinsic immunity" has emerged, that provides an immediate and direct antiviral defense mediated by host intrinsic restriction factors. This review focuses on the recent advances regarding the antiviral immune systems, highlighting the innate and intrinsic immunity against the viral infections in the skin, and describes how viral components are recognized by cutaneous immune systems. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  7. Longitudinal Liver Stiffness Assessment in Patients with Chronic Hepatitis C Undergoing Antiviral Therapy

    Science.gov (United States)

    Martinez, Stella M.; Foucher, Juliette; Combis, Jean-Marc; Métivier, Sophie; Brunetto, Maurizia; Capron, Dominique; Bourlière, Marc; Bronowicki, Jean-Pierre; Dao, Thong; Maynard-Muet, Marianne; Lucidarme, Damien; Merrouche, Wassil; Forns, Xavier; de Lédinghen, Victor

    2012-01-01

    Background/Aims Liver stiffness (LS) measurement by means of transient elastography (TE) is accurate to predict fibrosis stage. The effect of antiviral treatment and virologic response on LS was assessed and compared with untreated patients with chronic hepatitis C (CHC). Methods TE was performed at baseline, and at weeks 24, 48, and 72 in 515 patients with CHC. Results 323 treated (62.7%) and 192 untreated patients (37.3%) were assessed. LS experienced a significant decline in treated patients and remained stable in untreated patients at the end of study (P<0.0001). The decline was significant for patients with baseline LS ≥ 7.1 kPa (P<0.0001 and P 0.03, for LS ≥9.5 and ≥7.1 kPa vs lower values, respectively). Sustained virological responders and relapsers had a significant LS improvement whereas a trend was observed in nonresponders (mean percent change −16%, −10% and −2%, for SVR, RR and NR, respectively, P 0.03 for SVR vs NR). In multivariate analysis, high baseline LS (P<0.0001) and ALT levels, antiviral therapy and non-1 genotype were independent predictors of LS improvement. Conclusions LS decreases during and after antiviral treatment in patients with CHC. The decrease is significant in sustained responders and relapsers (particularly in those with high baseline LS) and suggests an improvement in liver damage. PMID:23082200

  8. Longitudinal liver stiffness assessment in patients with chronic hepatitis C undergoing antiviral therapy.

    Directory of Open Access Journals (Sweden)

    Stella M Martinez

    Full Text Available BACKGROUND/AIMS: Liver stiffness (LS measurement by means of transient elastography (TE is accurate to predict fibrosis stage. The effect of antiviral treatment and virologic response on LS was assessed and compared with untreated patients with chronic hepatitis C (CHC. METHODS: TE was performed at baseline, and at weeks 24, 48, and 72 in 515 patients with CHC. RESULTS: 323 treated (62.7% and 192 untreated patients (37.3% were assessed. LS experienced a significant decline in treated patients and remained stable in untreated patients at the end of study (P<0.0001. The decline was significant for patients with baseline LS ≥ 7.1 kPa (P<0.0001 and P 0.03, for LS ≥ 9.5 and ≥ 7.1 kPa vs lower values, respectively. Sustained virological responders and relapsers had a significant LS improvement whereas a trend was observed in nonresponders (mean percent change -16%, -10% and -2%, for SVR, RR and NR, respectively, P 0.03 for SVR vs NR. In multivariate analysis, high baseline LS (P<0.0001 and ALT levels, antiviral therapy and non-1 genotype were independent predictors of LS improvement. CONCLUSIONS: LS decreases during and after antiviral treatment in patients with CHC. The decrease is significant in sustained responders and relapsers (particularly in those with high baseline LS and suggests an improvement in liver damage.

  9. Liver stiffness becomes stable in patients with chronic hepatitis C three months after ALT normalization due to antiviral therapy

    Directory of Open Access Journals (Sweden)

    CHEN Feikai

    2013-10-01

    Full Text Available ObjectiveTo investigate the time for liver stiffness measurement (LSM to become stable in chronic hepatitis C (CHC patients with elevated alanine aminotransferase (ALT levels after ALT normalization due to antiviral therapy. MethodsCHC patients who sought initial treatment at Peking University People′s Hospital were screened for elevated ALT levels from May 2011. Liver stiffness was determined by FibroScan. A total of 29 patients had been included in the study by September 2012, who were followed up regularly after antiviral treatment. ALT tests were repeated every four weeks and LSM every eight weeks until their medians did not change significantly. Comparisons of matched data at two adjacent time points were made with the non-parametric Wilcoxon test, while multiple comparisons of repeated measurements were performed using Bonferroni correction. Correlation between two variables was analyzed with the Spearman rank test. ResultsPatients were followed up until 24 weeks after antiviral treatment, and 24 patients were included in analysis. The median ALT levels were 64, 26, 21, 20, and 22 U/L at baseline and 4, 8, 12, and 24 weeks, respectively (P= 0.000, 0.006, 0.337, and 0.109 for comparisons between two adjacent values. ALT decreased significantly below 1 ULN at 4 weeks after antiviral therapy and stabilized at 8 weeks. The median LSM values were 8.7, 7.8, 6.8, and 6.7 kPa at baseline and 8, 16, and 24 weeks, respectively (P= 0.009, 0.001, and 0188 for comparisons between two adjacent values. LSM decreased significantly within 16 weeks after antiviral therapy and stabilized afterwards. LSM stabilized 12 weeks after ALT normalization. ConclusionLSM becomes stable in CHC patients with elevated ALT levels three months after ALT normalization due to antiviral therapy.

  10. [Antiviral activity of different drugs in vitro against viruses of bovine infectious rhinotracheitis and bovine diarrhea].

    Science.gov (United States)

    Glotov, A G; Glotova, T I; Sergeev, A A; Belkina, T V; Sergeev, A N

    2004-01-01

    In vitro experiments studied the antiviral activity of 11 different drugs against viruses of bovine infective rhinotracheitis (BIRT) and bovine viral diarrhea (BVD). The 50% inhibiting concentrations of the test agents were determined in the monolayers of MDBK and KCT cell cultures. Only did phosprenyl show a virucidal activity against BIRT virus. All the tested drugs significantly inhibited the reproduction of BIRT virus in the sensitive MDBK cell cultures. Thus, bromuridin, acyclovir, ribavirin and methisazonum inhibited the virus by > or = 100,000 times; liposomal ribavirin, gossypolum, anandinum, polyprenolum, phosprenyl, by 1000-10,000 times; eracond and argovit, by 100 times. In experiments on BVD virus, the cultured KCT cells displayed the antiviral activity of bromuridin, phosprenil, polyprenolum, methisazonum, acyclovir, gossypolum, argovit, and ribavirin (in two variants), which caused a statistically significant (100-10,000-fold) decrease in the productive activity of this virus. Eracond and anandid proved to be ineffective.

  11. WITHDRAWN. Antiviral treatment for Bell's palsy (idiopathic facial paralysis).

    Science.gov (United States)

    Gagyor, Ildiko; Madhok, Vishnu B; Daly, Fergus; Somasundara, Dhruvashree; Sullivan, Michael; Gammie, Fiona; Sullivan, Frank

    2015-05-04

    Corticosteroids are widely used in the treatment of idiopathic facial paralysis (Bell's palsy), but the effectiveness of additional treatment with an antiviral agent is uncertain. Significant morbidity can be associated with severe cases of Bell's palsy. To assess the effects of antiviral treatments alone or in combination with any other therapy for Bell's palsy. On 7 October 2014 we searched the Cochrane Neuromuscular Disease Group Specialized Register, CENTRAL, MEDLINE, EMBASE, LILACS, DARE, NHS EED, and HTA. We also reviewed the bibliographies of the identified trials and contacted trial authors and known experts in the field and relevant drug companies to identify additional published or unpublished data. We searched clinical trials registries for ongoing studies. We considered randomised controlled trials or quasi-randomised controlled trials of antivirals with and without corticosteroids versus control therapies for the treatment of Bell's palsy. We excluded trials that had a high risk of bias in several domains. Pairs of authors independently assessed trials for relevance, eligibility, and risk of bias, using standard Cochrane procedures. Eleven trials, including 2883 participants, met the inclusion criteria and are included in the final analysis. We added four studies to the previous review for this update. Some of the trials were small, and a number were at high or unclear risk of bias. Other trials did not meet current best standards in allocation concealment and blinding. Incomplete recoveryWe found no significant benefit from adding antivirals to corticosteroids in comparison with corticosteroids alone for people with Bell's palsy (risk ratio (RR) 0.69, 95% confidence interval (CI) 0.47 to 1.02, n = 1715). For people with severe Bell's palsy (House-Brackmann scores of 5 and 6 or the equivalent in other scales), we found a reduction in the rate of incomplete recovery at month six when antivirals plus corticosteroids were used (RR 0.64, 95% CI 0.41 to 0

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

    Science.gov (United States)

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

    2017-10-01

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

  13. Down-Regulation of p53 by Double-Stranded RNA Modulates the Antiviral Response

    OpenAIRE

    Marques, Joao T.; Rebouillat, Dominique; Ramana, Chilakamarti V.; Murakami, Junko; Hill, Jason E.; Gudkov, Andrei; Silverman, Robert H.; Stark, George R.; Williams, Bryan R. G.

    2005-01-01

    p53 has been well characterized as a tumor suppressor gene, but its role in antiviral defense remains unclear. A recent report has demonstrated that p53 can be induced by interferons and is activated after vesicular stomatitis virus (VSV) infection. We observed that different nononcogenic viruses, including encephalomyocarditis virus (EMCV) and human parainfluenza virus type 3 (HPIV3), induced down-regulation of p53 in infected cells. Double-stranded RNA (dsRNA) and a mutant vaccinia virus la...

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

    Science.gov (United States)

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

    2014-07-01

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

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

    Science.gov (United States)

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

    2015-01-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2011-02-11

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

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

    International Nuclear Information System (INIS)

    Pei, Ying; Chen, Zhen-Ping; Ju, Huai-Qiang; Komatsu, Masaaki; Ji, Yu-hua; Liu, Ge; Guo, Chao-wan; Zhang, Ying-Jun; Yang, Chong-Ren; Wang, Yi-Fei; Kitazato, Kaio

    2011-01-01

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

  18. An antiviral protein from Bougainvillea spectabilis roots; purification and characterisation.

    Science.gov (United States)

    Balasaraswathi, R; Sadasivam, S; Ward, M; Walker, J M

    1998-04-01

    An antiviral protein active against mechanical transmission of tomato spotted wilt virus was identified in the root tissues of Bougainvillea spectabilis Willd. Bougainvillea Antiviral Protein I (BAP I) was purified to apparent homogeneity from the roots of Bougainvillea by ammonium sulphate precipitation, CM- and DEAE-Sepharose chromatography and reverse phase HPLC. BAP I is a highly basic protein (pI value > 8.6) with an Mr of 28,000. The N-terminal sequence of BAP I showed homology with other plant antiviral proteins. Preliminary tests suggest that purified BAP I is capable of interfering with in vitro protein synthesis.

  19. Current antiviral drugs and their analysis in biological materials - Part II: Antivirals against hepatitis and HIV viruses.

    Science.gov (United States)

    Nováková, Lucie; Pavlík, Jakub; Chrenková, Lucia; Martinec, Ondřej; Červený, Lukáš

    2018-01-05

    This review is a Part II of the series aiming to provide comprehensive overview of currently used antiviral drugs and to show modern approaches to their analysis. While in the Part I antivirals against herpes viruses and antivirals against respiratory viruses were addressed, this part concerns antivirals against hepatitis viruses (B and C) and human immunodeficiency virus (HIV). Many novel antivirals against hepatitis C virus (HCV) and HIV have been introduced into the clinical practice over the last decade. The recent broadening portfolio of these groups of antivirals is reflected in increasing number of developed analytical methods required to meet the needs of clinical terrain. Part II summarizes the mechanisms of action of antivirals against hepatitis B virus (HBV), HCV, and HIV, their use in clinical practice, and analytical methods for individual classes. It also provides expert opinion on state of art in the field of bioanalysis of these drugs. Analytical methods reflect novelty of these chemical structures and use by far the most current approaches, such as simple and high-throughput sample preparation and fast separation, often by means of UHPLC-MS/MS. Proper method validation based on requirements of bioanalytical guidelines is an inherent part of the developed methods. Copyright © 2017 Elsevier B.V. All rights reserved.

  20. Oral antiviral therapy for prevention of genital herpes outbreaks in immunocompetent and nonpregnant patients.

    Science.gov (United States)

    Le Cleach, Laurence; Trinquart, Ludovic; Do, Giao; Maruani, Annabel; Lebrun-Vignes, Benedicte; Ravaud, Philippe; Chosidow, Olivier

    2014-08-03

    acyclovir; pooled RR 1.04, 95% CI, 0.71 to 1.49 for famciclovir vs acyclovir; and pooled RR 1.26, 95% CI 0.89 to 1.75 for famciclovir vs valacyclovir). Safety data were sought but were reported as total numbers of adverse events. Owing to risk of bias and inconsistency, there is low quality evidence that suppressive antiviral therapy with acyclovir, valacyclovir or famciclovir in pacients experiencing at least four recurrences of genital herpes per year decreases the number of pacients with at least one recurrence as compared with placebo. Network meta-analysis of the few direct comparisons and the indirect comparisons did not show superiority of one drug over another.

  1. Potential Antiviral Agents from Marine Fungi: An Overview

    Directory of Open Access Journals (Sweden)

    Soheil Zorofchian Moghadamtousi

    2015-07-01

    Full Text Available Biodiversity of the marine world is only partially subjected to detailed scientific scrutiny in comparison to terrestrial life. Life in the marine world depends heavily on marine fungi scavenging the oceans of lifeless plants and animals and entering them into the nutrient cycle by. Approximately 150 to 200 new compounds, including alkaloids, sesquiterpenes, polyketides, and aromatic compounds, are identified from marine fungi annually. In recent years, numerous investigations demonstrated the tremendous potential of marine fungi as a promising source to develop new antivirals against different important viruses, including herpes simplex viruses, the human immunodeficiency virus, and the influenza virus. Various genera of marine fungi such as Aspergillus, Penicillium, Cladosporium, and Fusarium were subjected to compound isolation and antiviral studies, which led to an illustration of the strong antiviral activity of a variety of marine fungi-derived compounds. The present review strives to summarize all available knowledge on active compounds isolated from marine fungi with antiviral activity.

  2. Antiviral evaluation of an Hsp90 inhibitor, gedunin, against dengue ...

    African Journals Online (AJOL)

    Further, in silico molecular docking data revealed strong interaction of gedunin with the ATP/ADP ... Keywords: Dengue virus replication, Hsp90, Gedunin, Antiviral, Molecular docking ..... Conformational dynamics of the molecular chaperone.

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

    Science.gov (United States)

    ... Drooping of a corner of the mouth • Difficulty smiling, frowning, or making other facial expressions • Twitching or ... no definite added improvement. If there is any benefit to adding an antiviral to steroid treatment, it ...

  4. Antiviral Resistance to Influenza Viruses: Clinical and Epidemiological Aspects

    NARCIS (Netherlands)

    van der Vries, E.

    2017-01-01

    There are three classes of antiviral drugs approved for the treatment of influenza: the M2 ion channel inhibitors (amantadine, rimantadine), neuraminidase (NA) inhibitors (laninamivir, oseltamivir, peramivir, zanamivir), and the protease inhibitor (favipiravir); some of the agents are only available

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

    African Journals Online (AJOL)

    Mahera Shinwari

    2012-01-26

    Jan 26, 2012 ... Key words: Antiviral activity, tobacco mosaic virus, actinomycetes, Streptomyces, Datura metel ... have received less attention than those caused by fungal .... leaves were divided in to three partitions each containing triplicates.

  6. 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: 9.135, year: 2015

  7. HIV-1 accessory proteins VPR and Vif modulate antiviral response by targeting IRF-3 for degradation

    International Nuclear Information System (INIS)

    Okumura, Atsushi; Alce, Tim; Lubyova, Barbora; Ezelle, Heather; Strebel, Klaus; Pitha, Paula M.

    2008-01-01

    The activation of IRF-3 during the early stages of viral infection is critical for the initiation of the antiviral response; however the activation of IRF-3 in HIV-1 infected cells has not yet been characterized. We demonstrate that the early steps of HIV-1 infection do not lead to the activation and nuclear translocation of IRF-3; instead, the relative levels of IRF-3 protein are decreased due to the ubiquitin-associated proteosome degradation. Addressing the molecular mechanism of this effect we show that the degradation is independent of HIV-1 replication and that virion-associated accessory proteins Vif and Vpr can independently degrade IRF-3. The null mutation of these two genes reduced the capacity of the HIV-1 virus to down modulate IRF-3 levels. The degradation was associated with Vif- and Vpr-mediated ubiquitination of IRF-3 and was independent of the activation of IRF-3. N-terminal lysine residues were shown to play a critical role in the Vif- and Vpr-mediated degradation of IRF-3. These data implicate Vif and Vpr in the disruption of the initial antiviral response and point to the need of HIV-1 to circumvent the antiviral response during the very early phase of replication

  8. Decrease of the exposure to electromagnetic waves emitted by mobile phone relay antennas. Synthesis report on experimentations performed by the COPIC

    International Nuclear Information System (INIS)

    2013-01-01

    A synthetic introduction outlines that simulations reveal a globally low level of public exposure to waves emitted by relay antennas, discusses lessons learned from exposure measurements, indicates that possibilities of treatment exist for the most exposed places, outlines the consequences of a global decrease of exposure on service coverage and quality, outlines a necessary increase of the number of antennas to conceal low exposure and coverage, and that the deployment of 4G should result in an increase of public exposure. Then, the main part of the report presents the fundamental notions related to mobile phone networks and radio waves (electromagnetic radiation, radiofrequency waves and mobile phones, relay antennas and networks, legal thresholds), the implemented method the characteristics of studied areas. It reports the methodology, exposure simulations and exposure measurements, coverage simulations and service quality measurements. It discusses the treatment of the most exposed locations (results from simulations and from measurements). It discusses the results of simulations and experimentations of a decrease of the power of relay antennas, of the simulation of the impact of theoretical 4G additional antennas on exposure. Results obtained in different towns and locations are reported in appendix

  9. Research progress in antiviral therapy for chronic hepatitis C

    Directory of Open Access Journals (Sweden)

    YU Guoying

    2015-04-01

    Full Text Available Antiviral therapy is the most important treatment for chronic hepatitis C. This paper reviews the progress in antiviral treatment over recent years, including the combination therapy with polyethylene glycol-Interferon (PEG-IFN and ribavirin (RBV, specific target therapy, and gene therapy. The paper believes that the anti-hepatitis C virus treatment needs more effective drug combination therapies, shorter courses, less side effect, higher drug resistance threshold, etc.

  10. Antiviral resistance and the control of pandemic influenza.

    Directory of Open Access Journals (Sweden)

    Marc Lipsitch

    2007-01-01

    Full Text Available 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.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.The benefits of antiviral drug use to control an influenza pandemic may be reduced, although not completely offset, by drug resistance in the virus. Therefore, the risk of resistance

  11. Mushrooms as a source of substances with antiviral activity

    Directory of Open Access Journals (Sweden)

    Martyna Kandefer-Szerszeń

    2014-08-01

    Full Text Available Water extracts the fructifications of 56 species of fungi were examined as a source of antiviral substances with activity against VS and vaccinia viruses. Extracts from 16 fungal species exhibited the antiviral activity. Water extracts from Boletus edulis active against vaccinia virus and extract from Armillariella mellea active against VS virus are particularly worth nothing. Both of them in applied concentrations were not toxic in chick embryo fibroblasts tissue culture.

  12. Translational control in plant antiviral immunity

    Directory of Open Access Journals (Sweden)

    João Paulo B. Machado

    Full Text Available Abstract Due to the limited coding capacity of viral genomes, plant viruses depend extensively on the host cell machinery to support the viral life cycle and, thereby, interact with a large number of host proteins during infection. Within this context, as plant viruses do not harbor translation-required components, they have developed several strategies to subvert the host protein synthesis machinery to produce rapidly and efficiently the viral proteins. As a countermeasure against infection, plants have evolved defense mechanisms that impair viral infections. Among them, the host-mediated translational suppression has been characterized as an efficient mean to restrict infection. To specifically suppress translation of viral mRNAs, plants can deploy susceptible recessive resistance genes, which encode translation initiation factors from the eIF4E and eIF4G family and are required for viral mRNA translation and multiplication. Additionally, recent evidence has demonstrated that, alternatively to the cleavage of viral RNA targets, host cells can suppress viral protein translation to silence viral RNA. Finally, a novel strategy of plant antiviral defense based on suppression of host global translation, which is mediated by the transmembrane immune receptor NIK1 (nuclear shuttle protein (NSP-Interacting Kinase1, is discussed in this review.

  13. Antiviral Roles of Abscisic Acid in Plants

    Directory of Open Access Journals (Sweden)

    Mazen Alazem

    2017-10-01

    Full Text Available Abscisic acid (ABA is a key hormone involved in tuning responses to several abiotic stresses and also has remarkable impacts on plant defense against various pathogens. The roles of ABA in plant defense against bacteria and fungi are multifaceted, inducing or reducing defense responses depending on its time of action. However, ABA induces different resistance mechanisms to viruses regardless of the induction time. Recent studies have linked ABA to the antiviral silencing pathway, which interferes with virus accumulation, and the micro RNA (miRNA pathway through which ABA affects the maturation and stability of miRNAs. ABA also induces callose deposition at plasmodesmata, a mechanism that limits viral cell-to-cell movement. Bamboo mosaic virus (BaMV is a member of the potexvirus group and is one of the most studied viruses in terms of the effects of ABA on its accumulation and resistance. In this review, we summarize how ABA interferes with the accumulation and movement of BaMV and other viruses. We also highlight aspects of ABA that may have an effect on other types of resistance and that require further investigation.

  14. Probiotics as Antiviral Agents in Shrimp Aquaculture

    Directory of Open Access Journals (Sweden)

    Bestha Lakshmi

    2013-01-01

    Full Text Available Shrimp farming is an aquaculture business for the cultivation of marine shrimps or prawns for human consumption and is now considered as a major economic and food production sector as it is an increasingly important source of protein available for human consumption. Intensification of shrimp farming had led to the development of a number of diseases, which resulted in the excessive use of antimicrobial agents, which is finally responsible for many adverse effects. Currently, probiotics are chosen as the best alternatives to these antimicrobial agents and they act as natural immune enhancers, which provoke the disease resistance in shrimp farm. Viral diseases stand as the major constraint causing an enormous loss in the production in shrimp farms. Probiotics besides being beneficial bacteria also possess antiviral activity. Exploitation of these probiotics in treatment and prevention of viral diseases in shrimp aquaculture is a novel and efficient method. This review discusses the benefits of probiotics and their criteria for selection in shrimp aquaculture and their role in immune power enhancement towards viral diseases.

  15. Viral respiratory diseases: vaccines and antivirals.

    Science.gov (United States)

    Lennette, E H

    1981-01-01

    Acute respiratory diseases, most of which are generally attributed to viruses, account for about 6% of all deaths and for about 60% of the deaths associated with all respiratory disease. The huge cost attributable to viral respiratory infections as a result of absenteeism and the disruption of business and the burden of medical care makes control of these diseases an important objective. The viruses that infect the respiratory tract fall taxonomically into five viral families. Although immunoprophylaxis would appear to be the logical approach, the development of suitable vaccines has been confronted with numerous obstacles, including antigenic drift and shift in the influenzaviruses, the large number of antigenically distinct immunotypes among rhinoviruses, the occurrence after immunization of rare cases of a severe form of the disease following subsequent natural infection with respiratory syncytial virus, and the risk of oncogenicity of adenoviruses for man. Considerable expenditure on the development of new antiviral drugs has so far resulted in only three compounds that are at present officially approved and licensed for use in the USA. Efforts to improve the tools available for control should continue and imaginative and inventive approaches are called for. However, creativity and ingenuity must operate within the constraints imposed by economic, political, ethical, and legal considerations.

  16. Antiviral Action of Hydromethanolic Extract of Geopropolis from Scaptotrigona postica against Antiherpes Simplex Virus (HSV-1

    Directory of Open Access Journals (Sweden)

    Guilherme Rabelo Coelho

    2015-01-01

    Full Text Available The studies on chemical composition and biological activity of propolis had focused mainly on species Apis mellifera L. (Hymenoptera: Apidae. There are few studies about the uncommon propolis collected by stingless bees of the Meliponini tribe known as geopropolis. The geopropolis from Scaptotrigona postica was collected in the region of Barra do Corda, Maranhão state, Brazil. The chemical analysis of hydromethanolic extract of this geopropolis (HMG was carried out through HPLC-DAD-ESI-MS/MS and the main constituents found were pyrrolizidine alkaloids and C-glycosyl flavones. The presence of alkaloids in extracts of propolis is detected for the first time in this sample. The antiviral activity of HMG was evaluated through viral DNA quantification experiments and electron microscopy experiments. Quantification of viral DNA from herpes virus showed reduction of about 98% in all conditions and concentration tested of the HMG extract. The results obtained were corroborated by transmission electron microscopy, in which the images did not show particle or viral replication complex. The antiviral activity of C-glycosyl flavones was reported for a variety of viruses, being observed at different points in the viral replication. This work is the first report about the antiviral activity of geopropolis from Scaptotrigona postica, in vitro, against antiherpes simplex virus (HSV.

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

    Directory of Open Access Journals (Sweden)

    Philippe Roch

    2004-01-01

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

  18. Antiviral Action of Hydromethanolic Extract of Geopropolis from Scaptotrigona postica against Antiherpes Simplex Virus (HSV-1).

    Science.gov (United States)

    Coelho, Guilherme Rabelo; Mendonça, Ronaldo Zucatelli; Vilar, Karina de Senna; Figueiredo, Cristina Adelaide; Badari, Juliana Cuoco; Taniwaki, Noemi; Namiyama, Gisleine; de Oliveira, Maria Isabel; Curti, Suely Pires; Evelyn Silva, Patricia; Negri, Giuseppina

    2015-01-01

    The studies on chemical composition and biological activity of propolis had focused mainly on species Apis mellifera L. (Hymenoptera: Apidae). There are few studies about the uncommon propolis collected by stingless bees of the Meliponini tribe known as geopropolis. The geopropolis from Scaptotrigona postica was collected in the region of Barra do Corda, Maranhão state, Brazil. The chemical analysis of hydromethanolic extract of this geopropolis (HMG) was carried out through HPLC-DAD-ESI-MS/MS and the main constituents found were pyrrolizidine alkaloids and C-glycosyl flavones. The presence of alkaloids in extracts of propolis is detected for the first time in this sample. The antiviral activity of HMG was evaluated through viral DNA quantification experiments and electron microscopy experiments. Quantification of viral DNA from herpes virus showed reduction of about 98% in all conditions and concentration tested of the HMG extract. The results obtained were corroborated by transmission electron microscopy, in which the images did not show particle or viral replication complex. The antiviral activity of C-glycosyl flavones was reported for a variety of viruses, being observed at different points in the viral replication. This work is the first report about the antiviral activity of geopropolis from Scaptotrigona postica, in vitro, against antiherpes simplex virus (HSV).

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

    Directory of Open Access Journals (Sweden)

    Y. Zhang

    2017-08-01

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

  20. Antiviral Effect of Sub Fraction Cassia alata Leaves Extract to Dengue Virus Serotype-2 strain New Guinea C in Human Cell Line Huh-7 it-1

    Science.gov (United States)

    Angelina, Marissa; Hanafi, Muhammad; Suyatna, Franciscus D.; Mirawati S., T.; Ratnasari, Shirley; Ernawati Dewi, Beti

    2017-12-01

    Dengue virus (DENV) is one of the most common viral infections found Indonesia and tropical regions, and no specific antiviral for DENV. Indonesia has several of herbal medicine that were not explored of their potency as antiviral DENV. This study was done to evaluate the activity and toxicity of 4 derived fractions: Hexane (CA1), ethyl acetate (CA2), buthanol (CA3 ) and water (CA4) of Cassia alata leaf extract (CA) as an antiviral drug to DENV. The DENV was treated with various concentration of extract and added to Huh-7 it-1. The decrease of virus titer was determined by Focus assay. The toxicity of extract was measured by MTT assay. In our previous study, we found that CA on Huh-7 cells showed IC50, CC50 and SI values of <10 μg/mL, 323.45 μg/mL, and more than 32.3, respectively. For the fractions, CA3 showed best antiviral activity among other, with IC50, CC50 and SI of <10 μg/mL, 645.8 μg/mL, and more than 64.5, respectively. CA and CA3 were proven to possess antiviral activity that is potent when tested against DENV-2. Future study was needed to explore the inhibition mechanism and compound of CA that have potency as antiviral drug to DENV.

  1. Perspective of Use of Antiviral Peptides against Influenza Virus

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    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.

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

    Science.gov (United States)

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

    2016-01-11

    Ledipasvir (LDV; GS-5885), a component of Harvoni (a fixed-dose combination of LDV with sofosbuvir [SOF]), is approved to treat chronic hepatitis C virus (HCV) infection. Here, we report key preclinical antiviral properties of LDV, including in vitro potency, in vitro resistance profile, and activity in combination with other anti-HCV agents. LDV has picomolar antiviral activity against genotype 1a and genotype 1b replicons with 50% effective concentration (EC50) values of 0.031 nM and 0.004 nM, respectively. LDV is also active against HCV genotypes 4a, 4d, 5a, and 6a with EC50 values of 0.11 to 1.1 nM. LDV has relatively less in vitro antiviral activity against genotypes 2a, 2b, 3a, and 6e, with EC50 values of 16 to 530 nM. In vitro resistance selection with LDV identified the single Y93H and Q30E resistance-associated variants (RAVs) in the NS5A gene; these RAVs were also observed in patients after a 3-day monotherapy treatment. In vitro antiviral combination studies indicate that LDV has additive to moderately synergistic antiviral activity when combined with other classes of HCV direct-acting antiviral (DAA) agents, including NS3/4A protease inhibitors and the nucleotide NS5B polymerase inhibitor SOF. Furthermore, LDV is active against known NS3 protease and NS5B polymerase inhibitor RAVs with EC50 values equivalent to those for the wild type. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

  3. Zinc-finger antiviral protein inhibits XMRV infection.

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    Xinlu Wang

    Full Text Available BACKGROUND: The zinc-finger antiviral protein (ZAP is a host factor that specifically inhibits the replication of certain viruses, including Moloney murine leukemia virus (MoMLV, HIV-1, and certain alphaviruses and filoviruses. ZAP binds to specific viral mRNAs and recruits cellular mRNA degradation machinery to degrade the target RNA. The common features of ZAP-responsive RNA sequences remain elusive and thus whether a virus is susceptible to ZAP can only be determined experimentally. Xenotropic murine leukemia virus-related virus (XMRV is a recently identified γ-retrovirus that was originally thought to be involved in prostate cancer and chronic fatigue syndrome but recently proved to be a laboratory artefact. Nonetheless, XMRV as a new retrovirus has been extensively studied. Since XMRV and MoMLV share only 67.9% sequence identity in the 3'UTRs, which is the target sequence of ZAP in MoMLV, whether XMRV is susceptible to ZAP remains to be determined. FINDINGS: We constructed an XMRV-luc vector, in which the coding sequences of Gag-Pol and part of Env were replaced with luciferase-coding sequence. Overexpression of ZAP potently inhibited the expression of XMRV-luc in a ZAP expression-level-dependent manner, while downregulation of endogenous ZAP rendered cells more sensitive to infection. Furthermore, ZAP inhibited the spreading of replication-competent XMRV. Consistent with the previously reported mechanisms by which ZAP inhibits viral infection, ZAP significantly inhibited the accumulation of XMRV-luc mRNA in the cytoplasm. The ZAP-responsive element in XMRV mRNA was mapped to the 3'UTR. CONCLUSIONS: ZAP inhibits XMRV replication by preventing the accumulation of viral mRNA in the cytoplasm. Documentation of ZAP inhibiting XMRV helps to broaden the spectrum of ZAP's antiviral activity. Comparison of the target sequences of ZAP in XMRV and MoMLV helps to better understand the features of ZAP-responsive elements.

  4. ANTI-VIRAL ACTIVITY OF GLYCIRRHETINIC AND GLYCIRRHIZIC ACIDS

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    V. V. Zarubaev

    2016-01-01

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

  5. Antiviral activity of glycyrrhizin against hepatitis C virus in vitro.

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    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.

  6. Antiviral Activity of Lambda Interferon in Chickens

    Science.gov (United States)

    Reuter, Antje; Soubies, Sebastien; Härtle, Sonja; Schusser, Benjamin; Kaspers, Bernd

    2014-01-01

    Interferons (IFNs) are essential components of the antiviral defense system of vertebrates. In mammals, functional receptors for type III IFN (lambda interferon [IFN-λ]) are found mainly on epithelial cells, and IFN-λ was demonstrated to play a crucial role in limiting viral infections of mucosal surfaces. To determine whether IFN-λ plays a similar role in birds, we produced recombinant chicken IFN-λ (chIFN-λ) and we used the replication-competent retroviral RCAS vector system to generate mosaic-transgenic chicken embryos that constitutively express chIFN-λ. We could demonstrate that chIFN-λ markedly inhibited replication of various virus strains, including highly pathogenic influenza A viruses, in ovo and in vivo, as well as in epithelium-rich tissue and cell culture systems. In contrast, chicken fibroblasts responded poorly to chIFN-λ. When applied in vivo to 3-week-old chickens, recombinant chIFN-λ strongly induced the IFN-responsive Mx gene in epithelium-rich organs, such as lungs, tracheas, and intestinal tracts. Correspondingly, these organs were found to express high transcript levels of the putative chIFN-λ receptor alpha chain (chIL28RA) gene. Transfection of chicken fibroblasts with a chIL28RA expression construct rendered these cells responsive to chIFN-λ treatment, indicating that receptor expression determines cell type specificity of IFN-λ action in chickens. Surprisingly, mosaic-transgenic chickens perished soon after hatching, demonstrating a detrimental effect of constitutive chIFN-λ expression. Our data highlight fundamental similarities between the IFN-λ systems of mammals and birds and suggest that type III IFN might play a role in defending mucosal surfaces against viral intruders in most if not all vertebrates. PMID:24371053

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

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    Débora Scopel e Silva

    2014-09-01

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

  8. HIV enhancing activity of semen impairs the antiviral efficacy of microbicides

    Science.gov (United States)

    Zirafi, Onofrio; Kim, Kyeong-Ae; Roan, Nadia R.; Kluge, Silvia F.; Müller, Janis A.; Jiang, Shibo; Mayer, Benjamin; Greene, Warner C.; Kirchhoff, Frank; Münch, Jan

    2015-01-01

    Topically applied microbicides potently inhibit HIV in vitro but have largely failed to exert protective effects in clinical trials. One possible reason for this discrepancy is that the preclinical testing of microbicides does not faithfully reflect the conditions of HIV sexual transmission. Here, we report that candidate microbicides that target HIV components show greatly reduced antiviral efficacy in the presence of semen, the main vector for HIV transmission. This diminished antiviral activity was dependent on the ability of amyloid fibrils in semen to enhance the infectivity of HIV. Thus, the anti-HIV efficacy of microbicides determined in the absence of semen greatly underestimated the drug concentrations needed to block semen-exposed virus. One notable exception was Maraviroc. This HIV entry inhibitor targets the host cell CCR5 coreceptor and was highly active against both untreated and semen-exposed HIV. These data help explain why microbicides have failed to protect against HIV in clinical trials and suggest that antiviral compounds targeting host factors hold promise for further development. These findings also suggest that the in vitro efficacy of candidate microbicides should be determined in the presence of semen to identify the best candidates for the prevention of HIV sexual transmission. PMID:25391483

  9. Alisporivir Has Limited Antiviral Effects Against Ebola Virus Strains Makona and Mayinga.

    Science.gov (United States)

    Chiramel, Abhilash I; Banadyga, Logan; Dougherty, Jonathan D; Falzarano, Darryl; Martellaro, Cynthia; Brees, Dominique; Taylor, R Travis; Ebihara, Hideki; Best, Sonja M

    2016-10-15

    Antiviral therapeutics with existing clinical safety profiles would be highly desirable in an outbreak situation, such as the 2013-2016 emergence of Ebola virus (EBOV) in West Africa. Although, the World Health Organization declared the end of the outbreak early 2016, sporadic cases of EBOV infection have since been reported. Alisporivir is the most clinically advanced broad-spectrum antiviral that functions by targeting a host protein, cyclophilin A (CypA). A modest antiviral effect of alisporivir against contemporary (Makona) but not historical (Mayinga) EBOV strains was observed in tissue culture. However, this effect was not comparable to observations for an alisporivir-susceptible virus, the flavivirus tick-borne encephalitis virus. Thus, EBOV does not depend on (CypA) for replication, in contrast to many other viruses pathogenic to humans. Published by Oxford University Press for the Infectious Diseases Society of America 2016. This work is written by (a) US Government employee(s) and is in the public domain in the US.

  10. Discovery of dapivirine, a nonnucleoside HIV-1 reverse transcriptase inhibitor, as a broad-spectrum antiviral against both influenza A and B viruses.

    Science.gov (United States)

    Hu, Yanmei; Zhang, Jiantao; Musharrafieh, Rami Ghassan; Ma, Chunlong; Hau, Raymond; Wang, Jun

    2017-09-01

    The emergence of multidrug-resistant influenza viruses poses a persistent threat to public health. The current prophylaxis and therapeutic interventions for influenza virus infection have limited efficacy due to the continuous antigenic drift and antigenic shift of influenza viruses. As part of our ongoing effort to develop the next generation of influenza antivirals with broad-spectrum antiviral activity and a high genetic barrier to drug resistance, in this study we report the discovery of dapivirine, an FDA-approved HIV nonnucleoside reverse transcriptase inhibitor, as a broad-spectrum antiviral against multiple strains of influenza A and B viruses with low micromolar efficacy. Mechanistic studies revealed that dapivirine inhibits the nuclear entry of viral ribonucleoproteins at the early stage of viral replication. As a result, viral RNA and protein synthesis were inhibited. Furthermore, dapivirine has a high in vitro genetic barrier to drug resistance, and its antiviral activity is synergistic with oseltamivir carboxylate. In summary, the in vitro antiviral results of dapivirine suggest it is a promising candidate for the development of the next generation of dual influenza and HIV antivirals. Copyright © 2017 Elsevier B.V. All rights reserved.

  11. Antiviral treatment for Bell's palsy (idiopathic facial paralysis).

    Science.gov (United States)

    Gagyor, Ildiko; Madhok, Vishnu B; Daly, Fergus; Somasundara, Dhruvashree; Sullivan, Michael; Gammie, Fiona; Sullivan, Frank

    2015-11-09

    Corticosteroids are widely used in the treatment of idiopathic facial paralysis (Bell's palsy), but the effectiveness of additional treatment with an antiviral agent is uncertain. Significant morbidity can be associated with severe cases of Bell's palsy. This review was first published in 2001 and revised several times, most recently in 2009. This version replaces an update of the review in Issue 7 of the Cochrane Library subsequently withdrawn because of an ongoing investigation into the reliability of data from an included study. To assess the effects of antiviral treatments alone or in combination with any other therapy for Bell's palsy. On 7 October 2014 we searched the Cochrane Neuromuscular Disease Group Specialized Register, CENTRAL, MEDLINE, EMBASE, LILACS, DARE, NHS EED, and HTA. We also reviewed the bibliographies of the identified trials and contacted trial authors and known experts in the field and relevant drug companies to identify additional published or unpublished data. We searched clinical trials registries for ongoing studies. We considered randomised controlled trials or quasi-randomised controlled trials of antivirals with and without corticosteroids versus control therapies for the treatment of Bell's palsy. We excluded trials that had a high risk of bias in several domains. Pairs of authors independently assessed trials for relevance, eligibility, and risk of bias, using standard Cochrane procedures. Ten trials, including 2280 participants, met the inclusion criteria and are included in the final analysis. Some of the trials were small, and a number were at high or unclear risk of bias. Other trials did not meet current best standards in allocation concealment and blinding. Incomplete recoveryWe found a significant benefit from adding antivirals to corticosteroids in comparison with corticosteroids alone for people with Bell's palsy (risk ratio (RR) 0.61, 95% confidence interval (CI) 0.39 to 0.97, n = 1315). For people with severe Bell

  12. Antiviral agents: structural basis of action and rational design.

    Science.gov (United States)

    Menéndez-Arias, Luis; Gago, Federico

    2013-01-01

    During the last 30 years, significant progress has been made in the development of novel antiviral drugs, mainly crystallizing in the establishment of potent antiretroviral therapies and the approval of drugs inhibiting hepatitis C virus replication. Although major targets of antiviral intervention involve intracellular processes required for the synthesis of viral proteins and nucleic acids, a number of inhibitors blocking virus assembly, budding, maturation, entry or uncoating act on virions or viral capsids. In this review, we focus on the drug discovery process while presenting the currently used methodologies to identify novel antiviral drugs by using a computer-based approach. We provide examples illustrating structure-based antiviral drug development, specifically neuraminidase inhibitors against influenza virus (e.g. oseltamivir and zanamivir) and human immunodeficiency virus type 1 protease inhibitors (i.e. the development of darunavir from early peptidomimetic compounds such as saquinavir). A number of drugs in preclinical development acting against picornaviruses, hepatitis B virus and human immunodeficiency virus and their mechanism of action are presented to show how viral capsids can be exploited as targets of antiviral therapy.

  13. 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.

  14. Antiviral Screening of Multiple Compounds against Ebola Virus.

    Science.gov (United States)

    Dowall, Stuart D; Bewley, Kevin; Watson, Robert J; Vasan, Seshadri S; Ghosh, Chandradhish; Konai, Mohini M; Gausdal, Gro; Lorens, James B; Long, Jason; Barclay, Wendy; Garcia-Dorival, Isabel; Hiscox, Julian; Bosworth, Andrew; Taylor, Irene; Easterbrook, Linda; Pitman, James; Summers, Sian; Chan-Pensley, Jenny; Funnell, Simon; Vipond, Julia; Charlton, Sue; Haldar, Jayanta; Hewson, Roger; Carroll, Miles W

    2016-10-27

    In light of the recent outbreak of Ebola virus (EBOV) disease in West Africa, there have been renewed efforts to search for effective antiviral countermeasures. A range of compounds currently available with broad antimicrobial activity have been tested for activity against EBOV. Using live EBOV, eighteen candidate compounds were screened for antiviral activity in vitro. The compounds were selected on a rational basis because their mechanisms of action suggested that they had the potential to disrupt EBOV entry, replication or exit from cells or because they had displayed some antiviral activity against EBOV in previous tests. Nine compounds caused no reduction in viral replication despite cells remaining healthy, so they were excluded from further analysis (zidovudine; didanosine; stavudine; abacavir sulphate; entecavir; JB1a; Aimspro; celgosivir; and castanospermine). A second screen of the remaining compounds and the feasibility of appropriateness for in vivo testing removed six further compounds (ouabain; omeprazole; esomeprazole; Gleevec; D-LANA-14; and Tasigna). The three most promising compounds (17-DMAG; BGB324; and NCK-8) were further screened for in vivo activity in the guinea pig model of EBOV disease. Two of the compounds, BGB324 and NCK-8, showed some effect against lethal infection in vivo at the concentrations tested, which warrants further investigation. Further, these data add to the body of knowledge on the antiviral activities of multiple compounds against EBOV and indicate that the scientific community should invest more effort into the development of novel and specific antiviral compounds to treat Ebola virus disease.

  15. Antiviral Screening of Multiple Compounds against Ebola Virus

    Directory of Open Access Journals (Sweden)

    Stuart D. Dowall

    2016-10-01

    Full Text Available In light of the recent outbreak of Ebola virus (EBOV disease in West Africa, there have been renewed efforts to search for effective antiviral countermeasures. A range of compounds currently available with broad antimicrobial activity have been tested for activity against EBOV. Using live EBOV, eighteen candidate compounds were screened for antiviral activity in vitro. The compounds were selected on a rational basis because their mechanisms of action suggested that they had the potential to disrupt EBOV entry, replication or exit from cells or because they had displayed some antiviral activity against EBOV in previous tests. Nine compounds caused no reduction in viral replication despite cells remaining healthy, so they were excluded from further analysis (zidovudine; didanosine; stavudine; abacavir sulphate; entecavir; JB1a; Aimspro; celgosivir; and castanospermine. A second screen of the remaining compounds and the feasibility of appropriateness for in vivo testing removed six further compounds (ouabain; omeprazole; esomeprazole; Gleevec; D-LANA-14; and Tasigna. The three most promising compounds (17-DMAG; BGB324; and NCK-8 were further screened for in vivo activity in the guinea pig model of EBOV disease. Two of the compounds, BGB324 and NCK-8, showed some effect against lethal infection in vivo at the concentrations tested, which warrants further investigation. Further, these data add to the body of knowledge on the antiviral activities of multiple compounds against EBOV and indicate that the scientific community should invest more effort into the development of novel and specific antiviral compounds to treat Ebola virus disease.

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

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    Akram Astani

    2011-01-01

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

  17. Recent developments in antiviral agents against enterovirus 71 infection.

    Science.gov (United States)

    Tan, Chee Wah; Lai, Jeffrey Kam Fatt; Sam, I-Ching; Chan, Yoke Fun

    2014-02-12

    Enterovirus 71 (EV-71) is the main etiological agent of hand, foot and mouth disease (HFMD). Recent EV-71 outbreaks in Asia-Pacific were not limited to mild HFMD, but were associated with severe neurological complications such as aseptic meningitis and brainstem encephalitis, which may lead to cardiopulmonary failure and death. The absence of licensed therapeutics for clinical use has intensified research into anti-EV-71 development. This review highlights the potential antiviral agents targeting EV-71 attachment, entry, uncoating, translation, polyprotein processing, virus-induced formation of membranous RNA replication complexes, and RNA-dependent RNA polymerase. The strategies for antiviral development include target-based synthetic compounds, anti-rhinovirus and poliovirus libraries screening, and natural compound libraries screening. Growing knowledge of the EV-71 life cycle will lead to successful development of antivirals. The continued effort to develop antiviral agents for treatment is crucial in the absence of a vaccine. The coupling of antivirals with an effective vaccine will accelerate eradication of the disease.

  18. Terapia antiviral para VIH-SIDA

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    Alicia Tarinas Reyes

    2000-12-01

    Full Text Available En los últimos años, muchos agentes antivirales nuevos han sido incorporados a la quimioterapéutica. En esta revisión se resumen tanto los fármacos establecidos de años atrás como los nuevos medicamentos desarrollados para el tratamiento de individuos infectados por VIH. El AZT fue el primero aprobado en marzo de 1987, le siguió el ddl (1991, ddC (1992, d4T (1994, 3TC (1995. Luego fue aprobado el primer inhibidor de proteasa, saquinavir en diciembre de 1995, seguido de ritonavir (1996, indinavir (1996, nelfinavir (1997; además de otros inhibidores de la reverso transcriptasa como nevirapine (1996, delavirdine (1997, efavirenz (1998, entre otros. En estos momentos se siguen buscando y desarrollando nuevas terapias alternativas para esta afección. En este trabajo se exponen algunas de las características de dichos medicamentos, como son: mecanismos de acción (sobre qué enzima actúa cada uno y cómo lo hacen, el ciclo viral, dosificación, incompatibilidades y reacciones adversas.During the last years many new antiviral agents have been incorporated to the chemotherapeutics. The pharmaceuticals established years ago as well as the new ones developed to treat HIV infected individuals are included in this review. The AZT was the first approved in March, 1987, followed by ddl (1991, ddc (1992, d4t (1994, and 3TC (1995. Later, the first protease inhibitor, saquinovir, was approved in December, 1995, followed by ritonavir (1996, indinavir (1996, and nelfinavir (1997; in addition to other inhibitors of the reverse transcriptase as neviparine (1996, delavirdine (1997, and efavirenz (1998, among others. At present new alternative therapies for this affection are being searched and developed. Some of the characteristics of these dugs, such as: action mechanisms (on which enzime each of them act and how they do it, viral cycle, dosage, incompatibilites and adverse reactions are dealt with in this paper.

  19. Clinical use of Nintendo Wii bowling simulation to decrease fall risk in an elderly resident of a nursing home: a case report.

    Science.gov (United States)

    Clark, Robert; Kraemer, Theresa

    2009-01-01

    Of the estimated 1.7 million residents of nursing homes in the United States, approximately half fall annually; and 11% of these sustain injury. This is twice the rate for persons dwelling in the community. By addressing fall risk, physical therapists have an opportunity to reduce falls which are the leading cause of injury deaths, as well as the most common cause of nonfatal injuries for older adults in the United States. This case report examines the effect of a novel interactive video game intervention to address balance dysfunction in an elderly resident of a nursing home who was at risk for falls. The patient is an 89-year-old resident diagnosed with an unspecified balance disorder and a history of multiple falls. Self reports of gait abnormalities, scores on several clinical measures, and her fall history classified her as having substantial risk for future falls. A nontraditional approach to balance training, employing the Nintendo Wii bowling simulation, was used as intervention for this patient's balance disorder. After 6 one-hour treatment sessions, the patient's Berg Balance Score improved from 48 to 53. On the Dynamic Gait Index, the patient improved her score from 19 to 21. The patient's Timed Up and Go Test improved from 14.9 to 10.5 seconds, all suggesting a reduced risk of falling. The patient's ABC Score improved from 88 to 90%. Physical therapy intervention, using the Nintendo Wii bowling simulation, may have decreased fall risk for this individual.

  20. Favipiravir elicits antiviral mutagenesis during virus replication in vivo.

    Science.gov (United States)

    Arias, Armando; Thorne, Lucy; Goodfellow, Ian

    2014-10-21

    Lethal mutagenesis has emerged as a novel potential therapeutic approach to treat viral infections. Several studies have demonstrated that increases in the high mutation rates inherent to RNA viruses lead to viral extinction in cell culture, but evidence during infections in vivo is limited. In this study, we show that the broad-range antiviral nucleoside favipiravir reduces viral load in vivo by exerting antiviral mutagenesis in a mouse model for norovirus infection. Increased mutation frequencies were observed in samples from treated mice and were accompanied with lower or in some cases undetectable levels of infectious virus in faeces and tissues. Viral RNA isolated from treated animals showed reduced infectivity, a feature of populations approaching extinction during antiviral mutagenesis. These results suggest that favipiravir can induce norovirus mutagenesis in vivo, which in some cases leads to virus extinction, providing a proof-of-principle for the use of favipiravir derivatives or mutagenic nucleosides in the clinical treatment of noroviruses.

  1. 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.

  2. Aminoadamantanes versus other antiviral drugs for chronic hepatitis C

    DEFF Research Database (Denmark)

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

    2014-01-01

    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 all-cause mortality or liver-related morbidity and on adverse events in patients with hepatitis C. Overall, we did not observe a significant effect of amantadine on sustained virological response. In this review, we systematically review aminoadamantanes versus other antiviral drugs. OBJECTIVES...

  3. Corticosteroids vs corticosteroids plus antiviral agents in the treatment of Bell palsy: a systematic review and meta-analysis.

    Science.gov (United States)

    Goudakos, John K; Markou, Konstantinos D

    2009-06-01

    To review systematically and meta-analyze the results of all randomized controlled trials (RCTs) for the treatment of patients with Bell palsy with corticosteroids vs corticosteroids plus antiviral agents. A MEDLINE, EMBASE, Cochrane Library, and CENTRAL database search, followed by extensive hand-searching for the identification of relevant studies. No time and language limitations were applied. Prospective RCTs on the treatment of patients with Bell palsy. Odds ratios (ORs), 95% confidence intervals (CIs), and tests for heterogeneity were reported. Five studies were eventually identified and systematically reviewed. Meta-analysis was performed for 4 studies. Regarding the complete recovery rate of facial nerve paralysis 3 months after initiation of therapy, the current systematic review and meta-analysis suggests that the addition of an antiviral agent does not provide any benefit (OR, 1.03 [95% CI, 0.74-1.42]; P = .88). The same conclusion emerged at posterior (fourth, sixth, and ninth) months of assessment. Subgroup analysis, conducted on the basis of time point of therapy initiation, type of antiviral agent, and blindness of assessments did not change the results obtained. The occurrence rate of adverse effects attributable to therapy choice was not significantly different between patients receiving corticosteroids and those following combined treatment. The present systematic review and meta-analysis, based on the currently available evidence, suggests that the addition of an antiviral agent to corticosteroids for the treatment of Bell palsy is not associated with an increase in the complete recovery rate of the facial motor function.

  4. Neurological outcomes in symptomatic congenital cytomegalovirus-infected infants after introduction of newborn urine screening and antiviral treatment.

    Science.gov (United States)

    Nishida, Kosuke; Morioka, Ichiro; Nakamachi, Yuji; Kobayashi, Yoko; Imanishi, Takamitsu; Kawano, Seiji; Iwatani, Sota; Koda, Tsubasa; Deguchi, Masashi; Tanimura, Kenji; Yamashita, Daisuke; Nibu, Ken-Ichi; Funakoshi, Toru; Ohashi, Masanobu; Inoue, Naoki; Iijima, Kazumoto; Yamada, Hideto

    2016-02-01

    Newborn screening for urinary cytomegalovirus (CMV) and early introduction of antiviral treatment are expected to improve neurological outcomes in symptomatic congenital CMV-infected infants. This cohort study prospectively evaluated neurological outcomes in symptomatic congenital CMV-infected infants following the introduction of hospital-based newborn urinary CMV screening and antiviral treatment. Following institutional review board approval and written informed consent from their parents, newborns were prospectively screened from 2009 to 2014 for urinary CMV-DNA by PCR within 1 week after birth at Kobe University Hospital and affiliated hospitals. CMV-positive newborns were further examined at Kobe University Hospital, and those diagnosed as symptomatic were treated with valganciclovir for 6 weeks plus immunoglobulin. Clinical neurological outcomes were evaluated at age ⩾12 months and categorized by the presence and severity of neurologic sequelae. Urine samples of 6348 newborns were screened, with 32 (0.50%) positive for CMV. Of these, 16 were diagnosed with symptomatic infection and 12 received antiviral treatment. Four infants developed severe impairment (33%), three developed mild impairment (25%), and five developed normally (42%). This is the first Japanese report of neurological assessments in infants with symptomatic congenital CMV infection who received early diagnosis and antiviral treatment. Urinary screening, resulting in early diagnosis and treatment, may yield better neurological outcomes in symptomatic congenital CMV-infected infants. Copyright © 2015 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

  5. Antiviral and cytotoxic activities of some Indonesian plants.

    Science.gov (United States)

    Lohézic-Le Dévéhat, F; Bakhtiar, A; Bézivin, C; Amoros, M; Boustie, J

    2002-08-01

    Ten methanolic extracts from eight Indonesian medicinal plants were phytochemically screened and evaluated for antiviral (HSV-1 and Poliovirus) and cytotoxic activities on murine and human cancer lines (3LL, L1210, K562, U251, DU145, MCF-7). Besides Melastoma malabathricum (Melastomataceae), the Indonesian Loranthaceae species among which Elytranthe tubaeflora, E. maingayi, E. globosa and Scurrula ferruginea exhibited attractive antiviral and cytotoxic activities. Piper aduncum (Piperaceae) was found active on Poliovirus. S. ferruginea was selected for further studies because of its activity on the U251 glioblastoma cells.

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

    OpenAIRE

    Del Valle Mendoza, Juana; Pumarola, Tomas; Alzamora Gonzales, Libertad; Valle Mendoza, Luis Javier del

    2014-01-01

    Objective To investigate antiviral activity of maca to reduce viral load in Madin-Darby canine kidney (MDCK) cells infected with influenza type A and B viruses (Flu-A and Flu-B, respectively). Methods Maca were extracted with methanol (1:2, v/v). The cell viability and toxicity of the extracts were evaluated on MDCK cells using method MTT assay. Antiviral activity of compounds against Flu-A and Flu-B viruses was assayed using a test for determining the inhibition of the cytopathic ...

  7. RNA interference-mediated intrinsic antiviral immunity in invertebrates.

    Science.gov (United States)

    Nayak, Arabinda; Tassetto, Michel; Kunitomi, Mark; Andino, Raul

    2013-01-01

    In invertebrates such as insects and nematodes, RNA interference (RNAi) provides RNA-based protection against viruses. This form of immunity restricts viral replication and dissemination from infected cells and viruses, in turn, have evolved evasion mechanisms or RNAi suppressors to counteract host defenses. Recent advances indicate that, in addition to RNAi, other related small RNA pathways contribute to antiviral functions in invertebrates. This has led to a deeper understanding of fundamental aspects of small RNA-based antiviral immunity in invertebrates and its contribution to viral spread and pathogenesis.

  8. From genome to antivirals: SARS as a test tube.

    Science.gov (United States)

    Kliger, Yossef; Levanon, Erez Y; Gerber, Doron

    2005-03-01

    The severe acute respiratory syndrome (SARS) epidemic brought into the spotlight the need for rapid development of effective anti-viral drugs against newly emerging viruses. Researchers have leveraged the 20-year battle against AIDS into a variety of possible treatments for SARS. Most prominently, based solely on viral genome information, silencers of viral genes, viral-enzyme blockers and viral-entry inhibitors were suggested as potential therapeutic agents for SARS. In particular, inhibitors of viral entry, comprising therapeutic peptides, were based on the recently launched anti-HIV drug enfuvirtide. This could represent one of the most direct routes from genome sequencing to the discovery of antiviral drugs.

  9. The Hepatitis C Genotype 1 Paradox: Cost per Treatment Is Increasing, but Cost per Cure Is Decreasing

    Directory of Open Access Journals (Sweden)

    Stephen D Shafran

    2015-01-01

    Full Text Available Significant attention has been focused on the perceived increase in the cost of antiviral treatment for hepatitis C genotype 1 infection since the approval of the first direct-acting antiviral agents in 2011. Using Canadian list prices, the present analysis points out a paradox: while the cost per antiviral regimen is increasing, the cost per cure is decreasing, especially with interferon-free therapy. In a publicly funded health care system, the lowest cost per cure is a more valuable measure of value for public money than the cost per regimen.

  10. The hepatitis C genotype 1 paradox: cost per treatment is increasing, but cost per cure is decreasing.

    Science.gov (United States)

    Shafran, Stephen D

    2015-01-01

    Significant attention has been focused on the perceived increase in the cost of antiviral treatment for hepatitis C genotype 1 infection since the approval of the first direct-acting antiviral agents in 2011. Using Canadian list prices, the present analysis points out a paradox: while the cost per antiviral regimen is increasing, the cost per cure is decreasing, especially with interferon-free therapy. In a publicly funded health care system, the lowest cost per cure is a more valuable measure of value for public money than the cost per regimen.

  11. Antiviral therapy for prevention of hepatocellular carcinoma in chronic hepatitis C

    DEFF Research Database (Denmark)

    Kimer, Nina; Dahl, Emilie Kristine; Gluud, Lise Lotte

    2012-01-01

    To determine whether antiviral therapy reduces the risk of developing hepatocellular carcinoma (HCC) in chronic hepatitis C.......To determine whether antiviral therapy reduces the risk of developing hepatocellular carcinoma (HCC) in chronic hepatitis C....

  12. Characterization of vaniprevir, a hepatitis C virus NS3/4A protease inhibitor, in patients with HCV genotype 1 infection: safety, antiviral activity, resistance, and pharmacokinetics.

    Science.gov (United States)

    Lawitz, Eric; Sulkowski, Mark; Jacobson, Ira; Kraft, Walter K; Maliakkal, Benedict; Al-Ibrahim, Mohamed; Gordon, Stuart C; Kwo, Paul; Rockstroh, Juergen Kurt; Panorchan, Paul; Miller, Michelle; Caro, Luzelena; Barnard, Richard; Hwang, Peggy May; Gress, Jacqueline; Quirk, Erin; Mobashery, Niloufar

    2013-09-01

    Vaniprevir is a competitive inhibitor of the hepatitis C virus (HCV) NS3/4A protease that has potent anti-HCV activity in preclinical models. This placebo-controlled dose-ranging study assessed the safety, tolerability, and antiviral efficacy of vaniprevir monotherapy in patients with genotype 1 chronic HCV infection. Treatment-naive and treatment-experienced non-cirrhotic adult patients with baseline HCV RNA >10(6)IU/ml were randomized to receive placebo or vaniprevir at doses of 125 mg qd, 600 mg qd, 25mg bid, 75 mg bid, 250 mg bid, 500 mg bid, and 700 mg bid for 8 days. Forty patients (82.5% male, 75% genotype 1a) received at least one dose of placebo or vaniprevir. After 1 week of vaniprevir, the decrease in HCV RNA from baseline ranged from 1.8 to 4.6 log₁₀IU/ml across all treatment groups, and there was a greater than dose-proportional increase in vaniprevir exposure at doses above 75 mg bid. The most commonly reported drug-related adverse events (AEs) were diarrhea (n=5) and nausea (n=5). No pattern of laboratory or ECG abnormalities was observed, all AEs resolved during the study, and there were no discontinuations due to AEs. No serious AEs were reported. Resistance-associated amino acid variants were identified at positions R155 and D168 in patients infected with genotype 1a virus. Vaniprevir monotherapy demonstrated potent antiviral activity in patients with chronic genotype 1 HCV infection, and was generally well tolerated with no serious AEs or discontinuations due to AEs. Further development of vaniprevir, including studies in combination with other anti-HCV agents, is ongoing. Copyright © 2013 Elsevier B.V. All rights reserved.

  13. Mechanism of action of a pestivirus antiviral compound

    Science.gov (United States)

    Baginski, Scott G.; Pevear, Daniel C.; Seipel, Marty; Sun, Siu Chi Chang; Benetatos, Christopher A.; Chunduru, Srinivas K.; Rice, Charles M.; Collett, Marc S.

    2000-01-01

    We report here the discovery of a small molecule inhibitor of pestivirus replication. The compound, designated VP32947, inhibits the replication of bovine viral diarrhea virus (BVDV) in cell culture at a 50% inhibitory concentration of approximately 20 nM. VP32947 inhibits both cytopathic and noncytopathic pestiviruses, including isolates of BVDV-1, BVDV-2, border disease virus, and classical swine fever virus. However, the compound shows no activity against viruses from unrelated virus groups. Time of drug addition studies indicated that VP32947 acts after virus adsorption and penetration and before virus assembly and release. Analysis of viral macromolecular synthesis showed VP32947 had no effect on viral protein synthesis or polyprotein processing but did inhibit viral RNA synthesis. To identify the molecular target of VP32947, we isolated drug-resistant (DR) variants of BVDV-1 in cell culture. Sequence analysis of the complete genomic RNA of two DR variants revealed a single common amino acid change located within the coding region of the NS5B protein, the viral RNA-dependent RNA polymerase. When this single amino acid change was introduced into an infectious clone of drug-sensitive wild-type (WT) BVDV-1, replication of the resulting virus was resistant to VP32947. The RNA-dependent RNA polymerase activity of the NS5B proteins derived from WT and DR viruses expressed and purified from recombinant baculovirus-infected insect cells confirmed the drug sensitivity of the WT enzyme and the drug resistance of the DR enzyme. This work formally validates NS5B as a target for antiviral drug discovery and development. The utility of VP32947 and similar compounds for the control of pestivirus diseases, and for hepatitis C virus drug discovery efforts, is discussed. PMID:10869440

  14. Co-infection with HIV associated with reduced vulnerability to symptoms of depression during antiviral treatment for hepatitis C.

    Science.gov (United States)

    Fialho, Renata; Pereira, Marco; Harrison, Neil; Rusted, Jennifer; Whale, Richard

    2017-07-01

    In this prospective study, we examined new-onset major depressive disorder (MDD) and the differential expression of depressive symptoms in a sample of 132 HCV mono-infected and 40 HIV/HCV co-infected patients initiating pegylated interferon-based treatment, including protease inhibitor therapy. The semi-structured clinical interview (SCID-I) was used to assess MDD. Severity of depressive symptoms was assessed using the Hamilton Depression Rating Scale. Of the total sample, 60 patients (34.9%) developed SCID-I defined MDD during antiviral treatment. The proportion of HCV mono- and HIV/HCV patients developing MDD during treatment was not significantly different (37.9% vs. 25%; p=0.185). In both groups, there was a significant increase in HAMD total score from baseline to week 4, and a significant decrease between week 24 and 6 months post-treatment cessation. The greatest increase was observed in the symptoms of the neurovegetative syndrome. HCV mono-infected patients reported higher scores than co-infected patients, particularly impaired activity and somatic symptoms, but the differences were only significant at week 12. The finding that co-infected patients appear less vulnerable to the development of depressive symptoms during HCV treatment than HCV mono-infected patients warrants further exploration, including a thorough analysis of the biological and psychosocial factors associated with this emergence. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.

  15. Anti-viral therapy is associated with improved survival but is underutilised in patients with hepatitis B virus-related hepatocellular carcinoma: real-world east and west experience.

    Science.gov (United States)

    Chen, V L; Yeh, M-L; Le, A K; Jun, M; Saeed, W K; Yang, J D; Huang, C-F; Lee, H Y; Tsai, P-C; Lee, M-H; Giama, N; Kim, N G; Nguyen, P P; Dang, H; Ali, H A; Zhang, N; Huang, J-F; Dai, C-Y; Chuang, W-L; Roberts, L R; Jun, D W; Lim, Y-S; Yu, M-L; Nguyen, M H

    2018-07-01

    Hepatitis B virus (HBV) is the leading cause of hepatocellular carcinoma (HCC) worldwide. It remains incompletely understood in the real world how anti-viral therapy affects survival after HCC diagnosis. This was an international multicentre cohort study of 2518 HBV-related HCC cases diagnosed between 2000 and 2015. Cox proportional hazards models were utilised to estimate hazard ratios (HR) with 95% (CI) for anti-viral therapy and cirrhosis on patients' risk of death. Approximately, 48% of patients received anti-viral therapy at any time, but only 17% were on therapy at HCC diagnosis (38% at US centres, 11% at Asian centres). Anti-viral therapy would have been indicated for >60% of the patients not on anti-viral therapy based on American criteria. Patients with cirrhosis had lower 5-year survival (34% vs 46%; P < 0.001) while patients receiving anti-viral therapy had increased 5-year survival compared to untreated patients (42% vs 25% with cirrhosis and 58% vs 36% without cirrhosis; P < 0.001 for both). Similar findings were seen for other patient subgroups by cancer stages and cancer treatment types. Anti-viral therapy was associated with a decrease in risk of death, whether started before or after HCC diagnosis (adjusted HR 0.62 and 0.79, respectively; P < 0.001). Anti-viral therapy improved overall survival in patients with HBV-related HCC across cancer stages and treatment types but was underutilised at both US and Asia centres. Expanded use of anti-viral therapy in HBV-related HCC and better linkage-to-care for HBV patients are needed. © 2018 John Wiley & Sons Ltd.

  16. Systems Biology-Based Investigation of Cellular Antiviral Drug Targets Identified by Gene-Trap Insertional Mutagenesis.

    Directory of Open Access Journals (Sweden)

    Feixiong Cheng

    2016-09-01

    Full Text Available Viruses require host cellular factors for successful replication. A comprehensive systems-level investigation of the virus-host interactome is critical for understanding the roles of host factors with the end goal of discovering new druggable antiviral targets. Gene-trap insertional mutagenesis is a high-throughput forward genetics approach to randomly disrupt (trap host genes and discover host genes that are essential for viral replication, but not for host cell survival. In this study, we used libraries of randomly mutagenized cells to discover cellular genes that are essential for the replication of 10 distinct cytotoxic mammalian viruses, 1 gram-negative bacterium, and 5 toxins. We herein reported 712 candidate cellular genes, characterizing distinct topological network and evolutionary signatures, and occupying central hubs in the human interactome. Cell cycle phase-specific network analysis showed that host cell cycle programs played critical roles during viral replication (e.g. MYC and TAF4 regulating G0/1 phase. Moreover, the viral perturbation of host cellular networks reflected disease etiology in that host genes (e.g. CTCF, RHOA, and CDKN1B identified were frequently essential and significantly associated with Mendelian and orphan diseases, or somatic mutations in cancer. Computational drug repositioning framework via incorporating drug-gene signatures from the Connectivity Map into the virus-host interactome identified 110 putative druggable antiviral targets and prioritized several existing drugs (e.g. ajmaline that may be potential for antiviral indication (e.g. anti-Ebola. In summary, this work provides a powerful methodology with a tight integration of gene-trap insertional mutagenesis testing and systems biology to identify new antiviral targets and drugs for the development of broadly acting and targeted clinical antiviral therapeutics.

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

    Science.gov (United States)

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

    2014-09-01

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

  18. 78 FR 57166 - Antiviral Drugs Advisory Committee; Notice of Meeting

    Science.gov (United States)

    2013-09-17

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2013-N-0001] Antiviral Drugs Advisory Committee; Notice of Meeting AGENCY: Food and Drug Administration, HHS. ACTION: Notice. This notice announces a forthcoming meeting of a public advisory committee of the Food and Drug...

  19. Developing antiviral surgical gown using nonwoven fabrics for ...

    African Journals Online (AJOL)

    Objectives: To develop antiviral surgical gown comprising of Polypropylene nonwoven as outer layer, Polytetrafluroethylene (PTFE) film as middle layer and polyester nonwoven as inner layer and the surgical gown with a basic weight of 70 g/m2. Methods: The titanium dioxide (TiO2) nano dispersion was prepared with ...

  20. Antiviral acyclic nucleoside phosphonates: New structures and prodrugs

    Czech Academy of Sciences Publication Activity Database

    Krečmerová, Marcela; Tichý, Tomáš; Pomeisl, Karel; Andrei, G.; Balzarini, J.; Snoeck, R.

    2016-01-01

    Roč. 1, č. 2 (2016), s. 37 [PharmaMed-2016. International Conference on Medicinal and Pharmaceutical Chemistry . 05.12.2016-07.12.2016, Dubai] R&D Projects: GA ČR(CZ) GA14-00522S Institutional support: RVO:61388963 Keywords : acyclic nucleoside phosphonates * prodrugs * antivirals * 5-azacytosine Subject RIV: CC - Organic Chemistry

  1. The role of CC chemokine receptor 5 in antiviral immunity

    DEFF Research Database (Denmark)

    Nansen, Anneline; Christensen, Jan Pravsgaard; Andreasen, Susanne Ørding

    2002-01-01

    The CC chemokine receptor CCR5 is an important coreceptor for human immunodeficiency virus (HIV), and there is a major thrust to develop anti-CCR5-based therapies for HIV-1. However, it is not known whether CCR5 is critical for a normal antiviral T-cell response. This study investigated the immune...

  2. Interferon induced IFIT family genes in host antiviral defense.

    Science.gov (United States)

    Zhou, Xiang; Michal, Jennifer J; Zhang, Lifan; Ding, Bo; Lunney, Joan K; Liu, Bang; Jiang, Zhihua

    2013-01-01

    Secretion of interferons (IFNs) from virus-infected cells is a hallmark of host antiviral immunity and in fact, IFNs exert their antiviral activities through the induction of antiviral proteins. The IFN-induced protein with tetratricopeptide repeats (IFITs) family is among hundreds of IFN-stimulated genes. This family contains a cluster of duplicated loci. Most mammals have IFIT1, IFIT2, IFIT3 and IFIT5; however, bird, marsupial, frog and fish have only IFIT5. Regardless of species, IFIT5 is always adjacent to SLC16A12. IFIT family genes are predominantly induced by type I and type III interferons and are regulated by the pattern recognition and the JAK-STAT signaling pathway. IFIT family proteins are involved in many processes in response to viral infection. However, some viruses can escape the antiviral functions of the IFIT family by suppressing IFIT family genes expression or methylation of 5' cap of viral molecules. In addition, the variants of IFIT family genes could significantly influence the outcome of hepatitis C virus (HCV) therapy. We believe that our current review provides a comprehensive picture for the community to understand the structure and function of IFIT family genes in response to pathogens in human, as well as in animals.

  3. Antiviral evaluation of an Hsp90 inhibitor, gedunin, against dengue ...

    African Journals Online (AJOL)

    Purpose: To evaluate the antiviral potential of a tetranortriterpenoid, gedunin, against dengue virus (DENV) replication by targeting the host chaperone, Hsp90. Methods: The compound, gedunin, was tested against the replication of DENV in vitro using BHK-15 cells transfected with DENV-2 subgenomic replicon. Molecular ...

  4. Cellular Antiviral Factors that Target Particle Infectivity of HIV-1.

    Science.gov (United States)

    Goffinet, Christine

    2016-01-01

    In the past decade, the identification and characterization of antiviral genes with the ability to interfere with virus replication has established cell-intrinsic innate immunity as a third line of antiviral defense in addition to adaptive and classical innate immunity. Understanding how cellular factors have evolved to inhibit HIV-1 reveals particularly vulnerable points of the viral replication cycle. Many, but not all, antiviral proteins share type I interferon-upregulated expression and sensitivity to viral counteraction or evasion measures. Whereas well-established restriction factors interfere with early post-entry steps and release of HIV-1, recent research has revealed a diverse set of proteins that reduce the infectious quality of released particles using individual, to date poorly understood modes of action. These include induction of paucity of mature glycoproteins in nascent virions or self-incorporation into the virus particle, resulting in poor infectiousness of the virion and impaired spread of the infection. A better understanding of these newly discovered antiviral factors may open new avenues towards the design of drugs that repress the spread of viruses whose genomes have already integrated.

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

    Science.gov (United States)

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

    2017-10-01

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

  6. 75 FR 16151 - Antiviral Drugs Advisory Committee; Notice of Meeting

    Science.gov (United States)

    2010-03-31

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2010-N-0001] Antiviral Drugs Advisory Committee; Notice of Meeting AGENCY: Food and Drug Administration, HHS. ACTION: Notice. This notice announces a forthcoming meeting of a public advisory committee of the Food and Drug...

  7. 76 FR 62418 - Antiviral Drugs Advisory Committee; Notice of Meeting

    Science.gov (United States)

    2011-10-07

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2011-N-0002] Antiviral Drugs Advisory Committee; Notice of Meeting AGENCY: Food and Drug Administration, HHS. ACTION: Notice. This notice announces a forthcoming meeting of a public advisory committee of the Food and Drug...

  8. Antiviral activity of the extracts of Rhodophyceae from Morocco

    African Journals Online (AJOL)

    Administrator

    2010-11-15

    Nov 15, 2010 ... replication of HSV-1 in vitro at an EC50 (Effective Concentration 50%) ranging from <2.5 to 75.9 µg mL-1. No cytotoxic effect ... Keywords: Antiviral, Aqueous extracts, Organic extracts, Rhodophyceae, Herpes simplex virus. INTRODUCTION ... from a species of Bryopsis as a possible treatment of lung cancer ...

  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

  10. Developing antiviral surgical gown using nonwoven fabrics for ...

    African Journals Online (AJOL)

    EB

    Developing antiviral surgical gown using nonwoven fabrics for health care sector. *Parthasarathi V, Thilagavathi G. Department of Fashion Technology, PSG college of Technology, Peelamedu, Coimbatore – 641 004,. India. Abstract. Background: Healthcare workers' uniforms including surgical gowns are used as barriers ...

  11. Testing of disease-resistance of pokeweed antiviral protein gene ...

    African Journals Online (AJOL)

    Transformation of pokeweed antiviral protein gene (PAP) into plants was shown to improve plant resistance to several viruses or fungi pathogens with no much negative effect on plant growth. The non-virulent defective PAP inhibits only the virus but does not interfere with the host. A non-virulent defective PAP gene ...

  12. ANTIVIRAL ACTIVITY OF DIANTHUS SUPERBUSN L. AGAINST HEPATITIS B VIRUS IN VITRO AND IN VIVO.

    Science.gov (United States)

    Li, Wei-Guo; Wang, He-Qun

    2016-01-01

    Hepatitis is a viral infection of hepatitis B virus (HBV). Limitations of drug used in the management of it opens the interest related to alternative medicine. The given study deals with the antiviral activity of Dianthus superbusn L. (DSL) against HBV in vitro & in vivo . In vitro study liver cell line HepG2.2.15 was used by transinfected it with HBV. Cytotoxicity stduy was performed by using different concentrations of DSL such as 50, 100, 200, 500 & 1000 μg/ml. Anti HBV activity of DSL was estimated by assesing the concentration of HBsAg and HbeAg in cell culture medium by using ELISA. Whereas in vivo study was performed on ducklings and antiviral activity of DSL (100, 200, 400 mg/kg) was confirmed by estimating the serum concentration of HBV DNA and histopathology study of hepatocytes in HBV infected ducklings. Result of the study suggested that >500 μg/ml concentration of hydroalcoholic extract of DSL was found tobe cytotoxic. It was also observed that DSL significantly ( p <0.05) reduces the concentration of antigenes in cell culture media as per the concentration and days of treatment dependent. Moreover in vivo study confirms the anti viral activity of DSL (200 & 400 mg/kg) as it significantly ( p <0.05) decreases the serum concenetration of HBV DNA in HBV infected dukling compared to control group. Histopathology study was also reveals the hepatprotective effect of DSL in HBV infected ducklings. The given study concludes the antiviral activity DSL against HBV by in vitro and in vivo models.

  13. Utility of humanized BLT mice for analysis of dengue virus infection and antiviral drug testing.

    Science.gov (United States)

    Frias-Staheli, Natalia; Dorner, Marcus; Marukian, Svetlana; Billerbeck, Eva; Labitt, Rachael N; Rice, Charles M; Ploss, Alexander

    2014-02-01

    Dengue virus (DENV) is the cause of a potentially life-threatening disease that affects millions of people worldwide. The lack of a small animal model that mimics the symptoms of DENV infection in humans has slowed the understanding of viral pathogenesis and the development of therapies and vaccines. Here, we investigated the use of humanized "bone marrow liver thymus" (BLT) mice as a model for immunological studies and assayed their applicability for preclinical testing of antiviral compounds. Human immune system (HIS) BLT-NOD/SCID mice were inoculated intravenously with a low-passage, clinical isolate of DENV-2, and this resulted in sustained viremia and infection of leukocytes in lymphoid and nonlymphoid organs. In addition, DENV infection increased serum cytokine levels and elicited DENV-2-neutralizing human IgM antibodies. Following restimulation with DENV-infected dendritic cells, in vivo-primed T cells became activated and acquired effector function. An adenosine nucleoside inhibitor of DENV decreased the circulating viral RNA when administered simultaneously or 2 days postinfection, simulating a potential treatment protocol for DENV infection in humans. In summary, we demonstrate that BLT mice are susceptible to infection with clinical DENV isolates, mount virus-specific adaptive immune responses, and respond to antiviral drug treatment. Although additional refinements to the model are required, BLT mice are a suitable platform to study aspects of DENV infection and pathogenesis and for preclinical testing of drug and vaccine candidates. IMPORTANCE Infection with dengue virus remains a major medical problem. Progress in our understanding of the disease and development of therapeutics has been hampered by the scarcity of small animal models. Here, we show that humanized mice, i.e., animals engrafted with components of a human immune system, that were infected with a patient-derived dengue virus strain developed clinical symptoms of the disease and mounted

  14. ISG15 inhibits Nedd4 ubiquitin E3 activity and enhances the innate antiviral response.

    Science.gov (United States)

    Malakhova, Oxana A; Zhang, Dong-Er

    2008-04-04

    Interferons regulate diverse immune functions through the transcriptional activation of hundreds of genes involved in anti-viral responses. The interferon-inducible ubiquitin-like protein ISG15 is expressed in cells in response to a variety of stress conditions like viral or bacterial infection and is present in its free form or is conjugated to cellular proteins. In addition, protein ubiquitination plays a regulatory role in the immune system. Many viruses modulate the ubiquitin (Ub) pathway to alter cellular signaling and the antiviral response. Ubiquitination of retroviral group-specific antigen precursors and matrix proteins of the Ebola, vesicular stomatitis, and rabies viruses by Nedd4 family HECT domain E3 ligases is an important step in facilitating viral release. We found that Nedd4 is negatively regulated by ISG15. Free ISG15 specifically bound to Nedd4 and blocked its interaction with Ub-E2 molecules, thus preventing further Ub transfer from E2 to E3. Furthermore, overexpression of ISG15 diminished the ability of Nedd4 to ubiquitinate viral matrix proteins and led to a decrease in the release of Ebola VP40 virus-like particles from the cells. These results point to a mechanistically novel function of ISG15 in the enhancement of the innate anti-viral response through specific inhibition of Nedd4 Ub-E3 activity. To our knowledge, this is the first example of a Ub-like protein with the ability to interfere with Ub-E2 and E3 interaction to inhibit protein ubiquitination.

  15. 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

  16. 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 ant...iviral activity? PubmedID 15283983 Title What is disrupting IFN-alpha's antiviral activity? Authors Mbow ML,

  17. DMPD: Negative regulation of cytoplasmic RNA-mediated antiviral signaling. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 18703349 Negative regulation of cytoplasmic RNA-mediated antiviral signaling. Komur...Show Negative regulation of cytoplasmic RNA-mediated antiviral signaling. PubmedID 18703349 Title Negative r...egulation of cytoplasmic RNA-mediated antiviral signaling. Authors Komuro A, Bamm

  18. Dietary intake of fiber, fruit and vegetables decreases the risk of incident kidney stones in women: A women's health initiative report

    OpenAIRE

    Sorensen, MD; Hsi, RS; Chi, T; Shara, N; Wactawski-Wende, J; Kahn, AJ; Wang, H; Hou, L; Stoller, ML

    2014-01-01

    © 2014 American Urological Association Education and Research, Inc. Results Mean age of the women was 64±7 years, 85% were white and 2,937 (3.5%) experienced a kidney stone in a median followup of 8 years. In women with no history of kidney stones higher total dietary fiber (6% to 26% decreased risk, p < 0.001), greater fruit intake (12% to 25% decreased risk, p < 0.001) and greater vegetable intake (9% to 22% decreased risk, p=0.002) were associated with a decreased risk of incident kidney...

  19. 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.

  20. Transgenic Clustered Regularly Interspaced Short Palindromic Repeat/Cas9-Mediated Viral Gene Targeting for Antiviral Therapy of Bombyx mori Nucleopolyhedrovirus.

    Science.gov (United States)

    Chen, Shuqing; Hou, Chengxiang; Bi, Honglun; Wang, Yueqiang; Xu, Jun; Li, Muwang; James, Anthony A; Huang, Yongping; Tan, Anjiang

    2017-04-15

    We developed a novel antiviral strategy by combining transposon-based transgenesis and the clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated 9 (Cas9) system for the direct cleavage of Bombyx mori nucleopolyhedrovirus (BmNPV) genome DNA to promote virus clearance in silkworms. We demonstrate that transgenic silkworms constitutively expressing Cas9 and guide RNAs targeting the BmNPV immediate early-1 ( ie-1 ) and me53 genes effectively induce target-specific cleavage and subsequent mutagenesis, especially large (∼7-kbp) segment deletions in BmNPV genomes, and thus exhibit robust suppression of BmNPV proliferation. Transgenic animals exhibited higher and inheritable resistance to BmNPV infection than wild-type animals. Our approach will not only contribute to modern sericulture but also shed light on future antiviral therapy. IMPORTANCE Pathogen genome targeting has shown its potential in antiviral research. However, transgenic CRISPR/Cas9 system-mediated viral genome targeting has not been reported as an antiviral strategy in a natural animal host of a virus. Our data provide an effective approach against BmNPV infection in a real-world biological system and demonstrate the potential of transgenic CRISPR/Cas9 systems in antiviral research in other species. Copyright © 2017 Chen et al.

  1. A general strategy to endow natural fusion-protein-derived peptides with potent antiviral activity.

    Directory of Open Access Journals (Sweden)

    Antonello Pessi

    Full Text Available Fusion between the viral and target cell membranes is an obligatory step for the infectivity of all enveloped virus, and blocking this process is a clinically validated therapeutic strategy.Viral fusion is driven by specialized proteins which, although specific to each virus, act through a common mechanism, the formation of a complex between two heptad repeat (HR regions. The HR regions are initially separated in an intermediate termed "prehairpin", which bridges the viral and cell membranes, and then fold onto each other to form a 6-helical bundle (6HB, driving the two membranes to fuse. HR-derived peptides can inhibit viral infectivity by binding to the prehairpin intermediate and preventing its transition to the 6HB.The antiviral activity of HR-derived peptides differs considerably among enveloped viruses. For weak inhibitors, potency can be increased by peptide engineering strategies, but sequence-specific optimization is time-consuming. In seeking ways to increase potency without changing the native sequence, we previously reported that attachment to the HR peptide of a cholesterol group ("cholesterol-tagging" dramatically increases its antiviral potency, and simultaneously increases its half-life in vivo. We show here that antiviral potency may be increased by combining cholesterol-tagging with dimerization of the HR-derived sequence, using as examples human parainfluenza virus, Nipah virus, and HIV-1. Together, cholesterol-tagging and dimerization may represent strategies to boost HR peptide potency to levels that in some cases may be compatible with in vivo use, possibly contributing to emergency responses to outbreaks of existing or novel viruses.

  2. Rigid amphipathic fusion inhibitors demonstrate antiviral activity against African swine fever virus.

    Science.gov (United States)

    Hakobyan, Astghik; Galindo, Inmaculada; Nañez, Almudena; Arabyan, Erik; Karalyan, Zaven; Chistov, Alexey A; Streshnev, Philipp P; Korshun, Vladimir A; Alonso, Covadonga; Zakaryan, Hovakim

    2018-01-01

    Rigid amphipathic fusion inhibitors (RAFIs) are a family of nucleoside derivatives that inhibit the infectivity of several enveloped viruses by interacting with virion envelope lipids and inhibiting fusion between viral and cellular membranes. Here we tested the antiviral activity of two RAFIs, 5-(Perylen-3-ylethynyl)-arabino-uridine (aUY11) and 5-(Perylen-3-ylethynyl)uracil-1-acetic acid (cm1UY11) against African swine fever virus (ASFV), for which no effective vaccine is available. Both compounds displayed a potent, dose-dependent inhibitory effect on ASFV infection in Vero cells. The major antiviral effect was observed when aUY11 and cm1UY11 were added at early stages of infection and maintained during the complete viral cycle. Furthermore, virucidal assay revealed a significant extracellular anti-ASFV activity for both compounds. We also found decrease in the synthesis of early and late viral proteins in Vero cells treated with cm1UY11. Finally, the inhibitory effect of aUY11 and cm1UY11 on ASFV infection in porcine alveolar macrophages was confirmed. Overall, our study has identified novel anti-ASFV compounds with potential for future therapeutic developments.

  3. Arginine-rich histones have strong antiviral activity for influenza A viruses.

    Science.gov (United States)

    Hoeksema, Marloes; Tripathi, Shweta; White, Mitchell; Qi, Li; Taubenberger, Jeffery; van Eijk, Martin; Haagsman, Henk; Hartshorn, Kevan L

    2015-10-01

    While histones are best known for DNA binding and transcription-regulating properties, they also have antimicrobial activity against a broad range of potentially pathogenic organisms. Histones are abundant in neutrophil extracellular traps, where they play an important role in NET-mediated antimicrobial killing. Here, we show anti-influenza activity of histones against both seasonal H3N2 and H1N1, but not pandemic H1N1. The arginine rich histones, H3 and H4, had greater neutralizing and viral aggregating activity than the lysine rich histones, H2A and H2B. Of all core histones, histone H4 is most potent in neutralizing IAV, and incubation with IAV with histone H4 results in a decrease in uptake and viral replication by epithelial cells when measured by qRT-PCR. The antiviral activity of histone H4 is mediated principally by direct effects on viral particles. Histone H4 binds to IAV as assessed by ELISA and co-sedimentation of H4 with IAV. H4 also induces aggregation, as assessed by confocal microscopy and light transmission assays. Despite strong antiviral activity against the seasonal IAV strains, H4 was inactive against pandemic H1N1. These findings indicate a possible role for histones in the innate immune response against IAV. © The Author(s) 2015.

  4. Species-independent bioassay for sensitive quantification of antiviral type I interferons

    Directory of Open Access Journals (Sweden)

    Penski Nicola

    2010-02-01

    Full Text Available Abstract Background Studies of the host response to infection often require quantitative measurement of the antiviral type I interferons (IFN-α/β in biological samples. The amount of IFN is either determined via its ability to suppress a sensitive indicator virus, by an IFN-responding reporter cell line, or by ELISA. These assays however are either time-consuming and lack convenient readouts, or they are rather insensitive and restricted to IFN from a particular host species. Results An IFN-sensitive, Renilla luciferase-expressing Rift Valley fever virus (RVFV-Ren was generated using reverse genetics. Human, murine and avian cells were tested for their susceptibility to RVFV-Ren after treatment with species-specific IFNs. RVFV-Ren was able to infect cells of all three species, and IFN-mediated inhibition of viral reporter activity occurred in a dose-dependent manner. The sensitivity limit was found to be 1 U/ml IFN, and comparison with a standard curve allowed to determine the activity of an unknown sample. Conclusions RVFV-Ren replicates in cells of several species and is highly sensitive to pre-treatment with IFN. These properties allowed the development of a rapid, sensitive, and species-independent antiviral assay with a convenient luciferase-based readout.

  5. 6-methylmercaptopurine riboside, a thiopurine nucleoside with antiviral activity against canine distemper virus in vitro.

    Science.gov (United States)

    de Carvalho, Otávio Valério; Félix, Daniele Mendes; de Camargo Tozato, Claudia; Fietto, Juliana Lopes Rangel; de Almeida, Márcia Rogéria; Bressan, Gustavo Costa; Pena, Lindomar José; Silva-Júnior, Abelardo

    2017-06-26

    Canine distemper (CD) is a widespread infectious disease that can severely impact a variety of species in the order Carnivora, as well as non-carnivore species such as non-human primates. Despite large-scale vaccination campaigns, several fatal outbreaks have been reported in wild and domestic carnivore populations. This, in association with expansion of the disease host range and the development of vaccine-escape strains, has contributed to an increased demand for therapeutic strategies synergizing with vaccine programs for effectively controlling canine distemper. 6-methylmercaptopurine riboside (6MMPr) is a modified thiopurine nucleoside with known antiviral properties against certain RNA viruses. We tested the inhibitory effects of 6MMPr against a wild-type CDV strain infection in cell culture. We measured infectious particle production and viral RNA levels in treated and untreated CDV-infected cells. Ribavirin (RIB) was used as a positive control. Here, we report for the first time the antiviral effects of 6MMPr against canine distemper virus (CDV) in vitro. 6MMPr was able to reduce viral RNA levels and to inhibit the production of infectious CDV particles. The therapeutic selectivity of 6MMPr was approximately six times higher than that of ribavirin. Our results indicate that 6MMPr has high anti-CDV potential and warrants further testing against other paramyxoviruses, as well as clinical testing of the compound against CDV.

  6. Antiviral potency and functional analysis of tetherin orthologues encoded by horse and donkey.

    Science.gov (United States)

    Yin, Xin; Guo, Miaomiao; Gu, Qinyong; Wu, Xingliang; Wei, Ping; Wang, Xiaojun

    2014-08-27

    Tetherin is an interferon-inducible host cell factor that blocks the viral particle release of the enveloped viruses. Most knowledge regarding the interaction between tetherin and viruses has been obtained using the primate lentiviral system. However, much less is known about the functional roles of tetherin on other lentiviruses. Equine infectious anemia virus (EIAV) is an important macrophage-tropic lentivirus that has been widely used as a practical model for investigating the evolution of the host-virus relationship. The host range of EIAV is reported to include all members of the Equidae family. However, EIAV has different clinical responses in horse and donkey. It's intriguing to investigate the similarities and differences between the tetherin orthologues encoded by horse and donkey. We report here that there are two equine tetherin orthologues. Compared to horse tetherin, there are three valine amino acid deletions within the transmembrane domain and three distinct mutations within the ectodomain of donkey tetherin. However, the antiviral activity of donkey tetherin was not affected by amino acid deletion or substitution. In addition, both tetherin orthologues encoded by horse and donkey are similarly sensitive to EIAV Env protein, and equally activate NF-κB signaling. Our data suggest that both tetherin orthologues encoded by horse and donkey showed similar antiviral activities and abilities to induce NF-κB signaling. In addition, the phenomenon about the differential responses of horses and donkeys to infection with EIAV was not related with the differences in the structure of the corresponding tetherin orthologues.

  7. Antiviral cell therapy: is this the future?

    OpenAIRE

    Gea-Banacloche, Juan C.

    2013-01-01

    In this issue of Blood, Leen and colleagues report the first multicenter trial of third-party viral-specific T cells (VSTs) for the treatment of 50 patients with refractory viral infections (cytomegalovirus, adenovirus, and Epstein-Barr virus) after stem cell transplantation.1

  8. Novel drugs targeting Toll-like receptors for antiviral therapy.

    Science.gov (United States)

    Patel, Mira C; Shirey, Kari Ann; Pletneva, Lioubov M; Boukhvalova, Marina S; Garzino-Demo, Alfredo; Vogel, Stefanie N; Blanco, Jorge Cg

    2014-09-01

    Toll-like receptors (TLRs) are sentinel receptors of the host innate immune system that recognize conserved 'pathogen-associated molecular patterns' of invading microbes, including viruses. The activation of TLRs establishes antiviral innate immune responses and coordinates the development of long-lasting adaptive immunity in order to control viral pathogenesis. However, microbe-induced damage to host tissues may release 'danger-associated molecular patterns' that also activate TLRs, leading to an overexuberant inflammatory response and, ultimately, to tissue damage. Thus, TLRs have proven to be promising targets as therapeutics for the treatment of viral infections that result in inflammatory damage or as adjuvants in order to enhance the efficacy of vaccines. Here, we explore recent advances in TLR biology with a focus on novel drugs that target TLRs (agonists and antagonists) for antiviral therapy.

  9. Neonatal plasmacytoid dendritic cells (pDCs display subset variation but can elicit potent anti-viral innate responses.

    Directory of Open Access Journals (Sweden)

    Xiaoming Zhang

    Full Text Available Neonates are highly susceptible to infectious diseases and defective antiviral pDC immune responses have been proposed to contribute to this phenomenon. Isolated cord blood pDCs innately responded to a variety of TLR7 and TLR9 dependent viruses, including influenza A virus (IAV, human immunodeficiency virus (HIV or herpes-simplex virus (HSV by efficiently producing IFN-α, TNF-α as well as chemokines. Interestingly, following activation by CpGA, but not viruses, cord pDCs tend to survive less efficiently. We found that a hallmark of pDCs in neonates is an extended CD2+pDCs compartment compared to adult pDCs without affecting the antiviral IFN-α response. Within CD2+pDCs, we identified a subpopulation expressing CD5 and responsible for IL-12p40 production, however this population is significantly decreased in cord blood compared to adult blood. Therefore, neonatal pDCs clearly display variation in phenotype and subset composition, but without major consequences for their antiviral responses.

  10. Molecular Characterization, Tissue Distribution and Expression, and Potential Antiviral Effects of TRIM32 in the Common Carp (Cyprinus carpio)

    Science.gov (United States)

    Wang, Yeda; Li, Zeming; Lu, Yuanan; Hu, Guangfu; Lin, Li; Zeng, Lingbing; Zhou, Yong; Liu, Xueqin

    2016-01-01

    Tripartite motif-containing protein 32 (TRIM32) belongs to the tripartite motif (TRIM) family, which consists of a large number of proteins containing a RING (Really Interesting New Gene) domain, one or two B-box domains, and coiled coil motif followed by different C-terminal domains. The TRIM family is known to be implicated in multiple cellular functions, including antiviral activity. However, it is presently unknown whether TRIM32 of common carp (Cyprinus carpio) has the antiviral effect. In this study, the sequence, expression, and antiviral function of TRIM32 homolog from common carp were analyzed. The full-length coding sequence region of trim32 was cloned from common carp. The results showed that the expression of TRIM32 (mRNA) was highest in the brain, remained stably expressed during embryonic development, and significantly increased following spring viraemia of carp virus (SVCV) infection. Transient overexpression of TRIM32 in affected Epithelioma papulosum cyprinid cells led to significant decrease of SVCV production as compared to the control group. These results suggested a potentially important role of common carp TRIM32 in enhancing host immune response during SVCV infection both in vivo and in vitro. PMID:27735853

  11. 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.

    in large quantities by traditional methods and sold live in the market for human consumption. The economically important sp e cies of marine bivalves are green mussel ( Perna viridis ), e s tuarine oyster ( Crassostrea madrasensis ), giant oyster... in developing an effecti ve drug has been the unique characteristics of antigenic variation of virus resulting in the emergence of new variant virus strains 14 . There are a number of antiviral drugs introduced in the market such as tricyclic sy m- metric...

  12. In Vitro Bioavailability Study of an Antiviral Compound Enisamium Iodide

    OpenAIRE

    Eleonore Haltner-Ukomadu; Svitlana Gureyeva; Oleksii Burmaka; Andriy Goy; Lutz Mueller; Grygorii Kostyuk; Victor Margitich

    2018-01-01

    An investigation into the biopharmaceutics classification and a study of the in vitro bioavailability (permeability and solubility) of the antiviral compound enisamium iodide (4-(benzylcarbamoyl)-1-methylpyridinium iodide) were carried out. The solubility of enisamium iodide was determined in four different buffers. Apparent intestinal permeability (Papp) of enisamium iodide was assessed using human colon carcinoma (Caco-2) cells at three concentrations. The solubility of enisamium iodide in ...

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

    Directory of Open Access Journals (Sweden)

    Lecellier Charles-Henri

    2006-01-01

    Full Text Available 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 be similarly conserved from plants to insects, even in worms, RNA silencing does influence the replication of mammalian viruses but in a particular mode: micro(miRNAs, endogenous small RNAs naturally implicated in translational control, rather than virus-derived small interfering (siRNAs like in other organisms, are involved. In fact, these recent studies even suggest that RNA silencing may be beneficial for viral replication. Accordingly, several large DNA mammalian viruses have been shown to encode their own miRNAs. Here, we summarize the seminal studies that have implicated RNA silencing in viral infection and compare the different eukaryotic responses.

  14. Efficacy of Antiviral Drugs against Feline Immunodeficiency Virus

    Directory of Open Access Journals (Sweden)

    Katrin Hartmann

    2015-12-01

    Full Text Available Feline immunodeficiency virus (FIV is one of the most common infectious agents affecting cats worldwide .FIV and human immunodeficiency virus (HIV share many properties: both are lifelong persistent lentiviruses that are similar genetically and morphologically and both viruses propagate in T-lymphocytes, macrophages, and neural cells. Experimentally infected cats have measurable immune suppression, which sometimes progresses to an acquired immunodeficiency syndrome. A transient initial state of infection is followed by a long latent stage with low virus replication and absence of clinical signs. In the terminal stage, both viruses can cause severe immunosuppression. Thus, FIV infection in cats has become an important natural model for studying HIV infection in humans, especially for evaluation of antiviral compounds. Of particular importance for chemotherapeutic studies is the close similarity between the reverse transcriptase (RT of FIV and HIV, which results in high in vitro susceptibility of FIV to many RT-targeted antiviral compounds used in the treatment of HIV-infected patients. Thus, the aim of this article is to provide an up-to-date review of studies on antiviral treatment of FIV, focusing on commercially available compounds for human or animal use.

  15. Antiviral and Inflammatory Cellular Signaling Associated with Enterovirus 71 Infection

    Directory of Open Access Journals (Sweden)

    Yuefei Jin

    2018-03-01

    Full Text Available Enterovirus 71 (EV71 infection has become a major threat to global public health, especially in infants and young children. Epidemiological studies have indicated that EV71 infection is responsible for severe and even fatal cases of hand, foot, and mouth disease (HFMD. Accumulated evidence indicates that EV71 infection triggers a plethora of interactive signaling pathways, resulting in host immune evasion and inflammatory response. This review mainly covers the effects of EV71 infection on major antiviral and inflammatory cellular signal pathways. EV71 can activate cellular signaling networks including multiple cell surface and intracellular receptors, intracellular kinases, calcium flux, and transcription factors that regulate antiviral innate immunity and inflammatory response. Cellular signaling plays a critical role in the regulation of host innate immune and inflammatory pathogenesis. Elucidation of antiviral and inflammatory cellular signaling pathways initiated by EV71 will not only help uncover the potential mechanisms of EV71 infection-induced pathogenesis, but will also provide clues for the design of therapeutic strategies against EV71 infection.

  16. Antiviral activity of some South American medicinal plants.

    Science.gov (United States)

    Abad, M J; Bermejo, P; Sanchez Palomino, S; Chiriboga, X; Carrasco, L

    1999-03-01

    Folk medicinal plants are potential sources of useful therapeutic compounds including some with antiviral activities. Extracts prepared from 10 South American medicinal plants (Baccharis trinervis, Baccharis teindalensis, Eupatorium articulatum, Eupatorium glutinosum, Tagetes pusilla, Neurolaena lobata, Conyza floribunda, Phytolacca bogotensis, Phytolacca rivinoides and Heisteria acuminata) were screened for in vitro antiviral activity against herpes simplex type I (HSV-1), vesicular stomatitis virus (VSV) and poliovirus type 1. The most potent inhibition was observed with an aqueous extract of B. trinervis, which inhibited HSV-1 replication by 100% at 50-200 micrograms/mL, without showing cytotoxic effects. Good activities were also found with the ethanol extract of H. acuminata and the aqueous extract of E. articulatum, which exhibited antiviral effects against both DNA and RNA viruses (HSV-1 and VSV, respectively) at 125-250 micrograms/mL. The aqueous extracts of T. pusilla (100-250 micrograms/mL), B. teindalensis (50-125 micrograms/mL) and E. glutinosum (50-125 micrograms/mL) also inhibited the replication of VSV, but none of the extracts tested had any effect on poliovirus replication.

  17. Functional evaluation of synthetic flavonoids and chalcones for potential antiviral and anticancer properties.

    Science.gov (United States)

    Mateeva, Nelly; Eyunni, Suresh V K; Redda, Kinfe K; Ononuju, Ucheze; Hansberry, Tony D; Aikens, Cecilia; Nag, Anita

    2017-06-01

    Flavonoids, stilbenes, and chalcones are plant secondary metabolites that often possess diverse biological activities including anti-inflammatory, anti-cancer, and anti-viral activities. The wide range of bioactivities poses a challenge to identify their targets. Here, we studied a set of synthetically generated flavonoids and chalcones to evaluate for their biological activity, and compared similarly substituted flavonoids and chalcones. Substituted chalcones, but not flavonoids, showed inhibition of viral translation without significantly affecting viral replication in cells infected with hepatitis C virus (HCV). We suggest that the chalcones used in this study inhibit mammalian target of rapamycin (mTOR) pathway by ablating phosphorylation of ribosomal protein 6 (rps6), and also the kinase necessary for phosphorylating rps6 in Huh7.5 cells (pS6K1). In addition, selected chalcones showed inhibition of growth in Ishikawa, MCF7, and MDA-MB-231 cells resulting an IC 50 of 1-6µg/mL. When similarly substituted flavonoids were used against the same set of cancer cells, we did not observe any inhibitory effect. Together, we report that chalcones show potential for anti-viral and anti-cancer activities compared to similarly substituted flavonoids. Copyright © 2017 Elsevier Ltd. All rights reserved.

  18. Light-activated nanotube–porphyrin conjugates as effective antiviral agents

    International Nuclear Information System (INIS)

    Banerjee, Indrani; Douaisi, Marc P; Mondal, Dhananjoy; Kane, Ravi S

    2012-01-01

    Porphyrins have been used for photodynamic therapy (PDT) against a wide range of targets like bacteria, viruses and tumor cells. In this work, we report porphyrin-conjugated multi-walled carbon nanotubes (NT-P) as potent antiviral agents. Specifically, we used Protoporphyrin IX (PPIX), which we attached to acid-functionalized multi-walled carbon nanotubes (MWNTs). We decided to use carbon nanotubes as scaffolds because of their ease of recovery from a solution through filtration. In the presence of visible light, NT-P was found to significantly reduce the ability of Influenza A virus to infect mammalian cells. NT-P may be used effectively against influenza viruses with little or no chance of them developing resistance to the treatment. Furthermore, NT-P can be easily recovered through filtration which offers a facile strategy to reuse the active porphyrin moiety to its fullest extent. Thus NT-P conjugates represent a new approach for preparing ex vivo reusable antiviral agents. (paper)

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

    Directory of Open Access Journals (Sweden)

    Sandra Milena Gonzalez

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

  20. 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.

  1. An antiviral disulfide compound blocks interaction between arenavirus Z protein and cellular promyelocytic leukemia protein

    International Nuclear Information System (INIS)

    Garcia, C.C.; Topisirovic, I.; Djavani, M.; Borden, K.L.B.; Damonte, E.B.; Salvato, M.S.

    2010-01-01

    The promyelocytic leukemia protein (PML) forms nuclear bodies (NB) that can be redistributed by virus infection. In particular, lymphocytic choriomeningitis virus (LCMV) influences disruption of PML NB through the interaction of PML with the arenaviral Z protein. In a previous report, we have shown that the disulfide compound NSC20625 has antiviral and virucidal properties against arenaviruses, inducing unfolding and oligomerization of Z without affecting cellular RING-containing proteins such as the PML. Here, we further studied the effect of the zinc-finger-reactive disulfide NSC20625 on PML-Z interaction. In HepG2 cells infected with LCMV or transiently transfected with Z protein constructs, treatment with NSC20625 restored PML distribution from a diffuse-cytoplasmic pattern to punctate, discrete NB which appeared identical to NB found in control, uninfected cells. Similar results were obtained in cells transfected with a construct expressing a Z mutant in zinc-binding site 2 of the RING domain, confirming that this Z-PML interaction requires the integrity of only one zinc-binding site. Altogether, these results show that the compound NSC20625 suppressed Z-mediated PML NB disruption and may be used as a tool for designing novel antiviral strategies against arenavirus infection.

  2. Essential Oil Composition, Antioxidant, Cytotoxic and Antiviral Activities of Teucrium pseudochamaepitys Growing Spontaneously in Tunisia

    Directory of Open Access Journals (Sweden)

    Saoussen Hammami

    2015-11-01

    Full Text Available The chemical composition, antioxidant, cytotoxic and antiviral activities of the essential oil obtained by hydrodistillation from the aerial parts of Teucrium pseudochamaepitys (Lamiaceae collected from Zaghouan province of Tunisia are reported. The essential oil was analyzed by gas chromatography equipped with a flame ionization detector (GC-FID and gas chromatography coupled with mass spectrometry (GC/MS. Thirty-one compounds were identified representing 88.6% of the total essential oil. Hexadecanoic acid was found to be the most abundant component (26.1% followed by caryophyllene oxide (6.3%, myristicin (4.9% and α-cubebene (3.9%. The antioxidant capacity of the oil was measured on the basis of the scavenging activity to the stable 2,2-diphenyl-1-picrylhydrazyl (DPPH. The IC50 value of the oil was evaluated as 0.77 mg·mL−1. In addition, the essential oil was found to possess moderate cytotoxic effects on the HEp-2 cell line (50% cytotoxic concentration (CC50 = 653.6 µg·mL−1. The potential antiviral effect was tested against Coxsackievirus B (CV-B, a significant human and mouse pathogen that causes pediatric central nervous system disease, commonly with acute syndromes. The reduction of viral infectivity by the essential oil was measured using a cytopathic (CPE reduction assay.

  3. TRBP and eIF6 homologue in Marsupenaeus japonicus play crucial roles in antiviral response.

    Directory of Open Access Journals (Sweden)

    Shuai Wang

    Full Text Available Plants and invertebrates can suppress viral infection through RNA silencing, mediated by RNA-induced silencing complex (RISC. Trans-activation response RNA-binding protein (TRBP, consisting of three double-stranded RNA-binding domains, is a component of the RISC. In our previous paper, a TRBP homologue in Fenneropenaeus chinensis (Fc-TRBP was reported to directly bind to eukaryotic initiation factor 6 (Fc-eIF6. In this study, we further characterized the function of TRBP and the involvement of TRBP and eIF6 in antiviral RNA interference (RNAi pathway of shrimp. The double-stranded RNA binding domains (dsRBDs B and C of the TRBP from Marsupenaeus japonicus (Mj-TRBP were found to mediate the interaction of TRBP and eIF6. Gel-shift assays revealed that the N-terminal of Mj-TRBP dsRBD strongly binds to double-stranded RNA (dsRNA and that the homodimer of the TRBP mediated by the C-terminal dsRBD increases the affinity to dsRNA. RNAi against either Mj-TRBP or Mj-eIF6 impairs the dsRNA-induced sequence-specific RNAi pathway and facilitates the proliferation of white spot syndrome virus (WSSV. These results further proved the important roles of TRBP and eIF6 in the antiviral response of shrimp.

  4. Upregulation of innate antiviral restricting factor expression in the cord blood and decidual tissue of HIV-infected mothers.

    Science.gov (United States)

    Pereira, Nátalli Zanete; Cardoso, Elaine Cristina; Oliveira, Luanda Mara da Silva; de Lima, Josenilson Feitosa; Branco, Anna Cláudia Calvielli Castelo; Ruocco, Rosa Maria de Souza Aveiro; Zugaib, Marcelo; de Oliveira Filho, João Bosco; Duarte, Alberto José da Silva; Sato, Maria Notomi

    2013-01-01

    Programs for the prevention of mother-to-child transmission of HIV have reduced the transmission rate of perinatal HIV infection and have thereby increased the number of HIV-exposed uninfected (HEU) infants. Natural immunity to HIV-1 infection in both mothers and newborns needs to be further explored. In this study, we compared the expression of antiviral restricting factors in HIV-infected pregnant mothers treated with antiretroviral therapy (ART) in pregnancy (n=23) and in cord blood (CB) (n=16), placental tissues (n=10-13) and colostrum (n=5-6) samples and compared them to expression in samples from uninfected (UN) pregnant mothers (n=21). Mononuclear cells (MNCs) were prepared from maternal and CB samples following deliveries by cesarean section. Maternal (decidua) and fetal (chorionic villus) placental tissues were obtained, and colostrum was collected 24 h after delivery. The mRNA and protein expression levels of antiviral factors were then evaluated. We observed a significant increase in the mRNA expression levels of antiviral factors in MNCs from HIV-infected mothers and CB, including the apolipoprotein B mRNA-editing enzyme 3G (A3G), A3F, tripartite motif family-5α (TRIM-5α), TRIM-22, myxovirus resistance protein A (MxA), stimulator of interferon (IFN) genes (STING) and IFN-β, compared with the levels detected in uninfected (UN) mother-CB pairs. Moreover, A3G transcript and protein levels and α-defensin transcript levels were decreased in the decidua of HIV-infected mothers. Decreased TRIM-5α protein levels in the villi and increased STING mRNA expression in both placental tissues were also observed in HIV-infected mothers compared with uninfected (UN) mothers. Additionally, colostrum cells from infected mothers showed increased tetherin and IFN-β mRNA levels and CXCL9 protein levels. The data presented here indicate that antiviral restricting factor expression can be induced in utero in HIV-infected mothers. Future studies are warranted to determine

  5. [A new challenge in clinical practice: resistance to directly acting antivirals in hepatitis C treatment].

    Science.gov (United States)

    Chen, Z W; Hu, P; Ren, H

    2016-03-20

    Directly acting antivirals (DAAs) is a major treatment of hepatitis C virus (HCV) overseas. But DAAs resistance is getting more and more clinicians' attention. DAAs have not been approved in China to date, even though some of them are in clinical trials. However, a good knowledge of DAAs resistance is important on optimizing HCV treatment regimens, increasing sustained virological response (SVR) and decreasing treatment failure in clinical. In this review, DAAs resistance mechanism and virologic barrier to resistance, the prevalence of pre-existing DAAs resistance-associated variants (RAVs), the impact of RAVs on treatment outcome, the options of treatment regimens after resistance and drug resistance testing are discussed, hoping to provide some help for DAAs' standardized treatment in China in the future.

  6. High antiviral effects of hibiscus tea extract on the H5 subtypes of low and highly pathogenic avian influenza viruses.

    Science.gov (United States)

    Baatartsogt, Tugsbaatar; Bui, Vuong N; Trinh, Dai Q; Yamaguchi, Emi; Gronsang, Dulyatad; Thampaisarn, Rapeewan; Ogawa, Haruko; Imai, Kunitoshi

    2016-10-01

    Viral neuraminidase inhibitors are widely used as synthetic anti-influenza drugs for the prevention and treatment of influenza. However, drug-resistant influenza A virus variants, including H5N1 highly pathogenic avian influenza viruses (HPAIVs), have been reported. Therefore, the discovery of novel and effective antiviral agents is warranted. We screened the antiviral effects of 11 herbal tea extracts (hibiscus, black tea, tencha, rosehip tea, burdock tea, green tea, jasmine tea, ginger tea, lavender tea, rose tea and oak tea) against the H5N1 HPAIV in vitro. Among the tested extracts, only the hibiscus extract and its fractionated extract (frHibis) highly and rapidly reduced the titers of all H5 HPAIVs and low pathogenic AIVs (LPAIVs) used in the pre-treatment tests of Madin-Darby canine kidney (MDCK) cells that were inoculated with a mixture of the virus and the extract. Immunogold electron microscopy showed that anti-H5 monoclonal antibodies could not bind to the deformed H5 virus particles pretreated with frHibis. In post-treatment tests of MDCK cells cultured in the presence of frHibis after infection with H5N1 HPAIV, the frHibis inhibited viral replication and the expression of viral antigens and genes. Among the plants tested, hibiscus showed the most prominent antiviral effects against both H5 HPAIV and LPAIV.

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

    International Nuclear Information System (INIS)

    Sasaki, Yutaka; Kakisaka, Michinori; Chutiwitoonchai, Nopporn; Tajima, Shigeru; Hikono, Hirokazu; Saito, Takehiko; Aida, Yoko

    2014-01-01

    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 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

  8. 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.

  9. Antiviral Activity of Favipiravir (T-705) against a Broad Range of Paramyxoviruses In Vitro and against Human Metapneumovirus in Hamsters.

    Science.gov (United States)

    Jochmans, D; van Nieuwkoop, S; Smits, S L; Neyts, J; Fouchier, R A M; van den Hoogen, B G

    2016-08-01

    The clinical impact of infections with respiratory viruses belonging to the family Paramyxoviridae argues for the development of antiviral therapies with broad-spectrum activity. Favipiravir (T-705) has demonstrated potent antiviral activity against multiple RNA virus families and is presently in clinical evaluation for the treatment of influenza. Here we demonstrate in vitro activity of T-705 against the paramyxoviruses human metapneumovirus (HMPV), respiratory syncytial virus, human parainfluenza virus, measles virus, Newcastle disease virus, and avian metapneumovirus. In addition, we demonstrate activity against HMPV in hamsters. T-705 treatment inhibited replication of all paramyxoviruses tested in vitro, with 90% effective concentration (EC90) values of 8 to 40 μM. Treatment of HMPV-challenged hamsters with T-705 at 200 mg/kg of body weight/day resulted in 100% protection from infection of the lungs. In all treated and challenged animals, viral RNA remained detectable in the respiratory tract. The observation that T-705 treatment had a significant effect on infectious viral titers, with a limited effect on viral genome titers, is in agreement with its proposed mode of action of viral mutagenesis. However, next-generation sequencing of viral genomes isolated from treated and challenged hamsters did not reveal (hyper)mutation. Polymerase activity assays revealed a specific effect of T-705 on the activity of the HMPV polymerase. With the reported antiviral activity of T-705 against a broad range of RNA virus families, this small molecule is a promising broad-range antiviral drug candidate for limiting the viral burden of paramyxoviruses and for evaluation for treatment of infections with (re)emerging viruses, such as the henipaviruses. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

  10. Case report

    African Journals Online (AJOL)

    abp

    2013-11-04

    Nov 4, 2013 ... especially in developing countries. HBV can be complicated by acute glomerulonephritis , this association remains controversial. The optimal therapy is undefined, although in several studies, the antiviral drugs and the immunosuppressive therapy have been tried for those patients [1]. We report the case of ...

  11. Human Cytomegalovirus Encoded miR-US25-1-5p Attenuates CD147/EMMPRIN-Mediated Early Antiviral Response

    Directory of Open Access Journals (Sweden)

    Jun Chen

    2017-12-01

    Full Text Available Cellular receptor-mediated signaling pathways play critical roles during the initial immune response to Human Cytomegalovirus (HCMV infection. However, the involvement of type-I transmembrane glycoprotein CD147/EMMPRIN (extracellular matrix metalloproteinase inducer in the antiviral response to HCMV infection is still unknown. Here, we demonstrated the specific knockdown of CD147 significantly decreased HCMV-induced activation of NF-κB and Interferon-beta (IFN-β, which contribute to the cellular antiviral responses. Next, we confirmed that HCMV-encoded miR-US25-1-5p could target the 3′ UTR (Untranslated Region of CD147 mRNA, and thus facilitate HCMV lytic propagation at a low multiplicity of infection (MOI. The expression and secretion of Cyclophilin A (sCyPA, as a ligand for CD147 and a proinflammatory cytokine, were up-regulated in response to HCMV stimuli. Finally, we confirmed that CD147 mediated HCMV-triggered antiviral signaling via the sCyPA-CD147-ERK (extracellular regulated protein kinases/NF-κB axis signaling pathway. These findings reveal an important HCMV mechanism for evading antiviral innate immunity through its encoded microRNA by targeting transmembrane glycoprotein CD147, and a potential cause of HCMV inflammatory disorders due to the secretion of proinflammatory cytokine CyPA.

  12. Alpinone exhibited immunomodulatory and antiviral activities in Atlantic salmon.

    Science.gov (United States)

    Valenzuela, Beatriz; Rodríguez, Felipe E; Modak, Brenda; Imarai, Mónica

    2018-03-01

    In this study, we seek to identify flavonoids able to regulate the gene expression of a group of cytokines important for the control of infections in Atlantic salmon (Salmo salar). Particularly, we studied the potential immunomodulatory effects of two flavonoids, Alpinone and Pinocembrine, which were isolated and purified from resinous exudates of Heliotropium huascoense and Heliotropium sinuatum, respectively. The transcript levels of TNF-α and IL-1 (inflammatory cytokines), IFN-γ and IL-12 (T helper 1 type cytokines), IL4/13A (Th2-type cytokine), IL-17 (Th17 type cytokine) TGF-β1 (regulatory cytokine) and IFN-α (antiviral cytokine) were quantified by qRT-PCR in kidneys of flavonoid-treated and control fish. We demonstrated that the administration of a single intramuscular dose of purified Alpinone increased the transcriptional expression of five cytokines, named TNF-α, IL-1, IFN-α, IFN-γ and TGF-β1 in treated fish compared to untreated fish. Conversely, administration of purified Pinocembrine reduced the transcriptional expression of TNF-α, IL-1 and IL-12 in the kidney of treated fish. No other changes were observed. Interestingly, Alpinone also induced in vitro antiviral effects against Infectious Salmon Anaemia virus. Results showed that Alpinone but not Pinocembrine induces the expression of cytokines, which in vertebrates are essential to control viral infections while Pinocembrine reduces pro-inflammatory cytokines. Altogether results suggest that Alpinone is a good candidate to be further tested as immunostimulant and antiviral drug. Copyright © 2017 Elsevier Ltd. All rights reserved.

  13. Addressing the selectivity and toxicity of antiviral nucleosides.

    Science.gov (United States)

    Feng, Joy Y

    2018-01-01

    Nucleoside and nucleotide analogs have played significant roles in antiviral therapies and are valued for their impressive potency and high barrier to resistance. They have been approved for treatment of herpes simplex virus-1, HIV, HBV, HCV, and influenza, and new drugs are being developed for the treatment of RSV, Ebola, coronavirus MERS, and other emerging viruses. However, this class of compounds has also experienced a high attrition rate in clinical trials due to toxicity. In this review, we discuss the utility of different biochemical and cell-based assays and provide recommendations for assessing toxicity liability before entering animal toxicity studies.

  14. Antiviral therapy and prophylaxis of acute respiratory infections

    Directory of Open Access Journals (Sweden)

    L. V. Osidak

    2012-01-01

    Full Text Available Thearticle presents the results of years of studies (including biochemical and immunological of the effectiveness of application and prophylaxis (in relation to nosocomial infections and the safety of antiviral chemical preparation Arbidol in 694 children with influenza and influenza-like illness, including the coronavirus infection (43 children and combined lesions of respiratory tract (150, indicating the possible inclusion of the drug in the complex therapy for children with the listed diseases, regardless of the severity and nature of their course. The studies were conducted according to the regulated standard of test conditions and randomized clinical trials.

  15. Direct-acting antivirals for chronic hepatitis C

    DEFF Research Database (Denmark)

    Jakobsen, Janus C; Nielsen, Emil Eik; Feinberg, Joshua

    2017-01-01

    and Drug Administration (FDA) (www.fda.gov), and pharmaceutical company sources for ongoing or unpublished trials. Searches were last run in October 2016. SELECTION CRITERIA: Randomised clinical trials comparing DAAs versus no intervention or placebo, alone or with co-interventions, in adults with chronic......BACKGROUND: Millions of people worldwide suffer from hepatitis C, which can lead to severe liver disease, liver cancer, and death. Direct-acting antivirals (DAAs) are relatively new and expensive interventions for chronic hepatitis C, and preliminary results suggest that DAAs may eradicate...

  16. Potencial antiviral da quercetina sobre o parvovírus canino Antiviral potencial of quercetin in canine parvovirus

    Directory of Open Access Journals (Sweden)

    O.V. Carvalho

    2013-04-01

    Full Text Available Avaliou-se o efeito do flavonoide quercetina na replicação do parvovírus canino in vitro por meio do ensaio de determinação da atividade virucida (ensaio 1, ensaio de determinação da atividade sobre a célula (ensaio 2 e ensaio de tempo de adição das drogas em diferentes etapas do ciclo replicativo viral (ensaio 3. A quercetina apresentou significante atividade antiviral, com valores máximos de redução do título viral de 96,3% no ensaio 1, 90% no ensaio 2 e 90% no ensaio 3. Os efeitos mais expressivos ocorreram nas etapas de adsorção e penetração viral. Os resultados deste trabalho sugerem a importância da quercetina para a medicina veterinária.The in vitro effect of the flavonoid quercetin against canine parvovirus was evaluated. The antiviral activity of quercetin was evaluated by determining the virucidal activity (assay 1, determining the activity on the cell (assay 2 and using the time of addition assay to test the inhibition of the viral replication cycle (assay 3. Quercetin showed a significant antiviral activity, with maximum viral titer reduction of 96.3% in assay 1, 90% in assay 2 and 90% in assay 3. The most expressive effects occurred in the stages of viral adsorption and penetration. The results show the importance of quercetin for veterinary medicine.

  17. Evasion of Early Antiviral Responses by Herpes Simplex Viruses

    Science.gov (United States)

    Suazo, Paula A.; Ibañez, Francisco J.; Retamal-Díaz, Angello R.; Paz-Fiblas, Marysol V.; Bueno, Susan M.; Kalergis, Alexis M.; González, Pablo A.

    2015-01-01

    Besides overcoming physical constraints, such as extreme temperatures, reduced humidity, elevated pressure, and natural predators, human pathogens further need to overcome an arsenal of antimicrobial components evolved by the host to limit infection, replication and optimally, reinfection. Herpes simplex virus-1 (HSV-1) and herpes simplex virus-2 (HSV-2) infect humans at a high frequency and persist within the host for life by establishing latency in neurons. To gain access to these cells, herpes simplex viruses (HSVs) must replicate and block immediate host antiviral responses elicited by epithelial cells and innate immune components early after infection. During these processes, infected and noninfected neighboring cells, as well as tissue-resident and patrolling immune cells, will sense viral components and cell-associated danger signals and secrete soluble mediators. While type-I interferons aim at limiting virus spread, cytokines and chemokines will modulate resident and incoming immune cells. In this paper, we discuss recent findings relative to the early steps taking place during HSV infection and replication. Further, we discuss how HSVs evade detection by host cells and the molecular mechanisms evolved by these viruses to circumvent early antiviral mechanisms, ultimately leading to neuron infection and the establishment of latency. PMID:25918478

  18. The interferon response circuit in antiviral host defense.

    Science.gov (United States)

    Haller, O; Weber, F

    2009-01-01

    Viruses have learned to multiply in the face of a powerful innate and adaptive immune response of the host. They have evolved multiple strategies to evade the interferon (IFN) system which would otherwise limit virus growth at an early stage of infection. IFNs induce the synthesis of a range of antiviral proteins which serve as cell-autonomous intrinsic restriction factors. For example, the dynamin-like MxA GTPase inhibits the multiplication of influenza and bunyaviruses (such as La Crosse virus, Hantaan virus, Rift Valley Fever virus, and Crimean-Congo hemorrhagic fever virus) by binding and sequestering the nucleocapsid protein into large perinuclear complexes. To overcome such intracellular restrictions, virulent viruses either inhibit IFN synthesis, bind and inactivate secreted IFN molecules, block IFN-activated signaling, or disturb the action of IFN-induced antiviral proteins. Many viruses produce specialized proteins to disarm the danger signal or express virulence genes that target members of the IFN regulatory factor family (IRFs) or components of the JAK-STAT signaling pathway. An alternative evasion strategy is based on extreme viral replication speed which out-competes the IFN response. The identification of viral proteins with IFN antagonistic functions has great implications for disease prevention and therapy. Virus mutants lacking IFN antagonistic properties represent safe yet highly immunogenic candidate vaccines. Furthermore, novel drugs intercepting viral IFN-antagonists could be used to disarm the viral intruders.

  19. Mechanisms of Hepatitis C Viral Resistance to Direct Acting Antivirals.

    Science.gov (United States)

    Ahmed, Asma; Felmlee, Daniel J

    2015-12-18

    There has been a remarkable transformation in the treatment of chronic hepatitis C in recent years with the development of direct acting antiviral agents targeting virus encoded proteins important for viral replication including NS3/4A, NS5A and NS5B. These agents have shown high sustained viral response (SVR) rates of more than 90% in phase 2 and phase 3 clinical trials; however, this is slightly lower in real-life cohorts. Hepatitis C virus resistant variants are seen in most patients who do not achieve SVR due to selection and outgrowth of resistant hepatitis C virus variants within a given host. These resistance associated mutations depend on the class of direct-acting antiviral drugs used and also vary between hepatitis C virus genotypes and subtypes. The understanding of these mutations has a clear clinical implication in terms of choice and combination of drugs used. In this review, we describe mechanism of action of currently available drugs and summarize clinically relevant resistance data.

  20. Mechanisms of Hepatitis C Viral Resistance to Direct Acting Antivirals

    Directory of Open Access Journals (Sweden)

    Asma Ahmed

    2015-12-01

    Full Text Available There has been a remarkable transformation in the treatment of chronic hepatitis C in recent years with the development of direct acting antiviral agents targeting virus encoded proteins important for viral replication including NS3/4A, NS5A and NS5B. These agents have shown high sustained viral response (SVR rates of more than 90% in phase 2 and phase 3 clinical trials; however, this is slightly lower in real-life cohorts. Hepatitis C virus resistant variants are seen in most patients who do not achieve SVR due to selection and outgrowth of resistant hepatitis C virus variants within a given host. These resistance associated mutations depend on the class of direct-acting antiviral drugs used and also vary between hepatitis C virus genotypes and subtypes. The understanding of these mutations has a clear clinical implication in terms of choice and combination of drugs used. In this review, we describe mechanism of action of currently available drugs and summarize clinically relevant resistance data.

  1. RNAi and Antiviral Defense in the Honey Bee

    Science.gov (United States)

    Brutscher, Laura M.; Flenniken, Michelle L.

    2015-01-01

    Honey bees play an important agricultural and ecological role as pollinators of numerous agricultural crops and other plant species. Therefore, investigating the factors associated with high annual losses of honey bee colonies in the US is an important and active area of research. Pathogen incidence and abundance correlate with Colony Collapse Disorder- (CCD-) affected colonies in the US and colony losses in the US and in some European countries. Honey bees are readily infected by single-stranded positive sense RNA viruses. Largely dependent on the host immune response, virus infections can either remain asymptomatic or result in deformities, paralysis, or death of adults or larvae. RNA interference (RNAi) is an important antiviral defense mechanism in insects, including honey bees. Herein, we review the role of RNAi in honey bee antiviral defense and highlight some parallels between insect and mammalian immune systems. A more thorough understanding of the role of pathogens on honey bee health and the immune mechanisms bees utilize to combat infectious agents may lead to the development of strategies that enhance honey bee health and result in the discovery of additional mechanisms of immunity in metazoans. PMID:26798663

  2. RNAi and Antiviral Defense in the Honey Bee

    Directory of Open Access Journals (Sweden)

    Laura M. Brutscher

    2015-01-01

    Full Text Available Honey bees play an important agricultural and ecological role as pollinators of numerous agricultural crops and other plant species. Therefore, investigating the factors associated with high annual losses of honey bee colonies in the US is an important and active area of research. Pathogen incidence and abundance correlate with Colony Collapse Disorder- (CCD- affected colonies in the US and colony losses in the US and in some European countries. Honey bees are readily infected by single-stranded positive sense RNA viruses. Largely dependent on the host immune response, virus infections can either remain asymptomatic or result in deformities, paralysis, or death of adults or larvae. RNA interference (RNAi is an important antiviral defense mechanism in insects, including honey bees. Herein, we review the role of RNAi in honey bee antiviral defense and highlight some parallels between insect and mammalian immune systems. A more thorough understanding of the role of pathogens on honey bee health and the immune mechanisms bees utilize to combat infectious agents may lead to the development of strategies that enhance honey bee health and result in the discovery of additional mechanisms of immunity in metazoans.

  3. Antiviral Activity of Natural Products Extracted from Marine Organisms

    Directory of Open Access Journals (Sweden)

    Sobia Tabassum

    2011-11-01

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

  4. New antivirals for the treatment of chronic hepatitis B.

    Science.gov (United States)

    Soriano, Vincent; Barreiro, Pablo; Benitez, Laura; Peña, Jose M; de Mendoza, Carmen

    2017-07-01

    Current treatment with oral nucleos(t)ides entecavir or tenofovir provide sustained suppression of HBV replication and clinical benefit in most chronic hepatitis B virus (HBV) infected persons. However, HBV rebound generally occurs upon drug discontinuation due to persistence of genomic HBV reservoirs as episomic cccDNA and chromosomic integrated HBV-DNA. There is renewed enthusiasm on HBV drug discovery following recent successes with antivirals for hepatitis C and immunotherapies for some cancers. Areas covered: New drugs that target distinct steps of the HBV life cycle are been developed, including inhibitors of viral entry, new polymerase inhibitors, capsid and assembly inhibitors, virus release blockers, and disruptors of cccDNA formation and transcription. Alongside these antivirals, agents that enhance anti-HBV specific immune responses are being tested, including TLR agonists, checkpoint inhibitors and therapeutic vaccines. Expert opinion: The achievement of a 'functional cure' for chronic HBV infection, with sustained HBsAg clearance and undetectable viremia once medications are stopped, represents the next step in the pace towards HBV elimination. Hopefully, the combination of new drugs that eliminate or functionally inactivate the genomic HBV reservoirs (cccDNA and integrated HBV-DNA) along with agents that enhance or activate immune responses against HBV will lead to a 'definitive cure' for chronic HBV infection.

  5. Effectiveness of air vapor barriers combined with ventilated crawlspaces in decreasing residential exposure to radon daughters to radon daughters: preliminary report

    International Nuclear Information System (INIS)

    Sterling, T.D.; Arundel, A.; McIntyre, D.; Sterling, E.; Sterling, T.D.

    1986-01-01

    Radon gas is present in many homes. Concentrations may be increased in airtight, energy-efficient structures. This is especially true in cold climates where energy conservation is an important factor leading to the widespread application of sealing and tightening techniques both in older renovated homes and new construction. To reduce radon concentrations, it may be effective to ventilate crawlspaces and prevent infiltration of radon gas into the house by means of an air/vapor barrier. The authors report first results of comparing radon levels in homes with and without ventilated crawlspaces and air/vapor barriers. Radon emissions were measured in a tightly sealed home with ventilated crawlspaces and an air/vapor barrier and in two homes without such vapor barriers and ventilated crawlspaces, but differing in ventilation. Preliminary results suggest that use of ventilated crawlspaces and bottomside vapor barriers may reduce indoor radon levels by approximately 60%. 15 references, 1 table

  6. Decreases in self-reported sleep duration among U.S. adolescents 2009-2015 and association with new media screen time.

    Science.gov (United States)

    Twenge, Jean M; Krizan, Zlatan; Hisler, Garrett

    2017-11-01

    Insufficient sleep among adolescents carries significant health risks, making it important to determine social factors that change sleep duration. We sought to determine whether the self-reported sleep duration of U.S. adolescents changed between 2009 and 2015 and examine whether new media screen time (relative to other factors) might be responsible for changes in sleep. We drew from yearly, nationally representative surveys of sleep duration and time use among adolescents conducted since 1991 (Monitoring the Future) and 2007 (Youth Risk Behavior Surveillance System of the Centers for Disease Control; total N = 369,595). Compared to 2009, adolescents in 2015 were 16%-17% more likely to report sleeping less than 7 h a night on most nights, with an increase in short sleep duration after 2011-2013. New media screen time (electronic device use, social media, and reading news online) increased over this time period and was associated with increased odds of short sleep duration, with a clear exposure-response relationship for electronic devices after 2 or more hours of use per day. Other activities associated with short sleep duration, such as homework time, working for pay, and TV watching, were relatively stable or reduced over this time period, making it unlikely that these activities caused the sudden increase in short sleep duration. Increased new media screen time may be involved in the recent increases (from 35% to 41% and from 37% to 43%) in short sleep among adolescents. Public health interventions should consider electronic device use as a target of intervention to improve adolescent health. Copyright © 2017 Elsevier B.V. All rights reserved.

  7. Orange juice as dietary source of antioxidants for patients with hepatitis C under antiviral therapy.

    Science.gov (United States)

    Gonçalves, Danielle; Lima, Claudia; Ferreira, Paula; Costa, Paulo; Costa, Angela; Figueiredo, Walter; Cesar, Thais

    2017-01-01

    Background: HCV causes alterations in liver metabolism, resulting in biochemical and nutritional disorders. Supplementation with antioxidants has been suggested to minimize the diseases effects. Objective: This study assessed whether orange juice, a source of citrus flavonoids and vitamin C, may contribute to the treatment of patients with chronic hepatitis C. Design: Anthropometric, hemodynamic, dietary, and biochemical parameters, CRP and liver enzymes were measured in 43 adult patients of both genders who were diagnosed with chronic hepatitis C and were under antiviral therapy. Twenty-three patients were supplemented with orange juice for eight consecutive weeks, while 20 were enrolled as control group. Results: Following regular use of orange juice, no alterations were found in body mass, fat, and waist circumference. The serum levels of total cholesterol, LDL-cholesterol, CRP and parameters of oxidative stress decreased in the orange juice group. Furthermore, the levels of the liver enzyme AST decreased in those who had high levels before the intervention. Conclusion: The orange juice was a convenient food in the diet of patients due to the increase in antioxidant capacity and decreased inflammation and cholesterol in blood serum, in addition to maintaining body mass, which protect against the harmful effects caused by the chronic hepatitis C virus.​​​.

  8. Maternal and Child Supplementation with Lipid-Based Nutrient Supplements, but Not Child Supplementation Alone, Decreases Self-Reported Household Food Insecurity in Some Settings.

    Science.gov (United States)

    Adams, Katherine P; Ayifah, Emmanuel; Phiri, Thokozani E; Mridha, Malay K; Adu-Afarwuah, Seth; Arimond, Mary; Arnold, Charles D; Cummins, Joseph; Hussain, Sohrab; Kumwenda, Chiza; Matias, Susana L; Ashorn, Ulla; Lartey, Anna; Maleta, Kenneth M; Vosti, Stephen A; Dewey, Kathryn G

    2017-12-01

    Background: It is unknown whether self-reported measures of household food insecurity change in response to food-based nutrient supplementation. Objective: We assessed the impacts of providing lipid-based nutrient supplements (LNSs) to women during pregnancy and postpartum and/or to their children on self-reported household food insecurity in Malawi [DOSE and DYAD trial in Malawi (DYAD-M)], Ghana [DYAD trial in Ghana (DYAD-G)], and Bangladesh [Rang-Din Nutrition Study (RDNS) trial]. Methods: Longitudinal household food-insecurity data were collected during 3 individually randomized trials and 1 cluster-randomized trial testing the efficacy or effectiveness of LNSs (generally 118 kcal/d). Seasonally adjusted Household Food Insecurity Access Scale (HFIAS) scores were constructed for 1127 DOSE households, 732 DYAD-M households, 1109 DYAD-G households, and 3671 RDNS households. The impact of providing LNSs to women during pregnancy and the first 6 mo postpartum and/or to their children from 6 to 18-24 mo on seasonally adjusted HFIAS scores was assessed by using negative binomial models (DOSE, DYAD-M, and DYAD-G trials) and mixed-effect negative binomial models (RDNS trial). Results: In the DOSE and DYAD-G trials, seasonally adjusted HFIAS scores were not different between the LNS and non-LNS groups. In the DYAD-M trial, the average household food-insecurity scores were 14% lower ( P = 0.01) in LNS households than in non-LNS households. In the RDNS trial, compared with non-LNS households, food-insecurity scores were 17% lower ( P = 0.02) during pregnancy and the first 6 mo postpartum and 15% lower ( P = 0.02) at 6-24 mo postpartum in LNS households. Conclusions: The daily provision of LNSs to mothers and their children throughout much of the "first 1000 d" may improve household food security in some settings, which could be viewed as an additional benefit that may accrue in households should policy makers choose to invest in LNSs to promote child growth and development

  9. Carnitine deficiency presenting with a decreased mental state in a patient with amyotrophic lateral sclerosis receiving long-term tube feeding: a case report.

    Science.gov (United States)

    Isse, Naohi; Miura, Yoh; Obata, Toshiyuki; Takahara, Noriko

    2013-12-30

    L-carnitine is an important metabolic mediator involved in fatty acid transport. It is obtained from the diet, particularly from animal products, such as red meat. Previous reports have revealed that long-term tube feeding with a commercial product containing no or low levels of carnitine can lead to an altered mental state caused by hyperammonemia. A 72-year-old Japanese man had a 12-year history of amyotrophic lateral sclerosis. He was bedridden and had required mechanical ventilation and enteral tube feeding for 10 years at home. His main enteral solution was a commercial product that contained low carnitine levels, and he sometimes received coffee and homemade products such as miso soup. Our patient's ability to communicate gradually deteriorated over a period of one year. His serum total carnitine level was abnormally low, at 26.7μmol/L (normal range, 45 to 91μmol/L), but his ammonium level was normal. His mental state improved dramatically after starting L-carnitine supplementation (600mg twice daily). This case highlights the importance of avoiding carnitine deficiency in patients with amyotrophic lateral sclerosis undergoing long-term tube feeding. These patients experience progressive muscle atrophy that might cause impaired carnitine storage and might manifest as communication difficulties. Carnitine deficiency can be misdiagnosed as a progression of systemic muscle atrophy. Clinicians should be aware of this disorder and should consider periodically measuring carnitine levels, regardless of the patient's serum ammonium levels.

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

    African Journals Online (AJOL)

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

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

    African Journals Online (AJOL)

    SERVER

    2007-08-06

    Aug 6, 2007 ... In this study we tested the antiviral activity of a crude hot glycerine extract of Aloe vera gel which was grown in Bushehr (Southwest of Iran) against HSV-2 replication in Vero cell line. The extract showed antiviral activity against HSV-2 not only before attachment and entry of virus to the Vero cells but also.

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

    NARCIS (Netherlands)

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

    2014-01-01

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

  13. Antiviral treatment for chronic hepatitis C in patients with human immunodeficiency virus

    DEFF Research Database (Denmark)

    Iorio, Alfonso; Marchesini, Emanuela; Awad, Tahany

    2010-01-01

    Antiviral treatment for chronic hepatitis C may be less effective if patients are co-infected with human immunodeficiency virus (HIV).......Antiviral treatment for chronic hepatitis C may be less effective if patients are co-infected with human immunodeficiency virus (HIV)....

  14. Intelligent MONitoring System for antiviral pharmacotherapy in patients with chronic hepatitis C (SiMON-VC

    Directory of Open Access Journals (Sweden)

    Luis Margusino-Framiñán

    2017-01-01

    Full Text Available Two out of six strategic axes of pharmaceutical care in our hospital are quality and safety of care, and the incorporation of information technologies. Based on this, an information system was developed in the outpatient setting for pharmaceutical care of patients with chronic hepatitis C, SiMON-VC, which would improve the quality and safety of their pharmacotherapy. The objective of this paper is to describe requirements, structure and features of Si- MON-VC. Requirements demanded were that the information system would enter automatically all critical data from electronic clinical records at each of the visits to the Outpatient Pharmacy Unit, allowing the generation of events and alerts, documenting the pharmaceutical care provided, and allowing the use of data for research purposes. In order to meet these requirements, 5 sections were structured for each patient in SiMON-VC: Main Record, Events, Notes, Monitoring Graphs and Tables, and Follow-up. Each section presents a number of tabs with those coded data needed to monitor patients in the outpatient unit. The system automatically generates alerts for assisted prescription validation, efficacy and safety of using antivirals for the treatment of this disease. It features a completely versatile Indicator Control Panel, where temporary monitoring standards and alerts can be set. It allows the generation of reports, and their export to the electronic clinical record. It also allows data to be exported to the usual operating systems, through Big Data and Business Intelligence. Summing up, we can state that SiMON-VC improves the quality of pharmaceutical care provided in the outpatient pharmacy unit to patients with chronic hepatitis C, increasing the safety of antiviral therapy.

  15. Decreasing Relative Risk Premium

    DEFF Research Database (Denmark)

    Hansen, Frank

    relative risk premium in the small implies decreasing relative risk premium in the large, and decreasing relative risk premium everywhere implies risk aversion. We finally show that preferences with decreasing relative risk premium may be equivalently expressed in terms of certain preferences on risky......We consider the risk premium demanded by a decision maker with wealth x in order to be indifferent between obtaining a new level of wealth y1 with certainty, or to participate in a lottery which either results in unchanged present wealth or a level of wealth y2 > y1. We define the relative risk...... premium as the quotient between the risk premium and the increase in wealth y1–x which the decision maker puts on the line by choosing the lottery in place of receiving y1 with certainty. We study preferences such that the relative risk premium is a decreasing function of present wealth, and we determine...

  16. Distinct cytoplasmic domains of the growth hormone receptor are required for glucocorticoid- and phorbol ester-induced decreases in growth hormone (GH) binding. These domains are different from that reported for GH-induced receptor internalization

    DEFF Research Database (Denmark)

    King, A P; Tseng, M J; Logsdon, C D

    1996-01-01

    Glucocorticoids inhibit growth in children and antagonize the growth-promoting action of GH in peripheral tissues. Recently, they have been shown to decrease GH binding. In this study we examine the molecular mechanisms by which the glucocorticoid dexamethasone (DEX) and the phorbol ester phorbol...... of GH binding are also observed in a Chinese hamster ovary (CHO) cell line stably transfected with a rat liver GHR cDNA, further arguing that DEX and PMA act post-translationally on GHR. Using mutant GHRs stably expressed in CHO cells, amino acids 455-506 and tyrosines 333 and/or 338 of GHR were shown...... to be required for maximal DEX-induced inhibition of GH binding. DEX decreased GH binding to a GHR mutant F346A, which is reported to be deficient in ligand-induced internalization, suggesting that DEX decreases GH binding by a mechanism distinct from that of ligand-induced GHR internalization. PMA reduced GH...

  17. Decreasing Serial Cost Sharing

    DEFF Research Database (Denmark)

    Hougaard, Jens Leth; Østerdal, Lars Peter

    The increasing serial cost sharing rule of Moulin and Shenker [Econometrica 60 (1992) 1009] and the decreasing serial rule of de Frutos [Journal of Economic Theory 79 (1998) 245] have attracted attention due to their intuitive appeal and striking incentive properties. An axiomatic characterization...... of the increasing serial rule was provided by Moulin and Shenker [Journal of Economic Theory 64 (1994) 178]. This paper gives an axiomatic characterization of the decreasing serial rule...

  18. Decreasing serial cost sharing

    DEFF Research Database (Denmark)

    Hougaard, Jens Leth; Østerdal, Lars Peter Raahave

    2009-01-01

    The increasing serial cost sharing rule of Moulin and Shenker (Econometrica 60:1009-1037, 1992) and the decreasing serial rule of de Frutos (J Econ Theory 79:245-275, 1998) are known by their intuitive appeal and striking incentive properties. An axiomatic characterization of the increasing serial...... rule was provided by Moulin and Shenker (J Econ Theory 64:178-201, 1994). This paper gives an axiomatic characterization of the decreasing serial rule....

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

    Directory of Open Access Journals (Sweden)

    Anwei Ding

    2013-08-01

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

  20. Resistance to Rhabdoviridae Infection and Subversion of Antiviral Responses

    Directory of Open Access Journals (Sweden)

    Danielle Blondel

    2015-07-01

    Full Text Available Interferon (IFN treatment induces the expression of hundreds of IFN-stimulated genes (ISGs. However, only a selection of their products have been demonstrated to be responsible for the inhibition of rhabdovirus replication in cultured cells; and only a few have been shown to play a role in mediating the antiviral response in vivo using gene knockout mouse models. IFNs inhibit rhabdovirus replication at different stages via the induction of a variety of ISGs. This review will discuss how individual ISG products confer resistance to rhabdoviruses by blocking viral entry, degrading single stranded viral RNA, inhibiting viral translation or preventing release of virions from the cell. Furthermore, this review will highlight how these viruses counteract the host IFN system.

  1. Resistance to Rhabdoviridae Infection and Subversion of Antiviral Responses.

    Science.gov (United States)

    Blondel, Danielle; Maarifi, Ghizlane; Nisole, Sébastien; Chelbi-Alix, Mounira K

    2015-07-07

    Interferon (IFN) treatment induces the expression of hundreds of IFN-stimulated genes (ISGs). However, only a selection of their products have been demonstrated to be responsible for the inhibition of rhabdovirus replication in cultured cells; and only a few have been shown to play a role in mediating the antiviral response in vivo using gene knockout mouse models. IFNs inhibit rhabdovirus replication at different stages via the induction of a variety of ISGs. This review will discuss how individual ISG products confer resistance to rhabdoviruses by blocking viral entry, degrading single stranded viral RNA, inhibiting viral translation or preventing release of virions from the cell. Furthermore, this review will highlight how these viruses counteract the host IFN system.

  2. Resistance to Rhabdoviridae Infection and Subversion of Antiviral Responses

    Science.gov (United States)

    Blondel, Danielle; Maarifi, Ghizlane; Nisole, Sébastien; Chelbi-Alix, Mounira K.

    2015-01-01

    Interferon (IFN) treatment induces the expression of hundreds of IFN-stimulated genes (ISGs). However, only a selection of their products have been demonstrated to be responsible for the inhibition of rhabdovirus replication in cultured cells; and only a few have been shown to play a role in mediating the antiviral response in vivo using gene knockout mouse models. IFNs inhibit rhabdovirus  replication at different stages via the induction of a variety of ISGs. This review will discuss how individual ISG products confer resistance to rhabdoviruses by blocking viral entry, degrading single stranded viral RNA, inhibiting viral translation or preventing release of virions from the cell. Furthermore, this review will highlight how these viruses counteract the host IFN system. PMID:26198243

  3. Optimal antiviral switching to minimize resistance risk in HIV therapy.

    Directory of Open Access Journals (Sweden)

    Rutao Luo

    Full Text Available The development of resistant strains of HIV is the most significant barrier to effective long-term treatment of HIV infection. The most common causes of resistance development are patient noncompliance and pre-existence of resistant strains. In this paper, methods of antiviral regimen switching are developed that minimize the risk of pre-existing resistant virus emerging during therapy switches necessitated by virological failure. Two distinct cases are considered; a single previous virological failure and multiple virological failures. These methods use optimal control approaches on experimentally verified mathematical models of HIV strain competition and statistical models of resistance risk. It is shown that, theoretically, order-of-magnitude reduction in risk can be achieved, and multiple previous virological failures enable greater success of these methods in reducing the risk of subsequent treatment failures.

  4. Griffithsin: An Antiviral Lectin with Outstanding Therapeutic Potential

    Directory of Open Access Journals (Sweden)

    Sabrina Lusvarghi

    2016-10-01

    Full Text Available Griffithsin (GRFT, an algae-derived lectin, is one of the most potent viral entry inhibitors discovered to date. It is currently being developed as a microbicide with broad-spectrum activity against several enveloped viruses. GRFT can inhibit human immunodeficiency virus (HIV infection at picomolar concentrations, surpassing the ability of most anti-HIV agents. The potential to inhibit other viruses as well as parasites has also been demonstrated. Griffithsin’s antiviral activity stems from its ability to bind terminal mannoses present in high-mannose oligosaccharides and crosslink these glycans on the surface of the viral envelope glycoproteins. Here, we review structural and biochemical studies that established mode of action and facilitated construction of GRFT analogs, mechanisms that may lead to resistance, and in vitro and pre-clinical results that support the therapeutic potential of this lectin.

  5. Antiviral Activity of Some Plants Used in Nepalese Traditional Medicine

    Directory of Open Access Journals (Sweden)

    M. Rajbhandari

    2009-01-01

    Full Text Available Methanolic extracts of 41 plant species belonging to 27 families used in the traditional medicine in Nepal have been investigated for in vitro antiviral activity against Herpes simplex virus type 1 (HSV-1 and influenza virus A by dye uptake assay in the systems HSV-1/Vero cells and influenza virus A/MDCK cells. The extracts of Astilbe rivularis, Bergenia ciliata, Cassiope fastigiata and Thymus linearis showed potent anti-herpes viral activity. The extracts of Allium oreoprasum, Androsace strigilosa, Asparagus filicinus, Astilbe rivularis, Bergenia ciliata and Verbascum thapsus exhibited strong anti-influenza viral activity. Only the extracts of A. rivularis and B. ciliata demonstrated remarkable activity against both viruses.

  6. Final report on the behalf of the Commission for Economic Affairs on the law proposal aiming at supporting the decrease of CO2 production by developing distributed load management (nr 3146) - Nr 3229

    International Nuclear Information System (INIS)

    Jego, Yves

    2015-01-01

    This report first presents the distributed load management as a response to environmental and economic challenges faced by the energy market. Peak periods must be urgently faced and distributed load management appears to be a wonderful lever for energy transition, a particularly needed solution in times of strong budgetary constraints, and a particularly interesting solution in France. Then, it shows that distributed load management is a solution which could benefit to all actors of the electricity market: consumers (decrease of their electricity bill), load management operators (equipment are made profitable by selling this load managed electricity), grid manager (easier balance between supply and demand), and providers (decrease of supply costs). The authors then outline that introducing a law would be useful to boost the load management market. The next part reports the Commission discussion, notably about the bill project content. A table compares the content of the existing arrangement, the initial law proposal text, and the text adopted by the Commission

  7. 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

    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. Keywords: type III interferon, IFN-λ, IL-29, IL-28B, analog, antiviral

  8. Potential of small-molecule fungal metabolites in antiviral chemotherapy.

    Science.gov (United States)

    Roy, Biswajit G

    2017-08-01

    Various viral diseases, such as acquired immunodeficiency syndrome, influenza, and hepatitis, have emerged as leading causes of human death worldwide. Scientific endeavor since invention of DNA-dependent RNA polymerase of pox virus in 1967 resulted in better understanding of virus replication and development of various novel therapeutic strategies. Despite considerable advancement in every facet of drug discovery process, development of commercially viable, safe, and effective drugs for these viruses still remains a big challenge. Decades of intense research yielded a handful of natural and synthetic therapeutic options. But emergence of new viruses and drug-resistant viral strains had made new drug development process a never-ending battle. Small-molecule fungal metabolites due to their vast diversity, stereochemical complexity, and preapproved biocompatibility always remain an attractive source for new drug discovery. Though, exploration of therapeutic importance of fungal metabolites has started early with discovery of penicillin, recent prediction asserted that only a small percentage (5-10%) of fungal species have been identified and much less have been scientifically investigated. Therefore, exploration of new fungal metabolites, their bioassay, and subsequent mechanistic study bears huge importance in new drug discovery endeavors. Though no fungal metabolites so far approved for antiviral treatment, many of these exhibited high potential against various viral diseases. This review comprehensively discussed about antiviral activities of fungal metabolites of diverse origin against some important viral diseases. This also highlighted the mechanistic details of inhibition of viral replication along with structure-activity relationship of some common and important classes of fungal metabolites.

  9. Molecular evolution of the primate antiviral restriction factor tetherin.

    Directory of Open Access Journals (Sweden)

    Jun Liu

    Full Text Available BACKGROUND: Tetherin is a recently identified antiviral restriction factor that restricts HIV-1 particle release in the absence of the HIV-1 viral protein U (Vpu. It is reminiscent of APOBEC3G and TRIM5a that also antagonize HIV. APOBEC3G and TRIM5a have been demonstrated to evolve under pervasive positive selection throughout primate evolution, supporting the red-queen hypothesis. Therefore, one naturally presumes that Tetherin also evolves under pervasive positive selection throughout primate evolution and supports the red-queen hypothesis. Here, we performed a detailed evolutionary analysis to address this presumption. METHODOLOGY/PRINCIPAL FINDINGS: Results of non-synonymous and synonymous substitution rates reveal that Tetherin as a whole experiences neutral evolution rather than pervasive positive selection throughout primate evolution, as well as in non-primate mammal evolution. Sliding-window analyses show that the regions of the primate Tetherin that interact with viral proteins are under positive selection or relaxed purifying selection. In particular, the sites identified under positive selection generally focus on these regions, indicating that the main selective pressure acting on the primate Tetherin comes from virus infection. The branch-site model detected positive selection acting on the ancestral branch of the New World Monkey lineage, suggesting an episodic adaptive evolution. The positive selection was also found in duplicated Tetherins in ruminants. Moreover, there is no bias in the alterations of amino acids in the evolution of the primate Tetherin, implying that the primate Tetherin may retain broad spectrum of antiviral activity by maintaining structure stability. CONCLUSIONS/SIGNIFICANCE: These results conclude that the molecular evolution of Tetherin may be attributed to the host-virus arms race, supporting the Red Queen hypothesis, and Tetherin may be in an intermediate stage in transition from neutral to pervasive

  10. An antiviral defense role of AGO2 in plants.

    Directory of Open Access Journals (Sweden)

    Jagger J W Harvey

    2011-01-01

    Full Text Available Argonaute (AGO proteins bind to small-interfering (siRNAs and micro (miRNAs to target RNA silencing against viruses, transgenes and in regulation of mRNAs. Plants encode multiple AGO proteins but, in Arabidopsis, only AGO1 is known to have an antiviral role.To uncover the roles of specific AGOs in limiting virus accumulation we inoculated turnip crinkle virus (TCV to Arabidopsis plants that were mutant for each of the ten AGO genes. The viral symptoms on most of the plants were the same as on wild type plants although the ago2 mutants were markedly hyper-susceptible to this virus. ago2 plants were also hyper-susceptible to cucumber mosaic virus (CMV, confirming that the antiviral role of AGO2 is not specific to a single virus. For both viruses, this phenotype was associated with transient increase in virus accumulation. In wild type plants the AGO2 protein was induced by TCV and CMV infection.Based on these results we propose that there are multiple layers to RNA-mediated defense and counter-defense in the interactions between plants and their viruses. AGO1 represents a first layer. With some viruses, including TCV and CMV, this layer is overcome by viral suppressors of silencing that can target AGO1 and a second layer involving AGO2 limits virus accumulation. The second layer is activated when the first layer is suppressed because AGO2 is repressed by AGO1 via miR403. The activation of the second layer is therefore a direct consequence of the loss of the first layer of defense.

  11. Interferon-Mediated Regression of Fibrosis During Antiviral Therapy for Chronic Hepatitis C in Different Variants of IL28B Gene Polymorphism

    Directory of Open Access Journals (Sweden)

    D.Ye. Telegin

    2014-02-01

    Full Text Available The article considers the relationship between the degree of reduction of HCV-induced liver fibrosis by the end of antiviral therapy (AVT for chronic hepatitis C (CHC and the main variants of IL28b gene polymorphism. Materials and Methods. Retrospectively we analyzed the outcomes of treatment of 324 patients who received standard antiviral therapy (a combination of pegylated interferons PegIFN-alpha2b or PegIFN-alpha2a and ribavirin for CHC genotype 1b. The total duration of treatment was 12 months. We evaluated three types of virologic response: rapid (RVR, 4th week of AVT, early (EVR, 12th week of AVT and sustained (SVR, 24th week after the AVT. Results and Discussion. All types of detected changes of fibrosis stages by the end of antiviral treatment in comparison with baseline values were distributed into the following groups : 1 — a significant reduction of fibrosis (25 % of treated patients, 2 — moderate decrease in fibrosis (64 % patients, 3 — unchanged degree of fibrosis (7.6 %, increased fibrosis (3.4 %. A comparison of fibrosis dynamics during antiviral therapy was carried out in the two groups of patients: without (N = 110 and with (N = 214 T-allele of the gene IL28b. The most significant decrease in the degree of fibrosis detected among patients with favorable CC gene IL28b variant, because exactly in this group of patients the frequency of SVR was highest. Among those who have reached sustained aviremia, the lowest degree of reduction of fibrosis was found in T-allele carriers of the gene IL28b. Conclusions. The findings suggest that not all patients with CHC who achieved sustained virologic response escape the risks associated with the effects of viral persistence of HCV.

  12. Antiviral effect of Anthocleista nobilis root extract on the liver homogenate indices of poultry fowls infected with Newcastle Disease Virus (NDV)

    OpenAIRE

    Ayodele P. O,; Okonko I. O,; Chukwuka K. S,; Odu N. N; Michael V. I

    2011-01-01

    This study reports the preliminary investigation of the antiviral effect of Anthocleista nobilis root extract on the liver homogenate indices of poultry fowls treated for Newcastle Disease (ND). Eighteen (18) weeks-old fowls were used for this study. These were divided into 3 groups, A (infected and with treatment), B (infected and without treatment) and C (control). Groups A and B were challenged with Newcastle disease virus (NDV). Group A and C were given ethanolic root extract of A. nobili...

  13. Decreasing relative risk premium

    DEFF Research Database (Denmark)

    Hansen, Frank

    2007-01-01

    such that the corresponding relative risk premium is a decreasing function of present wealth, and we determine the set of associated utility functions. We find a new characterization of risk vulnerability and determine a large set of utility functions, closed under summation and composition, which are both risk vulnerable...

  14. Decreasing asthma morbidity

    African Journals Online (AJOL)

    1994-12-12

    Dec 12, 1994 ... Apart from the optimal use of drugs, various supplementary methods have been tested to decrease asthma morbidity, usually in patients from reiatively affluent socio-economic backgrounds. A study of additional measures taken in a group of moderate to severe adult asthmatics from very poor socio- ...

  15. Antibiotic-Mediated Inhibition of Porcine Reproductive and Respiratory Syndrome Virus (PRRSV Infection: A Novel Quinolone Function Which Potentiates the Antiviral Cytokine Response in MARC-145 Cells and Pig Macrophages

    Directory of Open Access Journals (Sweden)

    William A. Cafruny

    2008-01-01

    Full Text Available Porcine reproductive and respiratory syndrome virus (PRRSV is an economically significant agent for which there currently are no effective treatments. Development of antiviral agents for PRRSV as well as many other viruses has been limited by toxicity of known antiviral compounds. In contrast, antibiotics for non-virus microbial infections have been widely useful, in part because of their acceptable toxicity in animals. We report here the discovery that the quinolonecontaining compound Plasmocin™, as well as the quinolones nalidixic acid and ciprofloxacin, have potent anti-PRRSV activity in vitro. PRRSV replication was inhibited by these antibiotics in both cultured MARC-145 cells and cultured primary alveolar porcine macrophages (PAMs. Furthermore, sub-optimal concentrations of nalidixic acid synergized with antiviral cytokines (AK-2 or IFN-γ to quantitatively and qualitatively inhibit PRRSV replication in MARC-145 cells or PAMs. The antiviral activity of Plasmocin and nalidixic acid correlated with reduced actin expression in MARC-145 cells. Replication of the related lactate dehydrogenase-elevating virus (LDV was also inhibited in primary mouse macrophages by Plasmocin. These results are significant to the development of antiviral strategies with potentially reduced toxicity, and provide a model system to better understand regulation of arterivirus replication.

  16. Evaluation of the combination effect of different antiviral compounds against HIV in vitro

    DEFF Research Database (Denmark)

    Sørensen, A M; Nielsen, C; Mathiesen, Lars Reinhardt

    1993-01-01

    3'-azido-3'deoxythymidine (AZT), a clinically used anti-HIV compound, was evaluated for antiviral effect on HIV infection in combination with other antiviral compounds in vitro. Interactions were evaluated by the median-effect principle and the isobologram technique. Synergistic effect was obtained...... by combining many evaluated antiviral agents with AZT. We observed a difference in the degree of synergism depending on the evaluated compound; the results indicate that compounds with the same target in the viral replicative cycle (ddI: 2',3'-dideoxyinosine, didanosine; d4T: 2',3'-dideoxy-2...

  17. 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 player... or bystander? PubmedID 16027039 Title TLR3 in antiviral immunity: key player or bystander? Authors Schr... File (.png) SVG File (.svg) HTML File (.html) CSML File (.csml) Open .csml file with CIOPlayer Open .csml file with CIOPlayer... - ※CIO Playerのご利用上の注意 Open .csml file with CIO Open .csml file with CIO - ※CIOのご利用上の注意 ...

  18. Combination siRNA therapy against feline coronavirus can delay the emergence of antiviral resistance in vitro.

    Science.gov (United States)

    McDonagh, Phillip; Sheehy, Paul A; Norris, Jacqueline M

    2015-03-23

    Virulent biotypes of feline coronavirus (FCoV), commonly referred to as feline infectious peritonitis virus (FIPV), can result in the development of feline infectious peritonitis (FIP), a typically fatal immune mediated disease for which there is currently no effective antiviral treatment. We previously reported the successful in vitro inhibition of FIPV replication by synthetic siRNA mediated RNA interference (RNAi) in an immortalised cell line (McDonagh et al., 2011). A major challenge facing the development of any antiviral strategy is that of resistance, a problem which is particularly acute for RNAi based therapeutics due to the exquisite sequence specificity of the targeting mechanism. The development of resistance during treatment can be minimised using combination therapy to raise the genetic barrier or using highly potent compounds which result in a more rapid and pronounced reduction in the viral replication rate, thereby reducing the formation of mutant, and potentially resistant viruses. This study investigated the efficacy of combination siRNA therapy and its ability to delay or prevent viral escape. Virus serially passaged through cells treated with a single or dual siRNAs rapidly acquired resistance, with mutations identified in the siRNA target sites. Combination therapy with three siRNA prevented viral escape over the course of five passages. To identify more potent silencing molecules we also compared the efficacy, in terms of potency and duration of action, of canonical versus Dicer-substrate siRNAs for two previously identified effective viral motifs. Dicer-substrate siRNAs showed equivalent or better potency than canonical siRNAs for the target sites investigated, and may be a more appropriate molecule for in vivo use. Combined, these data inform the potential therapeutic application of antiviral RNAi against FIPV. Copyright © 2014 Elsevier B.V. All rights reserved.

  19. Thymosin From Bombyx mori Is Down-Regulated in Expression by BmNPV Exhibiting Antiviral Activity.

    Science.gov (United States)

    Zhang, Chen; Wang, Yongdi; Fang, Qiang; Xu, Minlin; Lv, Mengyuan; Liao, Jinxu; Li, Si; Nie, Zuoming; Zhang, Wenping

    2016-01-01

    Thymosins have been highly conserved during evolution. These hormones exist in many animal species and play an essential role in many biological events. However, little is known regarding the physiological function of silkworm Bombyx mori thymosin (BmTHY). In this study, we investigated the expression pattern of BmTHY in a Bombyx mori larval ovarian cell line (BmN) challenged with Bombyx mori nuclear polyhydrosis virus (BmNPV) and the antiviral effect of recombinant BmTHY (rBmTHY) for Bombyx mori against BmNPV. Western-blot assay and qRT-PCR analysis revealed that the level of BmTHY protein expression and transcription decreased over time when BmN cells were infected by BmNPV. Treatment with endotoxin-free rBmTHY led to a significant reduction in viral titer in the supernatant of BmN cells challenged with BmNPV. The results from antiviral tests performed in vitro and in vivo showed that endotoxin-free rBmTHY improved the survival rate of Bombyx mori infected with BmNPV. These findings suggest that BmTHY exerts immunomodulatory effects on Bombyx mori, rendering them resistant to viral infection. © The Authors 2016. Published by Oxford University Press on behalf of Entomological Society of America.

  20. In Vitro Antiviral Activity of Circular Triple Helix Forming Oligonucleotide RNA towards Feline Infectious Peritonitis Virus Replication

    Directory of Open Access Journals (Sweden)

    Oi Kuan Choong

    2014-01-01

    Full Text Available Feline Infectious Peritonitis (FIP is a severe fatal immune-augmented disease in cat population. It is caused by FIP virus (FIPV, a virulent mutant strain of Feline Enteric Coronavirus (FECV. Current treatments and prophylactics are not effective. The in vitro antiviral properties of five circular Triple-Helix Forming Oligonucleotide (TFO RNAs (TFO1 to TFO5, which target the different regions of virulent feline coronavirus (FCoV strain FIPV WSU 79-1146 genome, were tested in FIPV-infected Crandell-Rees Feline Kidney (CRFK cells. RT-qPCR results showed that the circular TFO RNAs, except TFO2, inhibit FIPV replication, where the viral genome copy numbers decreased significantly by 5-fold log10 from 1014 in the virus-inoculated cells to 109 in the circular TFO RNAs-transfected cells. Furthermore, the binding of the circular TFO RNA with the targeted viral genome segment was also confirmed using electrophoretic mobility shift assay. The strength of binding kinetics between the TFO RNAs and their target regions was demonstrated by NanoITC assay. In conclusion, the circular TFOs have the potential to be further developed as antiviral agents against FIPV infection.

  1. In vitro antiviral activity of circular triple helix forming oligonucleotide RNA towards Feline Infectious Peritonitis virus replication.

    Science.gov (United States)

    Choong, Oi Kuan; Mehrbod, Parvaneh; Tejo, Bimo Ario; Omar, Abdul Rahman

    2014-01-01

    Feline Infectious Peritonitis (FIP) is a severe fatal immune-augmented disease in cat population. It is caused by FIP virus (FIPV), a virulent mutant strain of Feline Enteric Coronavirus (FECV). Current treatments and prophylactics are not effective. The in vitro antiviral properties of five circular Triple-Helix Forming Oligonucleotide (TFO) RNAs (TFO1 to TFO5), which target the different regions of virulent feline coronavirus (FCoV) strain FIPV WSU 79-1146 genome, were tested in FIPV-infected Crandell-Rees Feline Kidney (CRFK) cells. RT-qPCR results showed that the circular TFO RNAs, except TFO2, inhibit FIPV replication, where the viral genome copy numbers decreased significantly by 5-fold log10 from 10(14) in the virus-inoculated cells to 10(9) in the circular TFO RNAs-transfected cells. Furthermore, the binding of the circular TFO RNA with the targeted viral genome segment was also confirmed using electrophoretic mobility shift assay. The strength of binding kinetics between the TFO RNAs and their target regions was demonstrated by NanoITC assay. In conclusion, the circular TFOs have the potential to be further developed as antiviral agents against FIPV infection.

  2. Extraribosomal l13a is a specific innate immune factor for antiviral defense.

    Science.gov (United States)

    Mazumder, Barsanjit; Poddar, Darshana; Basu, Abhijit; Kour, Ravinder; Verbovetskaya, Valentina; Barik, Sailen

    2014-08-01

    We report a novel extraribosomal innate immune function of mammalian ribosomal protein L13a, whereby it acts as an antiviral agent. We found that L13a is released from the 60S ribosomal subunit in response to infection by respiratory syncytial virus (RSV), an RNA virus of the Pneumovirus genus and a serious lung pathogen. Unexpectedly, the growth of RSV was highly enhanced in L13a-knocked-down cells of various lineages as well as in L13a knockout macrophages from mice. In all L13a-deficient cells tested, translation of RSV matrix (M) protein was specifically stimulated, as judged by a greater abundance of M protein and greater association of the M mRNA with polyribosomes, while general translation was unaffected. In silico RNA folding analysis and translational reporter assays revealed a putative hairpin in the 3'untranslated region (UTR) of M mRNA with significant structural similarity to the cellular GAIT (gamma-activated inhibitor of translation) RNA hairpin, previously shown to be responsible for assembling a large, L13a-containing ribonucleoprotein complex that promoted translational silencing in gamma interferon (IFN-γ)-activated myeloid cells. However, RNA-protein interaction studies revealed that this complex, which we named VAIT (respiratory syncytial virus-activated inhibitor of translation) is functionally different from the GAIT complex. VAIT is the first report of an extraribosomal L13a-mediated, IFN-γ-independent innate antiviral complex triggered in response to virus infection. We provide a model in which the VAIT complex strongly hinders RSV replication by inhibiting the translation of the rate-limiting viral M protein, which is a new paradigm in antiviral defense. The innate immune mechanisms of host cells are diverse in nature and act as a broad-spectrum cellular defense against viruses. Here, we report a novel innate immune mechanism functioning against respiratory syncytial virus (RSV), in which the cellular ribosomal protein L13a is released

  3. Separation methods for acyclovir and related antiviral compounds.

    Science.gov (United States)

    Loregian, A; Gatti, R; Palù, G; De Palo, E F

    2001-11-25

    Acyclovir (ACV) is an antiviral drug, which selectively inhibits replication of members of the herpes group of DNA viruses with low cell toxicity. Valaciclovir (VACV), a prodrug of ACV is usually preferred in the oral treatment of viral infections, mainly herpes simplex virus (HSV). Also other analogues such as ganciclovir and penciclovir are discussed here. The former acts against cytomegalovirus (CMV) in general and the latter against CMV retinitis. The action mechanism of these antiviral drugs is presented briefly here, mainly via phosphorylation and inhibition of the viral DNA polymerase. The therapeutic use and the pharmacokinetics are also outlined. The measurement of the concentration of acyclovir and related compounds in biological samples poses a particularly significant challenge because these drugs tend to be structurally similar to endogenous substances. The analysis requires the use of highly selective analytical techniques and chromatography methods are a first choice to determine drug content in pharmaceuticals and to measure them in body fluids. Chromatography can be considered the procedure of choice for the bio-analysis of this class of antiviral compounds, as this methodology is characterised by good specificity and accuracy and it is particularly useful when metabolites need to be monitored. Among chromatographic techniques, the reversed-phase (RP) HPLC is widely used for the analysis. C18 Silica columns from 7.5 to 30 cm in length are used, the separation is carried out mainly at room temperature and less than 10 min is sufficient for the analysis at 1.0-1.5 ml/min of flow-rate. The separation methods require an isocratic system, and various authors have proposed a variety of mobile phases. The detection requires absorbance or fluorescence measurements carried out at 250-254 nm and at lambdaex=260-285 nm, lambdaem=375-380 nm, respectively. The detection limit is about 0.3-10 ng/ml but the most important aspect is related to the sample treatment

  4. Structure-based lead optimization to improve antiviral potency and ADMET properties of phenyl-1H-pyrrole-carboxamide entry inhibitors targeted to HIV-1 gp120.

    Science.gov (United States)

    Curreli, Francesca; Belov, Dmitry S; Kwon, Young Do; Ramesh, Ranjith; Furimsky, Anna M; O'Loughlin, Kathleen; Byrge, Patricia C; Iyer, Lalitha V; Mirsalis, Jon C; Kurkin, Alexander V; Altieri, Andrea; Debnath, Asim K

    2018-05-12

    We are continuing our concerted effort to optimize our first lead entry antagonist, NBD-11021, which targets the Phe43 cavity of the HIV-1 envelope glycoprotein gp120, to improve antiviral potency and ADMET properties. In this report, we present a structure-based approach that helped us to generate working hypotheses to modify further a recently reported advanced lead entry antagonist, NBD-14107, which showed significant improvement in antiviral potency when tested in a single-cycle assay against a large panel of Env-pseudotyped viruses. We report here the synthesis of twenty-nine new compounds and evaluation of their antiviral activity in a single-cycle and multi-cycle assay to derive a comprehensive structure-activity relationship (SAR). We have selected three inhibitors with the high selectivity index for testing against a large panel of 55 Env-pseudotyped viruses representing a diverse set of clinical isolates of different subtypes. The antiviral activity of one of these potent inhibitors, 55 (NBD-14189), against some clinical isolates was as low as 63 nM. We determined the sensitivity of CD4-binding site mutated-pseudoviruses to these inhibitors to confirm that they target HIV-1 gp120. Furthermore, we assessed their ADMET properties and compared them to the clinical candidate attachment inhibitor, BMS-626529. The ADMET data indicate that some of these new inhibitors have comparable ADMET properties to BMS-626529 and can be optimized further to potential clinical candidates. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

  5. Antiviral and immunoregulatory role against PCV2 in vivo of Chinese herbal medicinal ingredients

    Directory of Open Access Journals (Sweden)

    Yang Haifeng

    2017-12-01

    Full Text Available Introduction: The aim of the research was to investigate the antiviral and immunoregulatory effects of saikosaponin A, saikosaponin D, Panax notoginseng saponins, notoginsenoside R1, and anemoside B4 saponins commonly found in Chinese herbal medicines.

  6. 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.

  7. Antiviral Efficacy of Verdinexor In Vivo in Two Animal Models of Influenza A Virus Infection

    Science.gov (United States)

    Perwitasari, Olivia; Johnson, Scott; Yan, Xiuzhen; Register, Emery; Crabtree, Jackelyn; Gabbard, Jon; Howerth, Elizabeth; Shacham, Sharon; Carlson, Robert; Tamir, Sharon; Tripp, Ralph A.

    2016-01-01

    Influenza A virus (IAV) causes seasonal epidemics of respiratory illness that can cause mild to severe illness and potentially death. Antiviral drugs are an important countermeasure against IAV; however, drug resistance has developed, thus new therapeutic approaches are being sought. Previously, we demonstrated the antiviral activity of a novel nuclear export inhibitor drug, verdinexor, to reduce influenza replication in vitro and pulmonary virus burden in mice. In this study, in vivo efficacy of verdinexor was further evaluated in two animal models or influenza virus infection, mice and ferrets. In mice, verdinexor was efficacious to limit virus shedding, reduce pulmonary pro-inflammatory cytokine expression, and moderate leukocyte infiltration into the bronchoalveolar space. Similarly, verdinexor-treated ferrets had reduced lung pathology, virus burden, and inflammatory cytokine expression in the nasal wash exudate. These findings support the anti-viral efficacy of verdinexor, and warrant its development as a novel antiviral therapeutic for influenza infection. PMID:27893810

  8. Antiviral Efficacy of Verdinexor In Vivo in Two Animal Models of Influenza A Virus Infection.

    Directory of Open Access Journals (Sweden)

    Olivia Perwitasari

    Full Text Available Influenza A virus (IAV causes seasonal epidemics of respiratory illness that can cause mild to severe illness and potentially death. Antiviral drugs are an important countermeasure against IAV; however, drug resistance has developed, thus new therapeutic approaches are being sought. Previously, we demonstrated the antiviral activity of a novel nuclear export inhibitor drug, verdinexor, to reduce influenza replication in vitro and pulmonary virus burden in mice. In this study, in vivo efficacy of verdinexor was further evaluated in two animal models or influenza virus infection, mice and ferrets. In mice, verdinexor was efficacious to limit virus shedding, reduce pulmonary pro-inflammatory cytokine expression, and moderate leukocyte infiltration into the bronchoalveolar space. Similarly, verdinexor-treated ferrets had reduced lung pathology, virus burden, and inflammatory cytokine expression in the nasal wash exudate. These findings support the anti-viral efficacy of verdinexor, and warrant its development as a novel antiviral therapeutic for influenza infection.

  9. Herpesvirus infections in immunocompromised patients : treatment, treatment failure and antiviral resistance

    NARCIS (Netherlands)

    Beek, Martha Trijntje van der

    2012-01-01

    The research described in this thesis aims to study determinants of the course and outcome of treatment of herpesvirus infections in immunocompromised patients. Both viral factors, such as antiviral resistance, and patient factors, including immunological parameters, were investigated. Techniques to

  10. 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

    2016-05-12

    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.

  11. Evaluation of the combination effect of different antiviral compounds against HIV in vitro

    DEFF Research Database (Denmark)

    Sørensen, A M; Nielsen, C; Mathiesen, Lars Reinhardt

    1993-01-01

    by combining many evaluated antiviral agents with AZT. We observed a difference in the degree of synergism depending on the evaluated compound; the results indicate that compounds with the same target in the viral replicative cycle (ddI: 2',3'-dideoxyinosine, didanosine; d4T: 2',3'-dideoxy-2......3'-azido-3'deoxythymidine (AZT), a clinically used anti-HIV compound, was evaluated for antiviral effect on HIV infection in combination with other antiviral compounds in vitro. Interactions were evaluated by the median-effect principle and the isobologram technique. Synergistic effect was obtained...... with the adhesion/penetration process of virus (ConA: Concanavalin A; DS: dextran sulfate) were most potent with AZT when used in rather high concentrations. At this moment in the HIV epidemic, these observations suggest that combinations of antiviral compounds should be evaluated in clinical trials, with the major...

  12. Limiting the access to direct-acting antivirals against HCV: an ethical dilemma.

    Science.gov (United States)

    Gentile, Ivan; Maraolo, Alberto E; Niola, Massimo; Graziano, Vincenzo; Borgia, Guglielmo; Paternoster, Mariano

    2016-11-01

    Hepatitis C virus (HCV) infection affects about 200 million people worldwide and represents a leading cause of liver-related mortality. Eradication of HCV infection, achieved mainly through direct-acting antivirals (DAA), results in a decrease of mortality and an improvement of quality of life. These drugs have a maximal efficacy and an optimal tolerability. However, their high cost precludes a universal access even in wealthy countries. Areas covered: This article deals with the policies adopted for the use of the new anti-HCV drugs, especially in Europe and most of all in Italy, supposedly the developed country with the highest HCV prevalence. The literature search was performed using Pubmed and Web of Science. Moreover, national regulatory institutional websites were consulted. Expert commentary: The current policy of limitation to the access of the DAA presents a series of ethical issues that makes it non-applicable. A 'treat-all' strategy should resolve all ethical dilemmas, by virtue of the wide benefits of anti-HCV treatment not only for the advanced stage of infection, but also for the initial stages. A reduction in price of the drugs is the actual condition to achieve such a change.

  13. Antiviral and immunological effects of tenofovir microbicide in vaginal herpes simplex virus 2 infection.

    Science.gov (United States)

    Vibholm, Line; Reinert, Line S; Søgaard, Ole S; Paludan, Søren R; Østergaard, Lars; Tolstrup, Martin; Melchjorsen, Jesper

    2012-11-01

    The anti-HIV microbicide, tenofovir (TFV) gel, has been shown to decrease HIV-1 acquisition by 39% and reduce herpes simplex virus 2 (HSV-2) transmission by 51%. We evaluated the effect of a 1% TFV gel on genital HSV-2 infection in a mouse vaginal challenge model. In vitro plaque assays and luminex multiplex bead analysis were used, respectively, to measure postinfection vaginal viral shedding (day 1) and cytokine secretion (day 2). To further investigate the anti-HSV-2 properties, we evaluated the direct antiviral effect of TFV and the oral prodrug tenofovir disoproxil fumerate (TDF) in cell culture. Compared to placebo-treated mice, TFV-treated mice had significantly lower clinical scores, developed later genital lesions, and showed reduced vaginal viral shedding. Furthermore, the levels of IFN-γ, IL-2, TNF-α, and other cytokines were altered in the vaginal fluid following topical tenofovir treatment and subsequent HSV-2 challenge. Finally, we found that both TFV and TDF inhibited HSV-2 infection in vitro; TDF showed a 50-fold greater potency than TFV. In conclusion, we confirmed that the microbicide TFV had direct anti-HSV-2 effects in a murine vaginal challenge model. Therefore, this model would be suitable for evaluating present and future microbicide candidates. Furthermore, the present study warrants further investigation of TDF in microbicides.

  14. Antiviral activity of Ecasol against feline calicivirus, a surrogate of human norovirus

    Directory of Open Access Journals (Sweden)

    Yogesh Chander

    2012-12-01

    Full Text Available Summary: Human norovirus (NoV is a major cause of acute gastroenteritis in closed settings such as hospitals, hotels and cruise ships. The virus survives on inanimate surfaces for extended periods of time, and environmental contamination has been implicated in its transmission. The disinfection of contaminated areas is important in controlling the spread of NoV infections. Neutral solutions of electrochemically activated (ECA-anolyte have been shown to be powerful disinfectants against a broad range of bacterial pathogens. The active chemical ingredient is hypochlorous acid (HOCl, which is registered as an approved food contact surface sanitizer in the United States by the Environmental Protection Agency, pursuant to 40 CFR 180.940. We evaluated the antiviral activity of Ecasol (an ECA-anolyte against feline calicivirus (FCV, a surrogate of NoV. FCV dried on plastic surfaces was exposed to Ecasol for 1, 2, or 5 min. After exposure to Ecasol, the virus titers were compared with untreated controls to determine the virus inactivation efficacy after different contact times. Ecasol was found to decrease the FCV titer by >5 log10 within 1 min of contact, indicating its suitability for inactivation of NoV on surfaces. Keywords: Ecasol, ECA-anolyte, Trustwater, Electrochemical activation, Norovirus, Feline calicivirus, Fomites

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

    Directory of Open Access Journals (Sweden)

    Luciano Polonelli

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

  16. Inhibition of post-transcriptional RNA processing by CDK inhibitors and its implication in anti-viral therapy.

    Directory of Open Access Journals (Sweden)

    Jitka Holcakova

    Full Text Available Cyclin-dependent kinases (CDKs are key regulators of the cell cycle and RNA polymerase II mediated transcription. Several pharmacological CDK inhibitors are currently in clinical trials as potential cancer therapeutics and some of them also exhibit antiviral effects. Olomoucine II and roscovitine, purine-based inhibitors of CDKs, were described as effective antiviral agents that inhibit replication of a broad range of wild type human viruses. Olomoucine II and roscovitine show high selectivity for CDK7 and CDK9, with important functions in the regulation of RNA polymerase II transcription. RNA polymerase II is necessary for viral transcription and following replication in cells. We analyzed the effect of inhibition of CDKs by olomoucine II on gene expression from viral promoters and compared its effect to widely-used roscovitine. We found that both roscovitine and olomoucine II blocked the phosphorylation of RNA polymerase II C-terminal domain. However the repression of genes regulated by viral promoters was strongly dependent on gene localization. Both roscovitine and olomoucine II inhibited expression only when the viral promoter was not integrated into chromosomal DNA. In contrast, treatment of cells with genome-integrated viral promoters increased their expression even though there was decreased phosphorylation of the C-terminal domain of RNA polymerase II. To define the mechanism responsible for decreased gene expression after pharmacological CDK inhibitor treatment, the level of mRNA transcription from extrachromosomal DNA was determined. Interestingly, our results showed that inhibition of RNA polymerase II C-terminal domain phosphorylation increased the number of transcribed mRNAs. However, some of these mRNAs were truncated and lacked polyadenylation, which resulted in decreased translation. These results suggest that phosphorylation of RNA polymerase II C-terminal domain is critical for linking transcription and posttrancriptional

  17. Deferoxamine Compensates for Decreases in B Cell Counts and Reduces Mortality in Enterovirus 71-Infected Mice

    OpenAIRE

    Yang, Yajun; Ma, Jing; Xiu, Jinghui; Bai, Lin; Guan, Feifei; Zhang, Li; Liu, Jiangning; Zhang, Lianfeng

    2014-01-01

    Enterovirus 71 is one of the major causative agents of hand, foot and mouth disease in children under six years of age. No vaccine or antiviral therapy is currently available. In this work, we found that the number of B cells was reduced in enterovirus 71-infected mice. Deferoxamine, a marine microbial natural product, compensated for the decreased levels of B cells caused by enterovirus 71 infection. The neutralizing antibody titer was also improved after deferoxamine treatment. Furthermore...

  18. The role of fluoxetine in antiviral therapy for chronic hepatitis C

    OpenAIRE

    QIN Yuan; ZHANG Ying; ZHAO Jieru

    2016-01-01

    More than 20% of chronic hepatitis C (CHC) patients receiving the antiviral therapy with interferonα(IFNα) experience depression, and fluoxetine is often used to alleviate this symptom. Fluoxetine has anti-inflammatory properties and can change the synthesis of liver lipids, but its influence on antiviral therapy for CHC and related mechanism remain unknown. Recent studies show that fluoxetine can inhibit hepatitis C virus (HCV) infection and reduce the production of reactive oxygen species (...

  19. Arbidol (Umifenovir): A broad-spectrum antiviral drug that inhibits medically important arthropod-borne flaviviruses

    Czech Academy of Sciences Publication Activity Database

    Haviernik, J.; Štefánik, M.; Fojtíková, M.; Kali, S.; Tordo, N.; Rudolf, Ivo; Hubálek, Zdeněk; Eyer, Luděk; Růžek, Daniel

    2018-01-01

    Roč. 10, č. 4 (2018), č. článku 184. ISSN 1999-4915 R&D Projects: GA ČR(CZ) GA16-20054S Institutional support: RVO:68081766 ; RVO:60077344 Keywords : Antiviral activity * Arbidol * Cell-type dependent antiviral effect * Cytotoxicity * Flavivirus * Umifenovir Subject RIV: EE - Microbiology, Virology OBOR OECD: Virology Impact factor: 3.465, year: 2016

  20. Topoisomerase 1 Inhibition Promotes Cyclic GMP-AMP Synthase-Dependent Antiviral Responses

    OpenAIRE

    Pépin, Geneviève; Nejad, Charlotte; Ferrand, Jonathan; Thomas, Belinda J.; Stunden, H. James; Sanij, Elaine; Foo, Chwan-Hong; Stewart, Cameron R.; Cain, Jason E.; Bardin, Philip G.; Williams, Bryan R. G.; Gantier, Michael P.

    2017-01-01

    ABSTRACT Inflammatory responses, while essential for pathogen clearance, can also be deleterious to the host. Chemical inhibition of topoisomerase 1 (Top1) by low-dose camptothecin (CPT) can suppress transcriptional induction of antiviral and inflammatory genes and protect animals from excessive and damaging inflammatory responses. We describe the unexpected finding that minor DNA damage from topoisomerase 1 inhibition with low-dose CPT can trigger a strong antiviral immune response through c...

  1. Antiviral activity of an N-allyl acridone against dengue virus

    OpenAIRE

    Mazzucco, María Belén; Talarico, Laura Beatriz; Vatansever, Sezen; Carro, Ana Clara; Fascio, Mirta Liliana; D'Accorso, Norma Beatriz; Garcia, Cybele; Damonte, Elsa Beatriz

    2016-01-01

    Dengue virus (DENV), a member of the family Flaviviridae, is at present the most widespread causative agent of a human viral disease transmitted by mosquitoes. Despite the increasing incidence of this pathogen, there are no antiviral drugs or vaccines currently available for treatment or prevention. In a previous screening assay, we identified a group of N-allyl acridones as effective virus inhibitors. Here, the antiviral activity and mode of action targeted to viral RNA replication of one of...

  2. Antiviral treatment among older adults hospitalized with influenza, 2006-2012.

    Directory of Open Access Journals (Sweden)

    Mary Louise Lindegren

    Full Text Available To describe antiviral use among older, hospitalized adults during six influenza seasons (2006-2012 in Davidson County, Tennessee, USA.Among adults ≥50 years old hospitalized with symptoms of respiratory illness or non-localizing fever, we collected information on provider-initiated influenza testing and nasal/throat swabs for influenza by RT-PCR in a research laboratory, and calculated the proportion treated with antivirals.We enrolled 1753 adults hospitalized with acute respiratory illness. Only 26% (457/1753 of enrolled patients had provider-initiated influenza testing. Thirty-eight patients had a positive clinical laboratory test, representing 2.2% of total patients and 8.3% of tested patients. Among the 38 subjects with clinical laboratory-confirmed influenza, 26.3% received antivirals compared to only 4.5% of those with negative clinical influenza tests and 0.7% of those not tested (p<0.001. There were 125 (7.1% patients who tested positive for influenza in the research laboratory. Of those with research laboratory-confirmed influenza, 0.9%, 2.7%, and 2.8% received antivirals (p=.046 during pre-pandemic, pandemic, and post-pandemic influenza seasons, respectively. Both research laboratory-confirmed influenza (adjusted odds ratio [AOR] 3.04 95%CI 1.26-7.35 and clinical laboratory-confirmed influenza (AOR 3.05, 95%CI 1.07-8.71 were independently associated with antiviral treatment. Severity of disease, presence of a high-risk condition, and symptom duration were not associated with antiviral use.In urban Tennessee, antiviral use was low in patients recognized to have influenza by the provider as well as those unrecognized to have influenza. The use of antivirals remained low despite recommendations to treat all hospitalized patients with confirmed or suspected influenza.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2012-10-15

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

  4. Human influenza is more effective than avian influenza at antiviral suppression in airway cells.

    Science.gov (United States)

    Hsu, Alan Chen-Yu; Barr, Ian; Hansbro, Philip M; Wark, Peter A

    2011-06-01

    Airway epithelial cells are the initial site of infection with influenza viruses. The innate immune responses of airway epithelial cells to infection are important in limiting virus replication and spread. However, relatively little is known about the importance of this innate antiviral response to infection. Avian influenza viruses are a potential source of future pandemics; therefore, it is critical to examine the effectiveness of the host antiviral system to different influenza viruses. We used a human influenza (H3N2) and a low-pathogenic avian influenza (H11N9) to assess and compare the antiviral responses of Calu-3 cells. After infection, H3N2 replicated more effectively than the H11N9 in Calu-3 cells. This was not due to differential expression of sialic acid residues on Calu-3 cells, but was attributed to the interference of host antiviral responses by H3N2. H3N2 induced a delayed antiviral signaling and impaired type I and type III IFN induction compared with the H11N9. The gene encoding for nonstructural (NS) 1 protein was transfected into the bronchial epithelial cells (BECs), and the H3N2 NS1 induced a greater inhibition of antiviral responses compared with the H11N9 NS1. Although the low-pathogenic avian influenza virus was capable of infecting BECs, the human influenza virus replicated more effectively than avian influenza virus in BECs, and this was due to a differential ability of the two NS1 proteins to inhibit antiviral responses. This suggests that the subversion of human antiviral responses may be an important requirement for influenza viruses to adapt to the human host and cause disease.

  5. Antisense Phosphorodiamidate Morpholino Oligomers as Novel Antiviral Compounds

    Directory of Open Access Journals (Sweden)

    Yuchen Nan

    2018-04-01

    Full Text Available Phosphorodiamidate morpholino oligomers (PMO are short single-stranded DNA analogs that are built upon a backbone of morpholine rings connected by phosphorodiamidate linkages. As uncharged nucleic acid analogs, PMO bind to complementary sequences of target mRNA by Watson–Crick base pairing to block protein translation through steric blockade. PMO interference of viral protein translation operates independently of RNase H. Meanwhile, PMO are resistant to a variety of enzymes present in biologic fluids, a characteristic that makes them highly suitable for in vivo applications. Notably, PMO-based therapy for Duchenne muscular dystrophy (DMD has been approved by the United States Food and Drug Administration which is now a hallmark for PMO-based antisense therapy. In this review, the development history of PMO, delivery methods for improving cellular uptake of neutrally charged PMO molecules, past studies of PMO antagonism against RNA and DNA viruses, PMO target selection, and remaining questions of PMO antiviral strategies are discussed in detail and new insights are provided.

  6. Detection of the antiviral drug oseltamivir in aquatic environments.

    Directory of Open Access Journals (Sweden)

    Hanna Söderström

    Full Text Available Oseltamivir (Tamiflu is the most important antiviral drug available and a cornerstone in the defence against a future influenza pandemic. Recent publications have shown that the active metabolite, oseltamivir carboxylate (OC, is not degraded in sewage treatment plants and is also persistent in aquatic environments. This implies that OC will be present in aquatic environments in areas where oseltamivir is prescribed to patients for therapeutic use. The country where oseltamivir is used most is Japan, where it is used to treat seasonal flu. We measured the levels of OC in water samples from the Yodo River system in the Kyoto and Osaka prefectures, Japan, taken before and during the flu-season 2007/8. No OC was detected before the flu-season but 2-58 ng L(-1 was detected in the samples taken during the flu season. This study shows, for the first time, that low levels of oseltamivir can be found in the aquatic environment. Therefore the natural reservoir of influenza virus, dabbling ducks, is exposed to oseltamivir, which could promote the evolution of viral resistance.

  7. IFITM3 requires an amphipathic helix for antiviral activity.

    Science.gov (United States)

    Chesarino, Nicholas M; Compton, Alex A; McMichael, Temet M; Kenney, Adam D; Zhang, Lizhi; Soewarna, Victoria; Davis, Matthew; Schwartz, Olivier; Yount, Jacob S

    2017-10-01

    Interferon-induced transmembrane protein 3 (IFITM3) is a cellular factor that blocks virus fusion with cell membranes. IFITM3 has been suggested to alter membrane curvature and fluidity, though its exact mechanism of action is unclear. Using a bioinformatic approach, we predict IFITM3 secondary structures and identify a highly conserved, short amphipathic helix within a hydrophobic region of IFITM3 previously thought to be a transmembrane domain. Consistent with the known ability of amphipathic helices to alter membrane properties, we show that this helix and its amphipathicity are required for the IFITM3-dependent inhibition of influenza virus, Zika virus, vesicular stomatitis virus, Ebola virus, and human immunodeficiency virus infections. The homologous amphipathic helix within IFITM1 is also required for the inhibition of infection, indicating that IFITM proteins possess a conserved mechanism of antiviral action. We further demonstrate that the amphipathic helix of IFITM3 is required to block influenza virus hemagglutinin-mediated membrane fusion. Overall, our results provide evidence that IFITM proteins utilize an amphipathic helix for inhibiting virus fusion. © 2017 The Authors.

  8. Resistance to antivirals in human cytomegalovirus: mechanisms and clinical significance.

    Science.gov (United States)

    Pérez, J L

    1997-09-01

    Long term therapies needed for managing human cytomegalovirus (HCMV) infections in immunosupressed patients provided the background for the emergence of the resistance to antivirals active against HCMV. In addition, laboratory selected mutants have also been readily achieved. Both clinical and laboratory resistant strains share the same determinants of resistance. Ganciclovir resistance may be due to a few mutations in the HCMV UL97 gene and/or viral DNA pol gene, the former being responsible for about 70% of clinical resistant isolates. Among them, V464, V594, S595 and F595 are the most frequent mutations. Because of their less extensive clinical use, much less is known about resistance to foscarnet and cidofovir (formerly, HPMPC) but in both cases, it has been associated to mutations in the DNA pol. Ganciclovir resistant strains showing DNA pol mutations are cross-resistant to cidofovir and their corresponding IC50 are normally higher than those from strains harboring only mutations at the UL97 gene. To date, foscarnet resistance seems to be independent of both ganciclovir and cidofovir resistance.

  9. Chemical diversity and antiviral potential in the pantropical Diospyros genus.

    Science.gov (United States)

    Peyrat, Laure-Anne; Eparvier, Véronique; Eydoux, Cécilia; Guillemot, Jean-Claude; Stien, Didier; Litaudon, Marc

    2016-07-01

    A screening using a dengue replicon virus-cell-based assay was performed on 3563 ethyl acetate (EtOAc) extracts from different parts of 1500 plants. The screening led to the selection of species from the genus Diospyros (Ebenaceae), among which 25 species distributed in tropical areas showed significant inhibitory activity on dengue virus replication. A metabolic analysis was conducted from the UPLC-HRMS profiles of 33 biologically active and inactive plant extracts, and their metabolic proximity is presented in the form of a dendrogram. The results of the study showed that chemical similarity is not related to plant species or organ. Overall, metabolomic profiling allowed us to define large groups of extracts, comprising both active and inactive ones. Closely related profiles from active extracts might indicate that the common major components of these extracts were responsible for the antiviral activity, while the comparison of chemically similar active and inactive extracts, will permit to find compounds of interest. Eventually, the phytochemical investigation of Diospyros glans bark EtOAc extract afforded usnic acid and 7 known ursane- and lupane-type triterpenoids, among which 5 were found significantly active against dengue virus replication. The inhibitory potency of these compounds was also evaluated on a DENV-NS5 RNA-dependant RNA polymerase assay. Copyright © 2016 Elsevier B.V. All rights reserved.

  10. Ribavirin: recent insights into antiviral mechanisms of action.

    Science.gov (United States)

    Reyes, G R

    2001-09-01

    Ribavirin, a nucleoside analog, used in combination with interferon-alpha (IFN alpha) results in a substantial improvement in the sustained virologic response in chronic hepatitis C. Identified antiviral mechanisms of action for ribavirin include: (i) inhibition of viral encoded polymerases; (ii) inhibition of genomic RNA capping; and (iii) inhibition of cellular encoded enzymes that control de novo synthesis of purine nucleosides. More recently, ribavirin has been shown to engender a bias toward helper T-cell (CD4+) type 1 (Th1) cytokine responses in models of immunity. Recent detailed analysis has also shown that ribavirin can be utilized and incorporated by the polio viral polymerase into genomic and antigenomic transcripts, and is capable of base pairing with either UMP (uridine monophosphate) or CMP (cytidine monophosphate). This results in ribavirin-mediated mutagenesis of the viral genome and has the potential to push the virus beyond tolerable set points in its mutation rate, leading to an overall reduced fitness of the viral population. Of the many mechanisms of action demonstrated for ribavirin, the current clinical trials of selective inosine 5'-monophosphate dehydrogenase (IMPDH) inhibitors and immunomodulating agents in hepatitis may facilitate our understanding of what activity (if any) predominates when ribavirin is used in combination with IFN alpha.

  11. Regulation of the Host Antiviral State by Intercellular Communications

    Directory of Open Access Journals (Sweden)

    Sonia Assil

    2015-08-01

    Full Text Available Viruses usually induce a profound remodeling of host cells, including the usurpation of host machinery to support their replication and production of virions to invade new cells. Nonetheless, recognition of viruses by the host often triggers innate immune signaling, preventing viral spread and modulating the function of immune cells. It conventionally occurs through production of antiviral factors and cytokines by infected cells. Virtually all viruses have evolved mechanisms to blunt such responses. Importantly, it is becoming increasingly recognized that infected cells also transmit signals to regulate innate immunity in uninfected neighboring cells. These alternative pathways are notably mediated by vesicular secretion of various virus- and host-derived products (miRNAs, RNAs, and proteins and non-infectious viral particles. In this review, we focus on these newly-described modes of cell-to-cell communications and their impact on neighboring cell functions. The reception of these signals can have anti- and pro-viral impacts, as well as more complex effects in the host such as oncogenesis and inflammation. Therefore, these “broadcasting” functions, which might be tuned by an arms race involving selective evolution driven by either the host or the virus, constitute novel and original regulations of viral infection, either highly localized or systemic.

  12. Targeted antiviral prophylaxis with oseltamivir in a summer camp setting.

    Science.gov (United States)

    Kimberlin, David W; Escude, Janell; Gantner, Janel; Ott, Jeanne; Dronet, Melissa; Stewart, Timothy A; Jester, Penelope; Redden, David T; Chapman, Whitney; Hammond, Rob

    2010-04-01

    To describe the effectiveness of containment of novel influenza A(H1N1) infection at a summer camp. Targeted use of oseltamivir phosphate by individuals in close contact with influenza-confirmed cases. Boys' camp in Alabama in July 2009. A total of 171 campers, 48 camp counselors, and 27 camp staff. Campers with confirmed influenza received oseltamivir and were immediately isolated and sent home. All boys and counselors in the infected child's adjoining cabins received prophylactic oseltamivir for 10 days, including 8 campers at higher risk for influenza infection (eg, those with asthma, seizure disorder, or diabetes). Alcohol-based hand sanitizer was provided at each of the daily activities, in the boys' cabins, and in the dining hall, and counselors were educated by the medical staff on the spread of influenza and its prevention through good hand hygiene. All cabins, bathrooms, and community sports equipment were sprayed or wiped down with disinfectant each day. Main Outcome Measure Virologic confirmation of influenza. Three of the 171 campers tested positive for influenza A during the course of the 2-week fourth session, for an attack rate of 1.8%. The probability of observing 3 or fewer infected campers if the attack rate was 12% is less than 1 in 10,000,000 (P hand sanitization and surface decontamination, a targeted approach to antiviral prophylaxis contained the spread of influenza in a summer camp setting.

  13. Antibacterial, antifungal, and antiviral activities of some flavonoids.

    Science.gov (United States)

    Orhan, Didem Deliorman; Ozçelik, Berrin; Ozgen, Selda; Ergun, Fatma

    2010-08-20

    Antibacterial and antifungal activities of six plant-derived flavonoids representing two different structural groups were evaluated against standard strains of Escherichia coli, Pseudomonas aeruginosa, Proteus mirabilis, Klebsiella pneumoniae, Acinetobacter baumannii, Staphylococcus aureus, Enterococcus faecalis, Bacillus subtilis and their drug-resistant isolates, as well as fungi (Candida albicans, C. krusei) using the microdilution broth method. Herpes simplex virus Type-1 and Parainfluenza-3 virus were employed for antiviral assessment of the flavonoids using Madin-Darby bovine kidney and Vero cell lines. Ampicillin, gentamycin, ofloxacin, levofloxacin, fluconazole, ketoconazole, acyclovir, and oseltamivir were used as the control agents. All tested compounds (32-128 microg/ml) showed strong antimicrobial and antifungal activities against isolated strains of P. aeruginosa, A. baumanni, S. aureus, and C. krusei. Rutin, 5,7-dimethoxyflavanone-4'-O-beta-D-glucopyranoside and 5,7,3'-trihydroxy-flavanone-4'-O-beta-D-glucopyranoside (0.2-0.05 microg/ml) were active against PI-3, while 5,7-dimethoxyflavanone-4'-O-[2''-O-(5'''-O-trans-cinnamoyl)-beta-D-apiofuranosyl]-beta-D-glucopyranoside (0.16-0.2 microg/ml) inhibited potently HSV-1. Copyright 2009 Elsevier GmbH. All rights reserved.

  14. [Antiviral activity of representatives of the family Crassulaceae].

    Science.gov (United States)

    Shirobokov, V P; Evtushenko, A I; Lapchik, V F; Shirobokova, D N; Suptel', E A

    1981-12-01

    The antiviral properties of the juice of 11 species of the orpine family were studied. 8 of them belonged to the genera Kalanchoe, i. e. Kalanchoe diagremontiona R. Hamet, K. pinnata (Zam.) Persoon, K. Peteri Werd., K. prolifera (Bovie) R. Hamet, K. marnierriana (Mann. et Boit) Jacobs; K. blossfeldiana v. Poelln, K. beharensis Drake del Gastillo, K. waldheimii R. Hamet et Perr and 3 belonged to the Sedum genera, i. e. Sedum telephium L., S. spectabile Boreau, S. acre L. A high virus neutralizing activity of the juice from 4 species of Kalanchoe, i. e. K. blossfeldiana, K. waldheimii, K. pinnata and K. beharensis was shown. Inhibition of the virus infecting activity was observed at the juice dilutions from 1-2 to 1-8000 and higher. The viricidal factor of Kalanchoe is stable. It is not destroyed by ether, alcohol and potassium periodate. It is not absorbed by bentonite at the acid pH values. Addition of cattle serum or purified proteins to the juice resulted in their precipitation which suppressed the viricidal activity of the juice.

  15. In Vitro Bioavailability Study of an Antiviral Compound Enisamium Iodide

    Directory of Open Access Journals (Sweden)

    Eleonore Haltner-Ukomadu

    2018-01-01

    Full Text Available An investigation into the biopharmaceutics classification and a study of the in vitro bioavailability (permeability and solubility of the antiviral compound enisamium iodide (4-(benzylcarbamoyl-1-methylpyridinium iodide were carried out. The solubility of enisamium iodide was determined in four different buffers. Apparent intestinal permeability (Papp of enisamium iodide was assessed using human colon carcinoma (Caco-2 cells at three concentrations. The solubility of enisamium iodide in four buffer solutions from pH 1.2 to 7.5 is about 60 mg/mL at 25 °C, and ranges from 130 to 150 mg/mL at 37 °C, depending on the pH. Based on these results, enisamium iodide can be classified as highly soluble. Enisamium iodide demonstrated low permeability in Caco-2 experiments in all tested concentrations of 10–100 μM with permeability coefficients between 0.2 × 10−6 cm s−1 and 0.3 × 10−6 cm s−1. These results indicate that enisamium iodide belongs to class III of the Biopharmaceutics Classification System (BCS due to its high solubility and low permeability. The bioavailability of enisamium iodide needs to be confirmed in animal and human studies.

  16. Type I and Type III Interferons Display Different Dependency on Mitogen-Activated Protein Kinases to Mount an Antiviral State in the Human Gut.

    Science.gov (United States)

    Pervolaraki, Kalliopi; Stanifer, Megan L; Münchau, Stephanie; Renn, Lynnsey A; Albrecht, Dorothee; Kurzhals, Stefan; Senís, Elena; Grimm, Dirk; Schröder-Braunstein, Jutta; Rabin, Ronald L; Boulant, Steeve

    2017-01-01

    Intestinal epithelial cells (IECs) are constantly exposed to commensal flora and pathogen challenges. How IECs regulate their innate immune response to maintain gut homeostasis remains unclear. Interferons (IFNs) are cytokines produced during infections. While type I IFN receptors are ubiquitously expressed, type III IFN receptors are expressed only on epithelial cells. This epithelium specificity strongly suggests exclusive functions at epithelial surfaces, but the relative roles of type I and III IFNs in the establishment of an antiviral innate immune response in human IECs are not clearly defined. Here, we used mini-gut organoids to define the functions of types I and III IFNs to protect the human gut against viral infection. We show that primary non-transformed human IECs, upon viral challenge, upregulate the expression of both type I and type III IFNs at the transcriptional level but only secrete type III IFN in the supernatant. However, human IECs respond to both type I and type III IFNs by producing IFN-stimulated genes that in turn induce an antiviral state. Using genetic ablation of either type I or type III IFN receptors, we show that either IFN can independently restrict virus infection in human IECs. Importantly, we report, for the first time, differences in the mechanisms by which each IFN establishes the antiviral state. Contrary to type I IFN, the antiviral activity induced by type III IFN is strongly dependent on the mitogen-activated protein kinases signaling pathway, suggesting a pathway used by type III IFNs that non-redundantly contributes to the antiviral state. In conclusion, we demonstrate that human intestinal epithelial cells specifically regulate their innate immune response favoring type III IFN-mediated signaling, which allows for efficient protection against pathogens without producing excessive inflammation. Our results strongly suggest that type III IFN constitutes the frontline of antiviral response in the human gut. We propose that

  17. 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.

  18. Studies on Antiviral and Immuno-Regulation Activity of Low Molecular Weight Fucoidan from Laminaria japonica

    Science.gov (United States)

    Sun, Taohua; Zhang, Xinhui; Miao, Ying; Zhou, Yang; Shi, Jie; Yan, Meixing; Chen, Anjin

    2018-06-01

    The antiviral activity in vitro and in vivo and the effect of the immune system of two fucoidan fractions with low molecular weight and different sulfate content from Laminaria japonica (LMW fucoidans) were investigated in order to examine the possible mechanism. In vitro, I-type influenza virus, adenovirus and Parainfluenza virus I were used to infect Hep-2, Hela and MDCK cells, respectively. And 50% tissue culture infective dose was calculated to detect the antiviral activity of two LMW fucoidans. The results indicated that compared with the control group, 2 kinds of LMW fucoidans had remarkable antiviral activity in vitro in middle and high doses, while at low doses, the antiviral activity of 2 kinds of LMW fucoidans was not statistically different from that in the blank control group. And there was no statistically difference between two LMW fucoidans in antiviral activity. In vivo, LMW fucoidans could prolong the survival time of virus-infected mice, and could improve the lung index of virus-infected mice significantly, which have statistical differences with the control group significantly ( p 0.05). In this study, it was shown that both of two LMW fucoidans (LF1, LF2) could increase the thymus index, spleen index, phagocytic index, phagocytosis coefficient and half hemolysin value in middle and high doses, which suggested that LMW fucoidans could play an antiviral role by improving the quality of immune organs, improving immune cell phagocytosis and humoral immunity.

  19. Strategies for antiviral stockpiling for future influenza pandemics: a global epidemic-economic perspective.

    Science.gov (United States)

    Carrasco, Luis R; Lee, Vernon J; Chen, Mark I; Matchar, David B; Thompson, James P; Cook, Alex R

    2011-09-07

    Influenza pandemics present a global threat owing to their potential mortality and substantial economic impacts. Stockpiling antiviral drugs to manage a pandemic is an effective strategy to offset their negative impacts; however, little is known about the long-term optimal size of the stockpile under uncertainty and the characteristics of different countries. Using an epidemic-economic model we studied the effect on total mortality and costs of antiviral stockpile sizes for Brazil, China, Guatemala, India, Indonesia, New Zealand, Singapore, the UK, the USA and Zimbabwe. In the model, antivirals stockpiling considerably reduced mortality. There was greater potential avoidance of expected costs in the higher resourced countries (e.g. from $55 billion to $27 billion over a 30 year time horizon for the USA) and large avoidance of fatalities in those less resourced (e.g. from 11.4 to 2.3 million in Indonesia). Under perfect allocation, higher resourced countries should aim to store antiviral stockpiles able to cover at least 15 per cent of their population, rising to 25 per cent with 30 per cent misallocation, to minimize fatalities and economic costs. Stockpiling is estimated not to be cost-effective for two-thirds of the world's population under current antivirals pricing. Lower prices and international cooperation are necessary to make the life-saving potential of antivirals cost-effective in resource-limited countries.

  20. T-bet- and STAT4-dependent IL-33 receptor expression directly promotes antiviral Th1 cell responses.

    Science.gov (United States)

    Baumann, Claudia; Bonilla, Weldy V; Fröhlich, Anja; Helmstetter, Caroline; Peine, Michael; Hegazy, Ahmed N; Pinschewer, Daniel D; Löhning, Max

    2015-03-31

    During infection, the release of damage-associated molecular patterns, so-called "alarmins," orchestrates the immune response. The alarmin IL-33 plays a role in a wide range of pathologies. Upon release, IL-33 signals through its receptor ST2, which reportedly is expressed only on CD4(+) T cells of the Th2 and regulatory subsets. Here we show that Th1 effector cells also express ST2 upon differentiation in vitro and in vivo during lymphocytic choriomeningitis virus (LCMV) infection. The expression of ST2 on Th1 cells was transient, in contrast to constitutive ST2 expression on Th2 cells, and marked highly activated effector cells. ST2 expression on virus-specific Th1 cells depended on the Th1-associated transcription factors T-bet and STAT4. ST2 deficiency resulted in a T-cell-intrinsic impairment of LCMV-specific Th1 effector responses in both mixed bone marrow-chimeric mice and adoptive cell transfer experiments. ST2-deficient virus-specific CD4(+) T cells showed impaired expansion, Th1 effector differentiation, and antiviral cytokine production. Consequently, these cells mediated little virus-induced immunopathology. Thus, IL-33 acts as a critical and direct cofactor to drive antiviral Th1 effector cell activation, with implications for vaccination strategies and immunotherapeutic approaches.

  1. Expression analysis of several antiviral related genes to BmNPV in different resistant strains of silkworm, Bombyx mori.

    Science.gov (United States)

    Cheng, Yang; Wang, Xue-yang; Du, Chang; Gao, Juan; Xu, Jia-ping

    2014-05-30

    Bombyx mori L. (Lepidoptera: Bombycidae) nucleopolyhedrovirus (BmNPV) is a highly pathogenic virus in the sericultural industry, often causing severe damage leading to large economic losses. The immune mechanisms of B. mori against this virus remain obscure. Previous studies had demonstrated Bmlipase-1, BmNox and Bmserine protease-2 showing antiviral activity in vitro, but data on the transcription levels of these proteins in different resistant strains were not reported. In order to determine the resistance level of the four different strains (P50, A35, A40, A53) and gain a better understanding of the mechanism of resistance to BmNPV in B. mori, the relative expression level of the genes coding the three antiviral proteins in larval haemolymph and midgut of different B. mori strains resistant to BmNPV was determined. The results showed that these genes expressed significantly higher in the resistant strains compared to the susceptible strain, and the differential expression levels were consistent with the LC50 values in different strains. The transcription level of the target genes almost all up-regulated in the larvae midgut and down-regulated in the haemolymph. The results indicate the correlation of these genes to BmNPV resistance in B. mori. This is an open access paper. We use the Creative Commons Attribution 3.0 license that permits unrestricted use, provided that the paper is properly attributed.

  2. A single WAP domain (SWD)-containing protein with antiviral activity from Pacific white shrimp Litopenaeus vannamei.

    Science.gov (United States)

    Yang, Linwei; Niu, Shengwen; Gao, Jiefeng; Zuo, Hongliang; Yuan, Jia; Weng, Shaoping; He, Jianguo; Xu, Xiaopeng

    2018-02-01

    The single whey acidic protein (WAP) domain (SWD)-containing proteins, also called type III crustins, are a group of antimicrobial peptides (AMPs) in crustaceans. At present, a number of SWDs have been identified in shrimp, which showed essential antibacterial activities. However, the roles of SWDs in antiviral immune responses have not been reported up to now. In this study, a novel SWD (LvSWD3) was identified from Pacific white shrimp, Litopenaeus vannamei, which contained a typical single WAP domain homologous to those of other crustacean SWDs. Although lacking the pro and arg-rich region between the signal peptide and the WAP domain, LvSWD3 was closely clustered with other shrimp SWDs in the phylogenetic tree. Similar to many shrimp SWDs, the highest expression of LvSWD3 was detected in hemocytes. The LvSWD3 expression exhibited only limited changes after challenges with Vibrio parahaemolyticus, Poly (I:C) and lipopolysaccharide, but was significantly up-regulated after white spot syndrome virus (WSSV) infection. Silencing of LvSWDs significantly accelerated the death of the WSSV-infected but not the V. parahaemolyticus-infected shrimp. The recombinant LvSWD3 protein did not show proteinase inhibitory and antibacterial activities but could significantly postpone the death of WSSV-infected shrimp and reduce the viral load in tissues. These suggested that LvSWD3 was a novel SWD with antiviral activity. Copyright © 2017 Elsevier Ltd. All rights reserved.

  3. Construction of self-replicating subgenomic West Nile virus replicons for screening antiviral compounds.

    Science.gov (United States)

    Alcaraz-Estrada, Sofia L; Reichert, Erin Donohue; Padmanabhan, Radhakrishnan

    2013-01-01

    Mosquito-borne flavivirus RNA genomes encode one long open reading frame flanking 5'- and 3'-untranslated regions (5'- and 3'-UTRs) which contain cis-acting RNA elements playing important roles for viral RNA translation and replication. The viral RNA encodes a single polyprotein, which is processed into three structural proteins and seven nonstructural (NS) proteins. The regions coding for the seven NS proteins are sufficient for replication of the RNA. The sequences encoding the structural genes can be deleted except for two short regions. The first one encompasses 32 amino acid (aa) residues from the N-terminal coding sequence of capsid (C) and the second, 27 aa region from the C-terminus of envelope (E) protein. The deleted region can be substituted with a gene coding for a readily quantifiable reporter to give rise to a subgenomic reporter replicon. Replicons containing a variety of reporter genes and marker genes for construction of stable mammalian cell lines are valuable reagents for studying the effects of mutations in translation and/or replication in isolation from processes like the entry and assembly of the virus particles. Here we describe the construction of two West Nile virus (WNV) replicons by overlap extension PCR and standard recombinant DNA techniques. One has a Renilla luciferase (Rluc) reporter gene followed by an internal ribosome entry site (element) for cap-independent translation of the open reading frame encompassing the carboxy-terminal sequence of E to NS5. The second replicon has in tandem the Rluc gene, foot and mouth disease virus 2A, and neomycin phosphotransferase gene that allows establishment of a stable mammalian cell line expressing the Rluc reporter in the presence of the neomycin analog, G418. The stable replicon-expressing Vero cell line has been used for cell-based screening and determination of EC50 values for antiviral compounds that inhibited WNV replication.

  4. Antiviral Combination Approach as a Perspective to Combat Enterovirus Infections.

    Science.gov (United States)

    Galabov, Angel S; Nikolova, Ivanka; Vassileva-Pencheva, Ralitsa; Stoyanova, Adelina

    2015-01-01

    Human enteroviruses distributed worldwide are causative agents of a broad spectrum of diseases with extremely high morbidity, including a series of severe illnesses of the central nervous system, heart, endocrine pancreas, skeleton muscles, etc., as well as the common cold contributing to the development of chronic respiratory diseases, including the chronic obstructive pulmonary disease. The above mentioned diseases along with the significantly high morbidity and mortality in children, as well as in the high-risk populations (immunodeficiencies, neonates) definitely formulate the chemotherapy as the main tool for the control of enterovirus infections. At present, clinically effective antivirals for use in the treatment of enteroviral infection do not exist, in spite of the large amount of work carried out in this field. The main reason for this is the development of drug resistance. We studied the process of development of resistance to the strongest inhibitors of enteroviruses, WIN compounds (VP1 protein hydrophobic pocket blockers), especially in the models in vivo, Coxsackievirus B (CV-B) infections in mice. We introduced the tracing of a panel of phenotypic markers (MIC50 value, plaque shape and size, stability at 50℃, pathogenicity in mice) for characterization of the drug-mutants (resistant and dependent) as a very important stage in the study of enterovirus inhibitors. Moreover, as a result of VP1 RNA sequence analysis performed on the model of disoxaril mutants of CVB1, we determined the molecular basis of the drug-resistance. The monotherapy courses were the only approach used till now. For the first time in the research for anti-enterovirus antivirals our team introduced the testing of combination effect of the selective inhibitors of enterovirus replication with different mode of action. This study resulted in the selection of a number of very effective in vitro double combinations with synergistic effect and a broad spectrum of sensitive

  5. Puromycin-sensitive aminopeptidase: an antiviral prodrug activating enzyme.

    Science.gov (United States)

    Tehler, Ulrika; Nelson, Cara H; Peterson, Larryn W; Provoda, Chester J; Hilfinger, John M; Lee, Kyung-Dall; McKenna, Charles E; Amidon, Gordon L

    2010-03-01

    Cidofovir (HPMPC) is a broad-spectrum antiviral agent, currently used to treat AIDS-related human cytomegalovirus retinitis. Cidofovir has recognized therapeutic potential for orthopox virus infections, although its use is hampered by its inherent low oral bioavailability. Val-Ser-cyclic HPMPC (Val-Ser-cHPMPC) is a promising peptide prodrug which has previously been shown by us to improve the permeability and bioavailability of the parent compound in rodent models (Eriksson et al., 2008. Molecular Pharmaceutics 5, 598-609). Puromycin-sensitive aminopeptidase was partially purified from Caco-2 cell homogenates and identified as a prodrug activating enzyme for Val-Ser-cHPMPC. The prodrug activation process initially involves an enzymatic step where the l-Valine residue is removed by puromycin-sensitive aminopeptidase, a step that is bestatin-sensitive. Subsequent chemical hydrolysis results in the generation of cHPMPC. A recombinant puromycin-sensitive aminopeptidase was generated and its substrate specificity investigated. The k(cat) for Val-pNA was significantly lower than that for Ala-pNA, suggesting that some amino acids are preferred over others. Furthermore, the three-fold higher k(cat) for Val-Ser-cHPMPC as compared to Val-pNA suggests that the leaving group may play an important role in determining hydrolytic activity. In addition to its ability to hydrolyze a variety of substrates, these observations strongly suggest that puromycin-sensitive aminopeptidase is an important enzyme for activating Val-Ser-cHPMPC in vivo. Taken together, our data suggest that puromycin-sensitive aminopeptidase makes an attractive target for future prodrug design.

  6. Antiviral type I and type III interferon responses in the central nervous system.

    Science.gov (United States)

    Sorgeloos, Frédéric; Kreit, Marguerite; Hermant, Pascale; Lardinois, Cécile; Michiels, Thomas

    2013-03-15

    The central nervous system (CNS) harbors highly differentiated cells, such as neurons that are essential to coordinate the functions of complex organisms. This organ is partly protected by the blood-brain barrier (BBB) from toxic substances and pathogens carried in the bloodstream. Yet, neurotropic viruses can reach the CNS either by crossing the BBB after viremia, or by exploiting motile infected cells as Trojan horses, or by using axonal transport. Type I and type III interferons (IFNs) are cytokines that are critical to control early steps of viral infections. Deficiencies in the IFN pathway have been associated with fatal viral encephalitis both in humans and mice. Therefore, the IFN system provides an essential protection of the CNS against viral infections. Yet, basal activity of the IFN system appears to be low within the CNS, likely owing to the toxicity of IFN to this organ. Moreover, after viral infection, neurons and oligodendrocytes were reported to be relatively poor IFN producers and appear to keep some susceptibility to neurotropic viruses, even in the presence of IFN. This review addresses some trends and recent developments concerning the role of type I and type III IFNs in: i) preventing neuroinvasion and infection of CNS cells; ii) the identity of IFN-producing cells in the CNS; iii) the antiviral activity of ISGs; and iv) the activity of viral proteins of neurotropic viruses that target the IFN pathway.

  7. Emergence of antiviral resistance during oral valganciclovir treatment of an infant with congenital cytomegalovirus (CMV) infection.

    Science.gov (United States)

    Choi, K Yeon; Sharon, B; Balfour, H H; Belani, K; Pozos, T C; Schleiss, M R

    2013-08-01

    Congenital infection with human cytomegalovirus (CMV) is a major cause of morbidity, including sensorineural hearing loss (SNHL), in newborns. Antiviral therapy with ganciclovir (GCV) and its oral prodrug, valganciclovir (VAL-GCV) are increasingly being administered to infected infants, toward the goal of improving neurodevelopmental and auditory outcomes. In this case report, we describe a symptomatic congenitally infected infant treated with VAL-GCV in whom GCV resistance was suspected, based on a 50-fold increase in viral load after 6 weeks of oral therapy. Analyses of CMV sequences from both blood and urine demonstrated populations of viruses with M460V and L595F mutations in the UL97 phosphotransferase gene. In contrast, analysis of viral DNA retrieved from the newborn dried blood spot demonstrated wild-type UL97 sequences. DNAemia resolved after the discontinuation of VAL-GCV. Long-term VAL-GCV therapy in congenitally infected infants can select for resistant viral variants, and anticipatory virological monitoring may be warranted. Copyright © 2013 Elsevier B.V. All rights reserved.

  8. Down-Regulation of p53 by Double-Stranded RNA Modulates the Antiviral Response

    Science.gov (United States)

    Marques, Joao T.; Rebouillat, Dominique; Ramana, Chilakamarti V.; Murakami, Junko; Hill, Jason E.; Gudkov, Andrei; Silverman, Robert H.; Stark, George R.; Williams, Bryan R. G.

    2005-01-01

    p53 has been well characterized as a tumor suppressor gene, but its role in antiviral defense remains unclear. A recent report has demonstrated that p53 can be induced by interferons and is activated after vesicular stomatitis virus (VSV) infection. We observed that different nononcogenic viruses, including encephalomyocarditis virus (EMCV) and human parainfluenza virus type 3 (HPIV3), induced down-regulation of p53 in infected cells. Double-stranded RNA (dsRNA) and a mutant vaccinia virus lacking the dsRNA binding protein E3L can also induce this effect, indicating that dsRNA formed during viral infection is likely the trigger for down-regulation of p53. The mechanism of down-regulation of p53 by dsRNA relies on translation inhibition mediated by the PKR and RNase L pathways. In the absence of p53, the replication of both EMCV and HPIV3 was retarded, whereas, conversely, VSV replication was enhanced. Cell cycle analysis indicated that wild-type (WT) but not p53 knockout (KO) fibroblasts undergo an early-G1 arrest following dsRNA treatment. Moreover, in WT cells the onset of dsRNA-induced apoptosis begins after p53 levels are down-regulated, whereas p53 KO cells, which lack the early-G1 arrest, rapidly undergo apoptosis. Hence, our data suggest that the down-regulation of p53 facilitates apoptosis, thereby limiting viral replication. PMID:16103161

  9. Antiviral activity of the exopolysaccharide produced by Serratia sp. strain Gsm01 against Cucumber mosaic virus.

    Science.gov (United States)

    Ipper, Nagesh S; Cho, Saeyoull; Lee, Seon Hwa; Cho, Jun Mo; Hur, Jang Hyun; Lim, Chun Keun

    2008-01-01

    The potential of the exopolysaccharide (EPS) from a Serratia sp. strain Gsm01 as an antiviral agent against a yellow strain of Cucumber mosaic virus (CMV-Y) was evaluated in tobacco plants (Nicotiana tabacum cv. Xanthi-nc). The spray treatment of plants using an EPS preparation, 72 before CMV-Y inoculation, protected them against symptom appearance. Fifteen days after challenge inoculation with CMVY, 33.33% of plants showed mosaic symptoms in EPS-treated plants compared with 100% in the control plants. The EPS-treated plants, which showed mosaic symptoms, appeared three days later than the controls. The enzyme-linked immunosorbent assay (ELISA) and reverse transcriptase polymerase chain reaction (RT-PCR) analyses of the leaves of the protected plants revealed that the EPS treatment affected virus accumulation in those plants. Analysis of phenylalanine ammonia lyase, peroxidase, and phenols in protected plants revealed enhanced accumulation of these substances. The pathogenesis-related (PR) genes expression represented by PR-1b was increased in EPS-treated plants. This is the first report of a systemic induction of protection triggered by EPS produced by Serratia sp. against CMV-Y.

  10. Antiviral Type I and Type III Interferon Responses in the Central Nervous System

    Directory of Open Access Journals (Sweden)

    Thomas Michiels

    2013-03-01

    Full Text Available The central nervous system (CNS harbors highly differentiated cells, such as neurons that are essential to coordinate the functions of complex organisms. This organ is partly protected by the blood-brain barrier (BBB from toxic substances and pathogens carried in the bloodstream. Yet, neurotropic viruses can reach the CNS either by crossing the BBB after viremia, or by exploiting motile infected cells as Trojan horses, or by using axonal transport. Type I and type III interferons (IFNs are cytokines that are critical to control early steps of viral infections. Deficiencies in the IFN pathway have been associated with fatal viral encephalitis both in humans and mice. Therefore, the IFN system provides an essential protection of the CNS against viral infections. Yet, basal activity of the IFN system appears to be low within the CNS, likely owing to the toxicity of IFN to this organ. Moreover, after viral infection, neurons and oligodendrocytes were reported to be relatively poor IFN producers and appear to keep some susceptibility to neurotropic viruses, even in the presence of IFN. This review addresses some trends and recent developments concerning the role of type I and type III IFNs in: i preventing neuroinvasion and infection of CNS cells; ii the identity of IFN-producing cells in the CNS; iii the antiviral activity of ISGs; and iv the activity of viral proteins of neurotropic viruses that target the IFN pathway.

  11. Interaction Research on the Antiviral Molecule Dufulin Targeting on Southern Rice Black Streaked Dwarf Virus P9-1 Nonstructural Protein

    Directory of Open Access Journals (Sweden)

    Zhenchao Wang

    2015-03-01

    Full Text Available ern rice black streaked dwarf virus (SRBSDV causes severe harm to rice production. Unfortunately, studies on effective antiviral drugs against SRBSDV and interaction mechanism of antiviral molecule targeting on SRBSDV have not been reported. This study found dufulin (DFL, an ideal anti-SRBSDV molecule, and investigated the interactions of DFL targeting on the nonstructural protein P9-1. The biological sequence information and bonding characterization of DFL to four kinds of P9-1 protein were described with fluorescence titration (FT and microscale thermophoresis (MST assays. The sequence analysis indicated that P9-1 had highly-conserved C- and N-terminal amino acid residues and a hypervariable region that differed from 131 aa to 160 aa. Consequently, wild-type (WT-His-P9-1, 23 C-terminal residues truncated (TR-ΔC23-His-P9-1, 6 N-terminal residues truncated (TR-ΔN6-His-P9-1, and Ser138 site-directed (MU-138-His-P9-1 mutant proteins were expressed. The FT and MST assay results indicated that DFL bounded to WT-His-P9-1 with micromole affinity and the 23 C-terminal amino acids were the potential targeting site. This system, which combines a complete sequence analysis, mutant protein expression, and binding action evaluating system, could further advance the understanding of the interaction abilities between antiviral drugs and their targets.

  12. 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.

  13. Identification of Novel 5,6-Dimethoxyindan-1-one Derivatives as Antiviral Agents.

    Science.gov (United States)

    Patil, Siddappa A; Patil, Vikrant; Patil, Renukadevi; Beaman, Kenneth; Patil, Shivaputra A

    2017-01-01

    Discovery of novel antiviral agents is essential because viral infection continues to threaten human life globally. Various heterocyclic small molecules have been developed as antiviral agents. The 5,6-dimethoxyindan-1-on nucleus is of considerable interest as this ring is the key constituent in a range of bioactive compounds, both naturally occurring and synthetic, and often of considerable complexity. The main purpose of this research was to discover and develop small molecule heterocycles as broad-spectrum of antiviral agents. A focused small set of 5,6-dimethoxyindan-1-one analogs (6-8) along with a thiopene derivative (9) was screened for selected viruses (Vaccinia virus - VACA, Human papillomavirus - HPV, Zika virus - ZIKV, Dengue virus - DENV, Measles virus - MV, Poliovirus 3 - PV, Rift Valley fever virus - RVFV, Tacaribe virus - TCRV, Venezuelan equine encephalitis virus - VEEV, Herpes simplex virus 1 -HSV-1 and Human cytomegalovirus - HCMV) using the National Institute of Allergy and Infectious Diseases (NIAID)'s Division of Microbiology and Infectious Diseases (DMID) antiviral screening program. These molecules demonstrated moderate to excellent antiviral activity towards variety of viruses. The 5,6-dimethoxyindan-1-one analog (7) demonstrated high efficacy towards vaccinia virus (EC50: 30.00 µM) in secondary plaque reduction assay. The thiophene analog (9) has shown very good viral inhibition towards several viruses such as Human papillomavirus, Measles virus, Rift Valley fever virus, Tacaribe virus and Herpes simplex virus 1. Our research identified a novel 5,6-dimethoxyindan-1-one analog (compound 7), as a potent antiviral agent for vaccinia virus, and heterocyclic chalcone analog (compound 9) as a broad spectrum antiviral agent. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  14. Antiviral stockpiles for influenza pandemics from the household perspective: treatment alone versus treatment with prophylaxis.

    Science.gov (United States)

    Kwok, Kin On; Leung, Gabriel M; Mak, Peter; Riley, Steven

    2013-06-01

    Model-based studies of antiviral use to mitigate the impact of moderate and severe influenza pandemics implicitly take the viewpoint of a central public health authority. However, it seems likely that the key decision of when to use antivirals will be made at the household level. We used a stochastic compartmental model of the transmission of influenza within and between households to evaluate the expected mortality under two strategies: households saving available antivirals for treatment only and households implementing prophylaxis as well as treatment. Given that every individual in the population was allocated a single course of antivirals, we investigated the impact of these two strategies for a wide range of AVED, the efficacy of antivirals in preventing death in severe cases (AVED=1 for complete protection). We found a cross-over point for our baseline parameter values in a regime where antivirals were still highly effective in reducing the chance of death: below AVED=0.9 the optimal strategy was for households to use both treatment and prophylaxis. We also considered the possibility that a small number of households might "cheat" by choosing to follow the treatment-only strategy when other households were following treatment with prophylaxis. The cross-over point for cheating households was considerably lower, at AVED=0.6, but substantially above 0. These results suggest that unless antivirals are almost completely effective in reducing the chance of death in serious cases, households will likely be better served implementing prophylaxis as well as treatment. More generally, our study illustrates the potential value of considering viewpoints other than a central authority when conducting model-based analysis of interventions against infectious disease. Copyright © 2013 Elsevier B.V. All rights reserved.

  15. La protéine CG4572 de Drosophile et la propagation du signal ARNi immun antiviral

    OpenAIRE

    Karlikow , Margot

    2015-01-01

    During viral infection, cell survival will depend on adequately giving, receiving and processing information to establish an efficient antiviral immune response. Cellular communication is therefore essential to allow the propagation of immune signals that will confer protection to the entire organism.The major antiviral defense in insects is the RNA interference (RNAi) mechanism that is activated by detection of viral double-stranded RNA (dsRNA). The antiviral RNAi mechanism can be divided in...

  16. Local dialogue and information within the frame of the setting up of relay antennas. Decreasing the exposure to electromagnetic waves emitted by mobile phone relay antennas. First phase report by Francois Brottes, chairman of the 'experimentations' COMOP

    International Nuclear Information System (INIS)

    Brottes, Francois

    2011-01-01

    The first part of this report describes the progress made on local dialogue and information within the frame of the setting up of relay antennas. It describes the implemented method with a selection of nine local communities, the main results of the dialogue (establishment of an information file, development of a tool set for the pilot communities, and operation, steering and assessment of experimentations). The second part describes the progress made on the exposure of population to electromagnetic waves emitted by mobile phone relay antennas (context, method, exposure status, simulation of the decreasing of relay antenna power, site experimentations). The third part proposes a set of recommendations related to local dialogue and information and to exposure

  17. In vitro and in vivo mechanism of immunomodulatory and antiviral activity of Edible Bird's Nest (EBN) against influenza A virus (IAV) infection.

    Science.gov (United States)

    Haghani, Amin; Mehrbod, Parvaneh; Safi, Nikoo; Aminuddin, Nur Ain; Bahadoran, Azadeh; Omar, Abdul Rahman; Ideris, Aini

    2016-06-05

    For centuries, Edible Bird Nest (EBN) has been used in treatment of variety of respiratory diseases such as flu and cough as a Chinese natural medicine. This natural remedy showed the potential to inhibit influenza A virus (IAV). However, little is known about the mechanism of this process and also the evaluation of this product in an animal model. Hence, the current study was designed to elucidate the antiviral and immunomodulatory effects of EBN against IAV strain A/Puerto Rico/8/1934 (H1N1). First, influenza infected MDCK cells treated with EBNs from two locations of Malaysia (Teluk Intan and Gua Madai) that prepared with different enzymatic preparations were analyzed by RT-qPCR and ELISA for detection of viral and cytokines genes. The sialic acid composition of these EBNs was evaluated by H-NMR. Subsequently, after toxicity evaluation of EBN from Teluk Intan, antiviral and immunomodulatory effects of this natural product was evaluated in BALB/c mice by analysis of the viral NA gene and cytokine expressions in the first week of the infection. EBN showed high neuraminidase inhibitory properties in both in vitro and in vivo, which was as effective as Oseltamivir phosphate. In addition, EBN decreased NS1 copy number (p<0.05) of the virus along with high immunomodulatory effects against IAV. Some of the immune changes during treatment of IAV with EBN included significant increase in IFNγ, TNFα, NFκB, IL2, some proinflammatory cytokines like IL1β, IL6, and cytokines with regulatory properties like IL10, IL27, IL12, CCL2 and IL4 depends on the stage of the infection. EBNs from two locations contained different composition of sialic acid and thymol derivatives, which gave them different antiviral properties. EBN from Gua Madai that contained more acetylated sialic acid (Neu2,4,7,8,9 Ac6) showed higher antiviral activity. The findings of this study support the antiviral activity of EBN against influenza virus and validate the traditional usage of this natural remedy

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

    International Nuclear Information System (INIS)

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

    2012-01-01

    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. - 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.

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

    Science.gov (United States)

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

    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. Importantly, they demonstrate potent antiviral activities against drug-resistant strains. In the study of mechanisms, we found that Xiaoqinglong mixture could increase antiviral interferon production by activating p38 MAPK, JNK/SAPK pathway, and relative nuclear transcription factors. Lastly, our studies also indicate that some of these medicines show inhibitory activities against EV71 and CVB strains. In conclusion, the 10 traditional Chinese medicines, as kind of compound combination medicines, show broad-spectrum antiviral activities, possibly also including inhibitory activities against strains resistant to available antiviral drugs.

  20. 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.

  1. In vitro antiviral activity of chestnut and quebracho woods extracts against avian reovirus and metapneumovirus.

    Science.gov (United States)

    Lupini, C; Cecchinato, M; Scagliarini, A; Graziani, R; Catelli, E

    2009-12-01

    Field evidences have suggested that a natural extract, containing tannins, could be effective against poultry enteric viral infections. Moreover previous studies have shown that vegetable tannins can have antiviral activity against human viruses. Based on this knowledge three different Chestnut (Castanea spp.) wood extracts and one Quebracho (Schinopsis spp.) wood extract, all containing tannins and currently used in the animal feed industry, were tested for in vitro antiviral activity against avian reovirus (ARV) and avian metapneumovirus (AMPV). The MTT assay was used to evaluate the 50% cytotoxic compounds concentration (CC(50)) on Vero cells. The antiviral properties were tested before and after the adsorption of the viruses to Vero cells. Antiviral activities were expressed as IC(50) (concentration required to inhibit 50% of viral cytopathic effect). CC(50)s of tested compounds were > 200 microg/ml. All compounds had an extracellular antiviral effect against both ARV and AMPV with IC(50) values ranging from 25 to 66 microg/ml. Quebracho extract had also evident intracellular anti-ARV activity (IC(50) 24 microg/ml). These preliminary results suggest that the examined vegetable extracts might be good candidates in the control of some avian virus infections. Nevertheless further in vivo experiments are required to confirm these findings.

  2. Mastery Learning and the Decreasing Variability Hypothesis.

    Science.gov (United States)

    Livingston, Jennifer A.; Gentile, J. Ronald

    1996-01-01

    This report results from studies that tested two variations of Bloom's decreasing variability hypothesis using performance on successive units of achievement in four graduate classrooms that used mastery learning procedures. Data do not support the decreasing variability hypothesis; rather, they show no change over time. (SM)

  3. Nerve Regeneration in Conditions of HSV-Infection and an Antiviral Drug Influence.

    Science.gov (United States)

    Gumenyuk, Alla; Rybalko, Svetlana; Ryzha, Alona; Savosko, Sergey; Labudzynskyi, Dmytro; Levchuk, Natalia; Chaikovsky, Yuri

    2018-05-05

    Herpes simplex virus type I (HSV-I) is a latent neuroinfection which can cause focal brain lesion. The role of HSV-infection in nerve regeneration has not been studied so far. The aim of the work was to study sciatic nerve regeneration in the presence of HSV-infection and the influence of an antiviral drug. BALB/c line mice were divided into five groups. Group 1 animals were infected with HSV-I. After resolution of neuroinfection manifestations the sciatic nerve of these animals was crushed. Group 2 mice were administered acyclovir following the same procedures. Groups 3-5 mice served as controls. Thirty days after the operation distal nerve stumps and m.gastrocnemius were studied morphologically and biochemically. Ultrastructural organization of the sciatic nerve in control animals remained intact. Morphometric parameters of the nerves from the experimental groups have not reach control values. However, in the group 1 diameter of nerve fibers was significantly smaller than in the group 2. Both nerve regeneration and m.gastrocnemius reinnervation were confirmed. The muscle hypotrophy was found in groups 1, 2, and 3 (the muscle fibers diameter decreased). Metabolic changes in the muscles of the infected animals (groups 1 and 2) were more pronounced than in control groups 3 and 4. The levels of TBA-active products, conjugated dienes, carbonyl and SH-groups were reduced in m.gastrocnemius of the experimental groups, however no significant difference associated with acyclovir administration was found. HSV-infection is not limited to the local neurodegenerative changes in the CNS but affects regeneration of the injured sciatic nerve. Anat Rec, 2018. © 2018 Wiley Periodicals, Inc. © 2018 Wiley Periodicals, Inc.

  4. Histophilus somni Stimulates Expression of Antiviral Proteins and Inhibits BRSV Replication in Bovine Respiratory Epithelial Cells.

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    C Lin

    Full Text Available Our previous studies showed that bovine respiratory syncytial virus (BRSV followed by Histophilus somni causes more severe bovine respiratory disease and a more permeable alveolar barrier in vitro than either agent alone. However, microarray analysis revealed the treatment of bovine alveolar type 2 (BAT2 epithelial cells with H. somni concentrated culture supernatant (CCS stimulated up-regulation of four antiviral protein genes as compared with BRSV infection or dual treatment. This suggested that inhibition of viral infection, rather than synergy, may occur if the bacterial infection occurred before the viral infection. Viperin (or radical S-adenosyl methionine domain containing 2--RSAD2 and ISG15 (IFN-stimulated gene 15--ubiquitin-like modifier were most up-regulated. CCS dose and time course for up-regulation of viperin protein levels were determined in treated bovine turbinate (BT upper respiratory cells and BAT2 lower respiratory cells by Western blotting. Treatment of BAT2 cells with H. somni culture supernatant before BRSV infection dramatically reduced viral replication as determined by qRT PCR, supporting the hypothesis that the bacterial infection may inhibit viral infection. Studies of the role of the two known H. somni cytotoxins showed that viperin protein expression was induced by endotoxin (lipooligosaccharide but not by IbpA, which mediates alveolar permeability and H. somni invasion. A naturally occurring IbpA negative asymptomatic carrier strain of H. somni (129Pt does not cause BAT2 cell retraction or permeability of alveolar cell monolayers, so lacks virulence in vitro. To investigate initial steps of pathogenesis, we showed that strain 129Pt attached to BT cells and induced a strong viperin response in vitro. Thus colonization of the bovine upper respiratory tract with an asymptomatic carrier strain lacking virulence may decrease viral infection and the subsequent enhancement of bacterial respiratory infection in vivo.

  5. Fatty liver in hepatitis C patients post-sustained virological response with direct-acting antivirals

    Science.gov (United States)

    Noureddin, Mazen; Wong, Micaela M; Todo, Tsuyoshi; Lu, Shelly C; Sanyal, Arun J; Mena, Edward A

    2018-01-01

    AIM To determine steatosis and fibrosis prevalence in hepatitis C patients after a sustained virological response achieved with direct-acting antivirals. METHODS Transient elastography with controlled attenuation parameter (CAP) was used to assess hepatic steatosis post-sustained virological response (SVR); the CAP technology was not available in the United States at study initiation. Liver stiffness/fibrosis was measured before and 47 wk after treatment completion. Patients with genotype 3 and patients with cirrhosis were excluded. RESULTS One hundred and one patients were included in the study. Post-SVR there were decreases from baseline in alanine aminotransferase (ALT) (63.1 to 17.8 U/L), aspartate aminotransferase (51.8 to 21.5 U/L) and fibrosis score (7.4 to 6.1 kPa) (P steatosis on CAP; of these, 6.25% had advanced fibrosis. Patients with steatosis had higher body mass index (29.0 vs 26.1 kg/m2), glucose (107.8 vs 96.6 mg/dL), ALT (20.4 vs 15.3 mg/dL), CAP score (296.3 vs 212.4 dB/m) and fibrosis score (7.0 vs 5.3 kPa); P steatosis had change in fibrosis score post-SVR (7.7 kPa vs 7.0 kPa and 7.0 kPa vs 5.3 kPa); alternatively, (P steatosis continued to have clinically significant stiffness (≥ 7 kPa). CONCLUSION Fatty liver is very common in hepatitis C virus (HCV) patients post-SVR. These patients continue to have elevated mean fibrosis score (≥ 7 kPa) compared to those without fatty liver; some have advanced fibrosis. Long term follow up is needed to assess steatosis and fibrosis in HCV patients post-SVR. PMID:29568207

  6. Glucose-6-Phosphate Dehydrogenase Enhances Antiviral Response through Downregulation of NADPH Sensor HSCARG and Upregulation of NF-κB Signaling

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    Yi-Hsuan Wu

    2015-12-01

    Full Text Available Glucose-6-phosphate dehydrogenase (G6PD-deficient cells are highly susceptible to viral infection. This study examined the mechanism underlying this phenomenon by measuring the expression of antiviral genes—tumor necrosis factor alpha (TNF-α and GTPase myxovirus resistance 1 (MX1—in G6PD-knockdown cells upon human coronavirus 229E (HCoV-229E and enterovirus 71 (EV71 infection. Molecular analysis revealed that the promoter activities of TNF-α and MX1 were downregulated in G6PD-knockdown cells, and that the IκB degradation and DNA binding activity of NF-κB were decreased. The HSCARG protein, a nicotinamide adenine dinucleotide phosphate (NADPH sensor and negative regulator of NF-κB, was upregulated in G6PD-knockdown cells with decreased NADPH/NADP+ ratio. Treatment of G6PD-knockdown cells with siRNA against HSCARG enhanced the DNA binding activity of NF-κB and the expression of TNF-α and MX1, but suppressed the expression of viral genes; however, the overexpression of HSCARG inhibited the antiviral response. Exogenous G6PD or IDH1 expression inhibited the expression of HSCARG, resulting in increased expression of TNF-α and MX1 and reduced viral gene expression upon virus infection. Our findings suggest that the increased susceptibility of the G6PD-knockdown cells to viral infection was due to impaired NF-κB signaling and antiviral response mediated by HSCARG.

  7. Metabolic syndrome is associated with poor treatment response to antiviral therapy in chronic hepatitis C genotype 3 patients.

    Science.gov (United States)

    Aziz, Hafsa; Gill, Uzma; Raza, Abida; Gill, Muzaffar L

    2014-05-01

    Hepatitis C viral (HCV) infection is caused by an RNA virus. HCV infection is considered to induce systemic disease that causes steatosis, alters lipid metabolism, and results in metabolic syndrome. This study aimed to investigate the therapeutic outcome in HCV genotype 3 patients with metabolic syndrome. A total of 621 HCV-positive patients who visited the hospital for treatment were screened. Among these, 441 patients were enrolled for antiviral therapy. These enrolled patients were assessed for metabolic syndrome according to the International Diabetes Federation criteria. Group A included patients with metabolic syndrome and group B included patients without metabolic syndrome. All patients received peginterferon-α2a (180 μg/week) and ribavirin (10 mg/kg/day) for 6 months. The prevalence of metabolic syndrome in chronic HCV patients was 37.9%. We observed that metabolic syndrome was more common among female compared with male participants (43.9 vs. 28.8%, P=0.005). It was found that sustained virologic response (SVR) rates were significantly higher in the patients in group B (without metabolic syndrome) compared with the patients in group A who had metabolic syndrome (72.2 vs. 43.7%, Pmetabolic syndrome and a correlation of metabolic syndrome with nonresponse to antiviral therapy was observed. An interesting correlation among metabolic syndrome, age, and SVR was found: with age, SVR decreases, while metabolic syndrome increases. Metabolic syndrome has an influence on therapeutic outcomes in terms of SVR. Moreover, this information can identify patients who might have a low chance of attaining an SVR and a timely decision may protect the patients from the adverse effects of therapy.

  8. Cellular impedance measurement as a new tool for poxvirus titration, antibody neutralization testing and evaluation of antiviral substances

    International Nuclear Information System (INIS)

    Witkowski, Peter T.; Schuenadel, Livia; Wiethaus, Julia; Bourquain, Daniel R.; Kurth, Andreas; Nitsche, Andreas

    2010-01-01

    Research highlights: → Real-time data acquisition by RT-CES requires low operative effort. → Time to result is reduced by using RT-CES instead of conventional methods. → RT-CES enables quantification of virus titers in unknown samples. → RT-CES is a useful tool for high-throughput characterization of antiviral agents. → An RT-CES-based virus neutralization test was established. -- Abstract: Impedance-based biosensing known as real-time cell electronic sensing (RT-CES) belongs to an emerging technology for analyzing the status of cells in vitro. In the present study protocols were developed for an RT-CES-based system (xCELLigence TM , Roche Applied Science, ACEA Biosciences Inc.) to supplement conventional techniques in pox virology. First, proliferation of cells susceptible to orthopoxviruses was monitored. For virus titration cells were infected with vaccinia virus and cell status, represented by the dimensionless impedance-based cell index (CI), was monitored. A virus-dose dependent decrease in electrical impedance could be shown. Calculation of calibration curves at a suitable CI covering a dynamic range of 4 log enabled the quantification of virus titers in unknown samples. Similarly, antiviral effects could be determined as shown for anti-poxviral agents ST-246 and Cidofovir. Published values for the in vitro concentration that inhibited virus replication by 50% (IC 50 ) could be confirmed while cytotoxicity in effective concentrations was excluded in long-term incubation experiments. Finally, an RT-CES-based virus neutralization test was established. Various poxvirus-specific antibodies were examined for their neutralizing activity and a calculation mode for the neutralizing antibody titer was introduced. In summary, the presented RT-CES-based methods outmatch end-point assays by observing the cell population throughout the entire experiment while workload and time to result are reduced.

  9. Antiviral Properties of Caffeic Acid Phenethyl Ester and Its Potential Application

    Directory of Open Access Journals (Sweden)

    Haci Kemal Erdemli

    2015-12-01

    Full Text Available Caffeic acid phenethyl ester (CAPE is found in variety of plants and well known active ingredient of the honeybee propolis. CAPE showed anti-inflammatory, anticarcinogenic, antimitogenic, antiviral and immunomodulatory properties in several studies. The beneficial effects of CAPE on different health issues attracted scientists to make more studies on CAPE. Specifically, the anti-viral effects of CAPE and its molecular mechanisms may reveal the important properties of virus-induced diseases. CAPE and its targets may have important roles to design new therapeutics and understand the molecular mechanisms of virus related diseases. In this mini-review, we summarize the antiviral effects of CAPE under the light of medical and chemical literature. [J Intercult Ethnopharmacol 2015; 4(4.000: 344-347

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

    Science.gov (United States)

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

    2015-09-01

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

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

    Directory of Open Access Journals (Sweden)

    Yuanan Lu

    2012-02-01

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

  12. Viruses transfer the antiviral second messenger cGAMP between cells.

    Science.gov (United States)

    Bridgeman, A; Maelfait, J; Davenne, T; Partridge, T; Peng, Y; Mayer, A; Dong, T; Kaever, V; Borrow, P; Rehwinkel, J

    2015-09-11

    Cyclic GMP-AMP synthase (cGAS) detects cytosolic DNA during virus infection and induces an antiviral state. cGAS signals by synthesis of a second messenger, cyclic GMP-AMP (cGAMP), which activates stimulator of interferon genes (STING). We show that cGAMP is incorporated into viral particles, including lentivirus and herpesvirus virions, when these are produced in cGAS-expressing cells. Virions transferred cGAMP to newly infected cells and triggered a STING-dependent antiviral program. These effects were independent of exosomes and viral nucleic acids. Our results reveal a way by which a signal for innate immunity is transferred between cells, potentially accelerating and broadening antiviral responses. Moreover, infection of dendritic cells with cGAMP-loaded lentiviruses enhanced their activation. Loading viral vectors with cGAMP therefore holds promise for vaccine development. Copyright © 2015, American Association for the Advancement of Science.

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

    Directory of Open Access Journals (Sweden)

    E. A. Kiprianova

    2017-02-01

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

  14. Viral Response to Specifically Targeted Antiviral Therapy for Hepatitis C and the Implications for Treatment Success

    Directory of Open Access Journals (Sweden)

    Curtis L Cooper

    2010-01-01

    Full Text Available Currently, hepatitis C virus (HCV antiviral therapy is characterized by long duration, a multitude of side effects, difficult administration and suboptimal success; clearly, alternatives are needed. Collectively, specifically targeted antiviral therapy for HCV (STAT-C molecules achieve rapid viral suppression and very high rapid virological response rates, and improve sustained virological response rates. The attrition rate of agents within this class has been high due to various toxicities. Regardless, several STAT-C molecules are poised to become the standard of care for HCV treatment in the foreseeable future. Optimism must be tempered with concerns related to the rapid development of drug resistance with resulting HCV rebound. Strategies including induction dosing with interferon and ribavirin, use of combination high-potency STAT-C molecules and an intensive emphasis on adherence to HCV antiviral therapy will be critical to the success of this promising advance in HCV therapy.

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

    Science.gov (United States)

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

    2014-09-01

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

  16. Antiviral Goes Viral: Harnessing CRISPR/Cas9 to Combat Viruses in Humans.

    Science.gov (United States)

    Soppe, Jasper Adriaan; Lebbink, Robert Jan

    2017-10-01

    The clustered regularly interspaced short palindromic repeats (CRISPR) and CRISPR-associated (Cas) systems are RNA-guided sequence-specific prokaryotic antiviral immune systems. In prokaryotes, small RNA molecules guide Cas effector endonucleases to invading foreign genetic elements in a sequence-dependent manner, resulting in DNA cleavage by the endonuclease upon target binding. A rewired CRISPR/Cas9 system can be used for targeted and precise genome editing in eukaryotic cells. CRISPR/Cas has also been harnessed to target human pathogenic viruses as a potential new antiviral strategy. Here, we review recent CRISPR/Cas9-based approaches to combat specific human viruses in humans and discuss challenges that need to be overcome before CRISPR/Cas9 may be used in the clinic as an antiviral strategy. Copyright © 2017 Elsevier Ltd. All rights reserved.

  17. Synthesis, biological evaluation and molecular modeling investigation of some new Benzimidazole analogs as antiviral agents

    International Nuclear Information System (INIS)

    Goda, Fatma E.; Tantawy, Atif S.; Abou-Zeid, Laila A.; Badr, Sahar M.; Selim, Khalid B.

    2008-01-01

    A set heterocyclic benzimidazole derivatives bearing 1, 3, 5-triazine group with different substituents at C-2 and C-5 of the benzimidazole ring have been synthesized and evaluated for their antiviral activities against HASV-1. The structures of these compounds have been established by analytical data, IR spectra, H NMR and mass spectra. Compounds 8a and 8b proved to be the most active antiherpetic agents in this study, at EC 50% concentrations of 2.9. 3.4 mg/ml, respectively. Computational evaluation of the quantum chemical descriptors such as hydrphobicity (log P), HOMO-LUMO and the gap energy were calculated and correlated with the antiviral activity. The tested compounds showed proper degree of hydrophobicity ( 5). The HOMO-LUMO gap energy values of the tested compounds are comparable with the observed values for the antiviral drug Acyclovir. (author)

  18. Decreasing incidence rates of bacteremia

    DEFF Research Database (Denmark)

    Nielsen, Stig Lønberg; Pedersen, C; Jensen, T G

    2014-01-01

    BACKGROUND: Numerous studies have shown that the incidence rate of bacteremia has been increasing over time. However, few studies have distinguished between community-acquired, healthcare-associated and nosocomial bacteremia. METHODS: We conducted a population-based study among adults with first......-time bacteremia in Funen County, Denmark, during 2000-2008 (N = 7786). We reported mean and annual incidence rates (per 100,000 person-years), overall and by place of acquisition. Trends were estimated using a Poisson regression model. RESULTS: The overall incidence rate was 215.7, including 99.0 for community......-acquired, 50.0 for healthcare-associated and 66.7 for nosocomial bacteremia. During 2000-2008, the overall incidence rate decreased by 23.3% from 254.1 to 198.8 (3.3% annually, p incidence rate of community-acquired bacteremia decreased by 25.6% from 119.0 to 93.8 (3.7% annually, p

  19. A petunia ethylene-responsive element binding factor, PhERF2, plays an important role in antiviral RNA silencing.

    Science.gov (United States)

    Sun, Daoyang; Nandety, Raja Sekhar; Zhang, Yanlong; Reid, Michael S; Niu, Lixin; Jiang, Cai-Zhong

    2016-05-01

    Virus-induced RNA silencing is involved in plant antiviral defense and requires key enzyme components, including RNA-dependent RNA polymerases (RDRs), Dicer-like RNase III enzymes (DCLs), and Argonaute proteins (AGOs). However, the transcriptional regulation of these critical components is largely unknown. In petunia (Petunia hybrida), an ethylene-responsive element binding factor, PhERF2, is induced by Tobacco rattle virus (TRV) infection. Inclusion of a PhERF2 fragment in a TRV silencing construct containing reporter fragments of phytoene desaturase (PDS) or chalcone synthase (CHS) substantially impaired silencing efficiency of both the PDS and CHS reporters. Silencing was also impaired in PhERF2- RNAi lines, where TRV-PhPDS infection did not show the expected silencing phenotype (photobleaching). In contrast, photobleaching in response to infiltration with the TRV-PhPDS construct was enhanced in plants overexpressing PhERF2 Transcript abundance of the RNA silencing-related genes RDR2, RDR6, DCL2, and AGO2 was lower in PhERF2-silenced plants but higher in PhERF2-overexpressing plants. Moreover, PhERF2-silenced lines showed higher susceptibility to Cucumber mosaic virus (CMV) than wild-type (WT) plants, while plants overexpressing PhERF2 exhibited increased resistance. Interestingly, growth and development of PhERF2-RNAi lines were substantially slower, whereas the overexpressing lines were more vigorous than the controls. Taken together, our results indicate that PhERF2 functions as a positive regulator in antiviral RNA silencing. © The Author 2016. Published by Oxford University Press on behalf of the Society for Experimental Biology.

  20. Topoisomerase 1 Inhibition Promotes Cyclic GMP-AMP Synthase-Dependent Antiviral Responses.

    Science.gov (United States)

    Pépin, Geneviève; Nejad, Charlotte; Ferrand, Jonathan; Thomas, Belinda J; Stunden, H James; Sanij, Elaine; Foo, Chwan-Hong; Stewart, Cameron R; Cain, Jason E; Bardin, Philip G; Williams, Bryan R G; Gantier, Michael P

    2017-10-03

    Inflammatory responses, while essential for pathogen clearance, can also be deleterious to the host. Chemical inhibition of topoisomerase 1 (Top1) by low-dose camptothecin (CPT) can suppress transcriptional induction of antiviral and inflammatory genes and protect animals from excessive and damaging inflammatory responses. We describe the unexpected finding that minor DNA damage from topoisomerase 1 inhibition with low-dose CPT can trigger a strong antiviral immune response through cyclic GMP-AMP synthase (cGAS) detection of cytoplasmic DNA. This argues against CPT having only anti-inflammatory activity. Furthermore, expression of the simian virus 40 (SV40) large T antigen was paramount to the proinflammatory antiviral activity of CPT, as it potentiated cytoplasmic DNA leakage and subsequent cGAS recruitment in human and mouse cell lines. This work suggests that the capacity of Top1 inhibitors to blunt inflammatory responses can be counteracted by viral oncogenes and that this should be taken into account for their therapeutic development. IMPORTANCE Recent studies suggest that low-dose DNA-damaging compounds traditionally used in cancer therapy can have opposite effects on antiviral responses, either suppressing (with the example of CPT) or potentiating (with the example of doxorubicin) them. Our work demonstrates that the minor DNA damage promoted by low-dose CPT can also trigger strong antiviral responses, dependent on the presence of viral oncogenes. Taken together, these results call for caution in the therapeutic use of low-dose chemotherapy agents to modulate antiviral responses in humans. Copyright © 2017 Pépin et al.

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

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    Qian Feng

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

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

    OpenAIRE

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

    2017-01-01

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

  3. The Antiviral Mechanism of an Influenza A Virus Nucleoprotein-Specific Single-Domain Antibody Fragment

    Energy Technology Data Exchange (ETDEWEB)

    Hanke, Leo; Knockenhauer, Kevin E.; Brewer, R. Camille; van Diest, Eline; Schmidt, Florian I.; Schwartz, Thomas U.; Ploegh, Hidde L. (Whitehead); (MIT)

    2016-12-13

    Alpaca-derived single-domain antibody fragments (VHHs) that target the influenza A virus nucleoprotein (NP) can protect cells from infection when expressed in the cytosol. We found that one such VHH, αNP-VHH1, exhibits antiviral activity similar to that of Mx proteins by blocking nuclear import of incoming viral ribonucleoproteins (vRNPs) and viral transcription and replication in the nucleus. We determined a 3.2-Å crystal structure of αNP-VHH1 in complex with influenza A virus NP. The VHH binds to a nonconserved region on the body domain of NP, which has been associated with binding to host factors and serves as a determinant of host range. Several of the NP/VHH interface residues determine sensitivity of NP to antiviral Mx GTPases. The structure of the NP/αNP-VHH1 complex affords a plausible explanation for the inhibitory properties of the VHH and suggests a rationale for the antiviral properties of Mx proteins. Such knowledge can be leveraged for much-needed novel antiviral strategies.

    IMPORTANCEInfluenza virus strains can rapidly escape from protection afforded by seasonal vaccines or acquire resistance to available drugs. Additional ways to interfere with the virus life cycle are therefore urgently needed. The influenza virus nucleoprotein is one promising target for antiviral interventions. We have previously isolated alpaca-derived single-domain antibody fragments (VHHs) that protect cells from influenza virus infection if expressed intracellularly. We show here that one such VHH exhibits antiviral activities similar to those of proteins of the cellular antiviral defense (Mx proteins). We determined the three-dimensional structure of this VHH in complex with the influenza virus nucleoprotein and identified the interaction site, which overlaps regions that determine sensitivity of the virus to Mx proteins. Our data define a new vulnerability of influenza virus, help us to better understand the cellular antiviral mechanisms, and

  4. Antiviral Inhibition of Enveloped Virus Release by Tetherin/BST-2: Action and Counteraction

    Directory of Open Access Journals (Sweden)

    Stuart J. D. Neil

    2011-05-01

    Full Text Available Tetherin (BST2/CD317 has been recently recognized as a potent interferon-induced antiviral molecule that inhibits the release of diverse mammalian enveloped virus particles from infected cells. By targeting an immutable structure common to all these viruses, the virion membrane, evasion of this antiviral mechanism has necessitated the development of specific countermeasures that directly inhibit tetherin activity. Here we review our current understanding of the molecular basis of tetherin’s mode of action, the viral countermeasures that antagonize it, and how virus/tetherin interactions may affect viral transmission and pathogenicity.

  5. Unidentified angular recurrent ulceration responsive to antiviral therapy

    Directory of Open Access Journals (Sweden)

    Rahmi Amtha

    2013-03-01

    Full Text Available Background: Recurrent ulcer on angular area is usually called stomatitis angularis. It is caused by many factors such as vertical dimension reduce, vitamin B12, and immune system deficiency, C. albicans and staphylococcus involvement. Clinically is characterized by painful fissure with erythematous base without fever. Purpose: to describe an unidentified angular ulcer proceeded by recurrent ulcers with no response of topical therapy. Case: An 18-years old male came to Oral Medicine clinic in RSCM who complained of angular recurrent ulcers since 3 years ago which developed on skin and bleed easily on mouth opening. Patient had fever before the onset of ulcers. Large, painful, irregular ulcers covered by red crustae on angular area bilaterally. Patient has been treated with various drugs without improvement and lead to mouth opening limitation. Intra oral shows herpetiformtype of ulcer and swollen of gingival. Case management: Provisional diagnosis was established as viral infection thus acyclovir 200 mg five times daily for two weeks and topical anti inflammation gel were administered. Blood test for IgG/IgM of HSV1 and HSV2 were non reactive, however ulceration showed a remarkable improvement. The ulcers healed completely after next 2 weeks with acyclovir. Conclusion: The angular ulceration on above patient failed to fulfill the criteria of stomatitis angularis or herpes labialis lesion. However it showed a good response to antiviral. Therefore, unidentified angular ulceration was appointed, as the lesion might be triggered by other type of human herpes virus or types of virus that response to acyclovir.Latar belakang: ulser rekuren pada sudut mulut biasanya disebut stomatitis angularis. Kelainan ini disebabkan oleh banyak faktor seperti berkurangnya dimensi vertikal, defisiensi vitamin B12 dan sistem kekebalan tubuh, infeksi C. albicans serta staphylococcus. Secara klinis kelainan ini ditandai dengan fisur sakit pada sudut mulut dengan dasar

  6. Utilisation of hepatocellular carcinoma screening in Australians at risk of hepatitis B virus-related carcinoma and prescribed anti-viral therapy.

    Science.gov (United States)

    Sheppard-Law, Suzanne; Zablotska-Manos, Iryna; Kermeen, Melissa; Holdaway, Susan; Lee, Alice; George, Jacob; Zekry, Amany; Maher, Lisa

    2018-07-01

    To investigate hepatocellular carcinoma screening utilisation and factors associated with utilisation among patients prescribed hepatitis B virus anti-viral therapy and at risk of hepatocellular carcinoma. The incidence of hepatocellular carcinoma has increased in Australia over the past three decades with chronic hepatitis B virus infection a major contributor. hepatocellular carcinoma surveillance programs aim to detect cancers early enabling curative treatment options, longer survival and longer times to recurrence. Multi-site cross-sectional survey. An online study questionnaire was administered to eligible participants attending three Sydney tertiary hospitals. Data were grouped into six mutually exclusive hepatocellular carcinoma risk factor categories as per American Association for the Study of Liver Diseases guidelines. All analyses were undertaken in STATA. Logistic regression was used to assess the associations between covariates and screening utilisation. Multivariate models described were assessed using the Hosmer-Lemeshow goodness of fit. Of the 177 participants, 137 (77.4%) self-reported that US had been performed in the last six months. Awareness that screening should be performed and knowing the correct frequency of US screening were independently associated with screening utilisation. Participants who knew that screening should be undertaken were three times more likely to have had pretreatment education or were prescribed hepatitis B virus anti-viral treatment for >4 years. Participants reporting a family history of hepatocellular carcinoma were less likely to know that screening should be undertaken every 6 months. While utilisation of hepatocellular carcinoma surveillance programs was higher in this study than in previous reports, strategies to further improve surveillance remain necessary. Findings from this research form the basis for proposing strategies to improve utilisation of hepatocellular carcinoma screening, inform hepatitis B virus

  7. Accessory factors of cytoplasmic viral RNA sensors required for antiviral innate immune response

    Directory of Open Access Journals (Sweden)

    Hiroyuki eOshiumi

    2016-05-01

    Full Text Available Type I interferon (IFN induces many antiviral factors in host cells. RIG-I-like receptors (RLRs are cytoplasmic viral RNA sensors that trigger the signal to induce the innate immune response that includes type I IFN production. RIG-I and MDA5 are RLRs that form nucleoprotein filaments along viral double-stranded RNA, resulting in the activation of MAVS adaptor molecule. The MAVS protein forms a prion-like aggregation structure, leading to type I IFN production. RIG-I and MDA5 undergo post-translational modification. TRIM25 and Riplet ubiquitin ligases deliver a K63-linked polyubiquitin moiety to the RIG-I N-terminal caspase activation and recruitment domains (CARDs and C-terminal region; the polyubiquitin chain then stabilizes the two-CARD tetramer structure required for MAVS assembly. MDA5 activation is regulated by phosphorylation. RIOK3 is a protein kinase that phosphorylates the MDA5 protein in a steady state, and PP1α/γ dephosphorylate this protein, resulting in its activation. RIG-I and MDA5 require cytoplasmic RNA helicases for their efficient activation. LGP2, another RLR, is an RNA helicase involved in RLR signaling. This protein does not possess N-terminal CARDs and thus cannot trigger downstream signaling by itself. Recent studies have revealed that this protein modulates MDA5 filament formation, resulting in enhanced type I IFN production. Several other cytoplasmic RNA helicases are involved in RLR signaling. DDX3, DHX29, DHX36, and DDX60 RNA helicases have been reported to be involved in RLR-mediated type I IFN production after viral infection. However, the underlying mechanism is largely unknown. Future studies are required to reveal the role of RNA helicases in the RLR signaling pathway.

  8. STING agonists enable antiviral cross-talk between human cells and confer protection against genital herpes in mice.

    Science.gov (United States)

    Skouboe, Morten K; Knudsen, Alice; Reinert, Line S; Boularan, Cedric; Lioux, Thierry; Perouzel, Eric; Thomsen, Martin K; Paludan, Søren R

    2018-04-01

    In recent years, there has been an increasing interest in immunomodulatory therapy as a means to treat various conditions, including infectious diseases. For instance, Toll-like receptor (TLR) agonists have been evaluated for treatment of genital herpes. However, although the TLR7 agonist imiquimod was shown to have antiviral activity in individual patients, no significant effects were observed in clinical trials, and the compound also exhibited significant side effects, including local inflammation. Cytosolic DNA is detected by the enzyme cyclic GMP-AMP (2'3'-cGAMP) synthase (cGAS) to stimulate antiviral pathways, mainly through induction of type I interferon (IFN)s. cGAS is activated upon DNA binding to produce the cyclic dinucleotide (CDN) 2'3'-cGAMP, which in turn binds and activates the adaptor protein Stimulator of interferon genes (STING), thus triggering type I IFN expression. In contrast to TLRs, STING is expressed broadly, including in epithelial cells. Here we report that natural and non-natural STING agonists strongly induce type I IFNs in human cells and in mice in vivo, without stimulating significant inflammatory gene expression. Systemic treatment with 2'3'-cGAMP reduced genital herpes simplex virus (HSV) 2 replication and improved the clinical outcome of infection. More importantly, local application of CDNs at the genital epithelial surface gave rise to local IFN activity, but only limited systemic responses, and this treatment conferred total protection against disease in both immunocompetent and immunocompromised mice. In direct comparison between CDNs and TLR agonists, only CDNs acted directly on epithelial cells, hence allowing a more rapid and IFN-focused immune response in the vaginal epithelium. Thus, specific activation of the STING pathway in the vagina evokes induction of the IFN system but limited inflammatory responses to allow control of HSV2 infections in vivo.

  9. Estudio de sensibilidad antiviral de Virus Herpes simplex en pacientes trasplantados Antiviral sensitivity of Herpes simplex virus in immunocompromised patients

    Directory of Open Access Journals (Sweden)

    H. Illán

    2004-06-01

    alteration in genes coding for the TK or the DNA-polymerase. A previous large-scale clinical study on ACVr HSV strains isolated from patients infected with human immunodeficiency virus indicated that 96 % of ACVr HSV mutants were low producers of, or deficient in, TK activity (TK-, with 4 % being TK mutants with an altered substrate specificity. No DNA Pol mutants were isolated. The pirophosphate analogs generate resistance in the gene of DNA-polymerase by mutation. In this paper we show the methodology used for the determination of sensibilite profiles to ACV and Phoscarnet (PFA in a population of inmunocompromised patients. We analized 46 HSV strain from vesicular injuries of transplanted patients. All samples, were inoculated in human fibroblasts and the HSV isolates were identified by inmunofluorescence whith monoclonal antibodies. These strains were amplified and the profile of susceptibility determinated in Vero cells, using 100 tissue culture inhibition dosis 50(TCID50of each Viral stock and the specific antiviral drugs in different concentrations. The cytopathic effect (CPE was evaluated after 72hs. post infection. The 50% inhibitory concentration (CI50 was calculated from the percentage of inhibition of the ECP based on the concentration of the drug. From 46 isolations, 26 were HSV-1 and 20 were HSV-2. Two of them, one HSV-1 andone HSV-2, were resistant to ACV and none of the isolates were resistant to PFA.

  10. Triazole nucleoside derivatives bearing aryl functionalities on the nucleobases show antiviral and anticancer activity.

    Science.gov (United States)

    Xia, Yi; Qu, Fanqi; Peng, Ling

    2010-08-01

    Synthetic nucleoside mimics are important candidates in the searing for antiviral and anticancer drugs. Ribavirin, the first antiviral nucleoside drug, is unique in its antiviral activity with mutilple modes of action, which are mainly due to its special triazole heterocycle as nucleobase. Additionally, introducing aromatic functionalities to the nucleobase is able to confer novel mechanisms of action for nucleoside mimics. With the aim to combine the special characteristics of unnatural triazole heterocycles with those of the appended aromatic groups on the nucleobases, novel 1,2,4-triazole nucleoside analogs bearing aromatic moieties were designed and developed. The present short review summarizes the molecular design, chemical synthesis and biological activity of these triazole nucleoside analogs. Indeed, the discovery of antiviral and anticancer activities shown by these triazole nucleosides as well as the new mechanism underlying the biological activity by one of the anticancer leads has validated the rationale for molecular design and impacted us to further explore the concept with the aim of developing structurally novel nucleoside drug candidates with new modes of action.

  11. Antiviral activity of Justicia gendarussa Burm.f. leaves against HIV ...

    African Journals Online (AJOL)

    Backgrounds: Justicia gendarussa Burm.f. has been known to have anti-HIV activity. This study was conducted to evaluate the effect of incubation time on the antiviral activity of the J. gendarussa leaves extract on HIV-infected MT-4 cells in vitro. Molecular docking test was also conducted to determine the interaction of ...

  12. Antiviral immunity following smallpox virus infection: a case-control study.

    Science.gov (United States)

    Hammarlund, Erika; Lewis, Matthew W; Hanifin, Jon M; Mori, Motomi; Koudelka, Caroline W; Slifka, Mark K

    2010-12-01

    Outbreaks of smallpox (i.e., caused by variola virus) resulted in up to 30% mortality, but those who survived smallpox infection were regarded as immune for life. Early studies described the levels of neutralizing antibodies induced after infection, but smallpox was eradicated before contemporary methods for quantifying T-cell memory were developed. To better understand the levels and duration of immunity after smallpox infection, we performed a case-control study comparing antiviral CD4(+) and CD8(+) T-cell responses and neutralizing antibody levels of 24 smallpox survivors with the antiviral immunity observed in 60 smallpox-vaccinated (i.e., vaccinia virus-immune) control subjects. We found that the duration of immunity following smallpox infection was remarkably similar to that observed after smallpox vaccination, with antiviral T-cell responses that declined slowly over time and antiviral antibody responses that remained stable for decades after recovery from infection. These results indicate that severe, potentially life-threatening disease is not required for the development of sustainable long-term immunity. This study shows that the levels of immunity induced following smallpox vaccination are comparable in magnitude to that achieved through natural variola virus infection, and this may explain the notable success of vaccination in eradicating smallpox, one of the world's most lethal diseases.

  13. Antiviral Immunity following Smallpox Virus Infection: a Case-Control Study▿

    Science.gov (United States)

    Hammarlund, Erika; Lewis, Matthew W.; Hanifin, Jon M.; Mori, Motomi; Koudelka, Caroline W.; Slifka, Mark K.

    2010-01-01

    Outbreaks of smallpox (i.e., caused by variola virus) resulted in up to 30% mortality, but those who survived smallpox infection were regarded as immune for life. Early studies described the levels of neutralizing antibodies induced after infection, but smallpox was eradicated before contemporary methods for quantifying T-cell memory were developed. To better understand the levels and duration of immunity after smallpox infection, we performed a case-control study comparing antiviral CD4+ and CD8+ T-cell responses and neutralizing antibody levels of 24 smallpox survivors with the antiviral immunity observed in 60 smallpox-vaccinated (i.e., vaccinia virus-immune) control subjects. We found that the duration of immunity following smallpox infection was remarkably similar to that observed after smallpox vaccination, with antiviral T-cell responses that declined slowly over time and antiviral antibody responses that remained stable for decades after recovery from infection. These results indicate that severe, potentially life-threatening disease is not required for the development of sustainable long-term immunity. This study shows that the levels of immunity induced following smallpox vaccination are comparable in magnitude to that achieved through natural variola virus infection, and this may explain the notable success of vaccination in eradicating smallpox, one of the world's most lethal diseases. PMID:20926574

  14. Defense and counterdefense in the RNAi-based antiviral immune system in insects

    NARCIS (Netherlands)

    van Mierlo, J.T.; van Cleef, K.W.; Rij, R.P. van

    2011-01-01

    RNA interference (RNAi) is an important pathway to combat virus infections in insects and plants. Hallmarks of antiviral RNAi in these organisms are: (1) an increase in virus replication after inactivation of major actors in the RNAi pathway, (2) production of virus-derived small interfering RNAs

  15. In-vitro antiviral efficacy of ribavirin and interferon-alpha against canine distemper virus.

    Science.gov (United States)

    Carvalho, Otávio V; Saraiva, Giuliana L; Ferreira, Caroline G T; Felix, Daniele M; Fietto, Juliana L R; Bressan, Gustavo C; Almeida, Márcia R; Silva Júnior, Abelardo

    2014-10-01

    Canine distemper is a highly contagious disease with high incidence and lethality in the canine population. The objective of this study was to evaluate the efficacy of antiviral action with ribavirin (RBV), interferon-alpha (IFNα), and combinations of RBV and IFNα against canine distemper virus (CDV). Vero cells inoculated with CDV were treated with RBV, IFNα, and combinations of these drugs. The efficacy to inhibit viral replication was evaluated by adding the compounds at different times to determine which step of the viral replicative process was affected. Both drugs were effective against CDV in vitro. The IFNα was the most active compound, with an average IC50 (50% inhibitory concentration) value lower than the IC50 of the RBV. Ribavirin (RBV) was more selective than IFNα, however, and neither drug showed extracellular antiviral activity. The combination of RBV and IFNα exhibited antiviral activity for the intra- and extracellular stages of the replicative cycle of CDV, although the intracellular viral inhibition was higher. Both RBV and IFNα showed high antiviral efficacy against CDV, and furthermore, RBV + IFNα combinations have shown greater interference range in viral infectivity. These compounds could potentially be used to treat clinical disease associated with CDV infection.

  16. Use of competitive polymerase chain reaction to determine HIV-1 levels in response to antiviral treatments

    NARCIS (Netherlands)

    Bruisten, S. M.; Koppelman, M. H.; Roos, M. T.; Loeliger, A. E.; Reiss, P.; Boucher, C. A.; Huisman, H. G.

    1993-01-01

    OBJECTIVE: To develop a competitive polymerase chain reaction technique with which to evaluate the usefulness of HIV-1 level as a marker of response to antiviral treatment. DESIGN: HIV-1 sequences were assessed by competitive polymerase chain reaction in four subjects participating in a double-blind

  17. Middle East Respiratory Coronavirus Accessory Protein 4a Inhibits PKR-Mediated Antiviral Stress Responses

    NARCIS (Netherlands)

    Rabouw, Huib H; Langereis, Martijn A; Knaap, Robert C M; Dalebout, Tim J; Canton, Javier; Sola, Isabel; Enjuanes, Luis; Bredenbeek, Peter J; Kikkert, Marjolein; de Groot, Raoul J; van Kuppeveld, Frank J M

    2016-01-01

    Middle East respiratory syndrome coronavirus (MERS-CoV) causes severe respiratory infections that can be life-threatening. To establish an infection and spread, MERS-CoV, like most other viruses, must navigate through an intricate network of antiviral host responses. Besides the well-known type I

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

    African Journals Online (AJOL)

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

  19. Ganciclovir Antiviral Therapy in Advanced Idiopathic Pulmonary Fibrosis: An Open Pilot Study

    Directory of Open Access Journals (Sweden)

    J. J. Egan

    2011-01-01

    Conclusion. This audit outcome suggests that 2-week course of ganciclovir (iv may attenuate disease progression in a subgroup of advanced IPF patients. These observations do not suggest that anti-viral treatment is a substitute for the standard care, however, suggests the need to explore the efficacy of ganciclovir as adjunctive therapy in IPF.

  20. Negative regulation of RIG-I-mediated antiviral signaling by TRK-fused gene (TFG) protein

    International Nuclear Information System (INIS)

    Lee, Na-Rae; Shin, Han-Bo; Kim, Hye-In; Choi, Myung-Soo; Inn, Kyung-Soo

    2013-01-01

    Highlights: •TRK-fused gene product (TFG) interacts with TRIM25 upon viral infection. •TFG negatively regulates RIG-I mediated antiviral signaling. •TFG depletion leads to enhanced viral replication. •TFG act downstream of MAVS. -- Abstract: RIG-I (retinoic acid inducible gene I)-mediated antiviral signaling serves as the first line of defense against viral infection. Upon detection of viral RNA, RIG-I undergoes TRIM25 (tripartite motif protein 25)-mediated K63-linked ubiquitination, leading to type I interferon (IFN) production. In this study, we demonstrate that TRK-fused gene (TFG) protein, previously identified as a TRIM25-interacting protein, binds TRIM25 upon virus infection and negatively regulates RIG-I-mediated type-I IFN signaling. RIG-I-mediated IFN production and nuclear factor (NF)-κB signaling pathways were upregulated by the suppression of TFG expression. Furthermore, vesicular stomatitis virus (VSV) replication was significantly inhibited by small inhibitory hairpin RNA (shRNA)-mediated knockdown of TFG, supporting the suppressive role of TFG in RIG-I-mediated antiviral signaling. Interestingly, suppression of TFG expression increased not only RIG-I-mediated signaling but also MAVS (mitochondrial antiviral signaling protein)-induced signaling, suggesting that TFG plays a pivotal role in negative regulation of RNA-sensing, RIG-I-like receptor (RLR) family signaling pathways

  1. Conformationally locked nucleoside analogues based on the bridgehead substituted 7-oxonorbornane and their antiviral properties

    Czech Academy of Sciences Publication Activity Database

    Dejmek, Milan; Hřebabecký, Hubert; Dračínský, Martin; Neyts, J.; Leyssen, P.; Mertlíková-Kaiserová, Helena; Nencka, Radim

    2011-01-01

    Roč. 76, č. 12 (2011), s. 1549-1566 ISSN 0010-0765 R&D Projects: GA MŠk 1M0508 Institutional research plan: CEZ:AV0Z40550506 Keywords : 1'-homonucleosides * Diels - Alder reaction * antiviral agents Subject RIV: CC - Organic Chemistry Impact factor: 1.283, year: 2011

  2. Arthropod-borne flaviviruses and RNA interference : seeking new approaches for antiviral therapy

    NARCIS (Netherlands)

    Diosa-Toro, Mayra; Urcuqui-Inchima, Silvio; Smit, Jolanda M

    2013-01-01

    Flaviviruses are the most prevalent arthropod-borne viruses worldwide, and nearly half of the 70 Flavivirus members identified are human pathogens. Despite the huge clinical impact of flaviviruses, there is no specific human antiviral therapy available to treat infection with any of the

  3. 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.

  4. Nose-to-Brain Delivery of Antiviral Drugs: A Way to Overcome Their Active Efflux?

    Directory of Open Access Journals (Sweden)

    Alessandro Dalpiaz

    2018-03-01

    Full Text Available Although several viruses can easily infect the central nervous system (CNS, antiviral drugs often show dramatic difficulties in penetrating the brain from the bloodstream since they are substrates of active efflux transporters (AETs. These transporters, located in the physiological barriers between blood and the CNS and in macrophage membranes, are able to recognize their substrates and actively efflux them into the bloodstream. The active transporters currently known to efflux antiviral drugs are P-glycoprotein (ABCB1 or P-gp or MDR1, multidrug resistance-associated proteins (ABCC1 or MRP1, ABCC4 or MRP4, ABCC5 or MRP5, and breast cancer resistance protein (ABCG2 or BCRP. Inhibitors of AETs may be considered, but their co-administration causes serious unwanted effects. Nasal administration of antiviral drugs is therefore proposed in order to overcome the aforementioned problems, but innovative devices, formulations (thermoreversible gels, polymeric micro- and nano-particles, solid lipid microparticles, nanoemulsions, absorption enhancers (chitosan, papaverine, and mucoadhesive agents (chitosan, polyvinilpyrrolidone are required in order to selectively target the antiviral drugs and, possibly, the AET inhibitors in the CNS. Moreover, several prodrugs of antiretroviral agents can inhibit or elude the AET systems, appearing as interesting substrates for innovative nasal formulations able to target anti-Human Immunodeficiency Virus (HIV agents into macrophages of the CNS, which are one of the most important HIV Sanctuaries of the body.

  5. Antiviral therapy for prevention of hepatocellular carcinoma and mortality in chronic hepatitis B

    DEFF Research Database (Denmark)

    Thiele, Maja; Gluud, Lise Lotte; Dahl, Emilie K

    2013-01-01

    The effect of antiviral therapy on clinical outcomes in chronic hepatitis B virus (HBV) is not established. We aimed to assess the effects of interferon and/or nucleos(t)ide analogues versus placebo or no intervention on prevention of hepatocellular carcinoma (HCC) and mortality in chronic HBV....

  6. Tannic acid modified silver nanoparticles show antiviral activity in herpes simplex virus type 2 infection.

    Directory of Open Access Journals (Sweden)

    Piotr Orlowski

    Full Text Available The interaction between silver nanoparticles and herpesviruses is attracting great interest due to their antiviral activity and possibility to use as microbicides for oral and anogenital herpes. In this work, we demonstrate that tannic acid modified silver nanoparticles sized 13 nm, 33 nm and 46 nm are capable of reducing HSV-2 infectivity both in vitro and in vivo. The antiviral activity of tannic acid modified silver nanoparticles was size-related, required direct interaction and blocked virus attachment, penetration and further spread. All tested tannic acid modified silver nanoparticles reduced both infection and inflammatory reaction in the mouse model of HSV-2 infection when used at infection or for a post-infection treatment. Smaller-sized nanoparticles induced production of cytokines and chemokines important for anti-viral response. The corresponding control buffers with tannic acid showed inferior antiviral effects in vitro and were ineffective in blocking in vivo infection. Our results show that tannic acid modified silver nanoparticles are good candidates for microbicides used in treatment of herpesvirus infections.

  7. Antiviral activity of human lactoferrin: inhibition of alphavirus interaction with heparan sulfate

    International Nuclear Information System (INIS)

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

    2005-01-01

    Human lactoferrin is a component of the non-specific immune system with distinct antiviral properties. We used alphaviruses, adapted to interaction with heparan sulfate (HS), as a tool to investigate the mechanism of lactoferrin's antiviral activity. Lactoferrin inhibited infection of BHK-21 cells by HS-adapted, but not by non-adapted, Sindbis virus (SIN) or Semliki Forest virus (SFV). Lactoferrin also inhibited binding of radiolabeled HS-adapted viruses to BHK-21 cells or liposomes containing lipid-conjugated heparin as a receptor analog. On the other hand, low-pH-induced fusion of the viruses with liposomes, which occurs independently of virus-receptor interaction, was unaffected. Studies involving preincubation of virus or cells with lactoferrin suggested that the protein does not bind to the virus, but rather blocks HS-moieties on the cell surface. Charge-modified human serum albumin, with a net positive charge, had a similar antiviral effect against HS-adapted SIN and SFV, suggesting that the antiviral activity of lactoferrin is related to its positive charge. It is concluded that human lactoferrin inhibits viral infection by interfering with virus-receptor interaction rather than by affecting subsequent steps in the viral cell entry or replication processes

  8. Antivirals Use During the Pandemic H1N1 2009 Outbreak

    Centers for Disease Control (CDC) Podcasts

    2012-01-23

    Charisma Atkins, CDC public health analyst, discusses antiviral use during the 2009 H1N1 pandemic flu outbreak.  Created: 1/23/2012 by National Center for Emerging and Zoonotic Infectious Diseases (NCEZID).   Date Released: 1/23/2012.

  9. NEOGLYCOPROTEINS AS CARRIERS FOR ANTIVIRAL DRUGS - SYNTHESIS AND ANALYSIS OF PROTEIN DRUG CONJUGATES

    NARCIS (Netherlands)

    Molema, Grietje; Jansen, Robert W.; Visser, Jan; Herdewijn, Piet; Moolenaar, Frits; Meijer, Dirk K.F.

    In order to investigate whether neoglycoproteins can potentially act as carriers for targeting of antiviral drugs to certain cell types in the body, various neoglycoproteins were synthesized using thiophosgene-activated p-aminophenyl sugar derivatives. These neoglycoproteins were conjugated with the

  10. Antiviral Goes Viral : Harnessing CRISPR/Cas9 to Combat Viruses in Humans

    NARCIS (Netherlands)

    Soppe, Jasper Adriaan; Lebbink, Robert Jan

    2017-01-01

    The clustered regularly interspaced short palindromic repeats (CRISPR) and CRISPR-associated (Cas) systems are RNA-guided sequence-specific prokaryotic antiviral immune systems. In prokaryotes, small RNA molecules guide Cas effector endonucleases to invading foreign genetic elements in a

  11. Anti-viral effects of medicinal plants in the management of dengue: a ...

    African Journals Online (AJOL)

    Anti-viral effects of medicinal plants in the management of dengue: a systematic review. Éric Heleno Freira Ferreira Frederico, André Luiz Bandeira Dionísio Cardoso, Eloá Moreira-Marconi, Danúbia da Cunha de Sá-Caputo, Carlos Alberto Sampaio Guimarães, Carla da Fontoura Dionello, Danielle Soares Morel, Laisa ...

  12. 75 FR 16810 - Determination and Declarations Regarding Emergency Use of Certain In vitro Diagnostic, Antiviral...

    Science.gov (United States)

    2010-04-02

    ... specified that these declarations are declarations of emergency as defined by former Secretary Michael O... essence in detecting, preventing, and treating illness and death by getting in vitro diagnostic, antiviral... that the declaration is a declaration of emergency, as defined in the December 17, 2008 Declaration...

  13. 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 - others: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

  14. A molecular arms race between host innate antiviral response and emerging human coronaviruses.

    Science.gov (United States)

    Wong, Lok-Yin Roy; Lui, Pak-Yin; Jin, Dong-Yan

    2016-02-01

    Coronaviruses have been closely related with mankind for thousands of years. Community-acquired human coronaviruses have long been recognized to cause common cold. However, zoonotic coronaviruses are now becoming more a global concern with the discovery of highly pathogenic severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS) coronaviruses causing severe respiratory diseases. Infections by these emerging human coronaviruses are characterized by less robust interferon production. Treatment of patients with recombinant interferon regimen promises beneficial outcomes, suggesting that compromised interferon expression might contribute at least partially to the severity of disease. The mechanisms by which coronaviruses evade host innate antiviral response are under intense investigations. This review focuses on the fierce arms race between host innate antiviral immunity and emerging human coronaviruses. Particularly, the host pathogen recognition receptors and the signal transduction pathways to mount an effective antiviral response against SARS and MERS coronavirus infection are discussed. On the other hand, the counter-measures evolved by SARS and MERS coronaviruses to circumvent host defense are also dissected. With a better understanding of the dynamic interaction between host and coronaviruses, it is hoped that insights on the pathogenesis of newly-identified highly pathogenic human coronaviruses and new strategies in antiviral development can be derived.

  15. Chronic Hepatitis C and Antiviral Treatment Regimens: Where Can Psychology Contribute?

    Science.gov (United States)

    Evon, Donna M.; Golin, Carol E.; Fried, Michael W.; Keefe, Francis J.

    2013-01-01

    Objective: Our goal was to evaluate the existing literature on psychological, social, and behavioral aspects of chronic hepatitis C viral (HCV) infection and antiviral treatment; provide the state of the behavioral science in areas that presently hinder HCV-related health outcomes; and make recommendations for areas in which clinical psychology…

  16. Application of Orem self-care theory on injection of interferon antiviral therapy in patients with

    Directory of Open Access Journals (Sweden)

    Xiujuan Tao

    2015-01-01

    Full Text Available Guided by Orem self-care theory, the nursing staff evaluate the injection of interferon antiviral therapy in patients, finding that patients with the presence of self-care was insufficient, so effective nursing care in different periods of application of different nursing system was necessary.

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

    Science.gov (United States)

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

    2017-07-01

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

  18. Influence of antiviral therapy on survival of patients with hepatitis B ...

    African Journals Online (AJOL)

    The mortality rates in two groups were evaluated with Kaplan-Meier estimate. ... 274 (76.9 %) died, with 89 patients belonging to the antiviral group while the ... TACE is different from systemic ... and identification of study participants was not ..... Table 3: Cox regression analysis to deteermine variables associated with overall ...

  19. Quantitative autoradiographic mapping of focal herpes simplex virus encephalitis using a radiolabeled antiviral drug

    International Nuclear Information System (INIS)

    Price, R.

    1984-01-01

    A method of mapping herpes simplex viral infection comprising administering a radiolabeled antiviral active 5-substituted 1-(2'-deoxy-2'-substituted-D-arabinofuranosyl) pyrimidine nucleoside to the infected subject, and scanning the area in which the infection is to be mapped for the radiolabel

  20. Antiviral Activity of Peanut (Arachis hypogaea L.) Skin Extract Against Human Influenza Viruses.

    Science.gov (United States)

    Makau, Juliann Nzembi; Watanabe, Ken; Mohammed, Magdy M D; Nishida, Noriyuki

    2018-05-30

    The high propensity of influenza viruses to develop resistance to antiviral drugs necessitates the continuing search for new therapeutics. Peanut skins, which are low-value byproducts of the peanut industry, are known to contain high levels of polyphenols. In this study, we investigated the antiviral activity of ethanol extracts of peanut skins against various influenza viruses using cell-based assays. Extracts with a higher polyphenol content exhibited higher antiviral activities, suggesting that the active components are the polyphenols. An extract prepared from roasted peanut skins effectively inhibited the replication of influenza virus A/WSN/33 with a half maximal inhibitory concentration of 1.3 μg/mL. Plaque assay results suggested that the extract inhibits the early replication stages of the influenza virus. It demonstrated activity against both influenza type A and type B viruses. Notably, the extract exhibited a potent activity against a clinical isolate of the 2009 H1N1 pandemic, which had reduced sensitivity to oseltamivir. Moreover, a combination of peanut skin extract with the anti-influenza drugs, oseltamivir and amantadine, synergistically increased their antiviral activity. These data demonstrate the potential application of peanut skin extract in the development of new therapeutic options for influenza management.

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

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

    2002-07-01

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

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

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

    2013-11-01

    Dengue virus infects millions of people worldwide, and there is no vaccine or anti-dengue therapeutic available. Antimicrobial peptides have been shown to possess effective antiviral activity against various viruses. One of the main limitations of developing these peptides as potent antiviral drugs is the high cost of production. In this study, high yield production of biologically active plectasin peptide was inexpensively achieved by producing tandem plectasin peptides as inclusion bodies in E. coli. Antiviral activity of the recombinant peptide towards dengue serotype-2 NS2B-NS3 protease (DENV2 NS2B-NS3pro) was assessed as a target to inhibit dengue virus replication in Vero cells. Single units of recombinant plectasin were collected after applying consecutive steps of refolding, cleaving by Factor Xa, and nickel column purification to obtain recombinant proteins of high purity. The maximal nontoxic dose (MNTD) of the recombinant peptide against Vero cells was 20 μM (100 μg/mL). The reaction velocity of DENV2 NS2B-NS3pro decreased significantly after increasing concentrations of recombinant plectasin were applied to the reaction mixture. Plectasin peptide noncompetitively inhibited DENV2 NS2B-NS3pro at Ki value of 5.03 ± 0.98 μM. The percentage of viral inhibition was more than 80% at the MNTD value of plectasin. In this study, biologically active recombinant plectasin which was able to inhibit dengue protease and viral replication in Vero cells was successfully produced in E. coli in a time- and cost- effective method. These findings are potentially important in the development of potent therapeutics against dengue infection.

  3. Public preferences for vaccination and antiviral medicines under different pandemic flu outbreak scenarios.

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    Rubinstein, Helena; Marcu, Afrodita; Yardley, Lucy; Michie, Susan

    2015-02-27

    During the 2009-2010 A(H1N1) pandemic, many people did not seek care quickly enough, failed to take a full course of antivirals despite being authorised to receive them, and were not vaccinated. Understanding facilitators and barriers to the uptake of vaccination and antiviral medicines will help inform campaigns in future pandemic influenza outbreaks. Increasing uptake of vaccines and antiviral medicines may need to address a range of drivers of behaviour. The aim was to identify facilitators of and barriers to being vaccinated and taking antiviral medicines in uncertain and severe pandemic influenza scenarios using a theoretical model of behaviour change, COM-B. Focus groups and interviews with 71 members of the public in England who varied in their at-risk status. Participants responded to uncertain and severe scenarios, and to messages giving advice on vaccination and antiviral medicines. Data were thematically analysed using the theoretical framework provided by the COM-B model. Influences on uptake of vaccines and antiviral medicines - capabilities, motivations and opportunities - are part of an inter-related behavioural system and different components influenced each other. An identity of being healthy and immune from infection was invoked to explain feelings of invulnerability and hence a reduced need to be vaccinated, especially during an uncertain scenario. The identity of being a 'healthy person' also included beliefs about avoiding medicine and allowing the body to fight disease 'naturally'. This was given as a reason for using alternative precautionary behaviours to vaccination. This identity could be held by those not at-risk and by those who were clinically at-risk. Promoters and barriers to being vaccinated and taking antiviral medicines are multi-dimensional and communications to promote uptake are likely to be most effective if they address several components of behaviour. The benefit of using the COM-B model is that it is at the core of an

  4. In Vitro Study of Eight Indonesian Natural Extracts as Antiviral Against Dengue Virus

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    Leli Saptawati

    2017-07-01

    Full Text Available 800x600 Background: Dengue hemorrhagic fever (DHF caused by a dengue viruses is still a major problem in tropical countries, including Indonesia. World Health Organization data showed that over 40% of world population are at risk of DHF.1In 2014 there were 71.668 of DHF cases in 34 provinces with 641 death.2 In Central Java in 2013, the incidence rate and fatality rate of DHF was 45.52 in 100.000 populations and 1.21% respectively.3 Until nowadays, there is no vaccine or effective therapy is available as yet.4 Thus research on discovering specific antiviral against dengue is needed. Indonesia is rich in indigenous herbal plants, which may has potential antiviral activity, such as Psidium guajava (Jambu biji, Euphorbia hirta (Patikn kerbau, Piper bettle L (Sirih, Carica papaya (Pepaya, Curcuma longa L(Kunyit/turmeric, Phyllanthus niruri L (meniran, Andrographis paniculata (Sambiloto, Cymbopogon citrates (Serai. Previous studies show that these plants have antiviral and antibacterial properties.5However, there is only limited study of these plants against dengue virus . Objective: This study aimed to know whether these plants have potential activity against dengue virus in vitro. Method: Leave extracts of eight indigenous herbal plants as mention before were originated from Solo, Central Java, the crude extracts were tested in vitro against dengue virus serotype 2 (DENV-2 strain NGC using Huh7it-1 cell line. Those crude extracts were screened for antiviral activity using doses of 20mg/ml. Candidates that showed inhibition activity were further tested in various doses to determine IC50 and CC50. Result: From eight leave extracts tested, one of them i.e Carica papaya (pepaya inhibited virus replication up to 89,5%. Dose dependent assay with C.papaya resulted in IC50, CC50 and selectivity index 6,57 μg/mL, 244,76 μg/mL and 37, 25 μg/mL respectively. Conclusion: C.papaya has potential antiviral activity against dengue virus in vitro. Further study

  5. Preemptive antiviral therapy with entecavir can reduce acute deterioration of hepatic function following transarterial chemoembolization

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    Sun Hong Yoo

    2016-12-01

    Full Text Available Background/Aims Hepatic damage during transarterial chemoembolization (TACE is a critical complication in patients with hepatitis B virus (HBV-related hepatocellular carcinoma (HCC. Apart from its role in preventing HBV reactivation, there is some evidence for the benefits of preemptive antiviral therapy in TACE. This study evaluated the effect of preemptive antiviral therapy on acute hepatic deterioration following TACE. Methods This retrospective observational study included a prospectively collected cohort of 108 patients with HBV-related HCC who underwent TACE between January 2007 and January 2013. Acute hepatic deterioration following TACE was evaluated. Treatment-related hepatic decompensation was defined as newly developed encephalopathy, ascites, variceal bleeding, elevation of the bilirubin level, prolongation of prothrombin time, or elevation of the Child-Pugh score by ≥2 within 2 weeks following TACE. Univariate and multivariate analyses were conducted to identify factors influencing treatment-related decompensation. Preemptive antiviral therapy involves directing prophylaxis only toward high-risk chronic hepatitis B patients in an attempt to prevent the progression of liver disease. We regarded at least 6 months as a significant duration of preemptive antiviral treatment before diagnosis of HCC. Results Of the 108 patients, 30 (27.8% patients received preemptive antiviral therapy. Treatment-related decompensation was observed in 25 (23.1% patients during the follow-up period. Treatment-related decompensation following TACE was observed more frequently in the nonpreemptive group than in the preemptive group (29.5% vs. 6.7%, P=0.008. In the multivariate analysis, higher serum total bilirubin (Hazard ratio [HR] =3.425, P=0.013, hypoalbuminemia (HR=3.990, P=0.015, and absence of antiviral therapy (HR=7.597, P=0.006 were significantly associated with treatment-related hepatic decompensation. Conclusions Our findings suggest that

  6. Knowledge, attitudes, and practices of business travelers regarding influenza and the use of antiviral medication.

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    Helfenberger, Salome; Tschopp, Alois; Robyn, Luc; Hatz, Christoph; Schlagenhauf, Patricia

    2010-01-01

    This study aimed to determine the knowledge, attitudes, and practices of Swiss business travelers with regard to influenza and the use of antiviral medication. Questionnaires, available in three languages, were distributed manually and online through companies, organizations, and travel medicine specialists in Switzerland to business travelers who were traveling during the period January 2005 to April 2009. In total, 661 questionnaires were fully completed and evaluated. A total of 58.9% (n = 388) of the respondents stated that they had contracted influenza in the past; some 48.6% (n = 321) of the travelers had been vaccinated against seasonal influenza at least once in their lifetime; 87.1% (n = 576) of the travelers knew that influenza can be transmitted by droplets; and 62.3% (n = 412) were aware of transmission by direct contact. Almost all respondents (96.8%; n = 633) recognized fever as a main symptom of influenza, 80.0% (n = 523) knew about muscular aches and pain, 79.5% (n = 520) about shivering, and 72.9% (n = 477) about joint pain. Some 38.0% (n = 250) of the respondents stated that the annual vaccination is their preferred prevention method for influenza, 35.6% (n = 234) would neither do an annual vaccination nor carry antiviral medication, 16.0% (n = 105) would carry antiviral medication, 8.5% (n = 56) would prefer to do both the annual vaccination and to carry antivirals, and 2.0% (n = 13) would use antivirals as influenza prophylaxis. Regarding prevention, the majority (78.9%; n = 498) of the travelers did not seek advice on influenza before going on their last business trip, 58.0% (n = 381) did not take any preventive measures against influenza, 27.2% (n = 179) had their annual vaccination, and 15.7% (n = 103) observed hand hygiene. Of the travelers, 9.7% (n = 64) carried antiviral medication on their last business trip and 7.0% (n = 46) actually used this medication. Business travelers have a good knowledge about the transmission and the symptoms of

  7. Antiviral potential of medicinal plants against HIV, HSV, influenza, hepatitis, and coxsackievirus: A systematic review.

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    Akram, Muhammad; Tahir, Imtiaz Mahmood; Shah, Syed Muhammad Ali; Mahmood, Zahed; Altaf, Awais; Ahmad, Khalil; Munir, Naveed; Daniyal, Muhammad; Nasir, Suhaila; Mehboob, Huma

    2018-05-01

    Viral infections are being managed therapeutically through available antiviral regimens with unsatisfactory clinical outcomes. The refractory viral infections resistant to available antiviral drugs are alarming threats and a serious health concern. For viral hepatitis, the interferon and vaccine therapies solely are not ultimate solutions due to recurrence of hepatitis C virus. Owing to the growing incidences of viral infections and especially of resistant viral strains, the available therapeutic modalities need to be improved, complemented with the discovery of novel antiviral agents to combat refractory viral infections. It is widely accepted that medicinal plant heritage is nature gifted, precious, and fueled with the valuable resources for treatment of metabolic and infectious disorders. The aims of this review are to assemble the facts and to conclude the therapeutic potential of medicinal plants in the eradication and management of various viral diseases such as influenza, human immunodeficiency virus (HIV), herpes simplex virus (HSV), hepatitis, and coxsackievirus infections, which have been proven in diverse clinical studies. The articles, published in the English language since 1982 to 2017, were included from Web of Science, Cochrane Library, AMED, CISCOM, EMBASE, MEDLINE, Scopus, and PubMed by using relevant keywords including plants possessing antiviral activity, the antiviral effects of plants, and plants used in viral disorders. The scientific literature mainly focusing on plant extracts and herbal products with therapeutic efficacies against experimental models of influenza, HIV, HSV, hepatitis, and coxsackievirus were included in the study. Pure compounds possessing antiviral activity were excluded, and plants possessing activity against viruses other than viruses in inclusion criteria were excluded. Hundreds of plant extracts with antiviral effect were recognized. However, the data from only 36 families investigated through in vitro and in vivo

  8. Evaluation of antivirals against corona- and lentiviruses in cell cultures

    NARCIS (Netherlands)

    Meer, F.J.U.M. van der

    2007-01-01

    Virus infections constitute a continuous health threat. As illustrated by the recent emergence of new - the SARS coronavirus - and the re-emergence of known viruses - influenza, ebola - this threat is certainly not yet decreasing. Rather, many conditions and considerations indicate that viruses will

  9. [Studies on evaluation of natural products for antiviral effects and their applications].

    Science.gov (United States)

    Hayashi, Toshimitsu

    2008-01-01

    In the search for novel antiviral molecules from natural products, we have discovered various antiviral molecules with characteristic mechanisms of action. Scopadulciol (SDC), isolated from the tropical medicinal plant Scoparia dulcis L., showed stimulatory effects on the antiviral potency of acyclovir (ACV) or ganciclovir (GCV). This effect of SDC was exerted via the activation of viral thymidine kinase (HSV-1 TK) and, as a result, an increase in the cellular concentration of the active form of ACV/GCV, i.e., the triphosphate of ACV or GCV. On the basis of these experimental results, cancer gene therapy using the HSV-1 tk gene and ACV/GCV together with SDC was found to be effective in suppressing the growth of cancer cells in animals. Acidic polysaccharides such as calcium spirulan (Ca-SP) from Spirulina platensis, nostoflan from Nostoc flagelliforme, and a fucoidan from the sporophyll of Undaria pinnatifida (mekabu fucoidan) were also found to be potent inhibitors against several enveloped viruses. Their antiviral potency was dependent on molecular weight and content of the sulfate or carboxyl group as well as counterion species chelating with sulfate groups, indicating the importance of the three-dimensional structure of the molecules. In addition, unlike dextran sulfate, Ca-SP was shown to target not only viral absorption/penetration stages but also some replication stages of progeny viruses after penetration into cells. When mekabu fucoidan or nostoflan was administered with oseltamivir phosphate, their synergistic antiviral effects on influenza A virus were confirmed in vitro as well as in vivo.

  10. Antiviral effects of Curcuma longa L. against dengue virus in vitro and in vivo

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    Ichsyani, M.; Ridhanya, A.; Risanti, M.; Desti, H.; Ceria, R.; Putri, D. H.; Sudiro, T. M.; Dewi, B. E.

    2017-12-01

    Dengue is the most common infective disease caused by dengue virus (DENV) and endemic diseases in tropical and subtropical areas. Until now, there is no specific antiviral for dengue infection. It is known that viral load is related to disease severity. Curcuma longa L. (turmeric) with curcumin as major active compound has been identified for its antiviral effect. This study to determine antiviral effect of C. longa extract on DENV-2 in vitro and in vivo along with its toxicity in liver and kidney of ddY mice. Antiviral activity (IC50) and toxicity (CC50) in vitro was examined on Huh7it-1 cells by focus assay and a MTT assay, respectively. To determine the selectivity index (SI), we used CC50 and IC50 value. The safe doses obtained were used for toxicity tests of liver and kidney with histopathological and biochemical observations. The C. longa extracts was given orally with dose of 0.147 mg/mL for each mice at 2 hours after injected with DENV-2 infected Huh7it-1 cells. Serum was collected from intraorbital at 6 hours and 24 hours after infection and focus assay was used to determine viral load. In this study, the acquired value of IC50 was 17,91 μg/mL whereas the value of CC50 was 85,4 μg/mL. The value of SI of C. longa was 4.8. In vivo, we found that C. longa remarkable reduced of viral load after 24 hour. Histopathological examination showed no specific abnormalities in liver and kidney. There was no significant increase in levels of SGPT, SGOT, urea, and creatinine. From this study it can be concluded that C. longa could potentially be used as antiviral against DENV with low cytotoxicity and effective inhibition.

  11. The antiviral effect of jiadifenoic acids C against coxsackievirus B3

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    Miao Ge

    2014-08-01

    Full Text Available Coxsackievirus B type 3 (CVB3 is one of the major causative pathogens associated with viral meningitis and myocarditis, which are widespread in the human population and especially prevalent in neonates and children. These infections can result in dilated cardiomyopathy (DCM and other severe clinical complications. There are no vaccines or drugs approved for the prevention or therapy of CVB3-induced diseases. During screening for anti-CVB3 candidates in our previous studies, we found that jiadifenoic acids C exhibited strong antiviral activities against CVB3 as well as other strains of Coxsackie B viruses (CVBs. The present studies were carried out to evaluate the antiviral activities of jiadifenoic acids C. Results showed that jiadifenoic acids C could reduce CVB3 RNA and proteins synthesis in a dose-dependent manner. Jiadifenoic acids C also had a similar antiviral effect on the pleconaril-resistant variant of CVB3. We further examined the impact of jiadifenoic acids C on the synthesis of viral structural and non-structural proteins, finding that jiadifenoic acids C could reduce VP1 and 3D protein production. A time-course study with Vero cells showed that jiadifenoic acids C displayed significant antiviral activities at 0–6 h after CVB3 inoculation, indicating that jiadifenoic acids C functioned at an early step of CVB3 replication. However, jiadifenoic acids C had no prophylactic effect against CVB3. Taken together, we show that jiadifenoic acids C exhibit strong antiviral activities against all strains of CVB, including the pleconaril-resistant variant. Our study could provide a significant lead for anti-CVB3 drug development.

  12. Impact of a new reimbursement program on hepatitis B antiviral medication cost and utilization in Beijing, China.

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    Qian Qiu

    Full Text Available BACKGROUND: Hepatitis B virus (HBV infection is a significant clinical and financial burden for chronic hepatitis B (CHB patients. In Beijing, China, partial reimbursement on antiviral agents was first implemented for the treatment of CHB patients in July 1, 2011. AIMS: In this study, we describe the medical cost and utilization rates of antiviral therapy for CHB patients to explore the impact of the new partial reimbursement policy on the medical care cost, the composition, and antivirals utilization. METHODS: Clinical and claims data of a retrospective cohort of 92,776 outpatients and 2,774 inpatients with non-cirrhotic CHB were retrieved and analyzed from You'an Hospital, Beijing between February 14, 2008 and December 31, 2012. The propensity score matching was used to adjust factors associated with the annual total cost, including age, gender, medical insurance type and treatment indicator. RESULTS: Compared to patients who paid out-of-pocket, medical cost, especially antiviral costs increased greater among patients with medical insurance after July 1, 2011, the start date of reimbursement policy. Outpatients with medical insurance had 16% more antiviral utilization; usage increased 3% among those who paid out-of-pocket after the new partial reimbursement policy was implemented. CONCLUSIONS: Direct medical costs and antiviral utilization rates of CHB patients with medical insurance were higher than those from paid out-of-pocket payments, even after adjusting for inflation and other factors. Thus, a new partial reimbursement program may positively optimize the cost and standardization of antiviral treatment.

  13. Tailoring acyclovir prodrugs with enhanced antiviral activity: rational design, synthesis, human plasma stability and in vitro evaluation.

    Science.gov (United States)

    Chayrov, Radoslav L; Stylos, Evgenios K; Chatziathanasiadou, Maria V; Chuchkov, Kiril N; Tencheva, Aleksandra I; Kostagianni, Androniki D; Milkova, Tsenka S; Angelova, Assia L; Galabov, Angel S; Shishkov, Stoyan A; Todorov, Daniel G; Tzakos, Andreas G; Stankova, Ivanka G

    2018-05-19

    Bile acid prodrugs have served as a viable strategy for refining the pharmaceutical profile of parent drugs through utilizing bile acid transporters. A series of three ester prodrugs of the antiherpetic drug acyclovir (ACV) with the bile acids cholic, chenodeoxycholic and deoxycholic were synthesized and evaluated along with valacyclovir for their in vitro antiviral activity against herpes simplex viruses type 1 and type 2 (HSV-1, HSV-2). The in vitro antiviral activity of the three bile acid prodrugs was also evaluated against Epstein-Barr virus (EBV). Plasma stability assays, utilizing ultra-high performance liquid chromatography coupled with tandem mass spectrometry, in vitro cytotoxicity and inhibitory experiments were conducted in order to establish the biological profile of ACV prodrugs. The antiviral assays demonstrated that ACV-cholate had slightly better antiviral activity than ACV against HSV-1, while it presented an eight-fold higher activity with respect to ACV against HSV-2. ACV-chenodeoxycholate presented a six-fold higher antiviral activity against HSV-2 with respect to ACV. Concerning EBV, the highest antiviral effect was demonstrated by ACV-chenodeoxycholate. Human plasma stability assays revealed that ACV-deoxycholate was more stable than the other two prodrugs. These results suggest that decorating the core structure of ACV with bile acids could deliver prodrugs with amplified antiviral activity.

  14. Protective Effect of Panax notoginseng Root Water Extract against Influenza A Virus Infection by Enhancing Antiviral Interferon-Mediated Immune Responses and Natural Killer Cell Activity

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    Jang-Gi Choi

    2017-11-01

    Full Text Available Influenza is an acute respiratory illness caused by the influenza A virus, which causes economic losses and social disruption mainly by increasing hospitalization and mortality rates among the elderly and people with chronic diseases. Influenza vaccines are the most effective means of preventing seasonal influenza, but can be completely ineffective if there is an antigenic mismatch between the seasonal vaccine virus and the virus circulating in the community. In addition, influenza viruses resistant to antiviral drugs are emerging worldwide. Thus, there is an urgent need to develop new vaccines and antiviral drugs against these viruses. In this study, we conducted in vitro and in vivo analyses of the antiviral effect of Panax notoginseng root (PNR, which is used as an herbal medicine and nutritional supplement in Korea and China. We confirmed that PNR significantly prevented influenza virus infection in a concentration-dependent manner in mouse macrophages. In addition, PNR pretreatment inhibited viral protein (PB1, PB2, HA, NA, M1, PA, M2, and NP and viral mRNA (NS1, HA, PB2, PA, NP, M1, and M2 expression. PNR pretreatment also increased the secretion of pro-inflammatory cytokines [tumor necrosis factor alpha and interleukin 6] and interferon (IFN-beta and the phosphorylation of type-I IFN-related proteins (TANK-binding kinase 1, STAT1, and IRF3 in vitro. In mice exposed to the influenza A H1N1 virus, PNR treatment decreased mortality by 90% and prevented weight loss (by approximately 10% compared with the findings in untreated animals. In addition, splenocytes from PNR-administered mice displayed significantly enhanced natural killer (NK cell activity against YAC-1 cells. Taking these findings together, PNR stimulates an antiviral response in murine macrophages and mice that protects against viral infection, which may be attributable to its ability to stimulate NK cell activity. Further investigations are needed to reveal the molecular

  15. Effect of ethanol on innate antiviral pathways and HCV replication in human liver cells

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    Fausto Nelson

    2005-12-01

    alcohol have extremely low response rates to IFN therapy 9, but the mechanisms involved have not been clarified. MAPKs play essential roles in regulation of differentiation, cell growth, and responses to cytokines, chemokines and stress. The core element in MAPK signaling consists of a module of 3 kinases, named MKKK, MKK, and MAPK, which sequentially phosphorylate each other 10. Currently, four MAPK modules have been characterized in mammalian cells: Extracellular Regulated Kinases (ERK1 and 2, Stress activated/c-Jun N terminal kinase (SAPK/JNK, p38 MAP kinases, and ERK5 11. Interestingly, ethanol modulates MAPKs 12. However, information on how ethanol affects MAPKs in the context of innate antiviral pathways such as the Jak-Stat pathway in human cells is extremely limited. When IFN-α binds its receptor, two receptor associated tyrosine kinases, Tyk2 and Jak1 become activated by phosphorylation, and phosphorylate Stat1 and Stat2 on conserved tyrosine residues 13. Stat1 and Stat2 combine with the IRF-9 protein to form the transcription factor interferon stimulated gene factor 3 (ISGF-3, which binds to the interferon stimulated response element (ISRE, and induces transcription of IFN-α-induced genes (ISG. The ISGs mediate the antiviral effects of IFN. The transcriptional activities of Stats 1, 3, 4, 5a, and 5b are also regulated by serine phosphorylation 14. Phosphorylation of Stat1 on a conserved serine amino acid at position 727 (S727, results in maximal transcriptional activity of the ISGF-3 transcription factor complex 15. Although cross-talk between p38 MAPK and the Jak-Stat pathway is essential for IFN-induced ISRE transcription, p38 does not participate in IFN induction of Stat1 serine phosphorylation 1416171819. However, cellular stress responses induced by stimuli such as ultraviolet light do induce p38 MAPK mediated Stat1 S727 phosphorylation 18. In the current report, we postulated that alcohol and HCV proteins modulate MAPK and Jak-Stat pathways in human

  16. Predictors of pain intensity and persistence in a prospective Italian cohort of patients with herpes zoster: relevance of smoking, trauma and antiviral therapy

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    Granchelli Carla

    2010-10-01

    Full Text Available Abstract Background Herpes zoster (HZ is a common disease, characterized by rash-associated localized pain. Its main complication, post-herpetic neuralgia (PHN, is difficult to treat and may last for months to years in the wake of rash resolution. Uncertainties remain as to the knowledge of predictors of HZ-related pain, including the role of antiviral therapy in preventing PHN in ordinary clinical practice. This prospective cohort study was aimed at investigating pain intensity at HZ presentation and its correlates, as well as the incidence of PHN and its predictors. Methods Patients diagnosed with HZ were consecutively enrolled by a network of Italian General Practitioners and Hospital Units in the health district of Pescara, Italy, over two years. Uncertain cases were referred for microbiological investigation. Data were collected through electronic case report form (e-CRFs at enrolment and at 1, 3, 6 and 12 months after enrolment. Pain intensity was coded on a five-degree semi-quantitative scale at each time point. PHN was defined as pain of any intensity during follow-up and quantified using an area-under-the-curve (AUC method. Results Four hundred and forty-one patients composed the final sample. Mean age was 58.1 years (SD = 20.4 years; 43.5% of patients were males; 7.9% did not receive prescription of antivirals. Intense/very intense pain at presentation was reported by 25.2% of patients and was significantly associated with female gender, older age, cigarette smoking, trauma and/or surgery at HZ site (logistic regression. PHN was diagnosed in 51.2% of patients at one month and in 30.0% of patients at three months. PHN was significantly associated with pain intensity at presentation, age, smoking, trauma and missed antiviral prescription (generalized estimating equations model. The same factors were also independent predictors of the overall pain burden as described by the AUC method (linear regression. Conclusions Smoking, traumas and

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

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    Yani Zhang

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

  18. IMPACT OF ANTIVIRAL THERAPY FOR CHRONIC HEPATITIS C ON CYTOKINE SYNTHESIS AND HEPATIC FIBROSING PROCESSES

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    V. V. Shchekotov

    2015-01-01

    Full Text Available Objective: to estimate the time course of changes in the levels of tumor necrosis factor-α (TNF-α, interleukin-4 (IL-4, IL-6, and the hepatic fibrosis indicators hyaluronic acid (HA and liver elasticity index during combined antiviral therapy (AVT with interferon alpha-2b and ribavirin in patients with chronic hepatitis C (CHC. Subjects and methods. Fifty patients with CHC were examined. Serum TNF-α, IL-6, IL-4, and HA were estimated using an enzyme immunoassay. The stage of hepatic fibrosis was determined by fibroelastography with the liver elastic index being measured; the time course of changes in the indicators was assessed in 20 patients at the end of AVT. A virological response was monitored at therapy completion and 6 months later. Results. The patients with CHC in the reactivation phase were found to have enhanced TNF-α, IL-6, and IL-4 activities in 84, 60, and 100 % of the cases, respectively (р < 0.001, р = 0.01, р < 0.001, respectively. The median serum concentration of HA in CHC was 1.8-fold higher than that in the control group (p = 0.03; the liver elastic index averaged 6.5 kPa. TNF-α and IL-6 levels correlated with viremia, transaminases, and hepatic fibrosis indicators. At combined AVT completion, the virological response rate was as high as 85 %, which was attended by a considerable reduction in cytolysis, HA concentrations, and liver density index to 5.4 kPa (3.6–6.8 kPa (p < 0.04, and in the activity of the examined cytokines. The sustained virological response rate was 80 %. Only IL-4 levels decreased and TNF-α and IL-6 concentration remained at the baseline level in patients unresponsive to AVT. Conclusion. It is expedient to monitor TNF-α, IL-4, IL-6, and HA to evaluate the severity of liver involvement in CHC and to predict the efficiency of AVT.

  19. Fatty liver in hepatitis C patients post-sustained virological response with direct-acting antivirals.

    Science.gov (United States)

    Noureddin, Mazen; Wong, Micaela M; Todo, Tsuyoshi; Lu, Shelly C; Sanyal, Arun J; Mena, Edward A

    2018-03-21

    To determine steatosis and fibrosis prevalence in hepatitis C patients after a sustained virological response achieved with direct-acting antivirals. Transient elastography with controlled attenuation parameter (CAP) was used to assess hepatic steatosis post-sustained virological response (SVR); the CAP technology was not available in the United States at study initiation. Liver stiffness/fibrosis was measured before and 47 wk after treatment completion. Patients with genotype 3 and patients with cirrhosis were excluded. One hundred and one patients were included in the study. Post-SVR there were decreases from baseline in alanine aminotransferase (ALT) (63.1 to 17.8 U/L), aspartate aminotransferase (51.8 to 21.5 U/L) and fibrosis score (7.4 to 6.1 kPa) ( P < 0.05). Post-SVR, 48 patients (47.5%) had steatosis on CAP; of these, 6.25% had advanced fibrosis. Patients with steatosis had higher body mass index (29.0 vs 26.1 kg/m 2 ), glucose (107.8 vs 96.6 mg/dL), ALT (20.4 vs 15.3 mg/dL), CAP score (296.3 vs 212.4 dB/m) and fibrosis score (7.0 vs 5.3 kPa); P < 0.05. Interestingly, compared to baseline, both patients with and without steatosis had change in fibrosis score post-SVR (7.7 kPa vs 7.0 kPa and 7.0 kPa vs 5.3 kPa); alternatively, ( P < 0.05) and therefore patients with steatosis continued to have clinically significant stiffness (≥ 7 kPa). Fatty liver is very common in hepatitis C virus (HCV) patients post-SVR. These patients continue to have elevated mean fibrosis score (≥ 7 kPa) compared to those without fatty liver; some have advanced fibrosis. Long term follow up is needed to assess steatosis and fibrosis in HCV patients post-SVR.

  20. Deferoxamine compensates for decreases in B cell counts and reduces mortality in enterovirus 71-infected mice.

    Science.gov (United States)

    Yang, Yajun; Ma, Jing; Xiu, Jinghui; Bai, Lin; Guan, Feifei; Zhang, Li; Liu, Jiangning; Zhang, Lianfeng

    2014-07-07

    Enterovirus 71 is one of the major causative agents of hand, foot and mouth disease in children under six years of age. No vaccine or antiviral therapy is currently available. In this work, we found that the number of B cells was reduced in enterovirus 71-infected mice. Deferoxamine, a marine microbial natural product, compensated for the decreased levels of B cells caused by enterovirus 71 infection. The neutralizing antibody titer was also improved after deferoxamine treatment. Furthermore, deferoxamine relieved symptoms and reduced mortality and muscle damage caused by enterovirus 71 infection. This work suggested that deferoxamine has the potential for further development as a B cell-immunomodulator against enterovirus 71.

  1. Molecular Characterization of Lys49 and Asp49 Phospholipases A2 from Snake Venom and Their Antiviral Activities against Dengue virus

    Science.gov (United States)

    Cecilio, Alzira B.; Caldas, Sergio; De Oliveira, Raiana A.; Santos, Arthur S. B.; Richardson, Michael; Naumann, Gustavo B.; Schneider, Francisco S.; Alvarenga, Valeria G.; Estevão-Costa, Maria I.; Fuly, Andre L.; Eble, Johannes A.; Sanchez, Eladio F.

    2013-01-01

    We report the detailed molecular characterization of two PLA2s, Lys49 and Asp49 isolated from Bothrops leucurus venom, and examined their effects against Dengue virus (DENV). The Bl-PLA2s, named BlK-PLA2 and BlD-PLA2, are composed of 121 and 122 amino acids determined by automated sequencing of the native proteins and peptides produced by digestion with trypsin. They contain fourteen cysteines with pIs of 9.05 and 8.18 for BlK- and BlD-PLA2s, and show a high degree of sequence similarity to homologous snake venom PLA2s, but may display different biological effects. Molecular masses of 13,689.220 (Lys49) and 13,978.386 (Asp49) were determined by mass spectrometry. DENV causes a prevalent arboviral disease in humans, and no clinically approved antiviral therapy is currently available to treat DENV infections. The maximum non-toxic concentration of the proteins to LLC-MK2 cells determined by MTT assay was 40 µg/mL for Bl-PLA2s (pool) and 20 µg/mL for each isoform. Antiviral effects of Bl-PLA2s were assessed by quantitative Real-Time PCR. Bl-PLA2s were able to reduce DENV-1, DENV-2, and DENV-3 serotypes in LLC-MK2 cells infection. Our data provide further insight into the structural properties and their antiviral activity against DENV, opening up possibilities for biotechnological applications of these Bl-PLA2s as tools of research. PMID:24131891

  2. Molecular Characterization of Lys49 and Asp49 Phospholipases A2 from Snake Venom and Their Antiviral Activities against Dengue virus

    Directory of Open Access Journals (Sweden)

    Andre L. Fuly

    2013-10-01

    Full Text Available We report the detailed molecular characterization of two PLA2s, Lys49 and Asp49 isolated from Bothrops leucurus venom, and examined their effects against Dengue virus (DENV. The Bl-PLA2s, named BlK-PLA2 and BlD-PLA2, are composed of 121 and 122 amino acids determined by automated sequencing of the native proteins and peptides produced by digestion with trypsin. They contain fourteen cysteines with pIs of 9.05 and 8.18 for BlK- and BlD-PLA2s, and show a high degree of sequence similarity to homologous snake venom PLA2s, but may display different biological effects. Molecular masses of 13,689.220 (Lys49 and 13,978.386 (Asp49 were determined by mass spectrometry. DENV causes a prevalent arboviral disease in humans, and no clinically approved antiviral therapy is currently available to treat DENV infections. The maximum non-toxic concentration of the proteins to LLC-MK2 cells determined by MTT assay was 40 µg/mL for Bl-PLA2s (pool and 20 µg/mL for each isoform. Antiviral effects of Bl-PLA2s were assessed by quantitative Real-Time PCR. Bl-PLA2s were able to reduce DENV-1, DENV-2, and DENV-3 serotypes in LLC-MK2 cells infection. Our data provide further insight into the structural properties and their antiviral activity against DENV, opening up possibilities for biotechnological applications of these Bl-PLA2s as tools of research.

  3. Antiviral Effect of Ribavirin against HCV Associated with Increased Frequency of G-to-A and C-to-U Transitions in Infectious Cell Culture Model

    DEFF Research Database (Denmark)

    Galli, Andrea; Mens, Helene; Gottwein, Judith M

    2018-01-01

    -polymerase gene was amplified, cloned, and sequenced to estimate genetic distances. We confirm that the antiviral effect of all three RBV-drug forms on HCV relies on induction of specific transitions (G-to-A and C-to-U). These mutations lead to generation of non-infectious virions, reflected by decreased spread......Ribavirin (RBV) is a broad-spectrum antiviral active against a wide range of RNA viruses. Despite having been used for decades in the treatment of chronic hepatitis C virus (HCV) infection, the precise mechanism of action of RBV is unknown. In other viruses, it inhibits propagation by increasing...... the rate of G-to-A and C-to-U transitions. Here, we utilized the J6/JFH1 HCV cell-culture system to investigate whether RBV inhibits HCV through the same mechanism. Infected Huh7.5 cells were treated with increasing concentrations of RBV or its phosphorylated forms. A fragment of the HCV NS5B...

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

    Directory of Open Access Journals (Sweden)

    Juteau Jean-Marc

    2009-12-01

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

  5. Clinical Evaluation of Ocular Antiviral Effect of Garcinia Kolanut ...

    African Journals Online (AJOL)

    Background: The claim of an Octogenarian on Garcinia kolanuts crude water extract on his open angle glaucoma has opened up a series of researchers into the native nuts as to their pharmocotherapeutic properties. Some of these have been reported as pressure lowering effects on laboratory animals and as antibacterials ...

  6. Pokeweed Antiviral Protein: Its Cytotoxicity Mechanism and Applications in Plant Disease Resistance

    Directory of Open Access Journals (Sweden)

    Rong Di

    2015-03-01

    Full Text Available Pokeweed antiviral protein (PAP is a 29 kDa type I ribosome inactivating protein (RIP found in pokeweed plants. Pokeweed produces different forms of PAP. This review focuses on the spring form of PAP isolated from Phytolacca americana leaves. PAP exerts its cytotoxicity by removing a specific adenine from the α-sarcin/ricin loop of the large ribosomal RNA. Besides depurination of the rRNA, PAP has additional activities that contribute to its cytotoxicity. The mechanism of PAP cytotoxicity is summarized based on evidence from the analysis of transgenic plants and the yeast model system. PAP was initially found to be anti-viral when it was co-inoculated with plant viruses onto plants. Transgenic plants expressing PAP and non-toxic PAP mutants have displayed broad-spectrum resistance to both viral and fungal infection. The mechanism of PAP-induced disease resistance in transgenic plants is summarized.

  7. Antiviral Activity of Sukomycin Against Potato Virus Y And Tomato Mosaic Virus

    Directory of Open Access Journals (Sweden)

    Nikolay Petrov

    2016-12-01

    Full Text Available Potato virus Y (PVY and Tomato mosaic virus (ToMV are one of the most important plant viruses that strongly influence the quality and quantity of vegetable production and cause substantial losses to farmers. The most convetional and common method of pest and disease control is trough the use of pesticides. Unfortunately, most of them are synthetic compounds without antiviral activities and possess inherent toxicities that endanger the health of the farm operators, consumers and the environment. In order to carry out a control of viral infections in plants and to reduce the loss of production it is necessary the search for alternative and environmentally friendly methods for control. Sukomycin is a complex of substances with antimicrobial and antiviral activities produced from Streptomyces hygroscopicus isolated from soil. This natural complex reduces significantly symptoms and DAS-ELISA values of Potato virus Y and Tomato mosaic virus in tobacco plants.

  8. Bugs Are Not to Be Silenced: Small RNA Pathways and Antiviral Responses in Insects.

    Science.gov (United States)

    Mongelli, Vanesa; Saleh, Maria-Carla

    2016-09-29

    Like every other organism on Earth, insects are infected with viruses, and they rely on RNA interference (RNAi) mechanisms to circumvent viral infections. A remarkable characteristic of RNAi is that it is both broadly acting, because it is triggered by double-stranded RNA molecules derived from virtually any virus, and extremely specific, because it targets only the particular viral sequence that initiated the process. Reviews covering the different facets of the RNAi antiviral immune response in insects have been published elsewhere. In this review, we build a framework to guide future investigation. We focus on the remaining questions and avenues of research that need to be addressed to move the field forward, including issues such as the activity of viral suppressors of RNAi, comparative genomics, the development of detailed maps of the subcellular localization of viral replication complexes with the RNAi machinery, and the regulation of the antiviral RNAi response.

  9. The human cathelicidin LL-37 has antiviral activity against respiratory syncytial virus.

    Directory of Open Access Journals (Sweden)

    Silke M Currie

    Full Text Available Respiratory syncytial virus is a leading cause of lower respiratory tract illness among infants, the elderly and immunocompromised individuals. Currently, there is no effective vaccine or disease modifying treatment available and novel interventions are urgently required. Cathelicidins are cationic host defence peptides expressed in the inflamed lung, with key roles in innate host defence against infection. We demonstrate that the human cathelicidin LL-37 has effective antiviral activity against RSV in vitro, retained by a truncated central peptide fragment. LL-37 prevented virus-induced cell death in epithelial cultures, significantly inhibited the production of new infectious particles and diminished the spread of infection, with antiviral effects directed both against the viral particles and the epithelial cells. LL-37 may represent an important targetable component of innate host defence against RSV infection. Prophylactic modulation of LL-37 expression and/or use of synthetic analogues post-infection may represent future novel strategies against RSV infection.

  10. Direct Acting Antivirals in Patients with Chronic Hepatitis C and Down Syndrome

    Directory of Open Access Journals (Sweden)

    Eric R. Yoo

    2016-01-01

    Full Text Available Patients with Down syndrome who received blood transfusions, likely in conjunction with cardiothoracic surgery for congenital heart disease and prior to the implementation of blood-donor screening for hepatitis C virus infection, face a substantial risk of acquiring the infection. In the past, interferon-based therapy for chronic hepatitis C infection in patients with Down syndrome was noted to have lower efficacy and potentially higher risk of adverse effects. Recently, the treatment for chronic hepatitis C has been revolutionized with the introduction of interferon-free direct acting antivirals with favorable safety, tolerability, and efficacy profile. Based on our experiences, the newly approved sofosbuvir-based direct acting antiviral therapy is well tolerated and highly efficacious in this subpopulation of hepatitis C virus infected patients with Down syndrome.

  11. Nuclear trafficking of proteins from RNA viruses: potential target for antivirals?

    Science.gov (United States)

    Caly, Leon; Wagstaff, Kylie M; Jans, David A

    2012-09-01

    A key aspect of the infectious cycle of many viruses is the transport of specific viral proteins into the host cell nucleus to perturb the antiviral response. Examples include a number of RNA viruses that are significant human pathogens, such as human immunodeficiency virus (HIV)-1, influenza A, dengue, respiratory syncytial virus and rabies, as well agents that predominantly infect livestock, such as Rift valley fever virus and Venezuelan equine encephalitis virus. Inhibiting the nuclear trafficking of viral proteins as a therapeutic strategy offers an attractive possibility, with important recent progress having been made with respect to HIV-1 and dengue. The results validate nuclear protein import as an antiviral target, and suggest the identification and development of nuclear transport inhibitors as a viable therapeutic approach for a range of human and zoonotic pathogenic viruses. Copyright © 2012 Elsevier B.V. All rights reserved.

  12. Hepatitis C virus cell-cell transmission and resistance to direct-acting antiviral agents

    DEFF Research Database (Denmark)

    Xiao, Fei; Fofana, Isabel; Heydmann, Laura

    2014-01-01

    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...

  13. Non-Specific dsRNA-Mediated Antiviral Response in the Honey Bee

    Science.gov (United States)

    Flenniken, Michelle L.; Andino, Raul

    2013-01-01

    Honey bees are essential pollinators of numerous agricultural crops. Since 2006, honey bee populations have suffered considerable annual losses that are partially attributed to Colony Collapse Disorder (CCD). CCD is an unexplained phenomenon that correlates with elevated incidence of pathogens, including RNA viruses. Honey bees are eusocial insects that live in colonies of genetically related individuals that work in concert to gather and store nutrients. Their social organization provides numerous benefits, but also facilitates pathogen transmission between individuals. To investigate honey bee antiviral defense mechanisms, we developed an RNA virus infection model and discovered that administration of dsRNA, regardless of sequence, reduced virus infection. Our results suggest that dsRNA, a viral pathogen associated molecular pattern (PAMP), triggers an antiviral response that controls virus infection in honey bees. PMID:24130869

  14. Antiviral RNA silencing suppression activity of Tomato spotted wilt virus NSs protein.

    Science.gov (United States)

    Ocampo Ocampo, T; Gabriel Peralta, S M; Bacheller, N; Uiterwaal, S; Knapp, A; Hennen, A; Ochoa-Martinez, D L; Garcia-Ruiz, H

    2016-06-17

    In addition to regulating gene expression, RNA silencing is an essential antiviral defense system in plants. Triggered by double-stranded RNA, silencing results in degradation or translational repression of target transcripts. Viruses are inducers and targets of RNA silencing. To condition susceptibility, most plant viruses encode silencing suppressors that interfere with this process, such as the Tomato spotted wilt virus (TSWV) NSs protein. The mechanism by which NSs suppresses RNA silencing and its role in viral infection and movement remain to be determined. We cloned NSs from the Hawaii isolate of TSWV and using two independent assays show for the first time that this protein restored pathogenicity and supported the formation of local infection foci by suppressor-deficient Turnip mosaic virus and Turnip crinkle virus. Demonstrating the suppression of RNA silencing directed against heterologous viruses establishes the foundation to determine the means used by NSs to block this antiviral process.

  15. CRISPR-Cas Targeting of Host Genes as an Antiviral Strategy.

    Science.gov (United States)

    Chen, Shuliang; Yu, Xiao; Guo, Deyin

    2018-01-16

    Currently, a new gene editing tool-the Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) associated (Cas) system-is becoming a promising approach for genetic manipulation at the genomic level. This simple method, originating from the adaptive immune defense system in prokaryotes, has been developed and applied to antiviral research in humans. Based on the characteristics of virus-host interactions and the basic rules of nucleic acid cleavage or gene activation of the CRISPR-Cas system, it can be used to target both the virus genome and host factors to clear viral reservoirs and prohibit virus infection or replication. Here, we summarize recent progress of the CRISPR-Cas technology in editing host genes as an antiviral strategy.

  16. Modelling Hepatitis B Virus Antiviral Therapy and Drug Resistant Mutant Strains

    Science.gov (United States)

    Bernal, Julie; Dix, Trevor; Allison, Lloyd; Bartholomeusz, Angeline; Yuen, Lilly

    Despite the existence of vaccines, the Hepatitis B virus (HBV) is still a serious global health concern. HBV targets liver cells. It has an unusual replication process involving an RNA pre-genome that the reverse transcriptase domain of the viral polymerase protein translates into viral DNA. The reverse transcription process is error prone and together with the high replication rates of the virus, allows the virus to exist as a heterogeneous population of mutants, known as a quasispecies, that can adapt and become resistant to antiviral therapy. This study presents an individual-based model of HBV inside an artificial liver, and associated blood serum, undergoing antiviral therapy. This model aims to provide insights into the evolution of the HBV quasispecies and the individual contribution of HBV mutations in the outcome of therapy.

  17. CEACAM1 induces B-cell survival and is essential for protective antiviral antibody production

    Science.gov (United States)

    Khairnar, Vishal; Duhan, Vikas; Maney, Sathish Kumar; Honke, Nadine; Shaabani, Namir; Pandyra, Aleksandra A.; Seifert, Marc; Pozdeev, Vitaly; Xu, Haifeng C.; Sharma, Piyush; Baldin, Fabian; Marquardsen, Florian; Merches, Katja; Lang, Elisabeth; Kirschning, Carsten; Westendorf, Astrid M.; Häussinger, Dieter; Lang, Florian; Dittmer, Ulf; Küppers, Ralf; Recher, Mike; Hardt, Cornelia; Scheffrahn, Inka; Beauchemin, Nicole; Göthert, Joachim R.; Singer, Bernhard B.; Lang, Philipp A.; Lang, Karl S.

    2015-01-01

    B cells are essential for antiviral immune defence because they produce neutralizing antibodies, present antigen and maintain the lymphoid architecture. Here we show that intrinsic signalling of CEACAM1 is essential for generating efficient B-cell responses. Although CEACAM1 exerts limited influence on the proliferation of B cells, expression of CEACAM1 induces survival of proliferating B cells via the BTK/Syk/NF-κB-axis. The absence of this signalling cascade in naive Ceacam1−/− mice limits the survival of B cells. During systemic infection with cytopathic vesicular stomatitis virus, Ceacam1−/− mice can barely induce neutralizing antibody responses and die early after infection. We find, therefore, that CEACAM1 is a crucial regulator of B-cell survival, influencing B-cell numbers and protective antiviral antibody responses. PMID:25692415

  18. Antiviral activity of platinum (II) and palladium (II) complexes of dimethyl sulfoxide (DMSO) in vitro

    International Nuclear Information System (INIS)

    Al-Allaf, T.; Rashan, L

    1996-01-01

    The antiviral activity of complexes cis-[Pt(DMSO) 2 CI 2 ] and trans-[Pd(DMSO) 2 CI 2 ] against the reverse transcriptase enzyme, herpes and influenza viruses have been studied in vitro. Both complexes demonstrated some activity against the reverse transcriptase enzyme in which the inhibition concentration (IC 5 0) of the cis-Pt and the trans-Pd complexes were shown to be 37.6 and 35.5 μ g/ml respectively. This activity was compared with that of the standard reference; the phosphonoformate (PFA). On the other hand, both complexes have no antiviral activity against herpes and influenza viruses No cytotoxic effects on the three cell lines, Raji, K562 and Mrc-5 were demonstrated by these complexes at the concentrations studied in vitro. (authors). 16 refs., 1 tab., 2 figs

  19. Antiviral activities of Radix Isatidis polysaccharide against type II herpes simplex virus in vitro

    Directory of Open Access Journals (Sweden)

    Chunmei WANG

    2018-03-01

    Full Text Available Abstract This study investigated the antiviral activities of Radix Isatidis polysaccharide (RIP against type II herpes simplex virus (HSV-2 in vitro. RIP was prepared from the Radix Isatidis root. The toxicity of RIP on Vero cells was detected. The direct killing effect of RIP on HSV-2, inhibitory effect of RIP on HSV-2 replication and inhibitory effect of RIP on HSV-2 adsorption were determined. Results showed that, RIP in concentration range of 25-800 mg/L had no toxic effect on Vero cells. RIP with different concentrations could not directly inactivate the HSV-2. The effective rates on inhibition of HSV-2 replication and adsorption in 800 mg/L RIP group were 71.57% and 48.37%, respectively, which were the highest among different groups. In conclusion, RIP has the antiviral effect against HSV-2 in vitro. This effect mainly occurs in inhibiting the virus duplication and adsorption.

  20. Management of hepatitis C infection in the era of direct-acting antiviral therapy

    Science.gov (United States)

    Zain, L. H.; Sungkar, T.

    2018-03-01

    Hepatitis C viral infection globally affects millions of people and commonly results in debilitating complications and mortality. Initial mainstay therapy consisted of pegylated interferon α (pegIFNα) with additional ribavirin that showed unsatisfactory cure rate, common side effects and complicated dosing, contributing to high discontinuation rate. Over the last few years, newer antivirals have been extensively studied, that are Direct-Acting Antivirals (DAAs). Specifically targeting viral protein mainly during replication phase, DAAs showed greater cure rate (commonly measured as sustained virologic response), improved safety profile and shorter treatment duration compared to traditional interferon-ribavirin therapy. Current guidelines have also included Interferon-free, often ribavirin-free, DAAs combinations that suggest promising outcomes. The current review highlights development of rapidly growing hepatitis C treatment including DAAs recommendations.

  1. Hedging against antiviral resistance during the next influenza pandemic using small stockpiles of an alternative chemotherapy.

    Directory of Open Access Journals (Sweden)

    Joseph T Wu

    2009-05-01

    Full Text Available The effectiveness of single-drug antiviral interventions to reduce morbidity and mortality during the next influenza pandemic will be substantially weakened if transmissible strains emerge which are resistant to the stockpiled antiviral drugs. We developed a mathematical model to test the hypothesis that a small stockpile of a secondary antiviral drug could be used to mitigate the adverse consequences of the emergence of resistant strains.We used a multistrain stochastic transmission model of influenza to show that the spread of antiviral resistance can be significantly reduced by deploying a small stockpile (1% population coverage of a secondary drug during the early phase of local epidemics. We considered two strategies for the use of the secondary stockpile: early combination chemotherapy (ECC; individuals are treated with both drugs in combination while both are available; and sequential multidrug chemotherapy (SMC; individuals are treated only with the secondary drug until it is exhausted, then treated with the primary drug. We investigated all potentially important regions of unknown parameter space and found that both ECC and SMC reduced the cumulative attack rate (AR and the resistant attack rate (RAR unless the probability of emergence of resistance to the primary drug p(A was so low (less than 1 in 10,000 that resistance was unlikely to be a problem or so high (more than 1 in 20 that resistance emerged as soon as primary drug monotherapy began. For example, when the basic reproductive number was 1.8 and 40% of symptomatic individuals were treated with antivirals, AR and RAR were 67% and 38% under monotherapy if p(A = 0.01. If the probability of resistance emergence for the secondary drug was also 0.01, then SMC reduced AR and RAR to 57% and 2%. The effectiveness of ECC was similar if combination chemotherapy reduced the probabilities of resistance emergence by at least ten times. We extended our model using travel data between 105

  2. Predictors of antiviral treatment initiation in hepatitis C virus-infected patients: a Danish cohort study

    DEFF Research Database (Denmark)

    Hansen, N; Obel, N; Christensen, P B

    2009-01-01

    Predictive factors for initiation of antiviral therapy in chronically infected hepatitis C virus (HCV) patients are not fully elucidated. The aim of this study was to determine predictive factors for initiation of treatment with standard or pegylated interferon either alone or combined...... with ribavirin. A Danish cohort of individuals chronically infected with HCV was used and observation time was calculated from the date of inclusion in the cohort to date of death, last clinical observation, 1 January 2007, or start of HCV antiviral treatment in treatment-naïve patients. Kaplan-Meier survival...... analysis was used to construct time to event curves. Cox regression was used to determine the incidence rate ratios as estimates of relative risk (RR) and 95% confidence intervals (CI). A total of 1780 patients were enrolled in the study. The cumulative chance of treatment initiation over 5 years was 33...

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

    OpenAIRE

    Zorofchian Moghadamtousi, Soheil; Abdul Kadir, Habsah; Hassandarvish, Pouya; Tajik, Hassan; Abubakar, Sazaly; Zandi, Keivan

    2014-01-01

    Curcuma longa L. (Zingiberaceae family) and its polyphenolic compound curcumin have been subjected to a variety of antimicrobial investigations due to extensive traditional uses and low side effects. Antimicrobial activities for curcumin and rhizome extract of C. longa against different bacteria, viruses, fungi, and parasites have been reported. The promising results for antimicrobial activity of curcumin made it a good candidate to enhance the inhibitory effect of existing antimicrobial agen...

  4. Evaluation of Orally Delivered ST-246 as Postexposure Prophylactic and Antiviral Therapeutic in an Aerosolized Rabbitpox Rabbit Model

    National Research Council Canada - National Science Library

    Nalca, Aysegul; Hatkin, Josh M; Garza, Nicole L; Nichols, Donald K; Norris, Sarah W; Hruby, Dennis E; Jordan, Robert

    2008-01-01

    ...) to treat smallpox or monkeypox infection. In this study, we showed that administration of the antiviral compound ST-246 to rabbits by oral gavage, once daily for 14 days beginning 1h postexposure (p.e.), resulted in 100...

  5. HBV reactivation in patients with HCV/HBV cirrhosis on treatment with direct-acting antivirals.

    Science.gov (United States)

    Calvaruso, V; Ferraro, D; Licata, A; Bavetta, M G; Petta, S; Bronte, F; Colomba, G; Craxì, A; Di Marco, V

    2018-01-01

    Anecdotal reports suggest that patients with chronic hepatitis C virus (HCV) hepatitis and overt or occult hepatitis B virus (HBV) coinfection may reactivate HBV when HCV is suppressed or cleared by direct-acting antivirals (DAAs). We assessed the prevalence of overt or previous HBV coinfection and the risk of HBV reactivation in patients with HCV cirrhosis treated with DAAs. This was a retrospective cohort of 104 consecutive patients with HCV cirrhosis treated with DAAs. Serum HCV-RNA and HBV-DNA were tested at weeks 4, 8 and 12 of DAAs therapy and at week 12 of follow-up. At the start of DAAs, eight patients (7.7%) were HBsAg positive/HBeAg negative with undetectable HBV-DNA and low levels of quantitative HBsAg (four on nucleos(t)ide analogues [NUCs] and four inactive carriers), 37 patients (35.6%) had markers of previous HBV infection (25 anti-HBc positive, 12 anti-HBc/anti-HBs positive) and 59 (56.7%) had no evidence of HBV infection. Sixty-seven patients (64.4%) were HCV-RNA negative at week 4 and 98 (94.2%) achieved sustained virological response. All four HBsAg-positive patients treated with NUCs remained HBV-DNA negative, but three of four untreated patients showed an increase in HBV-DNA of 2-3 log without a biochemical flare and achieved HBV-DNA suppression when given NUCs. During or after DAAs, by conventional assay, HBV-DNA remained not detectable in all 37 anti-HBc-positive patients but in three of them (8.1%) HBV-DNA became detectable with a highly sensitive PCR. HBV reactivation is likely to occur in untreated HBV/HCV-coinfected cirrhotic patients when they undergo HCV treatment with DAAs. Pre-emptive therapy with NUCs should be considered in this setting. Anti-HBc-positive patients rarely reactivate HBV without clinical or virological outcomes. © 2017 John Wiley & Sons Ltd.

  6. Antibacterial, Antiviral, and Oxygen-Sensing Nanoparticles Prepared from Electrospun Materials

    Czech Academy of Sciences Publication Activity Database

    Henke, P.; Kirakci, Kaplan; Kubát, Pavel; Fraiberk, M.; Forstová, J.; Mosinger, Jiří

    2016-01-01

    Roč. 8, č. 38 (2016), s. 25127-25136 ISSN 1944-8244 R&D Projects: GA ČR(CZ) GA16-15020S; GA MŠk(CZ) LM2015073 Institutional support: RVO:61388980 ; RVO:61388955 Keywords : antibacterial * antiviral * nanoparticles * oxygen-sensing * singlet oxygen Subject RIV: CA - Inorganic Chemistry; CF - Physical ; Theoretical Chemistry (UFCH-W) Impact factor: 7.504, year: 2016

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

    Energy Technology Data Exchange (ETDEWEB)

    Li, Xiaoguang [Tohoku University Graduate School of Medicine, Department of Internal Medicine/Division of Emerging Infectious Diseases, Sendai 980-8575 (Japan); Department of Medical Microbiology, Harbin Medical University, Harbin 150086 (China); Center for AIDS Research, Kumamoto University, 2-2-1 Honjo, Kumamoto 860-0811 (Japan); Qian, Hua [Tohoku University Graduate School of Medicine, Department of Internal Medicine/Division of Emerging Infectious Diseases, Sendai 980-8575 (Japan); Center for AIDS Research, Kumamoto University, 2-2-1 Honjo, Kumamoto 860-0811 (Japan); Miyamoto, Fusako [Tohoku University Graduate School of Medicine, Department of Internal Medicine/Division of Emerging Infectious Diseases, Sendai 980-8575 (Japan); Naito, Takeshi [Laboratory of Virus Control, Institute for Virus Research, Kyoto University, 53 Kawaramachi, Shogoin, Sakyo-ku, Kyoto 606-8507 (Japan); Kawaji, Kumi [Tohoku University Graduate School of Medicine, Department of Internal Medicine/Division of Emerging Infectious Diseases, Sendai 980-8575 (Japan); Kajiwara, Kazumi [Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, Kyoto 606-8501 (Japan); JST Innovation Plaza Kyoto, Japan Science and Technology Agency, Nishigyo-ku, Kyoto 615-8245 (Japan); Hattori, Toshio [Tohoku University Graduate School of Medicine, Department of Internal Medicine/Division of Emerging Infectious Diseases, Sendai 980-8575 (Japan); Matsuoka, Masao [Laboratory of Virus Control, Institute for Virus Research, Kyoto University, 53 Kawaramachi, Shogoin, Sakyo-ku, Kyoto 606-8507 (Japan); Watanabe, Kentaro; Oishi, Shinya; Fujii, Nobutaka [Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, Kyoto 606-8501 (Japan); and others

    2012-07-27

    Highlights: Black-Right-Pointing-Pointer We established a novel, simple and rapid in vivo system for evaluation of anti-HIV-1 drugs with rats. Black-Right-Pointing-Pointer The system may be applicable for other antiviral drugs, and/or useful for initial screening in vivo. Black-Right-Pointing-Pointer 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-1{sub IIIB} and HIV-1{sub BaL} as representative CXCR4- and CCR5-tropic HIV-1 strains, respectively. CXCR4 antagonists were shown to only possess anti-HIV-1{sub IIIB} activity, whereas fusion inhibitors showed both anti-HIV-1{sub IIIB} and anti-HIV-1{sub BaL} 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.

  8. Imaging analysis of nuclear antiviral factors through direct detection of incoming adenovirus genome complexes

    Energy Technology Data Exchange (ETDEWEB)

    Komatsu, Tetsuro [Microbiologie Fondamentale et Pathogénicité, MFP CNRS UMR 5234, Université de Bordeaux, Bordeaux 33076 (France); Department of Infection Biology, Faculty of Medicine, University of Tsukuba, Tsukuba 305-8575 (Japan); Will, Hans [Department of Tumor Biology, University Hospital Hamburg-Eppendorf, 20246 Hamburg (Germany); Nagata, Kyosuke [Department of Infection Biology, Faculty of Medicine, University of Tsukuba, Tsukuba 305-8575 (Japan); Wodrich, Harald, E-mail: harald.wodrich@u-bordeaux.fr [Microbiologie Fondamentale et Pathogénicité, MFP CNRS UMR 5234, Université de Bordeaux, Bordeaux 33076 (France)

    2016-04-22

    Recent studies involving several viral systems have highlighted the importance of cellular intrinsic defense mechanisms through nuclear antiviral proteins that restrict viral propagation. These factors include among others components of PML nuclear bodies, the nuclear DNA sensor IFI16, and a potential restriction factor PHF13/SPOC1. For several nuclear replicating DNA viruses, it was shown that these factors sense and target viral genomes immediately upon nuclear import. In contrast to the anticipated view, we recently found that incoming adenoviral genomes are not targeted by PML nuclear bodies. Here we further explored cellular responses against adenoviral infection by focusing on specific conditions as well as additional nuclear antiviral factors. In line with our previous findings, we show that neither interferon treatment nor the use of specific isoforms of PML nuclear body components results in co-localization between incoming adenoviral genomes and the subnuclear domains. Furthermore, our imaging analyses indicated that neither IFI16 nor PHF13/SPOC1 are likely to target incoming adenoviral genomes. Thus our findings suggest that incoming adenoviral genomes may be able to escape from a large repertoire of nuclear antiviral mechanisms, providing a rationale for the efficient initiation of lytic replication cycle. - Highlights: • Host nuclear antiviral factors were analyzed upon adenovirus genome delivery. • Interferon treatments fail to permit PML nuclear bodies to target adenoviral genomes. • Neither Sp100A nor B targets adenoviral genomes despite potentially opposite roles. • The nuclear DNA sensor IFI16 does not target incoming adenoviral genomes. • PHF13/SPOC1 targets neither incoming adenoviral genomes nor genome-bound protein VII.

  9. Identification of DreI as an antiviral factor regulated by RLR signaling pathway.

    Directory of Open Access Journals (Sweden)

    Shun Li

    Full Text Available BACKGROUND: Retinoic acid-inducible gene I (RIG-I-like receptors (RLRs had been demonstrated to prime interferon (IFN response against viral infection via the conserved RLR signaling in fish, and a novel fish-specific gene, the grass carp reovirus (GCRV-induced gene 2 (Gig2, had been suggested to play important role in host antiviral response. METHODOLOGY/PRINCIPAL FINDINGS: In this study, we cloned and characterized zebrafish Gig2 homolog (named Danio rerio Gig2-I, DreI, and revealed its antiviral role and expressional regulation signaling pathway. RT-PCR, Western blot and promoter activity assay indicate that DreI can be induced by poly I:C, spring viremia of carp virus (SVCV and recombinant IFN (rIFN, showing that DreI is a typical ISG. Using the pivotal signaling molecules of RLR pathway, including RIG-I, MDA5 and IRF3 from crucian carp, it is found that DreI expression is regulated by RLR cascade and IRF3 plays an important role in this regulation. Furthermore, promoter mutation assay confirms that the IFN-stimulated regulatory elements (ISRE in the 5' flanking region of DreI is essential for its induction. Finally, overexpression of DreI leads to establish a strong antiviral state against SVCV and Rana grylio virus (RGV infection in EPC (Epithelioma papulosum cyprinid cells. CONCLUSIONS/SIGNIFICANCE: These data indicate that DreI is an antiviral protein, which is regulated by RLR signaling pathway.

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

    Directory of Open Access Journals (Sweden)

    Strebel Klaus

    2007-08-01

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

  11. Anopheles gambiae antiviral immune response to systemic O'nyong-nyong infection.

    Directory of Open Access Journals (Sweden)

    Joanna Waldock

    Full Text Available Mosquito-borne viral diseases cause significant burden in much of the developing world. Although host-virus interactions have been studied extensively in the vertebrate host, little is known about mosquito responses to viral infection. In contrast to mosquitoes of the Aedes and Culex genera, Anopheles gambiae, the principal vector of human malaria, naturally transmits very few arboviruses, the most important of which is O'nyong-nyong virus (ONNV. Here we have investigated the A. gambiae immune response to systemic ONNV infection using forward and reverse genetic approaches.We have used DNA microarrays to profile the transcriptional response of A. gambiae inoculated with ONNV and investigate the antiviral function of candidate genes through RNAi gene silencing assays. Our results demonstrate that A. gambiae responses to systemic viral infection involve genes covering all aspects of innate immunity including pathogen recognition, modulation of immune signalling, complement-mediated lysis/opsonisation and other immune effector mechanisms. Patterns of transcriptional regulation and co-infections of A. gambiae with ONNV and the rodent malaria parasite Plasmodium berghei suggest that hemolymph immune responses to viral infection are diverted away from melanisation. We show that four viral responsive genes encoding two putative recognition receptors, a galectin and an MD2-like receptor, and two effector lysozymes, function in limiting viral load.This study is the first step in elucidating the antiviral mechanisms of A. gambiae mosquitoes, and has revealed interesting differences between A. gambiae and other invertebrates. Our data suggest that mechanisms employed by A. gambiae are distinct from described invertebrate antiviral immunity to date, and involve the complement-like branch of the humoral immune response, supressing the melanisation response that is prominent in anti-parasitic immunity. The antiviral immune response in A. gambiae is thus

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

    Science.gov (United States)

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

    2012-11-04

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

  13. An Antiviral Role for Antimicrobial Peptides during the Arthropod Response to Alphavirus Replication

    OpenAIRE

    Huang, Zhijing; Kingsolver, Megan B.; Avadhanula, Vasanthi; Hardy, Richard W.

    2013-01-01

    Alphaviruses establish a persistent infection in arthropod vectors which is essential for the effective transmission of the virus to vertebrate hosts. The development of persistence in insects is not well understood, although it is thought to involve the innate immune response. Using a transgenic fly system expressing a self-replicating viral RNA genome analog, we have previously demonstrated antiviral roles of the Drosophila Imd (immune deficiency) and Jak-STAT innate immunity pathways in re...

  14. Clinical case of Successful Treatment by Antiviral Preparations of a Patient with Guillain — Barre Syndrome

    Directory of Open Access Journals (Sweden)

    E.Yu. Vinnyk

    2015-11-01

    Full Text Available There is described a clinical case of treatment of patients with acute Guillain — Barre syndrome of significant viral etiology. It was used the complex therapy with antiviral drugs according to the recommendations of the infectious disease specialist. In addition to basic therapy and plasma depletion, there were prescribed the preparation of acyclic nucleosides group, interferon and normal human immunoglobulin. The age of the latter significantly reduced the period of recovery of the patient and allow avoid complications.

  15. Enhanced Topical and Transdermal Delivery of Antineoplastic and Antiviral Acyclic Nucleoside Phosphonate cPr-PMEDAP

    Czech Academy of Sciences Publication Activity Database

    Vávrová, K.; Kovaříková, P.; Školová, B.; Líbalová, M.; Roh, J.; Čáp, R.; Holý, Antonín; Hrabálek, A.

    2011-01-01

    Roč. 28, č. 12 (2011), s. 3105-3115 ISSN 0724-8741 R&D Projects: GA MŠk 1M0508 Grant - others:GA ČR(CZ) GAP207/11/0365 Institutional research plan: CEZ:AV0Z40550506 Keywords : acyclic nucleoside phosphonates * antivirals * antineoplastics * permeation enhancer * topical skin application * transdermal delivery Subject RIV: CC - Organic Chemistry Impact factor: 4.093, year: 2011

  16. Factors affecting the purpose suppressive antiviral therapy for patients with recurrent genital herpes

    Directory of Open Access Journals (Sweden)

    I. S. Коlova

    2017-01-01

    Full Text Available Objective: To study the factors that influence the destination of suppressive antiviral therapy in patients with recurrent genital herpes doctors of different specialties.Material and Methods: The study was conducted based on an anonymous survey of professionals providing medical care to patients with genital herpes. The survey involved 67 experts – 44 dermatologist, 13 obstetricians and 10 urologists working in Skin and Venereal Diseases, Women’s consuitation post and Saint Petersburg clinics.Results: Most respondents indicated that among patients with genital herpes, seeking an appointment, dominated by patients with relapsing nature of the disease. Suppressive antiviral therapy is recommended 68,7% of specialists, including dermatologists 61,3%, 84,6% of obstetricians and gynecologists, and 80% of urologists. The main indications for its experts consider high frequency of relapses, the patient’s tendency to promiscuity, the desire of the patient with fewer relapses, and the emotional response of the patient for the presence of the disease. Do not prescribe suppressive therapy for recurrent genital herpes 31,4% of the doctors surveyed. Among the reasons for which are not appointed by the type of treatment, the patient is dominated by the rejection of this type of treatment, the lack of experience of the destination suppressive therapy, as well as the uncertainty of specialists in its effectiveness.Conclusion: Suppressive antiviral therapy is recommended 68,7% of specialists. Do not prescribe this type of treatment for recurrent genital herpes 31,4% of the doctors surveyed. The proportion of professionals who refuse the appointment of suppressive antiviral therapy, the highest among dermatologists (38,7% compared with 15,4% among obstetricians and 20% of urologists. The most frequent grounds for refusal from this type of treatment is the lack of confidence in its effectiveness. 

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

    Directory of Open Access Journals (Sweden)

    Gloria Arriagada

    2011-04-01

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

  18. Delivery of multiple epitopes by recombinant detoxified adenylate cyclase of Bordetella pertussis induces protective antiviral immunity

    Czech Academy of Sciences Publication Activity Database

    Fayolle, C.; Osičková, Adriana; Osička, Radim; Henry, T.; Rojas, M. J.; Saron, M. F.; Šebo, Peter; Leclers, C.

    2001-01-01

    Roč. 75, č. 16 (2001), s. 7330-7338 ISSN 0022-538X R&D Projects: GA ČR GA310/98/0432; GA MŠk ME 167; GA MŠk VS96149 Institutional research plan: CEZ:AV0Z5020903 Keywords : antiviral immunity * Bordetella pertusis Subject RIV: EE - Microbiology, Virology Impact factor: 5.622, year: 2001

  19. Imaging analysis of nuclear antiviral factors through direct detection of incoming adenovirus genome complexes

    International Nuclear Information System (INIS)

    Komatsu, Tetsuro; Will, Hans; Nagata, Kyosuke; Wodrich, Harald

    2016-01-01

    Recent studies involving several viral systems have highlighted the importance of cellular intrinsic defense mechanisms through nuclear antiviral proteins that restrict viral propagation. These factors include among others components of PML nuclear bodies, the nuclear DNA sensor IFI16, and a potential restriction factor PHF13/SPOC1. For several nuclear replicating DNA viruses, it was shown that these factors sense and target viral genomes immediately upon nuclear import. In contrast to the anticipated view, we recently found that incoming adenoviral genomes are not targeted by PML nuclear bodies. Here we further explored cellular responses against adenoviral infection by focusing on specific conditions as well as additional nuclear antiviral factors. In line with our previous findings, we show that neither interferon treatment nor the use of specific isoforms of PML nuclear body components results in co-localization between incoming adenoviral genomes and the subnuclear domains. Furthermore, our imaging analyses indicated that neither IFI16 nor PHF13/SPOC1 are likely to target incoming adenoviral genomes. Thus our findings suggest that incoming adenoviral genomes may be able to escape from a large repertoire of nuclear antiviral mechanisms, providing a rationale for the efficient initiation of lytic replication cycle. - Highlights: • Host nuclear antiviral factors were analyzed upon adenovirus genome delivery. • Interferon treatments fail to permit PML nuclear bodies to target adenoviral genomes. • Neither Sp100A nor B targets adenoviral genomes despite potentially opposite roles. • The nuclear DNA sensor IFI16 does not target incoming adenoviral genomes. • PHF13/SPOC1 targets neither incoming adenoviral genomes nor genome-bound protein VII.

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

    International Nuclear Information System (INIS)

    Li, Xiaoguang; Qian, Hua; Miyamoto, Fusako; Naito, Takeshi; Kawaji, Kumi; Kajiwara, Kazumi; Hattori, Toshio; Matsuoka, Masao; Watanabe, Kentaro; Oishi, Shinya; Fujii, Nobutaka

    2012-01-01

    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-1 IIIB and HIV-1 BaL as representative CXCR4- and CCR5-tropic HIV-1 strains, respectively. CXCR4 antagonists were shown to only possess anti-HIV-1 IIIB activity, whereas fusion inhibitors showed both anti-HIV-1 IIIB and anti-HIV-1 BaL 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.

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

    Science.gov (United States)

    2013-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Jessica Jenkins Broglie

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

  3. Clinical Experience of Complex Application of Antiviral Therapy, Natural and Preformed Physical Factors in Patients with Chronic Hepatitis C

    Directory of Open Access Journals (Sweden)

    N.V. Dragomiretska

    2013-02-01

    Full Text Available The article deals with the results of complex application of antiviral therapy, low-mineralized hydrocarbonate-sulphate-chloride sodium mineral water, EHF- and vibroacoustic therapy of the patients with chronic viral hepatitis C. The developed complex liquidates adverse effects of the antiviral therapy (leukocytopenia, thrombocytopenia and flu-like syndromes, promotes the normalization of the functional tests of the liver and normalization of the majority of indicators of the immune status, stimulates the synthesis of the endogenous interferon α.

  4. Synergistic antiviral effect in vitro of azidothymidine and amphotericin B methyl ester in combination on HIV infection

    DEFF Research Database (Denmark)

    Hansen, J E; Nielsen, C; Svenningsen, A

    1992-01-01

    The nucleoside analogue azidothymidine (AZT) and the methyl ester of amphotericin B (AME) were assayed for antiviral effect on HIV infection singly and in combination. Both compounds were effective in inhibiting HIV infection of MT-4 cells. At concentrations where either compound alone had no sig...... synergistic antiviral properties. Amphotericin B itself significantly reduced HIV infectivity in vitro and should not be used as an antifungal agent in cultures intended to propagate HIV....

  5. IRF-4 and c-Rel expression in antiviral-resistant adult T-cell leukemia/lymphoma

    OpenAIRE

    Ramos, Juan Carlos; Ruiz, Phillip; Ratner, Lee; Reis, Isildinha M.; Brites, Carlos; Pedroso, Celia; Byrne, Gerald E.; Toomey, Ngoc L.; Andela, Valentine; Harhaj, Edward W.; Lossos, Izidore S.; Harrington, William J.

    2007-01-01

    Adult T-cell leukemia/lymphoma (ATLL) is a generally fatal malignancy. Most ATLL patients fare poorly with conventional chemotherapy; however, antiviral therapy with zidovudine (AZT) and interferon alpha (IFN-α) has produced long-term clinical remissions. We studied primary ATLL tumors and identified molecular features linked to sensitivity and resistance to antiviral therapy. Enhanced expression of the proto-oncogene c-Rel was noted in 9 of 27 tumors. Resistant tumors exhibited c-Rel (6 of 1...

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

    Directory of Open Access Journals (Sweden)

    Meyer Adam G

    2009-11-01

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

  7. The role of fluoxetine in antiviral therapy for chronic hepatitis C

    Directory of Open Access Journals (Sweden)

    QIN Yuan

    2016-09-01

    Full Text Available More than 20% of chronic hepatitis C (CHC patients receiving the antiviral therapy with interferonα(IFNα experience depression, and fluoxetine is often used to alleviate this symptom. Fluoxetine has anti-inflammatory properties and can change the synthesis of liver lipids, but its influence on antiviral therapy for CHC and related mechanism remain unknown. Recent studies show that fluoxetine can inhibit hepatitis C virus (HCV infection and reduce the production of reactive oxygen species (ROS and lipid accumulation in Huh7.5 cells; in addition, it can promote the antiviral effect mediated by IFNα through activating STAT1 and JNK signaling pathways and thus reduce HCV viral load and the level of alanine aminotransferase in CHC patients. Fluoxetine elevates PPAR response element activity in CHC patients, and its inhibitory effect on HCV infection and lipid accumulation were partly reversed by antagonists including PPARβ/γ, suggesting that fluoxetine inhibits HCV infection, ROS production, and lipid accumulation through regulating PPARβ/γ and JNK/STAT pathways.

  8. Arbidol: a broad-spectrum antiviral that inhibits acute and chronic HCV infection

    Directory of Open Access Journals (Sweden)

    Pécheur Eve-Isabelle

    2006-07-01

    Full Text Available Abstract Arbidol (ARB is an antiviral compound that was originally proven effective for treatment of influenza and several other respiratory viral infections. The broad spectrum of ARB anti-viral activity led us to evaluate its effect on hepatitis C virus (HCV infection and replication in cell culture. Long-term ARB treatment of Huh7 cells chronically replicating a genomic length genotype 1b replicon resulted in sustained reduction of viral RNA and protein expression, and eventually cured HCV infected cells. Pre-treatment of human hepatoma Huh7.5.1 cells with 15 μM ARB for 24 to 48 hours inhibited acute infection with JFH-1 virus by up to 1000-fold. The inhibitory effect of ARB on HCV was not due to generalized cytotoxicity, nor to augmentation of IFN antiviral signaling pathways, but involved impaired virus-mediated membrane fusion. ARB's affinity for membranes may inhibit several aspects of the HCV lifecycle that are membrane-dependent.

  9. Immune evasion of porcine enteric coronaviruses and viral modulation of antiviral innate signaling.

    Science.gov (United States)

    Zhang, Qingzhan; Yoo, Dongwan

    2016-12-02

    Porcine epidemic diarrhea virus (PEDV) and porcine deltacoronavirus (PDCoV) are emerged and reemerging viruses in pigs, and together with transmissible gastroenteritis virus (TGEV), pose significant economic concerns to the swine industry. These viruses infect epithelial cells of the small intestine and cause watery diarrhea, dehydration, and a high mortality in neonatal piglets. Type I interferons (IFN-α/β) are major antiviral cytokines forming host innate immunity, and in turn, these enteric coronaviruses have evolved to modulate the host innate immune signaling during infection. Accumulating evidence however suggests that IFN induction and signaling in the intestinal epithelial cells differ from other epithelial cells, largely due to distinct features of the gut epithelial mucosal surface and commensal microflora, and it appears that type III interferon (IFN-λ) plays a key role to maintain the antiviral state in the gut. This review describes the recent understanding on the immune evasion strategies of porcine enteric coronaviruses and the role of different types of IFNs for intestinal antiviral innate immunity. Copyright © 2016 Elsevier B.V. All rights reserved.

  10. 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.

  11. 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.

    2015-01-01

    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 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

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

    International Nuclear Information System (INIS)

    Stephen, E. R.; Wong, J.; Van Loon, D.

    2007-01-01

    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)

  13. In vitro antiviral activities of Caesalpinia pulcherrima and its related flavonoids.

    Science.gov (United States)

    Chiang, L C; Chiang, W; Liu, M C; Lin, C C

    2003-08-01

    The aim of this study was to search for new antiviral agents from Chinese herbal medicine. Pure flavonoids and aqueous extracts of Caesalpinia pulcherrima Swartz were used in experiments to test their influence on a series of viruses, namely herpesviruses (HSV-1, HSV-2) and adenoviruses (ADV-3, ADV-8, ADV-11). The EC50 was defined as the concentration required to achieve 50% protection against virus-induced cytopathic effects, and the selectivity index (SI) was determined as the ratio of CC50 (concentration of 50% cellular cytotoxicity) to EC50. Results showed that aqueous extracts of C. pulcherrima and its related quercetin possessed a broad-spectrum antiviral activity. Among them, the strongest activities against ADV-8 were fruit and seed (EC50 = 41.2 mg/l, SI = 83.2), stem and leaf (EC50 = 61.8 mg/l, SI = 52.1) and flower (EC50 = 177.9 mg/l, SI = 15.5), whereas quercetin possessed the strongest anti-ADV-3 activity (EC50 = 24.3 mg/l, SI = 20.4). In conclusion, some compounds of C. pulcherrima which possess antiviral activities may be derived from the flavonoid of quercetin. The mode of action of quercetin against HSV-1 and ADV-3 was found to be at the early stage of multiplication and with SI values greater than 20, suggesting the potential use of this compound for treatment of the infection caused by these two viruses.

  14. Systems-Biology Approaches to Discover Anti-Viral Effectors of the Human Innate Immune Response

    Directory of Open Access Journals (Sweden)

    Andreas F.R. Sommer

    2011-07-01

    Full Text Available Virus infections elicit an immediate innate response involving antiviral factors. The activities of some of these factors are, in turn, blocked by viral countermeasures. The ensuing battle between the host and the viruses is crucial for determining whether the virus establishes a foothold and/or induces adaptive immune responses. A comprehensive systems-level understanding of the repertoire of anti-viral effectors in the context of these immediate virus-host responses would provide significant advantages in devising novel strategies to interfere with the initial establishment of infections. Recent efforts to identify cellular factors in a comprehensive and unbiased manner, using genome-wide siRNA screens and other systems biology “omics” methodologies, have revealed several potential anti-viral effectors for viruses like Human immunodeficiency virus type 1 (HIV-1, Hepatitis C virus (HCV, West Nile virus (WNV, and influenza virus. This review describes the discovery of novel viral restriction factors and discusses how the integration of different methods in systems biology can be used to more comprehensively identify the intimate interactions of viruses and the cellular innate resistance.

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

    Science.gov (United States)

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

    2016-06-01

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

  16. Topoisomerase 1 Inhibition Promotes Cyclic GMP-AMP Synthase-Dependent Antiviral Responses

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    Geneviève Pèépin

    2017-10-01

    Full Text Available Inflammatory responses, while essential for pathogen clearance, can also be deleterious to the host. Chemical inhibition of topoisomerase 1 (Top1 by low-dose camptothecin (CPT can suppress transcriptional induction of antiviral and inflammatory genes and protect animals from excessive and damaging inflammatory responses. We describe the unexpected finding that minor DNA damage from topoisomerase 1 inhibition with low-dose CPT can trigger a strong antiviral immune response through cyclic GMP-AMP synthase (cGAS detection of cytoplasmic DNA. This argues against CPT having only anti-inflammatory activity. Furthermore, expression of the simian virus 40 (SV40 large T antigen was paramount to the proinflammatory antiviral activity of CPT, as it potentiated cytoplasmic DNA leakage and subsequent cGAS recruitment in human and mouse cell lines. This work suggests that the capacity of Top1 inhibitors to blunt inflammatory responses can be counteracted by viral oncogenes and that this should be taken into account for their therapeutic development.

  17. Solute Carrier NTCP Regulates Innate Antiviral Immune Responses Targeting Hepatitis C Virus Infection of Hepatocytes.

    Science.gov (United States)

    Verrier, Eloi R; Colpitts, Che C; Bach, Charlotte; Heydmann, Laura; Zona, Laetitia; Xiao, Fei; Thumann, Christine; Crouchet, Emilie; Gaudin, Raphaël; Sureau, Camille; Cosset, François-Loïc; McKeating, Jane A; Pessaux, Patrick; Hoshida, Yujin; Schuster, Catherine; Zeisel, Mirjam B; Baumert, Thomas F

    2016-10-25

    Chronic hepatitis B, C, and D virus (HBV, HCV, and HDV) infections are the leading causes of liver disease and cancer worldwide. Recently, the solute carrier and sodium taurocholate co-transporter NTCP has been identified as a receptor for HBV and HDV. Here, we uncover NTCP as a host factor regulating HCV infection. Using gain- and loss-of-function studies, we show that NTCP mediates HCV infection of hepatocytes and is relevant for cell-to-cell transmission. NTCP regulates HCV infection by augmenting the bile-acid-mediated repression of interferon-stimulated genes (ISGs), including IFITM3. In conclusion, our results uncover NTCP as a mediator of innate antiviral immune responses in the liver, and they establish a role for NTCP in the infection process of multiple viruses via distinct mechanisms. Collectively, our findings suggest a role for solute carriers in the regulation of innate antiviral responses, and they have potential implications for virus-host interactions and antiviral therapies. Copyright © 2016 The Author(s). Published by Elsevier Inc. All rights reserved.

  18. Antiviral activity against human immunodeficiency virus-1 in vitro by myristoylated-peptide from Heliothis virescens

    International Nuclear Information System (INIS)

    Ourth, Donald D.

    2004-01-01

    An insect antiviral compound was purified from Heliothis virescens larval hemolymph by gel-filtration high pressure liquid chromatography (HPLC) and C-18 reverse-phase HPLC and its structure was determined by mass spectrometry. The antiviral compound is an N-myristoylated-peptide containing six amino acids with calculated molecular weight of 916 Da. The N-terminus contains the fatty acid myristoyl, and the C-terminus contains histidine with two methyl groups giving the histidine a permanent positive charge. The remainder of the compound is essentially non-polar. The structure of the compound corresponds with the 'myristate plus basic' motif expressed by certain viral proteins in their binding to the cytoplasmic side of the plasma membrane to initiate viral assembly and budding from a host cell. The insect antiviral compound may inhibit viral assembly and/or budding of viruses from host cells that could include the human immunodeficiency virus-1 (HIV-1) and herpes simplex virus-1 that use this motif for exit from a host cell. Using the formazan assay, the myristoylated-peptide was effective against HIV-1, with a nine times increase in the viability and protection in vitro of treated CEM-SS cells when compared with infected but untreated control cells

  19. Solute Carrier NTCP Regulates Innate Antiviral Immune Responses Targeting Hepatitis C Virus Infection of Hepatocytes

    Directory of Open Access Journals (Sweden)

    Eloi R. Verrier

    2016-10-01

    Full Text Available Chronic hepatitis B, C, and D virus (HBV, HCV, and HDV infections are the leading causes of liver disease and cancer worldwide. Recently, the solute carrier and sodium taurocholate co-transporter NTCP has been identified as a receptor for HBV and HDV. Here, we uncover NTCP as a host factor regulating HCV infection. Using gain- and loss-of-function studies, we show that NTCP mediates HCV infection of hepatocytes and is relevant for cell-to-cell transmission. NTCP regulates HCV infection by augmenting the bile-acid-mediated repression of interferon-stimulated genes (ISGs, including IFITM3. In conclusion, our results uncover NTCP as a mediator of innate antiviral immune responses in the liver, and they establish a role for NTCP in the infection process of multiple viruses via distinct mechanisms. Collectively, our findings suggest a role for solute carriers in the regulation of innate antiviral responses, and they have potential implications for virus-host interactions and antiviral therapies.

  20. Antiviral activity of some Tunisian medicinal plants against Herpes simplex virus type 1.

    Science.gov (United States)

    Sassi, A Ben; Harzallah-Skhiri, F; Bourgougnon, N; Aouni, M

    2008-01-10

    Fifteen species of Tunisian traditional medicinal plants, belonging to 10 families, were selected for this study. They were Inula viscosa (L.) Ait and Reichardia tingitana (L.) Roth ssp. discolor (Pom.) Batt. (Asteraceae), Mesembryanthemum cristallinum L. and M. nodiflorum L. (Aizoaceae), Arthrocnemum indicum (Willd.) Moq., Atriplex inflata Muell., A. parvifolia Lowe var. ifiniensis (Caball) Maire, and Salicornia fruticosa L. (Chenopodiaceae), Cistus monspeliensis L. (Cistaceae), Juniperus phoenicea L. (Cupressaceae), Erica multiflora L. (Ericaceae), Frankenia pulverulenta L. (Frankeniaceae), Hypericum crispum L. (Hypericaceae), Plantago coronopus L. ssp. eu-coronopus Pilger var. vulgaris G.G. (Plantaginaceae) and Zygophyllum album L. (Zygophyllaceae). Fifty extracts prepared from those plants were screened in order to assay their antiviral activity against Herpes simplex virus type 1 (HSV-1), using neutral red incorporation. Extracts from eight plants among these 15 showed some degree of antiviral activity, while the methanolic extract of E. multiflora was highly active with EC(50) of 132.6 microg mL(-1). These results corroborate that medicinal plants from Tunisia can be a rich source of potential antiviral compounds.

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

    Science.gov (United States)

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

    2015-06-25

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

  2. Quantitative autoradiographic mapping of herpes simplex virus encephalitis with a radiolabeled antiviral drug

    International Nuclear Information System (INIS)

    Saito, Y.; Price, R.W.; Rottenberg, D.A.; Fox, J.J.; Su, T.L.; Watanabe, K.A.; Philips, F.S.

    1982-01-01

    2'-Fluoro-5-methyl-1-ν-D-arabinosyluracil (FMAU) labeled with carbon-14 was used to image herpes simplex virus type 1-infected regions of rat brain by quantitative autoradiography. FMAU is a potent antiviral pyrimidine nucleoside which is selectively phosphorylated by virus-coded thymidine kinase. When the labeled FMAU was administered 6 hours before the rats were killed, the selective uptake and concentration of the drug and its metabolites by infected cells (defined by immunoperoxidase staining of viral antigens) allowed quantitative definition and mapping of HSV-1-infected structures in autoradiograms of brain sections. These results shown that quantitative autoradiography can be used to characterize the local metabolism of antiviral drugs by infected cells in vivo. They also suggest that the selective uptake of drugs that exploit viral thymidine kinase for their antiviral effect can, by appropriate labeling, be used in conjunction with clinical neuroimaging techniques to define infected regions of human brain, thereby providing a new approach to the diagnosis of herpes encephalitis in man

  3. Antiviral Ability of Kalanchoe gracilis Leaf Extract against Enterovirus 71 and Coxsackievirus A16

    Science.gov (United States)

    Wang, Ching-Ying; Huang, Shun-Chueh; Zhang, Yongjun; Lai, Zhen-Rung; Kung, Szu-Hao; Chang, Yuan-Shiun; Lin, Cheng-Wen

    2012-01-01

    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. PMID:22666293

  4. Chemokines cooperate with TNF to provide protective anti-viral immunity and to enhance inflammation.

    Science.gov (United States)

    Alejo, Alí; Ruiz-Argüello, M Begoña; Pontejo, Sergio M; Fernández de Marco, María Del Mar; Saraiva, Margarida; Hernáez, Bruno; Alcamí, Antonio

    2018-05-03

    The role of cytokines and chemokines in anti-viral defense has been demonstrated, but their relative contribution to protective anti-viral responses in vivo is not fully understood. Cytokine response modifier D (CrmD) is a secreted receptor for TNF and lymphotoxin containing the smallpox virus-encoded chemokine receptor (SECRET) domain and is expressed by ectromelia virus, the causative agent of the smallpox-like disease mousepox. Here we show that CrmD is an essential virulence factor that controls natural killer cell activation and allows progression of fatal mousepox, and demonstrate that both SECRET and TNF binding domains are required for full CrmD activity. Vaccination with recombinant CrmD protects animals from lethal mousepox. These results indicate that a specific set of chemokines enhance the inflammatory and protective anti-viral responses mediated by TNF and lymphotoxin, and illustrate how viruses optimize anti-TNF strategies with the addition of a chemokine binding domain as soluble decoy receptors.

  5. AGO/RISC-mediated antiviral RNA silencing in a plant in vitro system.

    Science.gov (United States)

    Schuck, Jana; Gursinsky, Torsten; Pantaleo, Vitantonio; Burgyán, Jozsef; Behrens, Sven-Erik

    2013-05-01

    AGO/RISC-mediated antiviral RNA silencing, an important component of the plant's immune response against RNA virus infections, was recapitulated in vitro. Cytoplasmic extracts of tobacco protoplasts were applied that supported Tombusvirus RNA replication, as well as the formation of RNA-induced silencing complexes (RISC) that could be functionally reconstituted with various plant ARGONAUTE (AGO) proteins. For example, when RISC containing AGO1, 2, 3 or 5 were programmed with exogenous siRNAs that specifically targeted the viral RNA, endonucleolytic cleavages occurred and viral replication was inhibited. Antiviral RNA silencing was disabled by the viral silencing suppressor p19 when this was present early during RISC formation. Notably, with replicating viral RNA, only (+)RNA molecules were accessible to RISC, whereas (-)RNA replication intermediates were not. The vulnerability of viral RNAs to RISC activity also depended on the RNA structure of the target sequence. This was most evident when we characterized viral siRNAs (vsiRNAs) that were particularly effective in silencing with AGO1- or AGO2/RISC. These vsiRNAs targeted similar sites, suggesting that accessible parts of the viral (+)RNA may be collectively attacked by different AGO/RISC. The in vitro system was, hence, established as a valuable tool to define and characterize individual molecular determinants of antiviral RNA silencing.

  6. An antiviral RISC isolated from Tobacco rattle virus-infected plants.

    Science.gov (United States)

    Ciomperlik, Jessica J; Omarov, Rustem T; Scholthof, Herman B

    2011-03-30

    The RNAi model predicts that during antiviral defense a RNA-induced silencing complex (RISC) is programmed with viral short-interfering RNAs (siRNAs) to target the cognate viral RNA for degradation. We show that infection of Nicotiana benthamiana with Tobacco rattle virus (TRV) activates an antiviral nuclease that specifically cleaves TRV RNA in vitro. In agreement with known RISC properties, the nuclease activity was inhibited by NaCl and EDTA and stimulated by divalent metal cations; a novel property was its preferential targeting of elongated RNA molecules. Intriguingly, the specificity of the TRV RISC could be reprogrammed by exogenous addition of RNA (containing siRNAs) from plants infected with an unrelated virus, resulting in a newly acquired ability of RISC to target this heterologous genome in vitro. Evidently the virus-specific nuclease complex from N. benthamiana represents a genuine RISC that functions as a readily employable and reprogrammable antiviral defense unit. Copyright © 2011 Elsevier Inc. All rights reserved.

  7. A heritable antiviral RNAi response limits Orsay virus infection in Caenorhabditis elegans N2.

    Directory of Open Access Journals (Sweden)

    Mark G Sterken

    Full Text Available Orsay virus (OrV is the first virus known to be able to complete a full infection cycle in the model nematode species Caenorhabditis elegans. OrV is transmitted horizontally and its infection is limited by antiviral RNA interference (RNAi. However, we have no insight into the kinetics of OrV replication in C. elegans. We developed an assay that infects worms in liquid, allowing precise monitoring of the infection. The assay revealed a dual role for the RNAi response in limiting Orsay virus infection in C. elegans. Firstly, it limits the progression of the initial infection at the step of recognition of dsRNA. Secondly, it provides an inherited protection against infection in the offspring. This establishes the heritable RNAi response as anti-viral mechanism during OrV infections in C. elegans. Our results further illustrate that the inheritance of the anti-viral response is important in controlling the infection in the canonical wild type Bristol N2. The OrV replication kinetics were established throughout the worm life-cycle, setting a standard for further quantitative assays with the OrV-C. elegans infection model.

  8. Synthesis and antiviral activities of a novel class of thioflavone and flavonoid analogues

    Directory of Open Access Journals (Sweden)

    Dajun Zhang

    2012-12-01

    Full Text Available A novel class of thioflavone and flavonoid derivatives has been prepared and their antiviral activities against enterovirus 71 (EV71 and the coxsackievirus B3 (CVB3 and B6 (CVB6 were evaluated. Compounds 7d and 9b showed potent antiviral activities against EV71 with IC50 values of 8.27 and 5.48 μM, respectively. Compound 7f, which has been synthesized for the first time in this work, showed the highest level of inhibitory activity against both CVB3 and CVB6 with an IC50 value of 0.62 and 0.87 μM. Compounds 4b, 7a, 9c and 9e also showed strong inhibitory activities against both the CVB3 and CVB6 at low concentrations (IC50=1.42−7.15 μM, whereas compounds 4d, 7c, 7e and 7g showed strong activity against CVB6 (IC50=2.91–3.77 μM together with low levels of activity against CVB3. Compound 7d exhibited stronger inhibitory activity against CVB3 (IC50=6.44 μM than CVB6 (IC50>8.29 μM. The thioflavone derivatives 7a, 7c, 7d, 7e, 7f and 7g, represent a new class of lead compounds for the development of novel antiviral agents.

  9. Antiviral Therapy by HIV-1 Broadly Neutralizing and Inhibitory Antibodies

    Directory of Open Access Journals (Sweden)

    Zhiqing Zhang

    2016-11-01

    Full Text Available Human immunodeficiency virus type 1 (HIV-1 infection causes acquired immune deficiency syndrome (AIDS, a global epidemic for more than three decades. HIV-1 replication is primarily controlled through antiretroviral therapy (ART but this treatment does not cure HIV-1 infection. Furthermore, there is increasing viral resistance to ART, and side effects associated with long-term therapy. Consequently, there is a need of alternative candidates for HIV-1 prevention and therapy. Recent advances have discovered multiple broadly neutralizing antibodies against HIV-1. In this review, we describe the key epitopes on the HIV-1 Env protein and the reciprocal broadly neutralizing antibodies, and discuss the ongoing clinical trials of broadly neutralizing and inhibitory antibody therapy as well as antibody combinations, bispecific antibodies, and methods that improve therapeutic efficacy by combining broadly neutralizing antibodies (bNAbs with latency reversing agents. Compared with ART, HIV-1 therapeutics that incorporate these broadly neutralizing and inhibitory antibodies offer the advantage of decreasing virus load and clearing infected cells, which is a promising prospect in HIV-1 prevention and treatment.

  10. In vitro inhibition of canine distemper virus by flavonoids and phenolic acids: implications of structural differences for antiviral design.

    Science.gov (United States)

    Carvalho, O V; Botelho, C V; Ferreira, C G T; Ferreira, H C C; Santos, M R; Diaz, M A N; Oliveira, T T; Soares-Martins, J A P; Almeida, M R; Silva, A

    2013-10-01

    Infection caused by canine distemper virus (CDV) is a highly contagious disease with high incidence and lethality in the canine population. Antiviral activity of flavonoids quercetin, morin, rutin and hesperidin, and phenolic cinnamic, trans-cinnamic and ferulic acids were evaluated in vitro against the CDV using the time of addition assay to determine which step of the viral replicative cycle was affected. All flavonoids displayed great viral inhibition when they were added at the times 0 (adsorption) and 1h (penetration) of the viral replicative cycle. Both quercetin and hesperidin presented antiviral activity at the time 2h (intracellular). In the other hand, cinnamic acid showed antiviral activity at the times 0 and 2h while trans-cinnamic acid showed antiviral effect at the times -1h (pre-treatment) and 0 h. Ferulic acid inhibited CDV replicative cycle at the times 0 and 1h. Our study revealed promising candidates to be considered in the treatment of CDV. Structural differences among compounds and correlation to their antiviral activity were also explored. Our analysis suggest that these compounds could be useful in order to design new antiviral drugs against CDV as well as other viruses of great meaning in veterinary medicine. Copyright © 2013 Elsevier Ltd. All rights reserved.

  11. Liver metastasis from neuroendocrine carcinoma after the use of the new direct-action antivirals against hepatitis C virus in a patient with past history of hepatocellular carcinoma

    Directory of Open Access Journals (Sweden)

    María Caldas

    Full Text Available The use of the new direct-action antivirals against hepatitis C virus provides very high viral eradication rates. However, various recently published articles recommend caution with their use after the appearance of some cases of de novo tumors (originated in hepatic and extra-hepatic locations and a possible shorter time period of recurrence of hepatocellular carcinomas previously treated with surgery or loco-regional therapies. The sudden drop of the number of natural killer cells secondary to the use of these new medicines has been suggested as one of the possible mechanisms responsible for this process. However, due to the controversy concerning this subject and the absence of long-term follow-up studies in clinical practice, caution is needed before definitive conclusions are settled. We present the case report of a patient diagnosed of chronic liver disease secondary to hepatitis C virus infection and a past history of hepatocellular carcinoma in complete remission after radiofrequency ablation. He was treated with the new direct-action antivirals reaching sustained viral response. Six months later, the patient was diagnosed with liver metastasis from a small-cell neuroendocrine tumor of unknown primary site.

  12. Identification and expression analysis of irak1 gene in common carp Cyprinus carpio L.: indications for a role of antibacterial and antiviral immunity.

    Science.gov (United States)

    Shan, S J; Liu, D Z; Wang, L; Zhu, Y Y; Zhang, F M; Li, T; An, L G; Yang, G W

    2015-08-01

    In this study, the full-length complementary (c)DNA of interleukin-1 receptor-associated kinase 1 gene (irak1) was cloned from common carp Cyprinus carpio. The complete open reading frame of irak1 contained 2109 bp encoding a protein of 702 amino acid residues that comprised a death domain, a ProST region, a serine-threonine-specific protein kinase catalytic domain and a C-terminal domain. The amino-acid sequence of C. carpio Irak1 protein shared sequence homology with grass carp Ctenopharyngodon idellus (84.5%). The phylogenetic tree of IRAKs separated the polypeptides into four clades, comprising IRAK1s, IRAK2s, IRAK3s and IRAK4s. Cyprinus carpio Irak1 fell into the cluster with previously reported IRAK1s including teleost Irak1s. The irak1 gene was highly expressed in gills, followed by brain, skin, hindgut, buccal epithelium, spleen, foregut, head kidney and liver, and was expressed at lowest levels in gonad and muscle. The irak1 messenger (m)RNA expression was up-regulated in liver, spleen, head kidney, foregut, hindgut, gills and skin after stimulation with Vibrio anguillarum and poly(I:C), and significantly high up-regulated expression was observed in liver and spleen. These results implied that irak1 might participate in antibacterial and antiviral innate immunity. These findings gave the indications that irak1 may participate in antibacterial and antiviral immunity. © 2015 The Fisheries Society of the British Isles.

  13. Glycosaminoglycans mediate retention of the poxvirus type I interferon binding protein at the cell surface to locally block interferon antiviral responses

    Science.gov (United States)

    Montanuy, Imma; Alejo, Ali; Alcami, Antonio

    2011-01-01

    Eradication of smallpox was accomplished 30 yr ago, but poxviral infections still represent a public health concern due to the potential release of variola virus or the emergence of zoonotic poxviruses, such as monkeypox virus. A critical determinant of poxvirus virulence is the inhibition of interferons (IFNs) by the virus-encoded type I IFN-binding protein (IFNα/βBP). This immunomodulatory protein is secreted and has the unique property of interacting with the cell surface in order to prevent IFN-mediated antiviral responses. However, the mechanism of its attachment to the cell surface remains unknown. Using surface plasmon resonance and cell-binding assays, we report that the IFNα/βBP from vaccinia virus, the smallpox vaccine, interacts with cell surface glycosaminoglycans (GAGs). Analysis of the contribution of different regions of the protein to cell surface binding demonstrated that clusters of basic residues in the first immunoglobulin domain mediate GAG interactions. Furthermore, mutation of the GAG-interaction motifs does not affect its IFN-binding and -blocking capacity. Functional conservation of GAG-binding sites is demonstrated for the IFNα/βBP from variola and monkeypox viruses, extending our understanding of immune modulation by the most virulent human poxviruses. These results are relevant for the design of improved vaccines and intervention strategies.—Montanuy, I., Alejo, A., Alcami, A. Glycosaminoglycans mediate retention of the poxvirus type I interferon binding protein at the cell surface to locally block interferon antiviral responses. PMID:21372110

  14. Airplane radiation dose decrease during a strong Forbush decrease

    Czech Academy of Sciences Publication Activity Database

    Spurný, František; Kudela, K.; Dachev, T.

    2004-01-01

    Roč. 2, S05001 (2004), s. 1-4 ISSN 1542-7390 Grant - others:EC project(XE) FIGM-CT2000-00068 Institutional research plan: CEZ:AV0Z1048901 Keywords : airplane dose * Forbush decrease * cosmic rays Subject RIV: BG - Nuclear, Atomic and Molecular Physics, Colliders

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

    Science.gov (United States)

    Zorofchian Moghadamtousi, Soheil; Abdul Kadir, Habsah; Hassandarvish, Pouya; Tajik, Hassan; Abubakar, Sazaly; Zandi, Keivan

    2014-01-01

    Curcuma longa L. (Zingiberaceae family) and its polyphenolic compound curcumin have been subjected to a variety of antimicrobial investigations due to extensive traditional uses and low side effects. Antimicrobial activities for curcumin and rhizome extract of C. longa against different bacteria, viruses, fungi, and parasites have been reported. The promising results for antimicrobial activity of curcumin made it a good candidate to enhance the inhibitory effect of existing antimicrobial agents through synergism. Indeed, different investigations have been done to increase the antimicrobial activity of curcumin, including synthesis of different chemical derivatives to increase its water solubility as well ass cell up take of curcumin. This review aims to summarize previous antimicrobial studies of curcumin towards its application in the future studies as a natural antimicrobial agent. PMID:24877064

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

    Directory of Open Access Journals (Sweden)

    Soheil Zorofchian Moghadamtousi

    2014-01-01

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

  17. Considerably decreased risk of cardiovascular disease with combined reductions in HbA1c, blood pressure and blood lipids in type 2 diabetes: Report from the Swedish National Diabetes Register.

    Science.gov (United States)

    Eeg-Olofsson, Katarina; Zethelius, Björn; Gudbjörnsdottir, Soffia; Eliasson, Björn; Svensson, Ann-Marie; Cederholm, Jan

    2016-07-01

    Assess the effect of risk factors changes on risk for cardiovascular disease and mortality in patients with type 2 diabetes selected from the Swedish National Diabetes Register. Observational study of 13,477 females and males aged 30-75 years, with baseline HbA1c 41-67 mmol/mol, systolic blood pressure 122-154 mmHg and ratio non-HDL:HDL 1.7-4.1, followed for mean 6.5 years until 2012. Four groups were created: a reference group (n = 6757) with increasing final versus baseline HbA1c, systolic blood pressure and non-HDL:HDL cholesterol during the study period, and three groups with decreasing HbA1c (n = 1925), HbA1c and systolic blood pressure (n = 2050) or HbA1c and systolic blood pressure and non-HDL:HDL (n = 2745). Relative risk reduction for fatal/nonfatal cardiovascular disease was 35% with decrease in HbA1c only (mean 6 to final 49 mmol/mol), 56% with decrease in HbA1c and systolic blood pressure (mean 12 to final 128 mmHg) and 75% with combined decreases in HbA1c, systolic blood pressure and non-HDL:HDL (mean 0.8 to final 2.1), all p < 0.001 adjusting for clinical characteristics, other risk factors, treatments and previous cardiovascular disease. Similar risk reductions were found for fatal/nonfatal coronary heart disease, fatal cardiovascular disease, all-cause mortality and also in a subgroup of 3038 patients with albuminuria. Considerable risk reductions for cardiovascular disease and mortality were seen with combined long-term risk factor improvement. © The Author(s) 2016.

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

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    Blasi Elisabetta

    2011-03-01

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

  19. EVALUATION OF EFFECTIVENESS OF ANTIVIRAL THERAPY FOR CHRONIC HEPATITIS C, CAUSED BY HCV GENOTYPE 6

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    D. A. Lioznov

    2017-01-01

    Full Text Available Objectives: Evaluating the effectiveness of 2 therapeutic schemes for chronic hepatitis C (genotype 6 which combined sofosbuvir and ribavirin, one of them also included pegylated interferon. Materials and methods: The study included 110 patients with chronic hepatitis C (genotype 6, who have undergone antiviral therapy (HTP in Hepatology Clinic inHo Chi Minh City,Vietnamfrom November 2015 to July 2016. 24 patients were treated by Pegylated interferon alfa-2a, ribavirin and sofosbuvir for 12 weeks, 86 patients – by sofosbuvir and ribavirin for 24 weeks. Non-interferon regimen was administered primarily to patients with contraindications to the use of interferon. To monitor the effectiveness of antiviral therapy, quantification of HCV RNA in serum was performed by PCR prior to treatment, at 4th, 12th or 24th week (depending on the observation group from the starting of treatment and at 12th, 24th week after completion of treatment. Results: All patients, who were treated with pegylated interferon, ribavirin and sofosbuvir, completed the full course of treatment and 100% of them are registered with sustained virological response at 12th and 24th week after the end of antiviral therapy (SVR-12 and SVR-24, respectively. In the group of patients, who treated with ribavirin and sofosbuvir, 97,7% of patients completed full course of treatment (SVR-12 was registered in 93% of patients, and SVR-24 – in 91,9% of patients. Of 75 patients without a history of HCC, SVR24 was registered in 74 people (98,7%, of 11 patients with HCC – in 5 patients (45,5%. SVR-24 was registered in 98% of patients with cirrhosis (F4 without HCC. Conclusion: The results can serve as a justification for the use of these schemes of antiviral therapy for special groups of patients and/or conditions when it is impossible to follow the latest recommendations, which will help to expand the access of patients to effective antiviral therapy for chronic hepatitis C.

  20. Decrease in Self-Reported Tanning Frequency among Utah Teens following the Passage of Utah Senate Bill 41: An Analysis of the Effects of Youth-Access Restriction Laws on Tanning Behaviors

    OpenAIRE

    Simmons, Rebecca G.; Smith, Kristi; Balough, Meghan; Friedrichs, Michael

    2014-01-01

    Introduction. Adolescent use of indoor tanning facilities is associated with an increased risk in later development of melanoma skin cancers. States that have imposed age restrictions on access to indoor tanning generally show lower self-reported rates of indoor tanning than states with no restrictions, but currently no studies have assessed indoor tanning use before and after such restrictions. Methods. In 2013, we compared self-reported indoor tanning data collected in the Prevention Needs ...