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Sample records for antiviral drugs advisory

  1. Antiviral Drugs: Seasonal Flu

    Centers for Disease Control (CDC) Podcasts

    2010-09-29

    In this podcast, Dr. Joe Bresee explains the nature of antiviral drugs and how they are used for seasonal flu.  Created: 9/29/2010 by National Center for Immunization and Respiratory Diseases (NCIRD).   Date Released: 9/29/2010.

  2. Emerging antiviral drugs.

    Science.gov (United States)

    De Clercq, Erik

    2008-09-01

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

  3. Emerging antiviral drugs.

    Science.gov (United States)

    De Clercq, Erik

    2008-09-01

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

  4. Antiviral Drug Research Proposal Activity

    Directory of Open Access Journals (Sweden)

    Lisa Injaian

    2011-03-01

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

  5. Influenza Round Table: Antiviral Drugs

    Centers for Disease Control (CDC) Podcasts

    2009-11-04

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

  6. Can antiviral drugs contain pandemic influenza transmission?

    Directory of Open Access Journals (Sweden)

    Niels G Becker

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

  7. What You Should Know about Flu Antiviral Drugs

    Science.gov (United States)

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

  8. Vaccines and Antiviral Drugs in Pandemic Preparedness

    OpenAIRE

    Arnold S. Monto

    2006-01-01

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

  9. Antiviral Drug Resistance: Mechanisms and Clinical Implications

    OpenAIRE

    Strasfeld, Lynne; Chou, Sunwen

    2010-01-01

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

  10. Drug delivery approaches of an antiviral drug: A comprehensive review

    Directory of Open Access Journals (Sweden)

    Ramya Devi Durai

    2015-01-01

    Full Text Available The guanine derivative antiviral drug acyclovir (ACV is one of the oldest molecules laying successful market until date, being commercially available in various dosage forms for oral, topical and parenteral administrations. Clinical application of this drug is superior to new antiviral agents due to its potential values such as suppression of recurrence, safety profile, minimal drug interactions, and being inexpensive. ACV is slightly water-soluble, less permeable and poorly bioavailable, yet more potential antiviral molecule, the physicochemical modifications and novel dosage form approaches resulted with more than 100 research works within a decade. The survey of literature showed enormous reports on ACV formulation development, which includes modified tablets, particulate drug delivery, vesicular drug delivery, polymeric nanoparticles, bioadhesive systems, floating dosage forms, in situ gelling systems, transdermal delivery, implantable systems, emulsified dosage forms, polymeric films/patches, etc. As the drug could be administered via multiple routes for effective site targeted action at various doses, and attracted the attention of many researches, the review of the current approaches for the delivery of ACV could be more beneficial for the new scientists. This paper is a review of recent researches highlighting the development of newer techniques and novel dosage forms of ACV for better therapeutic efficacy, which were aimed at enhancing its solubility, permeability and bioavailability.

  11. HIV/HCV Antiviral Drug Interactions in the Era of Direct-acting Antivirals

    Science.gov (United States)

    Rice, Donald P.; Faragon, John J.; Banks, Sarah; Chirch, Lisa M.

    2016-01-01

    Abstract Therapy for human immunodeficiency virus (HIV) and chronic hepatitis C has evolved over the past decade, resulting in better control of infection and clinical outcomes; however, drug-drug interactions remain a significant hazard. Joint recommendations from the American Association for the Study of Liver Diseases and the Infectious Diseases Society of America regarding drug-drug interactions between HIV antiretroviral agents and direct-acting antiviral agents for treatment of hepatitis C virus (HCV) infection are reviewed here. This review is oriented to facilitate appropriate selection of an antiviral therapy regimen for HCV infection based on the choice of antiretroviral therapy being administered and, if necessary, switching antiretroviral regimens. PMID:27777891

  12. Hepatitis C Virus and Antiviral Drug Resistance

    Science.gov (United States)

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

    2016-01-01

    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. PMID:27784846

  13. 75 FR 10490 - Joint Meeting of the Arthritis Drugs Advisory Committee and the Drug Safety and Risk Management...

    Science.gov (United States)

    2010-03-08

    ... the Drug Safety and Risk Management Advisory Committee; Notice of Meeting AGENCY: Food and Drug...: Arthritis Drugs Advisory Committee and the Drug Safety and Risk Management Advisory Committee....

  14. Antiviral drug resistance of herpes simplex virus

    NARCIS (Netherlands)

    Stranska, Ruzena

    2004-01-01

    Infections with herpes simplex virus (HSV) usually have an asymptomatic or benign course. However, severe infections do occur, particularly in HIV/AIDS patients or transplant recipients, and may be life-threatening unless adequate antiviral therapy is given. Since its introduction in the early 1980

  15. The treatment of influenza with antiviral drugs

    OpenAIRE

    Stiver, Grant

    2003-01-01

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

  16. H1N1 Flu and Antiviral Drugs

    Centers for Disease Control (CDC) Podcasts

    2009-05-02

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

  17. INVESTMENT IN ANTIVIRAL DRUGS : A REAL OPTIONS APPROACH

    NARCIS (Netherlands)

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

    2010-01-01

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

  18. Flu Resistance to Antiviral Drug in North Carolina

    Centers for Disease Control (CDC) Podcasts

    2011-12-19

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

  19. Approved Antiviral Drugs over the Past 50 Years.

    Science.gov (United States)

    De Clercq, Erik; Li, Guangdi

    2016-07-01

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

  20. Antiviral drug discovery against SARS-CoV.

    Science.gov (United States)

    Wu, Yu-Shan; Lin, Wen-Hsing; Hsu, John T-A; Hsieh, Hsing-Pang

    2006-01-01

    Severe Acute Respiratory Syndrome (SARS) is a life-threatening infectious disease caused by SARS-CoV. In the 2003 outbreak, it infected more than 8,000 people worldwide and claimed the lives of more than 900 victims. The high mortality rate resulted, at least in part, from the absence of definitive treatment protocols or therapeutic agents. Although the virus spreading has been contained, due preparedness and planning, including the successful development of antiviral drugs against SARS-CoV, is necessary for possible reappearance of SARS. In this review, we have discussed currently available strategies for antiviral drug discovery and how these technologies have been utilized to identify potential antiviral agents for the inhibition of SARS-CoV replication. Moreover, progress in the drug development based on different molecular targets is also summarized, including 1) Compounds that block the S protein-ACE2-mediated viral entry; 2) Compounds targeting SARS-CoV M(pro); 3) Compounds targeting papain-like protease 2 (PLP2); 4) Compounds targeting SARS-CoV RdRp; 5) Compounds targeting SARS-CoV helicase; 6) Active compounds with unspecified targets; and 7) Research on siRNA. This review aims to provide a comprehensive account of drug discovery on SARS. The experiences with the SARS outbreak and drug discovery would certainly be an important lesson for the drug development for any new viral outbreaks that may emerge in the future.

  1. HIV antiviral drug resistance: patient comprehension.

    Science.gov (United States)

    Racey, C Sarai; Zhang, Wendy; Brandson, Eirikka K; Fernandes, Kimberly A; Tzemis, Despina; Harrigan, P Richard; Montaner, Julio S G; Barrios, Rolando; Toy, Junine; Hogg, Robert S

    2010-07-01

    A patient's understanding and use of healthcare information can affect their decisions regarding treatment. Better patient understanding about HIV resistance may improve adherence to therapy, decrease population viral load and extend the use of first-line HIV therapies. We examined knowledge of developing HIV resistance and explored treatment outcomes in a cohort of HIV+ persons on highly active antiretroviral therapy (HAART). The longitudinal investigations into supportive and ancillary health services (LISA) cohort is a prospective study of HIV+ persons on HAART. A comprehensive interviewer-administrated survey collected socio-demographic variables. Drug resistance knowledge was determined using a three-part definition. Clinical markers were collected through linkage with the Drug Treatment Program (DTP) at the British Columbia Centre for Excellence in HIV/AIDS. Categorical variables were compared using Fisher's Exact Test and continuous variables using the Wilcoxon rank-sum test. Proportional odds logistic regression was performed for the adjusted multivariable analysis. Of 457 LISA participants, less than 4% completely defined HIV resistance and 20% reported that they had not discussed resistance with their physician. Overall, 61% of the cohort is >or=95% adherent based on prescription refills. Owing to small numbers pooling was preformed for analyses. The model showed that being younger (OR=0.97, 95% CI: 0.95-0.99), having greater than high school education (OR=1.64, 95% CI: 1.07-2.51), discussing medication with physicians (OR=3.67, 95% CI: 1.76-7.64), having high provider trust (OR=1.02, 95% CI: 1.01-1.03), and receiving one-to-one counseling by a pharmacist (OR=2.14, 95% CI: 1.41-3.24) are predictive of a complete or partial definition of HIV resistance. The probability of completely defining HIV resistance increased from 15.8 to 63.9% if respondents had discussed HIV medication with both a physician and a pharmacist. Although the understanding of HIV

  2. A case for developing antiviral drugs against polio.

    Science.gov (United States)

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

    2008-09-01

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

  3. In vitro comparison of antiviral drugs against feline herpesvirus 1

    Directory of Open Access Journals (Sweden)

    Garré B

    2006-04-01

    Full Text Available Abstract Background Feline herpesvirus 1 (FHV-1 is a common cause of respiratory and ocular disease in cats. Especially in young kittens that have not yet reached the age of vaccination, but already lost maternal immunity, severe disease may occur. Therefore, there is a need for an effective antiviral treatment. In the present study, the efficacy of six antiviral drugs, i.e. acyclovir, ganciclovir, cidofovir, foscarnet, adefovir and 9-(2-phosphonylmethoxyethyl-2, 6-diaminopurine (PMEDAP, against FHV-1 was compared in Crandell-Rees feline kidney (CRFK cells using reduction in plaque number and plaque size as parameters. Results The capacity to reduce the number of plaques was most pronounced for ganciclovir, PMEDAP and cidofovir. IC50 (NUMBER values were 3.2 μg/ml (12.5 μM, 4.8 μg/ml (14.3 μM and 6 μg/ml (21.5 μM, respectively. Adefovir and foscarnet were intermediately efficient with an IC50 (NUMBER of 20 μg/ml (73.2 μM and 27 μg/ml (140.6 μM, respectively. Acyclovir was least efficient (IC50 (NUMBER of 56 μg/ml or 248.7 μM. All antiviral drugs were able to significantly reduce plaque size when compared with the untreated control. As observed for the reduction in plaque number, ganciclovir, PMEDAP and cidofovir were most potent in reducing plaque size. IC50 (SIZE values were 0.4 μg/ml (1.7 μM, 0.9 μg/ml (2.7 μM and 0.2 μg/ml (0.7 μM, respectively. Adefovir and foscarnet were intermediately potent, with an IC50 (SIZE of 4 μg/ml (14.6 μM and 7 μg/ml (36.4 μM, respectively. Acyclovir was least potent (IC50 (SIZE of 15 μg/ml or 66.6 μM. The results demonstrate that the IC50 (SIZE values were notably lower than the IC50 (NUMBER values. The most remarkable effect was observed for cidofovir and ganciclovir. None of the products were toxic for CRFK cells at antiviral concentrations. Conclusion In conclusion, measuring reduction in plaque number and plaque size are two valuable and complementary means of assessing the efficacy of

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

    OpenAIRE

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

    2012-01-01

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

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

    OpenAIRE

    Allen, Upton D.

    2013-01-01

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

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

    OpenAIRE

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

    2014-01-01

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

  7. 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.

  8. Effect of combinations of antiviral drugs on herpes simplex encephalitis

    Directory of Open Access Journals (Sweden)

    Bryan M Gebhardt

    2009-12-01

    Full Text Available Bryan M Gebhardt1, Federico Focher2, Richard Eberle3, Andrzej Manikowski4, George E Wright41LSU Eye Center, Department of Ophthalmology, Louisiana State University Health Sciences Center, New Orleans, LA, USA; 2Istituto di Genetica Molecolare, Consiglio Nazionale delle Ricerche, Pavia, Italy; 3Department of Veterinary Pathobiology, Center for Veterinary Health Sciences, Oklahoma State University, Stillwater, OK, USA; 4GLSynthesis Inc., Worcester, MA, USAAbstract: 2-Phenylamino-6-oxo-9-(4-hydroxybutylpurine (HBPG is a thymidine kinase inhibitor that prevents encephalitic death in mice caused by herpes simplex virus (HSV types 1 and 2, although its potency is somewhat less than that of acyclovir (ACV. The present study was undertaken to determine the effect of combinations of HBPG and either ACV, phosphonoformate (PFA, or cidofovir (CDF against HSV encephalitis. BALB/c mice were given ocular infections with HSV-1 or HSV-2, and treated twice daily intraperitoneally for five days with HBPG, alone or in combination with ACV, PFA, or CDF. Animals were observed daily for up to 30 days, and the day of death of each was recorded. All of the combinations showed additivity, and the combination of HBPG + ACV appeared to be synergistic, ie, protected more mice against HSV-1 encephalitis compared with each drug given alone. Delay of treatment with HBPG for up to two days was still effective in preventing HSV-2 encephalitis. The combination of the thymidine kinase inhibitor HBPG and the antiherpes drug ACV may have synergistic activity against HSV encephalitis. The development of a potent and safe combination therapy for the prevention and/or treatment of HSV infection of the central nervous system can improve the outcome of this infection in humans.Keywords: antivirals, herpetic encephalitis

  9. 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.

  10. 78 FR 57166 - Antiviral Drugs Advisory Committee; Notice of Meeting

    Science.gov (United States)

    2013-09-17

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

  11. 76 FR 36930 - National Advisory Council on Alcohol Abuse and Alcoholism and National Advisory Council on Drug...

    Science.gov (United States)

    2011-06-23

    ... HUMAN SERVICES National Institutes of Health National Advisory Council on Alcohol Abuse and Alcoholism... the National Advisory Council on Alcohol Abuse and Alcoholism and the National Institute on Drug Abuse... Committee: National Advisory Council on Alcohol Abuse and Alcoholism and National Advisory Council on...

  12. 75 FR 70932 - Joint Meeting of the Anesthetic and Life Support Drugs Advisory Committee and the Drug Safety and...

    Science.gov (United States)

    2010-11-19

    ... Advisory Committee and the Drug Safety and Risk Management Advisory Committee; Cancellation AGENCY: Food... Support Drugs Advisory Committee and the Drug Safety and Risk Management Advisory Committee scheduled for... FR 67093). This meeting has been cancelled because the Agency believes the information received...

  13. 75 FR 1395 - Cardiovascular and Renal Drugs Advisory Committee; Notice of Meeting

    Science.gov (United States)

    2010-01-11

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration Cardiovascular and Renal Drugs Advisory Committee; Notice of... to the public. ] Name of Committee: Cardiovascular and Renal Drugs Advisory Committee....

  14. 75 FR 59730 - Joint Meeting of the Anesthetic and Life Support Drugs Advisory Committee and the Drug Safety and...

    Science.gov (United States)

    2010-09-28

    ... Advisory Committee and the Drug Safety and Risk Management Advisory Committee; Notice of Meeting AGENCY... Risk Management Advisory Committee. General Function of the Committees: To provide advice and... public advisory committee of the Food and Drug Administration (FDA). The meeting will be open to...

  15. 75 FR 32189 - Joint Meeting of the Endocrinologic and Metabolic Drugs Advisory Committee and the Drug Safety...

    Science.gov (United States)

    2010-06-07

    ... Advisory Committee and the Drug Safety and Risk Management Advisory Committee; Notice of Meeting AGENCY... Risk Management Advisory Committee. General Function of the Committees: To provide advice and... public advisory committee of the Food and Drug Administration (FDA). The meeting will be open to...

  16. 75 FR 12767 - Joint Meeting of the Anesthetic and Life Support Drugs Advisory Committee and the Drug Safety and...

    Science.gov (United States)

    2010-03-17

    ... Advisory Committee and the Drug Safety and Risk Management Advisory Committee; Notice of Meeting AGENCY... Risk Management Advisory Committee. General Function of the Committees: To provide advice and... public advisory committee of the Food and Drug Administration (FDA). The meeting will be open to...

  17. 76 FR 40735 - Joint Meeting of the Advisory Committee for Reproductive Health Drugs and the Drug Safety and...

    Science.gov (United States)

    2011-07-11

    ... Health Drugs and the Drug Safety and Risk Management Advisory Committee; Notice of Meeting AGENCY: Food... of Committees: Advisory Committee for Reproductive Health Drugs and the Drug Safety and Risk Management Advisory Committee. General Function of the Committees: To provide advice and recommendations...

  18. 78 FR 20327 - Joint Meeting of the Advisory Committee for Reproductive Health Drugs and the Drug Safety and...

    Science.gov (United States)

    2013-04-04

    ... Health Drugs and the Drug Safety and Risk Management Advisory Committee; Amendment of Notice AGENCY: Food... Drug Safety and Risk Management Advisory Committee. This meeting was announced in the Federal Register... the Drug Safety and Risk Management Advisory Committee would be held on April 18, 2013. On page...

  19. 77 FR 75176 - Drug Safety and Risk Management Advisory Committee; Notice of Meeting

    Science.gov (United States)

    2012-12-19

    ... HUMAN SERVICES Food and Drug Administration Drug Safety and Risk Management Advisory Committee; Notice..., 2012, Drug Safety and Risk Management Advisory Committee meeting due to unanticipated weather conditions caused by Hurricane Sandy. Name of Committee: Drug Safety and Risk Management Advisory...

  20. 75 FR 23782 - Drug Safety and Risk Management Advisory Committee; Notice of Meeting

    Science.gov (United States)

    2010-05-04

    ... HUMAN SERVICES Food and Drug Administration Drug Safety and Risk Management Advisory Committee; Notice... forthcoming meeting of a public advisory committee of the Food and Drug Administration (FDA). The meeting will be open to the public. Name of Committee: Drug Safety and Risk Management Advisory Committee....

  1. Aminoadamantanes versus other antiviral drugs for chronic hepatitis C

    DEFF Research Database (Denmark)

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

    2014-01-01

    Registry Platform (www.who.int/ictrp), Google Scholar, and Eudrapharm up to December 2013. Furthermore, full text searches were conducted until December 2013. SELECTION CRITERIA: Randomised clinical trials assessing aminoadamantanes in participants with chronic hepatitis C virus infection. DATA COLLECTION...... to the low quality of the evidence, we are unable to determine definitively whether amantadine is less effective than other antivirals in patients with chronic hepatitis C. As it appears less likely that future trials assessing amantadine or potentially other aminoadamantanes for patients with chronic...

  2. Design Features of Drug-Drug Interaction Trials Between Antivirals and Oral Contraceptives.

    Science.gov (United States)

    Ayala, Ruben C; Arya, Vikram; Younis, Islam R

    2016-05-01

    The aim of this work was to explore the major design features of drug-drug interaction trials between antiviral medications (AVs) and oral contraceptives (OCs). Information on these trials (n = 27) was collected from approved drug labels and clinical pharmacology reviews conducted by the U.S. Food and Drug Administration. The primary objective of all trials was to evaluate changes in OC exposure following the coadministration of AVs. In addition, an evaluation of potential pharmacodynamic interaction was performed in 10 of these trials. Twenty-two trials were open label with a fixed-sequence design, and 5 trials used a double-blind crossover design. The trials were conducted using one, two, or three 28-day ovulatory cycles in 10, 8, and 9 trials, respectively. Only 1 trial enrolled HIV-infected women. The median number of women in a trial was 20 (range, 12 to 52). Norethindrone/ethinyl estradiol (EE) combination was the most commonly used OC (n = 16, 59%) followed by norgestimate/EE (n = 9, 33%). Labeling recommendations were based on exposure changes in 25 cases and on safety observations in the trial in 2 cases. In conclusion, a wide variety of trial designs was used, and there is no preferred design. The answer to the exposure question can be achieved using multiple designs.

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

    Science.gov (United States)

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

    2016-09-15

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

  4. 78 FR 64957 - Joint Meeting of the Gastrointestinal Drugs Advisory Committee and the Drug Safety and Risk...

    Science.gov (United States)

    2013-10-30

    ... Committee and the Drug Safety and Risk Management Advisory Committee; Notice of Joint Meeting AGENCY: Food... public. Name of Committees: Gastrointestinal Drugs Advisory Committee and the Drug Safety and Risk Management Advisory Committee. General Function of the Committees: To provide advice and recommendations...

  5. 76 FR 19374 - Joint Meeting of the Cardiovascular and Renal Drugs Advisory Committee and the Drug Safety and...

    Science.gov (United States)

    2011-04-07

    ... Committee and the Drug Safety and Risk Management Advisory Committee; Notice of Meeting AGENCY: Food and.... Name of Committees: Cardiovascular and Renal Drugs Advisory Committee and the Drug Safety and Risk Management Advisory Committee. General Function of the Committees: To provide advice and recommendations...

  6. Phyllanthus species versus antiviral drugs for chronic hepatitis B virus infection

    DEFF Research Database (Denmark)

    Yun, Xia; Luo, Hui; Liu, Jian Ping;

    2013-01-01

    Phyllanthus species for patients with chronic hepatitis B virus (HBV) infection have been assessed in clinical trials, but no consensus regarding their usefulness exists. When compared with placebo or no intervention, we were unable to identify convincing evidence that phyllanthus species...... are beneficial in patients with chronic hepatitis B. Some randomised clinical trials have compared phyllanthus species versus antiviral drugs....

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

    International Nuclear Information System (INIS)

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

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

    Directory of Open Access Journals (Sweden)

    Nathália Regina Porto Vieira Macedo

    2012-08-01

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

  9. 78 FR 30929 - Drug Safety and Risk Management Advisory Committee; Notice of Meeting

    Science.gov (United States)

    2013-05-23

    ... HUMAN SERVICES Food and Drug Administration Drug Safety and Risk Management Advisory Committee; Notice... be open to the public. Name of Committee: Drug Safety and Risk Management Advisory Committee. General... and Risk Management Advisory Committee (DSaRM). On July 10, 2013, the Agency plans to discuss the...

  10. 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.

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

    Science.gov (United States)

    Thomasy, Sara M; Maggs, David J

    2016-07-01

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

  12. 76 FR 37131 - Joint Meeting of the Gastrointestinal Drugs Advisory Committee and the Drug Safety and Risk...

    Science.gov (United States)

    2011-06-24

    ... Committee and the Drug Safety and Risk Management Advisory Committee; Notice of Meeting AGENCY: Food and... and Risk Management Advisory Committee. General Function of the Committees: To provide advice and... advisory committee of the Food and Drug Administration (FDA). At least one portion of the meeting will...

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

    Indian Academy of Sciences (India)

    Peter Duesberg; Claus Koehnlein; David Rasnick

    2003-06-01

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

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

    OpenAIRE

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

    2006-01-01

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

  15. Recent advances in flavivirus antiviral drug discovery and vaccine development.

    Science.gov (United States)

    Ray, Debashish; Shi, Pei-Yong

    2006-01-01

    Many flaviviruses, including yellow fever virus, dengue virus, Japanese encephalitis virus, tick-borne encephalitis virus, and West Nile virus, are globally important human pathogens. Despite an emergence and resurgence of flavivirus-mediated disease, specific therapies are not yet available; however, significant progress has been made toward the prevention and treatment of flavivirus infections. In this article we review recent advances made in the areas of (i) flavivirus vaccine development, and (ii) antiflavivirus drug discovery reported in literature and patents, and highlight strategies used in these investigations. PMID:18221133

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

    Science.gov (United States)

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

    2015-12-01

    The administration of drugs to inhibit metabolic pathways not only reduces the risk of obesity-induced diseases in humans but may also hamper the replication of different viral pathogens. In order to investigate the value of the US Food and Drug Administration-approved anti-obesity drug orlistat in view of its anti-viral activity against different human-pathogenic viruses, several anti-viral studies, electron microscopy analyses as well as fatty acid uptake experiments were performed. The results indicate that administrations of non-cytotoxic concentrations of orlistat reduced the replication of coxsackievirus B3 (CVB3) in different cell types significantly. Moreover, orlistat revealed cell protective effects and modified the formation of multi-layered structures in CVB3-infected cells, which are necessary for viral replication. Lowering fatty acid uptake from the extracellular environment by phloretin administrations had only marginal impact on CVB3 replication. Finally, orlistat reduced also the replication of varicella-zoster virus moderately but had no significant influence on the replication of influenza A viruses. The data support further experiments into the value of orlistat as an inhibitor of the fatty acid synthase to develop new anti-viral compounds, which are based on the modulation of cellular metabolic pathways. PMID:25680890

  17. Antiviral drug resistance in Cuban children infected with HIV-1

    Directory of Open Access Journals (Sweden)

    L Pérez

    2012-11-01

    Full Text Available Between 1986 and 2011, 100 children have been diagnosed with HIV-1 in Cuba. 38 have acquired HIV-1 by vertical transmission, 6 by blood transfusion and 56 by sexual contacts (teenager. Currently, AZT/D4T + 3TC + NVP/KALETRA are available for the treatment of pediatric patients. The aim of the study was to monitor the subtype distribution and emergence of drug resistance in pediatric HIV-1 infections. Plasma from 46 HIV-1-infected children were collected from November 2005 to November 2011, subsequently extracted, amplified and sequenced. Phylogenetic analysis was performed using Mega 4 (Neighbour joining, Kimura 2. The CPR tool v6.0 (WHO list 2009 was used to interpret transmitted drug resistance (TDR. In addition, acquired drug resistance was interpreted according to HIVdb v6.1.1. Experiments were successful for 28 samples from 20 patients (5 patients with multiple samples. At the moment of analysis, 17 children were receiving ART. The median age at diagnosis was 1.9 years, whereas the median age at sampling was 4.5 years. Ten children were male (50%, 16 (80% were infected by vertical transmission, 1 by blood transfusion (5% and 3 by sexual route (15%. The subtypes were CRF18_cpx (25%, CRF19_cpx (25%, B (20%, CRF20_BG (10%, G (10%, CRF24_BG (5% and C (5%. 82.3% of the children who were receiving ART at sampling (14/17 displayed at least one drug resistance mutation. The most common NRTI and NNRT mutations were: M184V (55.5%, T215FY (16.6% and K70R (16.6%; and K103NS (61.1% and G190A (22.0%. In contrast, only one PI mutation, L90M (5.5%, was observed. 5.8% of these children displayed single NRTI class resistance, 17.4% single NNRTI class resistance, 59% double NRTI + NNRTI class resistance and 5.8% triple NRTI + NNRTI + PI class resistance. According to HIVdb, NRTI, NNRTI and PI resistance was present in respectively 42.8%, 58.7% and 8.08% of the treated children. High-level NVP and EFV resistance was observed in 76.5% and 58

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

    OpenAIRE

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

    2014-01-01

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

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

    OpenAIRE

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

    2015-01-01

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

  20. 75 FR 17417 - Joint Meeting of the Arthritis Advisory Committee and the Drug Safety and Risk Management...

    Science.gov (United States)

    2010-04-06

    ... Drug Safety and Risk Management Advisory Committee; Amendment of Notice AGENCY: Food and Drug... Management Advisory Committee. This meeting was announced in the Federal Register of March 8, 2010 (75 FR... meeting of the Arthritis Advisory Committee and the Drug Safety and Risk Management Advisory...

  1. Letermovir and inhibitors of the terminase complex: a promising new class of investigational antiviral drugs against human cytomegalovirus

    Directory of Open Access Journals (Sweden)

    Melendez DP

    2015-08-01

    Full Text Available Dante P Melendez,1,2 Raymund R Razonable1,2 1Division of Infectious Diseases, 2William J von Liebig Center for Transplantation and Clinical Regeneration, Mayo Clinic, Rochester, MN, USA Abstract: Infection with cytomegalovirus is prevalent in immunosuppressed patients. In solid organ transplant and hematopoietic stem cell transplant recipients, cytomegalovirus infection is associated with high morbidity and preventable mortality. Prevention and treatment of cytomegalovirus with currently approved antiviral drugs is often associated with side effects that sometimes preclude their use. Moreover, cytomegalovirus has developed mutations that confer resistance to standard antiviral drugs. During the last decade, there have been calls to develop novel antiviral drugs that could provide better options for prevention and treatment of cytomegalovirus. Letermovir (AIC246 is a highly specific antiviral drug that is currently undergoing clinical development for the management of cytomegalovirus infection. It acts by inhibiting the viral terminase complex. Letermovir is highly potent in vitro and in vivo against cytomegalovirus. Because of a distinct mechanism of action, it does not exhibit cross-resistance with other antiviral drugs. It is predicted to be active against strains that are resistant to ganciclovir, foscarnet, and cidofovir. To date, early-phase clinical trials suggest a very low incidence of adverse effects. Herein, we present a comprehensive review on letermovir, from its postulated novel mechanism of action to the results of most recent clinical studies. Keywords: cytomegalovirus, letermovir, AIC246, terminase, antivirals, transplantation 

  2. 77 FR 14404 - Guidance for the Public, Food and Drug Administration (FDA) Advisory Committee Members, and FDA...

    Science.gov (United States)

    2012-03-09

    ... HUMAN SERVICES Food and Drug Administration Guidance for the Public, Food and Drug Administration (FDA) Advisory Committee Members, and FDA Staff: Public Availability of Advisory Committee Members' Financial Interest Information and Waivers; Availability AGENCY: Food and Drug Administration, HHS. ACTION:...

  3. 77 FR 65000 - Drug Safety and Risk Management Advisory Committee; Notice of Meeting

    Science.gov (United States)

    2012-10-24

    ... HUMAN SERVICES Food and Drug Administration Drug Safety and Risk Management Advisory Committee; Notice... be open to the public. Name of Committee: Drug Safety and Risk Management Advisory Committee. General... Committee (DSaRM). The Agency plans to present information on the risk management of teratogens, some...

  4. 77 FR 34051 - Drug Safety and Risk Management Advisory Committee; Notice of Meeting

    Science.gov (United States)

    2012-06-08

    ... HUMAN SERVICES Food and Drug Administration Drug Safety and Risk Management Advisory Committee; Notice... be open to the public. Name of Committee: Drug Safety and Risk Management Advisory Committee. General... 29 and 30, 2012, the committee will discuss the public health benefits and risks, including...

  5. 77 FR 43600 - Cardiovascular and Renal Drugs Advisory Committee; Notice of Meeting

    Science.gov (United States)

    2012-07-25

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration Cardiovascular and Renal Drugs Advisory Committee; Notice of... to the public. Name of Committee: Cardiovascular and Renal Drugs Advisory Committee. General...

  6. 77 FR 21982 - Cardiovascular and Renal Drugs Advisory Committee; Notice of Meeting

    Science.gov (United States)

    2012-04-12

    ... HUMAN SERVICES Food and Drug Administration Cardiovascular and Renal Drugs Advisory Committee; Notice of... to the public. Name of Committee: Cardiovascular and Renal Drugs Advisory Committee. General Function... patients with acute coronary syndrome (ACS) [ST elevation myocardial infarction (STEMI), non-ST...

  7. 78 FR 76307 - Cardiovascular and Renal Drugs Advisory Committee; Notice of Meeting

    Science.gov (United States)

    2013-12-17

    ... HUMAN SERVICES Food and Drug Administration Cardiovascular and Renal Drugs Advisory Committee; Notice of... to the public. Name of Committee: Cardiovascular and Renal Drugs Advisory Committee. General Function... atherothrombotic events in patients with a history of myocardial infarction (MI). The applicant also proposes...

  8. 78 FR 76308 - Cardiovascular and Renal Drugs Advisory Committee; Notice of Meeting

    Science.gov (United States)

    2013-12-17

    ... HUMAN SERVICES Food and Drug Administration Cardiovascular and Renal Drugs Advisory Committee; Notice of... to the public. Name of Committee: Cardiovascular and Renal Drugs Advisory Committee. General Function... coronary syndrome [ST elevation myocardial infarction, non-ST elevation myocardial infarction, or...

  9. 76 FR 23324 - Endocrinologic and Metabolic Drugs Advisory Committee; Notice of Meeting

    Science.gov (United States)

    2011-04-26

    ... HUMAN SERVICES Food and Drug Administration Endocrinologic and Metabolic Drugs Advisory Committee... be open to the public. Name of Committee: Endocrinologic and Metabolic Drugs Advisory Committee... and coronary heart disease (CHD) or CHD risk equivalent who are on optimal statin therapy to...

  10. 78 FR 50423 - Endocrinologic and Metabolic Drugs Advisory Committee; Notice of Meeting

    Science.gov (United States)

    2013-08-19

    ... HUMAN SERVICES Food and Drug Administration Endocrinologic and Metabolic Drugs Advisory Committee... be open to the public. Name of Committee: Endocrinologic and Metabolic Drugs Advisory Committee...) or a CHD risk equivalent. FDA intends to make background material available to the public no...

  11. 76 FR 29766 - Pulmonary-Allergy Drugs Advisory Committee; Notice of Meeting

    Science.gov (United States)

    2011-05-23

    ... HUMAN SERVICES Food and Drug Administration Pulmonary-Allergy Drugs Advisory Committee; Notice of... to the public. Name of Committee: Pulmonary-Allergy Drugs Advisory Committee. General Function of the... (proposed trade name Firazyr), Shire Human Genetic Therapies, for the proposed indication of treatment...

  12. 75 FR 82031 - Pulmonary-Allergy Drugs Advisory Committee; Notice of Meeting

    Science.gov (United States)

    2010-12-29

    ... HUMAN SERVICES Food and Drug Administration Pulmonary-Allergy Drugs Advisory Committee; Notice of... to the public. Name of Committee: Pulmonary-Allergy Drugs Advisory Committee. General Function of the... Pharmaceuticals Corp., for the long-term once daily maintenance bronchodilator treatment of airflow obstruction...

  13. 77 FR 4566 - Pulmonary-Allergy Drugs Advisory Committee; Notice of Meeting

    Science.gov (United States)

    2012-01-30

    ... HUMAN SERVICES Food and Drug Administration Pulmonary-Allergy Drugs Advisory Committee; Notice of... to the public. Name of Committee: Pulmonary-Allergy Drugs Advisory Committee. General Function of the... Laboratories, for the proposed ] indication of long-term maintenance treatment of bronchospasm associated...

  14. 77 FR 69635 - Pulmonary-Allergy Drugs Advisory Committee; Notice of Meeting

    Science.gov (United States)

    2012-11-20

    ... HUMAN SERVICES Food and Drug Administration Pulmonary-Allergy Drugs Advisory Committee; Notice of... to the public. Name of Committee: Pulmonary-Allergy Drugs Advisory Committee. General Function of the... bronchodilator treatment of airflow obstruction in patients with chronic obstructive pulmonary disease...

  15. 75 FR 9420 - Pulmonary-Allergy Drugs Advisory Committee; Notice of Meeting

    Science.gov (United States)

    2010-03-02

    ... HUMAN SERVICES Food and Drug Administration Pulmonary-Allergy Drugs Advisory Committee; Notice of... to the public. Name of Committee: Pulmonary-Allergy Drugs Advisory Committee. General Function of the... (NDA) 22-522, roflumilast (DAXAS), Forest Research Institute, for the maintenance treatment of...

  16. 75 FR 5334 - Pulmonary-Allergy Drugs Advisory Committee; Notice of Meeting

    Science.gov (United States)

    2010-02-02

    ... HUMAN SERVICES Food and Drug Administration Pulmonary-Allergy Drugs Advisory Committee; Notice of... to the public. Name of Committee: Pulmonary-Allergy Drugs Advisory Committee. General Function of the... in the treatment of asthma in adults, adolescents, and children. FDA intends to make...

  17. 78 FR 46976 - Pulmonary-Allergy Drugs Advisory Committee; Notice of Meeting

    Science.gov (United States)

    2013-08-02

    ... HUMAN SERVICES Food and Drug Administration Pulmonary-Allergy Drugs Advisory Committee; Notice of... to the public. Name of Committee: Pulmonary-Allergy Drugs Advisory Committee. General Function of the... (d/b/a/GSK) for the long-term, once- daily, maintenance treatment of airflow obstruction in...

  18. 77 FR 74486 - Pulmonary-Allergy Drugs Advisory Committee; Notice of Meeting

    Science.gov (United States)

    2012-12-14

    ... HUMAN SERVICES Food and Drug Administration Pulmonary-Allergy Drugs Advisory Committee; Notice of... to the public. Name of Committee: Pulmonary-Allergy Drugs Advisory Committee. General Function of the... (proposed tradename BREO ELLIPTA), sponsored by GlaxoSmithKline, for the long-term maintenance treatment...

  19. 78 FR 63224 - Endocrinologic and Metabolic Drugs Advisory Committee; Notice of Meeting

    Science.gov (United States)

    2013-10-23

    ... HUMAN SERVICES Food and Drug Administration Endocrinologic and Metabolic Drugs Advisory Committee... be open to the public. Name of Committee: Endocrinologic and Metabolic Drugs Advisory Committee... Type IVA (Morquio A syndrome). Morquio A syndrome is a rare congenital disorder caused by the...

  20. 75 FR 5333 - Pulmonary-Allergy Drugs Advisory Committee; Notice of Meeting

    Science.gov (United States)

    2010-02-02

    ... pulmonary fibrosis (scarring of the lungs without a known cause) to decrease the decline in lung function... HUMAN SERVICES Food and Drug Administration Pulmonary-Allergy Drugs Advisory Committee; Notice of... to the public. Name of Committee: Pulmonary-Allergy Drugs Advisory Committee. General Function of...

  1. 77 FR 69636 - Pulmonary-Allergy Drugs Advisory Committee; Notice of Meeting

    Science.gov (United States)

    2012-11-20

    ... HUMAN SERVICES Food and Drug Administration Pulmonary-Allergy Drugs Advisory Committee; Notice of... to the public. Name of Committee: Pulmonary-Allergy Drugs Advisory Committee. General Function of the... sponsored by Pharmaxis, for the proposed indication of management of cystic fibrosis in patients aged...

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

    OpenAIRE

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

    2012-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Upton D Allen

    2006-01-01

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

  4. The Food and Drug Administration advisory committees and panels: how they are applied to the drug regulatory process.

    Science.gov (United States)

    Ciociola, Arthur A; Karlstadt, Robyn G; Pambianco, Daniel J; Woods, Karen L; Ehrenpreis, Eli D

    2014-10-01

    Food and Drug Administration (FDA) advisory panels and committees play a critical role in advising the FDA on the safety and efficacy of medical devices and drugs marketed in the US. Advisory panel recommendations are used by the FDA to make decisions regarding medical products. Currently, the FDA utilizes over 50 advisory panels that serve the three major FDA centers, including the Centers for Biologics, Drugs and Device Products. Members of an advisory panel typically include academicians, clinicians, consumers, patients, and industry representatives. The FDA establishes the schedules for advisory panel meetings on an annual basis and a panel usually meets several times a year for two consecutive days in Washington, DC. Typically, the advisory panel discusses issues highlighted by the FDA and is then asked to vote a response to the questions posed in advance by the FDA. Advisory panel recommendations have a strong influence on FDA's decision to approve a product, as evidenced by the 214 Advisory Panels FDA convened between January 2008 to November 2012, during which advisory panel members voted to approve the product (or use of the product) ∼74% of the time, with FDA ultimately approving the medical product (or use of the product) ∼79% of the time. The ACG membership are encouraged to consider serving the public's interest by participating in an FDA advisory panel utilizing their expertise for the evaluation of a new drug or medical device, and providing advice about whether the product should be sold in the US.

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

    DEFF Research Database (Denmark)

    Rosenkilde, Mette M

    2005-01-01

    Large DNA viruses, in particular herpes- and poxviruses, have evolved proteins that serve as mimics or decoys for endogenous proteins in the host. The chemokines and their receptors serve key functions in both innate and adaptive immunity through control of leukocyte trafficking, and have...... to their closest endogenous homologs, are interactions with a wider range of chemokines, which can act as agonists, antagonists and inverse agonists, and the exploitation of many signal transduction pathways. High constitutive activity is another key property of some--but not all--of these receptors. The chemokine...... receptors belong to the superfamily of G-protein coupled 7TM receptors that per se are excellent drug targets. At present, non-peptide antagonists have been developed against many chemokine receptors. The potentials of the virus-encoded chemokine receptors as drug targets--ie. as novel antiviral strategies...

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

    Directory of Open Access Journals (Sweden)

    Charlotte A Romain

    2010-01-01

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

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

    Science.gov (United States)

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

    2016-06-01

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

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

    OpenAIRE

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

    2013-01-01

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

  9. Update on dengue: epidemiology, virus evolution, antiviral drugs, and vaccine development.

    Science.gov (United States)

    Wilder-Smith, Annelies; Ooi, Eng-Eong; Vasudevan, Subhash G; Gubler, Duane J

    2010-05-01

    Dengue virus is the most widespread geographically of the arboviruses and a major public health threat in the tropics and subtropics. Scientific advances in recent years have provided new insights about the pathogenesis of more severe disease and novel approaches into the development of antiviral compounds and dengue vaccines. Phylogenetic studies show an association between specific subtypes (within serotypes) and severity of dengue. The lack of association between maternal antibodies and development of severe dengue in infants in a recent study has called for the rethinking or refinement of the current antibody-dependent enhancement theory of dengue hemorrhagic syndrome in infancy. Such studies should stimulate new directions of research into mechanisms responsible for the development of severe dengue. The life cycle of dengue virus readily shows that virus entry and replication can be targeted by small molecules. Advances in a mouse model (AG 129 mice) have made it easier to test such antiviral compounds. The efforts to find specific dengue inhibitors are intensifying and the tools to evaluate the efficacy of new drugs are now in place for rapid translation into trials in humans. Furthermore, several dengue vaccine candidates are in development, of which the chimeric dengue/yellow fever vaccine has now entered phase 3 trials. Until the availability of a licensed vaccine, disease surveillance and vector population control remain the mainstay of dengue prevention. PMID:21308524

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

    Directory of Open Access Journals (Sweden)

    Fred Y Aoki

    2012-01-01

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

  11. Impact of emerging antiviral drug resistance on influenza containment and spread: influence of subclinical infection and strategic use of a stockpile containing one or two drugs.

    Directory of Open Access Journals (Sweden)

    James M McCaw

    Full Text Available BACKGROUND: Wide-scale use of antiviral agents in the event of an influenza pandemic is likely to promote the emergence of drug resistance, with potentially deleterious effects for outbreak control. We explored factors promoting resistance within a dynamic infection model, and considered ways in which one or two drugs might be distributed to delay the spread of resistant strains or mitigate their impact. METHODS AND FINDINGS: We have previously developed a novel deterministic model of influenza transmission that simulates treatment and targeted contact prophylaxis, using a limited stockpile of antiviral agents. This model was extended to incorporate subclinical infections, and the emergence of resistant virus strains under the selective pressure imposed by various uses of one or two antiviral agents. For a fixed clinical attack rate, R(0 rises with the proportion of subclinical infections thus reducing the number of infections amenable to treatment or prophylaxis. In consequence, outbreak control is more difficult, but emergence of drug resistance is relatively uncommon. Where an epidemic may be constrained by use of a single antiviral agent, strategies that combine treatment and prophylaxis are most effective at controlling transmission, at the cost of facilitating the spread of resistant viruses. If two drugs are available, using one drug for treatment and the other for prophylaxis is more effective at preventing propagation of mutant strains than either random allocation or drug cycling strategies. Our model is relatively straightforward, and of necessity makes a number of simplifying assumptions. Our results are, however, consistent with the wider body of work in this area and are able to place related research in context while extending the analysis of resistance emergence and optimal drug use within the constraints of a finite drug stockpile. CONCLUSIONS: Combined treatment and prophylaxis represents optimal use of antiviral agents to

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

    Science.gov (United States)

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

    2016-01-01

    Type III interferons (IFNs) (also called IFN-λ: IFN-λ1, IFN-λ2, IFN-λ3, and IFN-λ4) are critical players in the defense against viral infection of mucosal epithelial cells, where the activity of type I IFNs is weak, and unlike type I IFNs that are associated with severe and diverse side effects, type III IFNs cause minimal side effects due to the highly restricted expression of their receptors, and thus appear to be promising agents for the treatment and prevention of respiratory and gastrointestinal viral infection. However, the antiviral potency of natural type III IFNs is weak compared to type I and, although IFN-λ3 possesses the highest bioactivity among the type III IFNs, IFN-λ1, instead of IFN-λ3, is being developed as a therapeutic drug due to the difficulty to express IFN-λ3 in the prokaryotic expression system. Here, to develop optimal IFN-λ molecules with improved drug attributes, we designed a series of IFN-λ analogs by replacing critical amino acids of IFN-λ1 with the IFN-λ3 counterparts, and vice versa. Four of the designed analogs were successfully expressed in Escherichia coli with high yield and were easily purified from inclusion bodies. Interestingly, all four analogs showed potent activity in inducing the expression of the antiviral genes MxA and OAS and two of them, analog-6 and -7, displayed an unexpected high potency that is higher than that of type I IFN (IFN-α2a) in activating the IFN-stimulated response element (ISRE)-luciferase reporter. Importantly, both analog-6 and -7 effectively inhibited replication of hepatitis C virus in Huh-7.5.1 cells, with an IC50 that is comparable to that of IFN-α2a; and consistent with the roles of IFN-λ in mucosal epithelia, both analogs potently inhibited replication of H3N2 influenza A virus in A549 cells. Together, these studies identified two IFN-λ analogs as candidates to be developed as novel antiviral biologics. PMID:26792983

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

    Science.gov (United States)

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

    2016-01-01

    Type III interferons (IFNs) (also called IFN-λ: IFN-λ1, IFN-λ2, IFN-λ3, and IFN-λ4) are critical players in the defense against viral infection of mucosal epithelial cells, where the activity of type I IFNs is weak, and unlike type I IFNs that are associated with severe and diverse side effects, type III IFNs cause minimal side effects due to the highly restricted expression of their receptors, and thus appear to be promising agents for the treatment and prevention of respiratory and gastrointestinal viral infection. However, the antiviral potency of natural type III IFNs is weak compared to type I and, although IFN-λ3 possesses the highest bioactivity among the type III IFNs, IFN-λ1, instead of IFN-λ3, is being developed as a therapeutic drug due to the difficulty to express IFN-λ3 in the prokaryotic expression system. Here, to develop optimal IFN-λ molecules with improved drug attributes, we designed a series of IFN-λ analogs by replacing critical amino acids of IFN-λ1 with the IFN-λ3 counterparts, and vice versa. Four of the designed analogs were successfully expressed in Escherichia coli with high yield and were easily purified from inclusion bodies. Interestingly, all four analogs showed potent activity in inducing the expression of the antiviral genes MxA and OAS and two of them, analog-6 and -7, displayed an unexpected high potency that is higher than that of type I IFN (IFN-α2a) in activating the IFN-stimulated response element (ISRE)-luciferase reporter. Importantly, both analog-6 and -7 effectively inhibited replication of hepatitis C virus in Huh-7.5.1 cells, with an IC50 that is comparable to that of IFN-α2a; and consistent with the roles of IFN-λ in mucosal epithelia, both analogs potently inhibited replication of H3N2 influenza A virus in A549 cells. Together, these studies identified two IFN-λ analogs as candidates to be developed as novel antiviral biologics.

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

    DEFF Research Database (Denmark)

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

    2008-01-01

    The present study describes the synthesis and antiviral evaluation of a series of novel 6-(3-trifluoromethylbenzyl) and 6-(fluorobenzyl) analogues of the HIV drugs emivirine and GCA-186. The objective was to investigate whether the fluoro or trifluoromethyl substituents could lead to an improved ...

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

    Directory of Open Access Journals (Sweden)

    Yu D

    2016-01-01

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

  16. Turning an antiviral into an anticancer drug: nanoparticle delivery of acyclovir monophosphate.

    Science.gov (United States)

    Yao, Jing; Zhang, Yuan; Ramishetti, Srinivas; Wang, Yuhua; Huang, Leaf

    2013-09-28

    Anti-herpes simplex virus (HSV) drug acyclovir (ACV) is phosphorylated by the viral thymidine kinase (TK), but not the cellular TK. Phosphorylated ACV inhibits cellular DNA synthesis and kills the infected cells. We hypothesize that ACV monophosphate (ACVP), which is an activated metabolite of ACV, should be efficient in killing cells independent of HSV-TK. If so, ACVP should be a cytotoxic agent if properly delivered to the cancer cells. The Lipid/Calcium/Phosphate (LCP) nanoparticles (NPs) with a membrane/core structure were used to encapsulate ACVP to facilitate the targeted delivery of ACVP to the tumor. The LCP NPs showed entrapment efficiency of ~70%, the nano-scaled particle size and positive zeta potential. Moreover, ACVP-loaded LCP NPs (A-LCP NPs) exhibited concentration-dependent cytotoxicity against H460 cells and increased S-phase arrest. More importantly, a significant reduction of the tumor volume over 4 days following administration (pACV and ACVP) and blank LCP NPs showed little or no therapeutic effect. It was also found that the high efficacy of A-LCP NPs was associated with the ability to induce dramatic apoptosis of the tumor cells, as well as significantly inhibit tumor cell proliferation and cell cycle progression. In conclusion, with the help of LCP NPs, monophosphorylation modification of ACV can successfully modify an HSV-TK-dependent antiviral drug into an anti-tumor drug.

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

    Science.gov (United States)

    Cheng, Feixiong; Murray, James L; Zhao, Junfei; Sheng, Jinsong; Zhao, Zhongming; Rubin, Donald H

    2016-09-01

    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. PMID:27632082

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

    Science.gov (United States)

    Zhao, Junfei; Sheng, Jinsong; Rubin, Donald H.

    2016-01-01

    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. PMID:27632082

  19. Inclusion complex of the antiviral drug acyclovir with cyclodextrin in aqueous solution and in solid phase

    Directory of Open Access Journals (Sweden)

    Carlos von Plessing Rossel

    2000-12-01

    Full Text Available Complexation between acyclovir (ACV, an antiviral drug used for the treatment of herpes simplex virus infection, and beta-cyclodextrin (beta-CD was studied in solution and in solid states. Complexation in solution was evaluated using solubility studies and nuclear magnetic resonance spectroscopy (¹H-NMR. In the solid state, X-ray diffraction, differential scanning calorimetry (DSC, thermal gravimetric analysis (TGA and dissolution studies were used. Solubility studies suggested the existence of a 1:1 complex between ACV and beta-CD. ¹H-NMR spectroscopy studies showed that the complex formed occurs with a stoichiometry ratio of 1:1. Powder X-ray diffraction indicated that ACV exists in a semicrystalline state in the complexed form with beta-CD. DSC studies showed the existence of a complex of ACV with beta-CD. The TGA studies confirmed the DSC results of the complex. Solubility of ACV in solid complexes was studied by the dissolution method and it was found to be much more soluble than the uncomplexed drug.

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

    Directory of Open Access Journals (Sweden)

    Vivian Kouri

    2014-11-01

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

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

    Science.gov (United States)

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

    2014-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Dhara A Patel

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

  3. 77 FR 61609 - Endocrinologic and Metabolic Drugs Advisory Committee; Notice of Meeting

    Science.gov (United States)

    2012-10-10

    ... HUMAN SERVICES Food and Drug Administration Endocrinologic and Metabolic Drugs Advisory Committee... efficacy of new drug applications (NDAs) 203313, insulin degludec/insulin aspart [rDNA origin] injection and 203314, insulin degludec injection, manufactured by Novo Nordisk Inc. The proposed indication...

  4. 78 FR 13348 - Science Board to the Food and Drug Administration Advisory Committee; Amendment of Notice

    Science.gov (United States)

    2013-02-27

    ... HUMAN SERVICES Food and Drug Administration Science Board to the Food and Drug Administration Advisory... Administration (FDA) is announcing an amendment to the notice of meeting of the Science Board to the Food and... that a meeting of the Science Board to the Food and Drug Administration would be held on February...

  5. The antiviral drug acyclovir is a slow-binding inhibitor of (D)-amino acid oxidase.

    Science.gov (United States)

    Katane, Masumi; Matsuda, Satsuki; Saitoh, Yasuaki; Sekine, Masae; Furuchi, Takemitsu; Koyama, Nobuhiro; Nakagome, Izumi; Tomoda, Hiroshi; Hirono, Shuichi; Homma, Hiroshi

    2013-08-20

    d-Amino acid oxidase (DAO) is a degradative enzyme that is stereospecific for d-amino acids, including d-serine and d-alanine, which are believed to be coagonists of the N-methyl-d-aspartate (NMDA) receptor. To identify a new class of DAO inhibitor(s) that can be used to elucidate the molecular details of the active site environment of DAO, manifold biologically active compounds of microbial origin and pre-existing drugs were screened for their ability to inhibit DAO activity, and several compounds were identified as candidates. One of these compounds, acyclovir (ACV), a well-known antiviral drug used for the treatment of herpesvirus infections, was characterized and evaluated as a novel DAO inhibitor in vitro. Analysis showed that ACV acts on DAO as a reversible slow-binding inhibitor, and interestingly, the time required to achieve equilibrium between DAO, ACV, and the DAO/ACV complex was highly dependent on temperature. The binding mechanism of ACV to DAO was investigated in detail by several approaches, including kinetic analysis, structural modeling of DAO complexed with ACV, and site-specific mutagenesis of an active site residue postulated to be involved in the binding of ACV. The results confirm that ACV is a novel, active site-directed inhibitor of DAO that can be a valuable tool for investigating the structure-function relationships of DAO, including the molecular details of the active site environment of DAO. In particular, it appears that ACV can serve as an active site probe to study the structural basis of temperature-induced conformational changes of DAO.

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

    OpenAIRE

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

    2015-01-01

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

  7. 76 FR 63929 - Joint Meeting of the Drug Safety and Risk Management Advisory Committee and the Dermatologic and...

    Science.gov (United States)

    2011-10-14

    ... public. Name of Committees: Drug Safety and Risk Management Advisory Committee and Dermatologic and... Management Advisory Committee (DSaRM). On December 1, 2011, the DSaRM and the Dermatologic and Ophthalmic... HUMAN SERVICES Food and Drug Administration Joint Meeting of the Drug Safety and Risk...

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

    Science.gov (United States)

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

    2016-01-01

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

  9. 75 FR 56548 - Joint Meeting of the Peripheral and Central Nervous System Drugs Advisory Committee and the Drug...

    Science.gov (United States)

    2010-09-16

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration Joint Meeting of the Peripheral and Central Nervous System... the public. Name of Committees: Peripheral and Central Nervous System Drugs Advisory Committee and...

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2008-07-21

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

  11. Spectroscopic, thermal and X-ray structural study of the antiparasitic and antiviral drug nitazoxanide

    Science.gov (United States)

    Bruno, Flavia P.; Caira, Mino R.; Monti, Gustavo A.; Kassuha, Diego E.; Sperandeo, Norma R.

    2010-12-01

    Nitazoxanide [2-(acetyloxy)- N-(5-nitro-2-thiazolyl)benzamide, NTZ] is a potent antiparasitic and antiviral agent recently approved. The anti-protozoal activity of NTZ is believed to be due to interference with the pyruvate:ferredoxin oxidoreductase (PFOR) enzyme dependent electron transfer reaction. As drug-enzyme interactions are governed by the three-dimensional stereochemistry of both participants, the crystal structure of NTZ was determined for the first time to identify the conformational preferences that may be related to biological activity. NTZ crystallizes as the carboxamide tautomer in the orthorhombic system, space group Pna2 1 with the following parameters at 100(2) K: a = 14.302(2) Å, b = 5.2800(8) Å, c = 33.183(5) Å, V = 2505.8(6) Å 3, Z = 8, D x = 1.629 g cm -3, R = 0.0319, wR2 = 0.0799 for 5121 reflections. In addition, the spectroscopic and thermal properties were determined and related to the molecular structure. The 13C CPMAS NMR spectra showed resolved signals for each carbon of NTZ, some signals being broad due to residual dipolar interaction with quadrupolar 14N nuclei. In particular, the resonance at about 127 ppm showed multiplicity, indicating more than one molecule in the asymmetric unit and this is consistent with the crystallographic data. The DSC and TG data revealed that NTZ shows a single DSC melting peak with extrapolated onset at 201 °C which is accompanied by a TG weight loss, indicating that NTZ melts with decomposition.

  12. 75 FR 17417 - Peripheral and Central Nervous System Drugs Advisory Committee; Notice of Meeting

    Science.gov (United States)

    2010-04-06

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration Peripheral and Central Nervous System Drugs Advisory...). The meeting will be open to the public. Name of Committee: Peripheral and Central Nervous System...

  13. 76 FR 3912 - Peripheral and Central Nervous System Drugs Advisory Committee; Notice of Meeting

    Science.gov (United States)

    2011-01-21

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration Peripheral and Central Nervous System Drugs Advisory...). The meeting will be open to the public. Name of Committee: Peripheral and Central Nervous System...

  14. 78 FR 20328 - Peripheral and Central Nervous System Drugs Advisory Committee; Notice of Meeting

    Science.gov (United States)

    2013-04-04

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration Peripheral and Central Nervous System Drugs Advisory...). The meeting will be open to the public. Name of Committee: Peripheral and Central Nervous System...

  15. 78 FR 63478 - Peripheral and Central Nervous System Drugs Advisory Committee; Notice of Meeting

    Science.gov (United States)

    2013-10-24

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration Peripheral and Central Nervous System Drugs Advisory...). The meeting will be open to the public. Name of Committee: Peripheral and Central Nervous System...

  16. 76 FR 44595 - Peripheral and Central Nervous System Drugs Advisory Committee; Notice of Meeting

    Science.gov (United States)

    2011-07-26

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration Peripheral and Central Nervous System Drugs Advisory...). The meeting will be open to the public. Name of Committee: Peripheral and Central Nervous System...

  17. 75 FR 12768 - Peripheral and Central Nervous System Drugs Advisory Committee; Notice of Meeting

    Science.gov (United States)

    2010-03-17

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration Peripheral and Central Nervous System Drugs Advisory...). The meeting will be open to the public. Name of Committee: Peripheral and Central Nervous System...

  18. 77 FR 20037 - Peripheral and Central Nervous System Drugs Advisory Committee; Notice of Meeting

    Science.gov (United States)

    2012-04-03

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration Peripheral and Central Nervous System Drugs Advisory...). The meeting will be open to the public. Name of Committee: Peripheral and Central Nervous System...

  19. 75 FR 75681 - Peripheral and Central Nervous System Drugs Advisory Committee; Notice of Meeting

    Science.gov (United States)

    2010-12-06

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration Peripheral and Central Nervous System Drugs Advisory...). The meeting will be open to the public. Name of Committee: Peripheral and Central Nervous System...

  20. 78 FR 63481 - Peripheral and Central Nervous System Drugs Advisory Committee; Notice of Meeting

    Science.gov (United States)

    2013-10-24

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration Peripheral and Central Nervous System Drugs Advisory...). The meeting will be open to the public. Name of Committee: Peripheral and Central Nervous System...

  1. 75 FR 36428 - Peripheral and Central Nervous System Drugs Advisory Committee; Notice of Meeting

    Science.gov (United States)

    2010-06-25

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration Peripheral and Central Nervous System Drugs Advisory...). The meeting will be open to the public. Name of Committee: Peripheral and Central Nervous System...

  2. Ophthalmic antiviral chemotherapy : An overview

    Directory of Open Access Journals (Sweden)

    Athmanathan Sreedharan

    1997-01-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2010-02-18

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

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

    Science.gov (United States)

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

    2016-07-01

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

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

    Directory of Open Access Journals (Sweden)

    Ana Maria Viana Pinto

    2012-08-01

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

  6. the denver tube Combined with antiviral drugs In the treatment of HBV-related Cirrhosis with Refractory ascites:a Report of three Cases

    Institute of Scientific and Technical Information of China (English)

    Xiao-jin Wang; Li-qin Shi; Qing-chun Fu; Liu-da Ni; Feng Zhou; Jin-wei Chen; Cheng-wei Chen

    2014-01-01

    Treatment of nucleos(t)ide antiviral drugs for decompensated HBV-related cirrhosis can signiifcantly improve the prognosis. But those patients with refractory ascites possibly deteriorate due to the complications of ascites before any beneift from anti-viral drugs could be observed. Therefore, it is important to ifnd a way to help the patients with HBV-related cirrhosis and refractory ascites to receive the full beneifts 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 beneifts and maximize efifcacy of antiviral treatment.

  7. 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.

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

    Directory of Open Access Journals (Sweden)

    Mark A. Wainberg

    2012-01-01

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

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

    OpenAIRE

    Vries, Erhard

    2014-01-01

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

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

    Science.gov (United States)

    Ma, Chunlong; Zhang, Jiantao; Wang, Jun

    2016-09-01

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

  11. 76 FR 45578 - Request for Nominations for Members on a Public Advisory Committee; Medical Imaging Drugs...

    Science.gov (United States)

    2011-07-29

    ... requesting nominations for voting members on the Medical Imaging Drugs Advisory Committee (the Committee... more qualified persons for membership on the Committee. Self-nominations are also accepted. Nominations... committee for which the nominee is recommended. Nominations must also acknowledge that the nominee is...

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

    Directory of Open Access Journals (Sweden)

    V A Potdar

    2014-01-01

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

  13. 75 FR 21000 - Draft Guidance for the Public, Food and Drug Administration Advisory Committee Members, and Food...

    Science.gov (United States)

    2010-04-22

    ... HUMAN SERVICES Food and Drug Administration (formerly Docket No. 02D-0049) Draft Guidance for the Public, Food and Drug Administration Advisory Committee Members, and Food and Drug Administration Staff: Public...) (added by the Food and Drug Administration Amendments Act of 2007, Public Law No. 110-85), and...

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

    Directory of Open Access Journals (Sweden)

    Hunter Jennifer C

    2012-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Alex N. Manin

    2015-12-01

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

  16. Antiviral Information Management System (AIMS): a prototype for operational innovation in drug development.

    Science.gov (United States)

    Jadhav, Pravin R; Neal, Lauren; Florian, Jeff; Chen, Ying; Naeger, Lisa; Robertson, Sarah; Soon, Guoxing; Birnkrant, Debra

    2010-09-01

    This article presents a prototype for an operational innovation in knowledge management (KM). These operational innovations are geared toward managing knowledge efficiently and accessing all available information by embracing advances in bioinformatics and allied fields. The specific components of the proposed KM system are (1) a database to archive hepatitis C virus (HCV) treatment data in a structured format and retrieve information in a query-capable manner and (2) an automated analysis tool to inform trial design elements for HCV drug development. The proposed framework is intended to benefit drug development by increasing efficiency of dose selection and improving the consistency of advice from US Food and Drug Administration (FDA). It is also hoped that the framework will encourage collaboration among FDA, industry, and academic scientists to guide the HCV drug development process using model-based quantitative analysis techniques. PMID:20881217

  17. Antiviral Information Management System (AIMS): a prototype for operational innovation in drug development.

    Science.gov (United States)

    Jadhav, Pravin R; Neal, Lauren; Florian, Jeff; Chen, Ying; Naeger, Lisa; Robertson, Sarah; Soon, Guoxing; Birnkrant, Debra

    2010-09-01

    This article presents a prototype for an operational innovation in knowledge management (KM). These operational innovations are geared toward managing knowledge efficiently and accessing all available information by embracing advances in bioinformatics and allied fields. The specific components of the proposed KM system are (1) a database to archive hepatitis C virus (HCV) treatment data in a structured format and retrieve information in a query-capable manner and (2) an automated analysis tool to inform trial design elements for HCV drug development. The proposed framework is intended to benefit drug development by increasing efficiency of dose selection and improving the consistency of advice from US Food and Drug Administration (FDA). It is also hoped that the framework will encourage collaboration among FDA, industry, and academic scientists to guide the HCV drug development process using model-based quantitative analysis techniques.

  18. Portraying Persons Who Inject Drugs Recently Infected with Hepatitis C Accessing Antiviral Treatment: A Cluster Analysis

    OpenAIRE

    Jean-Marie Bamvita; Elise Roy; Geng Zang; Didier Jutras-Aswad; Andreea Adelina Artenie; Annie Levesque; Julie Bruneau

    2014-01-01

    Objectives. To empirically determine a categorization of people who inject drug (PWIDs) recently infected with hepatitis C virus (HCV), in order to identify profiles most likely associated with early HCV treatment uptake. Methods. The study population was composed of HIV-negative PWIDs with a documented recent HCV infection. Eligibility criteria included being 18 years old or over, and having injected drugs in the previous 6 months preceding the estimated date of HCV exposure. Participant cla...

  19. 76 FR 82309 - Oncologic Drugs Advisory Committee; Notice of Meeting

    Science.gov (United States)

    2011-12-30

    ... Research, Food and Drug Administration, 10903 New Hampshire Ave., Bldg. 31, rm. 2417, Silver Spring, MD... product is for the treatment of acute myelogenous leukemia (AML) in adults 65 years of age or older...

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2016-03-21

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

  1. OxyContin: Prescription Drug Abuse. CSAT Advisory.

    Science.gov (United States)

    Substance Abuse and Mental Health Services Administration (DHHS/PHS), Rockville, MD. Center for Substance Abuse Treatment.

    Recently, the media have issued numerous reports about the apparent increase in OxyContin abuse and addiction. OxyContin has been heralded as a miracle drug that allows patients with chronic pain to resume a normal life. It has also been called pharmaceutical heroin and is thought to have been responsible for a number of deaths and robberies in…

  2. 75 FR 30045 - Oncologic Drugs Advisory Committee; Notice of Meeting

    Science.gov (United States)

    2010-05-28

    ... cancer known as HER2-negative breast cancer, in combination with the chemotherapy drug docetaxel; and (2) first-line treatment of HER2-negative metastatic breast cancer in combination with one of two classes of... for their locally recurrent or metastatic HER2 negative breast cancer. FDA intends to make...

  3. Photocatalytic degradation of the antiviral drug Tamiflu by UV-A/TiO2: Kinetics and mechanisms.

    Science.gov (United States)

    Wang, Wen-Long; Wu, Qian-Yuan; Wang, Zheng-Ming; Hu, Hong-Ying; Negishi, Nobuaki; Torimura, Masaki

    2015-07-01

    The photocatalytic degradation of the antiviral drug Tamiflu (oseltamivir phosphate, OP) by TiO2 - P25, ST-01 and ATO was investigated in aqueous solution under ultraviolet (UV-A) irradiation. The photocatalysis of OP is well described by pseudo-first-order kinetics with r2>98.0% for all cases. The kinetic constant of P25 with 80% anatase and 20% rutile (0.040 min(-1)) is 4 and 10 times higher than that of ATO and ST-01 with 100% purity of anatase, respectively. We examined the effects of the catalyst loading and initial OP concentration on the photodegradation of OP, and used potassium iodine, isopropanol, and calcium fluorine as radical quenchers to evaluate the contributions of the hydroxyl radical (OH) and photo hole (h+) in the photodegradation. Results confirmed that 80% of the contribution came from the OH species. Although more than 95% of the OP (21 μM) was removed after 80 min of UV-A irradiation with 20 and 100 mg L(-1) P25, the removal efficiencies of total organic carbon (TOC) were only 45.6% and 67.0%, respectively, after 360 min UV-A irradiation. Based on an intermediate analysis by HPLC coupled with a triple quadrupole spectrometer and an ion trap mass spectrometer, typical intermediate species such as hydration derivatives, hydroxyl substitutes and keto-derivatives were identified and possible degradation pathways of OP by P25 were proposed.

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

    Directory of Open Access Journals (Sweden)

    Isabelle Poizot-Martin

    Full Text Available Development of direct acting antivirals (DAA offers new benefits for patients with chronic hepatitis C. The combination of these drugs with antiretroviral treatment (cART is a real challenge in HIV/HCV coinfected patients. The aim of this study was to describe potential drug-drug interactions between DAAs and antiretroviral drugs in a cohort of HIV/HCV coinfected patients.Cross-sectional study of all HIV/HCV coinfected patients attending at least one visit in 2012 in the multicenter French Dat'AIDS cohort. A simulation of drug-drug interactions between antiretroviral treatment and DAAs available in 2015 was performed.Of 16,634 HIV-infected patients, 2,511 had detectable anti-HCV antibodies, of whom 1,196 had a detectable HCV-RNA and were not receiving HCV treatment at the time of analysis. 97.1% of these patients were receiving cART and 81.2% had a plasma HIV RNA <50 copies/mL. cART included combinations of nucleoside reverse transcriptase inhibitors with a boosted protease inhibitor in 43.6%, a non-nucleoside reverse transcriptase inhibitor in 17.3%, an integrase inhibitor in 15.4% and various combinations or antiretroviral drugs in 23.7% of patients. A previous treatment against HCV had been administered in 64.4% of patients. Contraindicated associations/potential interactions were expected between cART and respectively sofosbuvir (0.2%/0%, sofosbuvir/ledipasvir (0.2%/67.6%, daclatasvir (0%/49.4%, ombitasvir/boosted paritaprevir (with or without dasabuvir (34.4%/52.2% and simeprevir (78.8%/0%.Significant potential drug-drug interactions are expected between cART and the currently available DAAs in the majority of HIV/HCV coinfected patients. Sofosbuvir/ledipasvir and sofosbuvir/daclatasvir with or without ribavirin appeared the most suitable combinations in our population. A close collaboration between hepatologists and HIV/AIDS specialists appears necessary for the management of HCV treatment concomitantly to cART.

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

    Directory of Open Access Journals (Sweden)

    Adly M M Abd-Alla

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

  6. Portraying Persons Who Inject Drugs Recently Infected with Hepatitis C Accessing Antiviral Treatment: A Cluster Analysis

    Directory of Open Access Journals (Sweden)

    Jean-Marie Bamvita

    2014-01-01

    Full Text Available Objectives. To empirically determine a categorization of people who inject drug (PWIDs recently infected with hepatitis C virus (HCV, in order to identify profiles most likely associated with early HCV treatment uptake. Methods. The study population was composed of HIV-negative PWIDs with a documented recent HCV infection. Eligibility criteria included being 18 years old or over, and having injected drugs in the previous 6 months preceding the estimated date of HCV exposure. Participant classification was carried out using a TwoStep cluster analysis. Results. From September 2007 to December 2011, 76 participants were included in the study. 60 participants were eligible for HCV treatment. Twenty-one participants initiated HCV treatment. The cluster analysis yielded 4 classes: class 1: Lukewarm health seekers dismissing HCV treatment offer; class 2: multisubstance users willing to shake off the hell; class 3: PWIDs unlinked to health service use; class 4: health seeker PWIDs willing to reverse the fate. Conclusion. Profiles generated by our analysis suggest that prior health care utilization, a key element for treatment uptake, differs between older and younger PWIDs. Such profiles could inform the development of targeted strategies to improve health outcomes and reduce HCV infection among PWIDs.

  7. Portraying persons who inject drugs recently infected with hepatitis C accessing antiviral treatment: a cluster analysis.

    Science.gov (United States)

    Bamvita, Jean-Marie; Roy, Elise; Zang, Geng; Jutras-Aswad, Didier; Artenie, Andreea Adelina; Levesque, Annie; Bruneau, Julie

    2014-01-01

    Objectives. To empirically determine a categorization of people who inject drug (PWIDs) recently infected with hepatitis C virus (HCV), in order to identify profiles most likely associated with early HCV treatment uptake. Methods. The study population was composed of HIV-negative PWIDs with a documented recent HCV infection. Eligibility criteria included being 18 years old or over, and having injected drugs in the previous 6 months preceding the estimated date of HCV exposure. Participant classification was carried out using a TwoStep cluster analysis. Results. From September 2007 to December 2011, 76 participants were included in the study. 60 participants were eligible for HCV treatment. Twenty-one participants initiated HCV treatment. The cluster analysis yielded 4 classes: class 1: Lukewarm health seekers dismissing HCV treatment offer; class 2: multisubstance users willing to shake off the hell; class 3: PWIDs unlinked to health service use; class 4: health seeker PWIDs willing to reverse the fate. Conclusion. Profiles generated by our analysis suggest that prior health care utilization, a key element for treatment uptake, differs between older and younger PWIDs. Such profiles could inform the development of targeted strategies to improve health outcomes and reduce HCV infection among PWIDs. PMID:25349730

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

    Directory of Open Access Journals (Sweden)

    Soliman S. Ibrahim, Amr Shalaby and Mahmoud Rabeh

    2005-09-01

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

  9. Anti-diabetic drugs, insulin and metformin, have no direct interaction with hepatitis C virus infection or anti-viral interferon response

    Directory of Open Access Journals (Sweden)

    Mohamad S. Hakim

    2014-01-01

    Full Text Available Hepatitis C virus (HCV infection is associated with insulin resistance (IR and type 2 diabetes (T2D. Chronic HCV patients with IR and T2D appear to have a decreased response to the standard pegylated-interferon-alpha and ribavirin (PEG-IFN/RBV anti-viral therapy. Insulin and metformin are anti-diabetic drugs regularly used in the clinic. A previous in vitro study has shown a negative effect of insulin on interferon signaling. In the clinic, adding metformin to PEG-IFN/RBV therapy was reported to increase the response rate in chronic HCV patients and it has been suggested this effect derives from an improved anti-viral action of interferon. The goal of this study was to further investigate the molecular insight of insulin and metformin interaction with HCV infection and the anti-viral action of interferon. We used two cell culture models of HCV infection. One is a sub-genomic model that assays viral replication through luciferase reporter gene expression. The other one is a full-length infectious model derived from the JFH1 genotype 2a isolate. We found that both insulin and metformin do not affect HCV infection. Insulin and metformin also do not influence the anti-viral potency of interferon. In addition, there is no direct interaction between these two drugs and interferon signaling. Our results do not confirm the previous laboratory observation that insulin interferes with interferon signaling and suggest that classical nutritional signaling through mTOR may be not involved in HCV replication. If metformin indeed can increase the response rate to interferon therapy in patients, our data indicate that this could be mediated via an indirect mechanisms.

  10. Targeted delivery of macromolecular drugs: asialoglycoprotein receptor (ASGPR) expression by selected hepatoma cell lines used in antiviral drug development.

    Science.gov (United States)

    Li, Yan; Huang, Guifang; Diakur, James; Wiebe, Leonard I

    2008-10-01

    The asialoglycoprotein receptor (ASGPR), an endocytotic cell surface receptor expressed by hepatocytes, is triggered by triantennary binding to galactose residues of macromolecules such as asialoorosomucoid (ASOR). The capacity of this receptor to import large molecules across the cellular plasma membrane makes it an enticing target for receptor-mediated drug delivery to hepatocytes and hepatoma cells via ASGPR-mediated endocytosis. This study describes the preparation and characterization of (125)I-ASOR, and its utility in the assessment of ASGPR expression by HepG2, HepAD38 and Huh5-2 human hepatoma cell lines. ASOR was prepared from human orosomucoid, using acid hydrolysis to remove sialic acid residues, then radioiodinated using iodogen. (125)I-ASOR was purified by gel column chromatography and characterized by SDS-PAGE electrophoresis. The ASOR yield by acid hydrolysis was 75%, with approximately 87 % of the sialic acid residues removed. Electrophoresis and gel chromatography demonstrated substantial differences in (125)I-ASOR quality depending on the method of radioiodination. ASGPR densities per cell were estimated at 76,000 (HepG2), 17,000 (HepAD38) and 3,000 (Huh-5-2). (125)I-ASOR binding to ASGPR on HepG2 cells was confirmed through galactose- and EDTA- challenge studies. It is concluded that (125)I-ASOR is a facilely-prepared, stable assay reagent for ASGPR expression if appropriately prepared, and that HepG2 cells, but not HepAD38 or Huh-5-2 cells, are suitable for studies exploiting the endocytotic ASGPR.

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

    Science.gov (United States)

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

    2016-06-15

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

  12. Antiviral drug valacyclovir treatment combined with a clean feeding system enhances the suppression of salivary gland hypertrophy in laboratory colonies of Glossina pallidipes

    Science.gov (United States)

    2014-01-01

    Background Hytrosaviridae cause salivary gland hypertrophy (SGH) syndrome in some infected tsetse flies (Diptera: Glossinidae). Infected male and female G. pallidipes with SGH have a reduced fecundity and fertility. Due to the deleterious impact of the virus on G. pallidipes colonies, adding the antiviral drug valacyclovir to the blood diet and changing the feeding regime to a clean feeding system (each fly receives for each feeding a fresh clean blood meal) have been investigated to develop virus management strategies. Although both approaches used alone successfully reduced the virus load and the SGH prevalence in small experimental groups, considerable time was needed to obtain the desired SGH reduction and both systems were only demonstrated with colonies that had a low initial virus prevalence (SGH ≤ 10%). As problems with SGH are often only recognized once the incidence is already high, it was necessary to demonstrate that this combination would also work for high prevalence colonies. Findings Combining both methods at colony level successfully suppressed the SGH in G. pallidipes colonies that had a high initial virus prevalence (average SGH of 24%). Six months after starting the combined treatment SGH symptoms were eliminated from the treated colony, in contrast to 28 months required to obtain the same results using clean feeding alone and 21 months using antiviral drug alone. Conclusions Combining valacyclovir treatment with the clean feeding system provides faster control of SGH in tsetse than either method alone and is effective even when the initial SGH prevalence is high. PMID:24886248

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

    OpenAIRE

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

    2011-01-01

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

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

    OpenAIRE

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

    2011-01-01

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

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

    OpenAIRE

    Qingxia Zhang; Dingcheng Wang

    2014-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Ružić Maja

    2010-01-01

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

  17. 78 FR 69991 - Advisory Committee; Veterinary Medicine Advisory Committee; Termination

    Science.gov (United States)

    2013-11-22

    ... HUMAN SERVICES Food and Drug Administration 21 CFR Part 14 Advisory Committee; Veterinary Medicine... Food and Drug Administration (FDA) is announcing the termination of the Veterinary Medicine Advisory... Michael.Ortwerth@fda.hhs.gov . SUPPLEMENTARY INFORMATION: The Veterinary Medicine Committee...

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

    Directory of Open Access Journals (Sweden)

    Thomas Efferth

    2011-09-01

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

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

    OpenAIRE

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

    2012-01-01

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

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

    Science.gov (United States)

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

    2016-10-01

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

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

    Science.gov (United States)

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

    2011-06-01

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

  2. Application of Neurofuzzy Systems to HIV Drug Resistance Problems Aplicación de sistemas neuroborrosos a problemas de resistencia antiviral del VIH

    Directory of Open Access Journals (Sweden)

    Carlos Morell Pérez

    2012-09-01

    Full Text Available The high mutability of Human Immunodeficiency Virus (HIV leads to serious problems on designing efficient antiviral drugs. In fact, in last years the study of drug resistance prediction for HIV mutations has become an open problem for researchers. Several statistical and machine learning techniques have been proposed for modelling this sequence classification problem, but most of them are difficult to interpret. This paper presents a modelling of the protease protein as a dynamic system through Neurofuzzy Systems, using the amino acid contact energies for the sequence description. In addition, three neurofuzzy learning algorithms are used to predict the resistance to five protease antivirals. Finally, we propose rules extracted from these algorithms for interpreting the influence of each sequence position on the resistance to five well-known inhibitor drugs. La alta capacidad de mutación del Virus de Inmunodeficiencia Humana (VIH afecta seriamente el diseño eficiente de fármacos antivirales para combatirlo.  De hecho, en los últimos años el estudio de la predicción de resistencia a fármacos del VIH se ha convertido en un campo abierto de investigación. Varias técnicas estadísticas y de inteligencia artificial han sido propuestas para modelar este problema de clasificación de secuencias, pero la mayoría de ellas son difíciles de interpretar. Este trabajo presenta el modelado de la proteína proteasa como un sistema dinámico a través de Sistemas Neuroborrosos, utilizando las energías de contacto de los aminoácidos para la descripción de la secuencia. Además, se utilizan tres algoritmos de aprendizaje neuroborrosos para predecir la resistencia a cinco inhibidores de la proteasa. Finalmente, se proponen las reglas extraídas de estos algoritmos para interpretar la influencia de cada posición de la secuencia en la resistencia a cinco fármacos inhibidores conocidos.

  3. Aplicación de sistemas neuroborrosos a problemas de resistencia antiviral del VIH Application of Neurofuzzy Systems to HIV Drug Resistance Problems

    Directory of Open Access Journals (Sweden)

    Carlos Morell Pérez

    2012-09-01

    Full Text Available La alta capacidad de mutación del Virus de Inmunodeficiencia Humana (VIH afecta seriamente el diseño eficiente de fármacos antivirales para combatirlo.  De hecho, en los últimos años el estudio de la predicción de resistencia a fármacos del VIH se ha convertido en un campo abierto de investigación. Varias técnicas estadísticas y de inteligencia artificial han sido propuestas para modelar este problema de clasificación de secuencias, pero la mayoría de ellas son difíciles de interpretar. Este trabajo presenta el modelado de la proteína proteasa como un sistema dinámico a través de Sistemas Neuroborrosos, utilizando las energías de contacto de los aminoácidos para la descripción de la secuencia. Además, se utilizan tres algoritmos de aprendizaje neuroborrosos para predecir la resistencia a cinco inhibidores de la proteasa. Finalmente, se proponen las reglas extraídas de estos algoritmos para interpretar la influencia de cada posición de la secuencia en la resistencia a cinco fármacos inhibidores conocidos.The high mutability of Human Immunodeficiency Virus (HIV leads to serious problems on designing efficient antiviral drugs. In fact, in last years the study of drug resistance prediction for HIV mutations has become an open problem for researchers. Several statistical and machine learning techniques have been proposed for modelling this sequence classification problem, but most of them are difficult to interpret. This paper presents a modelling of the protease protein as a dynamic system through Neurofuzzy Systems, using the amino acid contact energies for the sequence description. In addition, three neurofuzzy learning algorithms are used to predict the resistance to five protease antivirals. Finally, we propose rules extracted from these algorithms for interpreting the influence of each sequence position on the resistance to five well-known inhibitor drugs.

  4. Genetic Diversity and Selective Pressure in Hepatitis C Virus Genotypes 1–6: Significance for Direct-Acting Antiviral Treatment and Drug Resistance

    Science.gov (United States)

    Cuypers, Lize; Li, Guangdi; Libin, Pieter; Piampongsant, Supinya; Vandamme, Anne-Mieke; Theys, Kristof

    2015-01-01

    Treatment with pan-genotypic direct-acting antivirals, targeting different viral proteins, is the best option for clearing hepatitis C virus (HCV) infection in chronically infected patients. However, the diversity of the HCV genome is a major obstacle for the development of antiviral drugs, vaccines, and genotyping assays. In this large-scale analysis, genome-wide diversity and selective pressure was mapped, focusing on positions important for treatment, drug resistance, and resistance testing. A dataset of 1415 full-genome sequences, including genotypes 1–6 from the Los Alamos database, was analyzed. In 44% of all full-genome positions, the consensus amino acid was different for at least one genotype. Focusing on positions sharing the same consensus amino acid in all genotypes revealed that only 15% was defined as pan-genotypic highly conserved (≥99% amino acid identity) and an additional 24% as pan-genotypic conserved (≥95%). Despite its large genetic diversity, across all genotypes, codon positions were rarely identified to be positively selected (0.23%–0.46%) and predominantly found to be under negative selective pressure, suggesting mainly neutral evolution. For NS3, NS5A, and NS5B, respectively, 40% (6/15), 33% (3/9), and 14% (2/14) of the resistance-related positions harbored as consensus the amino acid variant related to resistance, potentially impeding treatment. For example, the NS3 variant 80K, conferring resistance to simeprevir used for treatment of HCV1 infected patients, was present in 39.3% of the HCV1a strains and 0.25% of HCV1b strains. Both NS5A variants 28M and 30S, known to be associated with resistance to the pan-genotypic drug daclatasvir, were found in a significant proportion of HCV4 strains (10.7%). NS5B variant 556G, known to confer resistance to non-nucleoside inhibitor dasabuvir, was observed in 8.4% of the HCV1b strains. Given the large HCV genetic diversity, sequencing efforts for resistance testing purposes may need to be

  5. 75 FR 35496 - Cardiovascular and Renal Drugs Advisory Committee; Notice of Meeting

    Science.gov (United States)

    2010-06-22

    ... Inn and Conference Center, University of Maryland University College, 3501 University Blvd. East... attendance of the public at its advisory committee meetings and will make every effort to accommodate...

  6. 75 FR 57474 - Cardiovascular and Renal Drugs Advisory Committee; Notice of Meeting

    Science.gov (United States)

    2010-09-21

    ... Marriott Inn and Conference Center, University of Maryland University College, 3501 University Boulevard... attendance of the public at its advisory committee meetings and will make every effort to accommodate...

  7. 76 FR 30176 - Dermatologic and Ophthalmic Drugs Advisory Committee; Notice of Meeting

    Science.gov (United States)

    2011-05-24

    ... Marriott Inn and Conference Center, University of Maryland University College (UMUC), 3501 University Blvd... attendance of the public at its advisory committee meetings and will make every effort to accommodate...

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

    Science.gov (United States)

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

    2016-01-01

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

  9. HCV Drug Resistance Challenges in Japan: The Role of Pre-Existing Variants and Emerging Resistant Strains in Direct Acting Antiviral Therapy

    Directory of Open Access Journals (Sweden)

    Kazuaki Chayama

    2015-10-01

    Full Text Available Sustained virological response (SVR rates have increased dramatically following the approval of direct acting antiviral (DAA therapies. While individual DAAs have a low barrier to resistance, most patients can be successfully treated using DAA combination therapy. However, DAAs are vulnerable to drug resistance, and resistance-associated variants (RAVs may occur naturally prior to DAA therapy or may emerge following drug exposure. While most RAVs are quickly lost in the absence of DAAs, compensatory mutations may reinforce fitness. However, the presence of RAVs does not necessarily preclude successful treatment. Although developments in hepatitis C virus (HCV therapy in Asia have largely paralleled those in the United States, Japan’s July 2014 approval of asunaprevir plus daclatasvir combination therapy as the first all-oral interferon-free therapy was not repeated in the United States. Instead, two different combination therapies were approved: sofosbuvir/ledipasvir and paritaprevir/ritonavir/ombitasvir/dasabuvir. This divergence in treatment approaches may lead to differences in resistance challenges faced by Japan and the US. However, the recent approval of sofosbuvir plus ledipasvir in Japan and the recent submissions of petitions for approval of paritaprevir/ritonavir plus ombitasvir suggest a trend towards a new consensus on emerging DAA regimens.

  10. P1-Substituted Symmetry-Based Human Immunodeficiency Virus Protease Inhibitors with Potent Antiviral Activity against Drug-Resistant Viruses

    Energy Technology Data Exchange (ETDEWEB)

    DeGoey, David A.; Grampovnik, David J.; Chen, Hui-Ju; Flosi, William J.; Klein, Larry L.; Dekhtyar, Tatyana; Stoll, Vincent; Mamo, Mulugeta; Molla, Akhteruzzaman; Kempf, Dale J. (Abbott)

    2013-03-07

    Because there is currently no cure for HIV infection, patients must remain on long-term drug therapy, leading to concerns over potential drug side effects and the emergence of drug resistance. For this reason, new and safe antiretroviral agents with improved potency against drug-resistant strains of HIV are needed. A series of HIV protease inhibitors (PIs) with potent activity against both wild-type (WT) virus and drug-resistant strains of HIV was designed and synthesized. The incorporation of substituents with hydrogen bond donor and acceptor groups at the P1 position of our symmetry-based inhibitor series resulted in significant potency improvements against the resistant mutants. By this approach, several compounds, such as 13, 24, and 29, were identified that demonstrated similar or improved potencies compared to 1 against highly mutated strains of HIV derived from patients who previously failed HIV PI therapy. Overall, compound 13 demonstrated the best balance of potency against drug resistant strains of HIV and oral bioavailability in pharmacokinetic studies. X-ray analysis of an HIV PI with an improved resistance profile bound to WT HIV protease is also reported.

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

    NARCIS (Netherlands)

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

    1990-01-01

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

  12. Evaluation of Antiviral Compounds Against Avian Influenza

    OpenAIRE

    Call, Evan W.

    1991-01-01

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

  13. 76 FR 59143 - Joint Meeting of the Advisory Committee for Reproductive Health Drugs and the Drug Safety and...

    Science.gov (United States)

    2011-09-23

    ..., from 8 a.m. to 5 p.m. Location: The Marriott Inn and Conference Center, University of Maryland University College, The Ballroom, 3501 University Blvd. East, Adelphi, MD. The conference center telephone... welcomes the attendance of the public at its advisory committee meetings and will make every effort...

  14. 76 FR 59142 - Joint Meeting of the Advisory Committee for Reproductive Health Drugs and the Drug Safety and...

    Science.gov (United States)

    2011-09-23

    ..., from 8 a.m. to 5 p.m. Location: The Marriott Inn and Conference Center, University of Maryland University College (UMUC), The Ballroom, 3501 University Blvd., ] East, Adelphi, MD. The conference center... welcomes the attendance of the public at its advisory committee meetings and will make every effort...

  15. 75 FR 32188 - Joint Meeting of the Anesthetic and Life Support Drugs Advisory Committee and the Drug Safety and...

    Science.gov (United States)

    2010-06-07

    ... 23, 2010, from 8 a.m. to 4:30 p.m. Location: The Marriott Inn and Conference Center, University of Maryland University College, 3501 University Boulevard East, Adelphi, MD. The conference center telephone... attendance of the public at its advisory committee meetings and will make every effort to accommodate...

  16. Study on the interaction of the antiviral drug, zidovudine with DNA using neutral red (NR) and methylene blue (MB) dyes

    Energy Technology Data Exchange (ETDEWEB)

    Shahabadi, Nahid, E-mail: nahidshahabadi@yahoo.com [Department of Inorganic Chemistry, Faculty of Chemistry, Razi University, Kermanshah (Iran, Islamic Republic of); Moghadam, Neda Hossein pour [Department of Inorganic Chemistry, Faculty of Chemistry, Razi University, Kermanshah (Iran, Islamic Republic of)

    2013-02-15

    The interaction between the drug, zidovudine and calf thymus DNA (CT-DNA) in physiological buffer (pH 7.4) was investigated using neutral red (NR) and methylene blue (MB) dyes as a spectral probes by UV-vis absorption and fluorescence spectroscopy, as well as circular dichroism (CD) spectroscopy. The experimental results showed that the conformational changes in DNA helix induced by zidovudine are the reason for the fluorescence quenching of the DNA-NR system. In addition, by increasing zidovudine to DNA-MB solution, the fluorescence has no change. From the experimental results, it was found that zidovudine can cause structural changes on CT-DNA and bind with DNA via groove binding mode. At the same time, the paper proved that conformational changes of DNA can also lead to the fluorescence decrease of DNA-probe systems. - Highlights: Black-Right-Pointing-Pointer Search for new molecular structures which exhibit effective antitumor activities among popular drugs. Black-Right-Pointing-Pointer The DRUG can bind to DNA via groove binding mode. Black-Right-Pointing-Pointer Several spectroscopic techniques have been used in this research.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2012-11-14

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

  18. Oxidation of the antiviral drug acyclovir and its biodegradation product carboxy-acyclovir with ozone: kinetics and identification of oxidation products.

    Science.gov (United States)

    Prasse, Carsten; Wagner, Manfred; Schulz, Ralf; Ternes, Thomas A

    2012-02-21

    The oxidation of the antiviral drug acyclovir (ACV) and its main biotransformation product carboxy-acyclovir (carboxy-ACV) by ozone was investigated. Both compounds have recently been detected in surface water, and carboxy-ACV has also been detected in drinking water. The experiments revealed a strong pH dependence of the oxidation of ACV and carboxy-ACV with reaction rate constants increasing by 4 orders of magnitude between the protonated, positively charged form (k(ox,PH(+)), ∼2.5 × 10(2) M(-1) s(-1)) and the deprotonated, negatively charged form (k(ox,P(-)), 3.4 × 10(6) M(-1) s(-1)). At pH 8 a single oxidation product was formed which was identified via LC-LTQ-Orbitrap MS and NMR as N-(4-carbamoyl-2-imino-5-oxoimidazolidin)formamido-N-methoxyacetic acid (COFA). Using Vibrio fischeri , an acute bacterial toxicity was found for COFA while carboxy-ACV revealed no toxic effects. Ozonation experiments with guanine and guanosine at pH 8 led to the formation of the respective 2-imino-5-oxoimidazolidines, confirming that guanine derivatives such as carboxy-ACV are undergoing the same reactions during ozonation. Furthermore, COFA was detected in finished drinking water of a German waterworks after ozonation and subsequent activated carbon treatment.

  19. Vaccinia virus lacking the deoxyuridine triphosphatase gene (F2L replicates well in vitro and in vivo, but is hypersensitive to the antiviral drug (N-methanocarbathymidine

    Directory of Open Access Journals (Sweden)

    Moyer Richard W

    2008-03-01

    Full Text Available Abstract Background The vaccinia virus (VV F2L gene encodes a functional deoxyuridine triphosphatase (dUTPase that catalyzes the conversion of dUTP to dUMP and is thought to minimize the incorporation of deoxyuridine residues into the viral genome. Previous studies with with a complex, multigene deletion in this virus suggested that the gene was not required for viral replication, but the impact of deleting this gene alone has not been determined in vitro or in vivo. Although the crystal structure for this enzyme has been determined, its potential as a target for antiviral therapy is unclear. Results The F2L gene was replaced with GFP in the WR strain of VV to assess its effect on viral replication. The resulting virus replicated well in cell culture and its replication kinetics were almost indistinguishable from those of the wt virus and attained similar titers. The virus also appeared to be as pathogenic as the WR strain suggesting that it also replicated well in mice. Cells infected with the dUTPase mutant would be predicted to affect pyrimidine deoxynucleotide pools and might be expected to exhibit altered susceptibility to pyrimidine analogs. The antiviral activity of cidofovir and four thymidine analogs were evaluated both in the mutant and the parent strain of this virus. The dUTPase knockout remained fully susceptible to cidofovir and idoxuridine, but was hypersensitive to the drug (N-methanocarbathymidine, suggesting that pyrimidine metabolism was altered in cells infected with the mutant virus. The absence of dUTPase should reduce cellular dUMP pools and may result in a reduced conversion to dTMP by thymidylate synthetase or an increased reliance on the salvage of thymidine by the viral thymidine kinase. Conclusion We confirmed that F2L was not required for replication in cell culture and determined that it does not play a significant role on virulence of the virus in intranasally infected mice. The recombinant virus is hypersensitive

  20. In silico study of rotavirus VP7 surface accessible conserved regions for antiviral drug/vaccine design.

    Directory of Open Access Journals (Sweden)

    Ambarnil Ghosh

    Full Text Available BACKGROUND: Rotaviral diarrhoea kills about half a million children annually in developing countries and accounts for one third of diarrhea related hospitalizations. Drugs and vaccines against the rotavirus are handicapped, as in all viral diseases, by the rapid mutational changes that take place in the DNA and protein sequences rendering most of these ineffective. As of now only two vaccines are licensed and approved by the WHO (World Health Organization, but display reduced efficiencies in the underdeveloped countries where the disease is more prevalent. We approached this issue by trying to identify regions of surface exposed conserved segments on the surface glycoproteins of the virion, which may then be targeted by specific peptide vaccines. We had developed a bioinformatics protocol for these kinds of problems with reference to the influenza neuraminidase protein, which we have refined and expanded to analyze the rotavirus issue. RESULTS: Our analysis of 433 VP7 (Viral Protein 7 from rotavirus surface protein sequences across 17 subtypes encompassing mammalian hosts using a 20D Graphical Representation and Numerical Characterization method, identified four possible highly conserved peptide segments. Solvent accessibility prediction servers were used to identify that these are predominantly surface situated. These regions analyzed through selected epitope prediction servers for their epitopic properties towards possible T-cell and B-cell activation showed good results as epitopic candidates (only dry lab confirmation. CONCLUSIONS: The main reasons for the development of alternative vaccine strategies for the rotavirus are the failure of current vaccines and high production costs that inhibit their application in developing countries. We expect that it would be possible to use the protein surface exposed regions identified in our study as targets for peptide vaccines and drug designs for stable immunity against divergent strains of the

  1. Small molecules with antiviral activity against the Ebola virus

    OpenAIRE

    Nadia Litterman; Christopher Lipinski; Sean Ekins

    2015-01-01

    The recent outbreak of the Ebola virus in West Africa has highlighted the clear shortage of broad-spectrum antiviral drugs for emerging viruses. There are numerous FDA approved drugs and other small molecules described in the literature that could be further evaluated for their potential as antiviral compounds. These molecules are in addition to the few new antivirals that have been tested in Ebola patients but were not originally developed against the Ebola virus, and may play an important r...

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

    Directory of Open Access Journals (Sweden)

    Margarita Clara Alvarez-Ros

    2014-06-01

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

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

    Directory of Open Access Journals (Sweden)

    Desarae Echevarria

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

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

    Science.gov (United States)

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

    2016-03-24

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

  5. Influenza A(H1N1)pdm09 resistance and cross-decreased susceptibility to oseltamivir and zanamivir antiviral drugs.

    Science.gov (United States)

    Correia, Vanessa; Santos, Luis A; Gíria, Marta; Almeida-Santos, Maria M; Rebelo-de-Andrade, Helena

    2015-01-01

    Neuraminidase inhibitors (NAIs) oseltamivir and zanamivir are currently the only effective antiviral drugs available worldwide for the management of influenza. The potential development of resistance is continually threatening their use, rationalizing and highlighting the need for a close and sustained evaluation of virus susceptibility. This study aimed to analyze and characterize the phenotypic and genotypic NAIs susceptibility profiles of A(H1N1)pdm09 viruses circulating in Portugal from 2009 to 2010/2011. A total of 144 cases of A(H1N1)pdm09 virus infection from community and hospitalized patients were studied, including three suspected cases of clinical resistance to oseltamivir. Oseltamivir resistance was confirmed for two of the suspected cases. Neuraminidase (NA) H275Y resistant marker was found in viruses from both cases but for one it was only present in 26.2% of virus population, raising questions about the minimal percentage of resistant virus that should be considered relevant. Cross-decreased susceptibility to oseltamivir and zanamivir (2-4 IC50 fold-change) was detected on viruses from two potentially linked community patients from 2009. Both viruses harbored the NA I223V mutation. NA Y155H mutation was found in 18 statistical non-outlier viruses from 2009, having no impact on virus susceptibility. The mutations at NA N369K and V241I may have contributed to the significantly higher baseline IC50 value obtained to oseltamivir for 2010/2011 viruses, compared to viruses from the pandemic period. These results may contribute to a better understanding of the relationship between phenotype and genotype, which is currently challenging, and to the global assessment of A(H1N1)pdm09 virus susceptibility profile and baseline level to NAIs.

  6. 78 FR 37821 - Joint Meeting of the Risk Communication Advisory Committee and Tobacco Products Scientific...

    Science.gov (United States)

    2013-06-24

    ...: Risk Communication Advisory Committee and Tobacco Products Scientific Advisory Committee. General... HUMAN SERVICES Food and Drug Administration Joint Meeting of the Risk Communication Advisory Committee and Tobacco Products Scientific Advisory Committee; Notice of Joint Meeting AGENCY: Food and...

  7. Complex of the herpes simplex virus type 1 origin binding protein UL9 with DNA as a platform for the design of a new type of antiviral drugs.

    Science.gov (United States)

    Bazhulina, N P; Surovaya, A N; Gursky, Y G; Andronova, V L; Moiseeva, E D; Nikitin, Capital A Cyrillic M; Golovkin, M V; Galegov, G А; Grokhovsky, S L; Gursky, G V

    2014-01-01

    The herpes simplex virus type 1 origin-binding protein, OBP, is a DNA helicase encoded by the UL9 gene. The protein binds in a sequence-specific manner to the viral origins of replication, two OriS sites and one OriL site. In order to search for efficient inhibitors of the OBP activity, we have obtained a recombinant origin-binding protein expressed in Escherichia coli cells. The UL9 gene has been amplified by PCR and inserted into a modified plasmid pET14 between NdeI and KpnI sites. The recombinant protein binds to Box I and Box II sequences and possesses helicase and ATPase activities. In the presence of ATP and viral protein ICP8 (single-strand DNA-binding protein), the initiator protein induces unwinding of the minimal OriS duplex (≈80 bp). The protein also binds to a single-stranded DNA (OriS*) containing a stable Box I-Box III hairpin and an unstable AT-rich hairpin at the 3'-end. In the present work, new minor groove binding ligands have been synthesized which are capable to inhibit the development of virus-induced cytopathic effect in cultured Vero cells. Studies on binding of these compounds to DNA and synthetic oligonucleotides have been performed by fluorescence methods, gel mobility shift analysis and footprinting assays. Footprinting studies have revealed that Pt-bis-netropsin and related molecules exhibit preferences for binding to the AT-spacer in OriS. The drugs stabilize structure of the AT-rich region and inhibit the fluctuation opening of AT-base pairs which is a prerequisite to unwinding of DNA by OBP. Kinetics of ATP-dependent unwinding of OriS in the presence and absence of netropsin derivatives have been studied by measuring the efficiency of Forster resonance energy transfer (FRET) between fluorophores attached to 5'- and 3'- ends of an oligonucleotide in the minimal OriS duplex. The results are consistent with the suggestion that OBP is the DNA Holiday junction (HJ) binding helicase. The protein induces conformation changes (bending

  8. Antiviral Strategies for Pandemic and Seasonal Influenza

    OpenAIRE

    Fang Fang; Maria Hedlund; Larson, Jeffrey L.

    2010-01-01

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

  9. Antiviral resistance and the control of pandemic influenza: The roles of stochasticity, evolution and model details

    OpenAIRE

    Handel, Andreas; Longini, Ira M.; Antia, Rustom

    2008-01-01

    Antiviral drugs, most notably the neuraminidase inhibitors, are an important component of control strategies aimed to prevent or limit any future influenza pandemic. The potential large-scale use of antiviral drugs brings with it the danger of drug resistance evolution. A number of recent studies have shown that the emergence of drug-resistant influenza could undermine the usefulness of antiviral drugs for the control of an epidemic or pandemic outbreak. While these studies have provided impo...

  10. Antiviral Effect of Agaricomycetes Mushrooms (Review).

    Science.gov (United States)

    Teplyakova, Tamara V; Kosogova, Tatiana A

    2016-01-01

    This review presents data on the studied antiviral activities of Agaricomycetes mushrooms against the herpes, West Nile, influenza, human immunodeficiency, and hepatitis viruses, as well as orthopoxviruses, including the variola virus. Polysaccharides and other compounds (e.g., proteins, glycoproteins, terpenoids, melanins, nucleosides) exhibit antiviral activity against many viruses that are pathogenic in humans. Effective strains isolated from wild mushrooms in culture represent promising objects for the development of biotechnological drugs, including ones possessing antiviral activity. The data on antitumor and antiviral activities of compounds from the same mushroom species indicate the correlation of these properties. With regard to this connection, preparations of Basidiomycetes may have prophylactic value in preventing cancers with a viral etiology. PMID:27649599

  11. Determining Mechanism of Action of Antivirals for Respiratory Illness

    Science.gov (United States)

    Rodriguez, Irma; Dobrovolny, Hana

    2015-03-01

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

  12. 78 FR 63222 - Pediatric Oncology Subcommittee of the Oncologic Drugs Advisory Committee; Notice of Meeting

    Science.gov (United States)

    2013-10-23

    ... HUMAN SERVICES Food and Drug Administration Pediatric Oncology Subcommittee of the Oncologic Drugs... ] (FDA). The meeting will be open to the public. Name of Committee: Pediatric Oncology Subcommittee of... relevance and potential use of such measures in the pediatric development plans of oncology products....

  13. 75 FR 66773 - Pediatric Oncology Subcommittee of the Oncologic Drugs Advisory Committee; Notice of Meeting

    Science.gov (United States)

    2010-10-29

    ... HUMAN SERVICES Food and Drug Administration Pediatric Oncology Subcommittee of the Oncologic Drugs... (FDA). The meeting will be open to the public. Name of Committee: Pediatric Oncology Subcommittee of... were either recently approved by FDA or, are in late stage development for an adult oncology...

  14. 78 FR 63224 - Pediatric Oncology Subcommittee of the Oncologic Drugs Advisory Committee; Notice of Meeting

    Science.gov (United States)

    2013-10-23

    ... HUMAN SERVICES Food and Drug Administration Pediatric Oncology Subcommittee of the Oncologic Drugs... (FDA). The meeting will be open to the public. Name of Committee: Pediatric Oncology Subcommittee of... late stage development for various adult oncology indications. The subcommittee will consider...

  15. 76 FR 58520 - Pediatric Oncology Subcommittee of the Oncologic Drugs Advisory Committee; Notice of Meeting

    Science.gov (United States)

    2011-09-21

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration Pediatric Oncology Subcommittee of the Oncologic Drugs... (FDA). The meeting will be open to the public. Name of Committee: Pediatric Oncology Subcommittee...

  16. 77 FR 57095 - Pediatric Oncology Subcommittee of the Oncologic Drugs Advisory Committee; Notice of Meeting

    Science.gov (United States)

    2012-09-17

    ... HUMAN SERVICES Food and Drug Administration Pediatric Oncology Subcommittee of the Oncologic Drugs... (FDA). The meeting will be open to the public. Name of Committee: Pediatric Oncology Subcommittee of... plans for four products that are in development for an adult oncology indication. The subcommittee...

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

    OpenAIRE

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

    2010-01-01

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

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

    Institute of Scientific and Technical Information of China (English)

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

    2012-01-01

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

  19. 77 FR 6567 - Endocrinologic and Metabolic Drugs Advisory Committee; Notice of Meeting

    Science.gov (United States)

    2012-02-08

    ... the heading ``Resources for You,'' click on ``Public Meetings at the FDA White Oak Campus.'' Please... enough to provide timely notice. Therefore, you should always check the Agency's Web site and call the... preapproval and postapproval settings for drugs and biologics developed for the treatment of obesity....

  20. Hepatitis C Drugs: The End of the Pegylated Interferon Era and the Emergence of All-Oral, Interferon-Free Antiviral Regimens: A Concise Review

    Directory of Open Access Journals (Sweden)

    Alan Hoi Lun Yau

    2014-01-01

    Full Text Available Between 2001 and 2011, the standard of care for chronic hepatitis C virus (HCV infection was a combination of pegylated interferon (PEGIFN and ribavirin (RBV. In May 2011, boceprevir and telaprevir, two first-generation NS3/4A protease inhibitors, were approved in combination with PEG-IFN and RBV for 24 to 48 weeks in hepatitis C virus genotype 1 infections. In December 2013, simeprevir, a second-generation NS3/4A protease inhibitor, was approved for use with PEG-IFN and RBV for 12 weeks in genotype 1, while sofosbuvir, a NS5B nucleotide polymerase inhibitor, was approved for use with PEG-IFN and RBV for 12 weeks in genotypes 1 and 4, as well as with RBV alone for 12 weeks in genotype 2 and for 24 weeks in genotype 3. Sofosbuvir combined with simeprevir or an NS5A replication complex inhibitor (ledipasvir or daclatasvir with or without RBV for 12 weeks in genotype 1 resulted in a sustained virological response >90%, irrespective of previous treatment history or presence of cirrhosis. Similarly impressive sustained virological response rates have been shown with ABT-450/r (ritonavir-boosted NS3/4A protease inhibitor-based regimens in combination with other direct-acting antiviral agent(s with or without RBV for 12 weeks in genotype 1. The optimal all-oral interferon-free antiviral regimen likely entails a combination of an NS5B nucleotide polymerase inhibitor with either a second-generation NS3/4A protease inhibitor or an NS5A replication complex inhibitor with or without RBV. Further research is needed to determine the role of resistance testing, clarify the optimal follow-up duration post-treatment, and evaluate the antiviral efficacy and safety in difficult-to-cure patient populations.

  1. Antiviral activity of luteolin against Japanese encephalitis virus.

    Science.gov (United States)

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

    2016-07-15

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

  2. 78 FR 17414 - Risk Communications Advisory Committee; Notice of Meeting

    Science.gov (United States)

    2013-03-21

    ...: Luis G. Bravo, Designated Federal Officer, Risk Communication Staff, Office of Planning, Food and Drug... HUMAN SERVICES Food and Drug Administration Risk Communications Advisory Committee; Notice of Meeting... the public. Name of Committee: Risk Communications Advisory Committee. General Function of...

  3. Analysis of the Utilization of Antiviral Drugs in 32 Hospitals from Wuhan Area during the Period of 2009-2011%武汉地区32家医院2009-2011年抗病毒药利用分析

    Institute of Scientific and Technical Information of China (English)

    姜鸽; 徐艳娇; 刘东

    2012-01-01

    OBJECTIVE: To investigate the utilization and trends of antiviral drugs in hospitals of Wuhan area. METHODS: Using a retrospective method, the utilization of antiviral drugs in 32 hospitals from Wuhan area during 2009 - 2011 was analyzed statistically in respect of consumption sum, DDDs and DDC. RESULTS: The consumption sum of antiviral drugs was increasing year by year during 2009-2011. Top 5 drugs were nucleoside antiviral drugs, accounting for about 90% of total consumption sum. The DDDs of adefovir dipivoxil and telbivudine took up top places in the list of DDDs. The DDC of valganciclovir was the highest (5 475 yuan per day) and amantadine was the lowest (about 0.13 yuan per day), followed by ribavirin (about 3 yuan per day). CONCLUSION: The kinds of antiviral drugs are relatively single in hospitals from Wuhan area, and they are mainly nucleotide an-tivirus drugs. The antiviral drugs are mostly used for treatment of hepatitis virus, and small amount are used for AIDS. As a result, the R&D of antiviral drugs still has some room for development in China.%目的:了解武汉地区医院抗病毒药的利用情况及趋势.方法:采用回顾性方法,对武汉地区32家医院2009-2011年抗病毒药的销售金额、用药频度(DDDs)和日均费用(DDC)等进行统计、分析.结果:3年来该地区医院抗病毒药总销售金额呈逐年上升趋势,居前5位的均为核苷类药,约占总销售额的90%;阿德福韦酯、替比夫定的DDDs较高,一直居前2位;缬更昔洛韦的DDC值最高(达5475元/日),金刚烷胺的DDC最低(约0.13元/日),其次是三氮唑核苷(约3元/日).结论:该地区医院临床应用抗病毒药品种相对单一,主要为核苷类抗病毒药;抗病毒药基本用于病毒性肝炎的治疗,用于艾滋病治疗的药品较少.

  4. 76 FR 78931 - Advisory Committees; Tentative Schedule of Meetings for 2012

    Science.gov (United States)

    2011-12-20

    ... Advisory Committee..... May 16-17. Arthritis Advisory Committee March 12. Cardiovascular and Renal Drugs...-6. Ophthalmic Devices Panel November 8-9. Orthopedic and Rehabilitation Devices September...

  5. 78 FR 70954 - Risk Communications Advisory Committee; Notice of Meeting

    Science.gov (United States)

    2013-11-27

    ... the free Webcast. Visit the Risk Communication Advisory Committee Web site at http://www.fda.gov/AdvisoryCommittees/CommitteesMeetingMaterials/RiskCommunicationAdvisoryCommittee/default.htm . The link... HUMAN SERVICES Food and Drug Administration Risk Communications Advisory Committee; Notice of...

  6. Antiviral effects of Glycyrrhiza species.

    Science.gov (United States)

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

    2008-02-01

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

  7. Antiviral targets of human noroviruses.

    Science.gov (United States)

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

    2016-06-01

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

  8. Ethical guidelines in pandemic influenza: recommendations of the Ethics Subcommittee of the Advisory Committee of the Director, Centers for Disease Control and Prevention.

    Science.gov (United States)

    Kinlaw, Kathy; Barrett, Drue H; Levine, Robert J

    2009-12-01

    Because of the importance of including ethical considerations in planning efforts for pandemic influenza, in February 2005 the Centers for Disease Control and Prevention requested that the Ethics Subcommittee of the Advisory Committee to the Director develop guidance that would serve as a foundation for decision making in preparing for and responding to pandemic influenza. Specifically, the ethics subcommittee was asked to make recommendations regarding ethical considerations relevant to decision making about vaccine and antiviral drug distribution prioritization and development of interventions that would limit individual freedom and create social distancing. The ethics subcommittee identified a number of general ethical considerations including identification of clear goals for pandemic planning, responsibility to maximize preparedness, transparency and public engagement, sound science, commitment to the global community, balancing individual liberty and community interests, diversity in ethical decision making, and commitment to justice. These general ethical considerations are applied to the issues of vaccine and antiviral drug distribution and use of community mitigation interventions. PMID:19675459

  9. 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.

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

    OpenAIRE

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

    2014-01-01

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

  11. Exploiting Genetic Interference for Antiviral Therapy.

    Science.gov (United States)

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

    2016-05-01

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

  12. ANTIVIRAL POTENTIAL OF MEDICINAL PLANTS: AN OVERVIEW

    OpenAIRE

    Ruwali Pushpa; Rai Nishant; Kumar Navin; Gautam Pankaj

    2013-01-01

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

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

    OpenAIRE

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

    2009-01-01

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

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

    OpenAIRE

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

    2007-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Shuai Chang

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

  16. Drug: D02267 [KEGG MEDICUS

    Lifescience Database Archive (English)

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

  17. Antiviral resistance and the control of pandemic influenza.

    Directory of Open Access Journals (Sweden)

    Marc Lipsitch

    2007-01-01

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

  18. 77 FR 70450 - Risk Communication Advisory Committee; Notice of Meeting

    Science.gov (United States)

    2012-11-26

    ... HUMAN SERVICES Food and Drug Administration Risk Communication Advisory Committee; Notice of Meeting... the public. Name of Committee: Risk Communication Advisory Committee. General Function of the... Campus must enter through Building 1. Contact Person: Lee L. Zwanziger, Risk Communication Staff,...

  19. 75 FR 57279 - Risk Communication Advisory Committee; Notice of Meeting

    Science.gov (United States)

    2010-09-20

    ... HUMAN SERVICES Food and Drug Administration Risk Communication Advisory Committee; Notice of Meeting... the public. Name of Committee: Risk Communication Advisory Committee. General Function of the... programs, such as FDA's Strategic Plan for Risk Communication, FDA's Transparency Initiative, and...

  20. 77 FR 62242 - Risk Communication Advisory Committee; Notice of Meeting

    Science.gov (United States)

    2012-10-12

    ... HUMAN SERVICES Food and Drug Administration Risk Communication Advisory Committee; Notice of Meeting... the public. Name of Committee: Risk Communication Advisory Committee. General Function of the... enter through Building 1. Contact Person: Lee L. Zwanziger, Risk Communication Staff, Office of...

  1. 77 FR 31025 - Risk Communication Advisory Committee; Notice of Meeting

    Science.gov (United States)

    2012-05-24

    ... HUMAN SERVICES Food and Drug Administration Risk Communication Advisory Committee; Notice of Meeting... the public. Name of Committee: Risk Communication Advisory Committee. General Function of the... enter through Building 1. Contact Person: Lee L. Zwanziger, Risk Communication Staff, Office of...

  2. 75 FR 52605 - Veterinary Medicine Advisory Committee; Notice of Meeting

    Science.gov (United States)

    2010-08-26

    ... HUMAN SERVICES Food and Drug Administration Veterinary Medicine Advisory Committee; Notice of Meeting... the public. Name of Committee: Veterinary Medicine Advisory Committee. General Function of the...-1100. Contact Person: Aleta Sindelar, Center for Veterinary Medicine (HFV-3), Food and...

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

    Institute of Scientific and Technical Information of China (English)

    陈执中

    2009-01-01

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

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

    Science.gov (United States)

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

    2015-10-01

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

  5. Perspective of Use of Antiviral Peptides against Influenza Virus

    Directory of Open Access Journals (Sweden)

    Sylvie Skalickova

    2015-10-01

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

  6. FORMULATION AND DEVELOPMENT OF TOPICAL NIOSOMAL GEL OF BCS CLASS - III ANTI-VIRAL DRUG FOR BETTER EFFICACY AS HERPES TREATMENT

    Directory of Open Access Journals (Sweden)

    Modi Kushal A.

    2012-03-01

    Full Text Available The objective of present research work was to formulate niosomal gel of ACV and to evaluate it for enhancements of skin permeation and skin retention characteristics. ACV niosomes were prepared by classical thin layer hydration method. The niosomal vesicles were separated by centrifugation method and further evaluated for percentage drug entrapment (PDE and vesicle mean geometric diameter. The separated niosomal vesicles were incorporated into the Carbopol® 971 gel base. The niosomal gel was further evaluated for skin retention characteristics, in vitro diffusion study and stability studies at accelerated and non-accelerated conditions. The batch F12 was considered as optimized batch as it showed minimum geometric mean diameter of vesicles (1.23 ± 0.19 μm and maximum PDE (58.71 ± 0.89 %. The in vitro diffusion study using human cadaver skin (HCS showed 1.57 times higher flux as compared to conventional ACV gel. The skin retention study reveals that the percentage drug retained was 4.92 times higher as compared to conventional ACV gel. The stability studies at 2-8 °C showed PDE 94.23% after 12 weeks whereas at accelerated condition it was found to be 90.11%.

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

    Science.gov (United States)

    Nagarakanti, Sandhya; Bishburg, Eliahu

    2016-01-01

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

  8. Neuropsychiatric Effects of HIV Antiviral Medications.

    Science.gov (United States)

    Treisman, Glenn J; Soudry, Olivia

    2016-10-01

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

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

    Directory of Open Access Journals (Sweden)

    Ajelli Marco

    2009-07-01

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

  10. ANTI-VIRAL ACTIVITY OF GLYCIRRHETINIC AND GLYCIRRHIZIC ACIDS

    Directory of Open Access Journals (Sweden)

    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

  11. Drug: D10469 [KEGG MEDICUS

    Lifescience Database Archive (English)

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

  12. Atividade de três drogas antivirais sobre os herpesvírus bovino tipos 1, 2 e 5 em cultivo celular Activity of three antiviral drugs against bovine herpesviruses 1, 2 and 5 in cell culture

    Directory of Open Access Journals (Sweden)

    Renata Dezengrini

    2010-10-01

    Full Text Available A atividade de três fármacos antivirais (Aciclovir [ACV], Ganciclovir [GCV] e Foscarnet [PFA] foi testada in vitro frente aos herpesvírus bovino tipos 1 (BoHV-1, 2 (BoHV-2 e 5 (BoHV-5. Para isso, utilizou-se o teste de reducao de placas virais em cultivo celular, testando-se diferentes concentracoes dos farmacos frente a 100 doses infectantes para 50% dos cultivos celulares (DICC50 dos respectivos virus. Pelo teste de MTT (3-(4,5-Dimethylthiazol- 2-yl-2,5-diphenyltetrazolium bromide, verificou-se que concentracoes inferiores a 200ƒÊg/mL dos tres antivirais resultaram em indices de viabilidade de celulas MDBK e Hep2 superiores a 80%. Com base na concentracao citotoxica para 50% das celulas (CC50 e na concentracao dos farmacos efetiva para inibir em 50% o numero de placas virais (EC50, calculou-se o indice de seletividade (IS dos antivirais para os tres herpesvirus. Assim, o ACV demonstrou ser moderadamente ativo frente ao BoHV-1 (EC50: 112,9ƒÊg/mL e IS: 4,5, ao BoHV-2 (EC50: 114,2 ƒÊg/mL e IS: 4,5 e BoHV-5 (EC50: 96,9ƒÊg/mL e IS: 5,3. O GCV apresentou atividade moderada frente ao BoHV-2 (EC50: 33,5ƒÊg/mL e IS: 16,6 e, em menor grau, contra o BoHV-5 (EC50: 123,2ƒÊg/mL e IS: 4,5, sendo ineficaz frente ao BoHV-1 (EC50: 335,8ƒÊg/mL e IS: 1,7. O PFA apresentou atividade antiviral mais pronunciada, sendo o unico farmaco que, na concentracao de 100ƒÊg/mL, inibiu completamente a producao de placas pelos tres virus testados. O PFA foi o mais efetivo in vitro frente ao BoHV-1 (EC50: 29,5ƒÊg/mL e IS: 42,2, ao BoHV-2 (EC50: 45,2ƒÊg/mL e IS: 27,6 e ao BoHV-5 (EC50: 7,8ƒÊg/mL e IS: 160,6. Portanto, os resultados obtidos indicam que o PFA pode se constituir em um candidato para terapia experimental de infeccoes pelos herpesvirus de bovinos in vivo.The activity of three anti-herpetic drugs (Acyclovir [ACV], Gancyclovir [GCV] and Foscarnet [PFA] was tested against bovine herpesvirus 1 (BoHV-1, 2 (BoHV-2 and 5 (BoHV-5 in vitro using the

  13. Antiviral immunity in amphibians.

    Science.gov (United States)

    Chen, Guangchun; Robert, Jacques

    2011-11-01

    Although a variety of virus species can infect amphibians, diseases caused by ranaviruses ([RVs]; Iridoviridae) have become prominent, and are a major concern for biodiversity, agriculture and international trade. The relatively recent and rapid increase in prevalence of RV infections, the wide range of host species infected by RVs, the variability in host resistance among population of the same species and among different developmental stages, all suggest an important involvement of the amphibian immune system. Nevertheless, the roles of the immune system in the etiology of viral diseases in amphibians are still poorly investigated. We review here the current knowledge of antiviral immunity in amphibians, focusing on model species such as the frog Xenopus and the salamander (Ambystoma tigrinum), and on recent progress in generating tools to better understand how host immune defenses control RV infections, pathogenicity, and transmission.

  14. 21 CFR 14.142 - Functions of a color additive advisory committee.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 1 2010-04-01 2010-04-01 false Functions of a color additive advisory committee. 14.142 Section 14.142 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL PUBLIC HEARING BEFORE A PUBLIC ADVISORY COMMITTEE Color Additive Advisory Committees §...

  15. 21 CFR 14.147 - Membership of a color additive advisory committee.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 1 2010-04-01 2010-04-01 false Membership of a color additive advisory committee. 14.147 Section 14.147 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL PUBLIC HEARING BEFORE A PUBLIC ADVISORY COMMITTEE Color Additive Advisory Committees §...

  16. 21 CFR 14.145 - Procedures of a color additive advisory committee.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 1 2010-04-01 2010-04-01 false Procedures of a color additive advisory committee. 14.145 Section 14.145 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL PUBLIC HEARING BEFORE A PUBLIC ADVISORY COMMITTEE Color Additive Advisory Committees §...

  17. 21 CFR 14.140 - Establishment of a color additive advisory committee.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 1 2010-04-01 2010-04-01 false Establishment of a color additive advisory committee. 14.140 Section 14.140 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL PUBLIC HEARING BEFORE A PUBLIC ADVISORY COMMITTEE Color Additive Advisory Committees §...

  18. 75 FR 5335 - Risk Communication Advisory Committee; Notice of Meeting

    Science.gov (United States)

    2010-02-02

    ... HUMAN SERVICES Food and Drug Administration Risk Communication Advisory Committee; Notice of Meeting... the public. Name of Committee: Risk Communication Advisory Committee. General Function of the... and call the appropriate advisory committee hot line/phone line to learn about possible...

  19. 76 FR 16427 - Risk Communication Advisory Committee; Notice of Meeting

    Science.gov (United States)

    2011-03-23

    ... HUMAN SERVICES Food and Drug Administration Risk Communication Advisory Committee; Notice of Meeting... the public. Name of Committee: Risk Communication Advisory Committee. General Function of the... appropriate advisory committee hot line/phone line to learn about possible modifications before coming to...

  20. 接受抗病毒治疗的乙型肝炎患者妊娠期耐药20例分析%Analysis of drug resistance in 20 chronic hepatitis B patients receiving antiviral therapy during pregnancy

    Institute of Scientific and Technical Information of China (English)

    曹彦君; 方芳; 刘敏; 蔡晧东

    2013-01-01

    Objective To explore the cause of drug resistance in patients with chronic hepatitis B during pregnancy and the management policy.Methods The clinical data of 20 pregnant women with chronic hepatitis B received lamivudine (LAM) or telbivudine (LdT),developed drug resistance during pregnancy,and delivered full-term newborns from January 1,2007 to December 31,2012 in Beijing Ditan Hospital were collected and analyzed retrospectively.The main indicators of analysis included the situation of antiviral drug use before and after pregnancy,the occurrence time of drug resistance and the restriction measures during pregnancy,HBV-DNA load,liver function,maternal and neonatal outcomes.Results LAM group comprised 12 patients with age of 26 to 38 (31 ±3) years,received LAM 100 mg/d for 1.5 to 8 years before pregnancy.Of them,3 patients had received entecavir for 2 years and then changed to LAM.LdT group comprised 8 patients with age of 27 to 34 (31 ± 2) years,received LdT 600 rng/d for 2.0 to 4.5 years.Of them,a patient had received entecavir for 2 years and then changed to LdT.The drug resistance occurred during 0-12,13-27,and 28-40 weeks of pregnancy in LAM group in 1,2,and 9 cases,in LdT group in 1,1,and 6 cases,respectively.A total of 15 (75%) patients developed drug resistance during 28-40 weeks of pregnancy.Of 12 patients in LAM group,4 substituted tenofovir (TDF) 300 mg/d for LAM,3 received LAM and added adefovir dipivoxil after 28 weeks of pregnancy,4 received LAM continually and added adefovir dipivoxil after childbirth,another one substituted telbivudine for LAM but was not effective and added adefovir dipivoxil after childbirth.Of 8 patients in LdT group,2 substituted TDF 300 mg/d for LdT,6 received LdT continually and combined with adefovir dipivoxil 10 mg/d after childbirth.Twenty pregnant women were all singleton and had full-term natural labor.In LAM group,a newbom's venous HBV DNA load was 1.56 × 106 copies/ml and diagnosed as intrauterine infection

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

    Directory of Open Access Journals (Sweden)

    Akram Astani

    2011-01-01

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

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

    Science.gov (United States)

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

    2013-11-01

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

  3. Are Cancer Drugs Less Likely to be Recommended for Listing by the Pharmaceutical Benefits Advisory Committee in Australia?

    OpenAIRE

    Lesley Chim; Kelly, Patrick J; Glenn Salkeld; Stockler, Martin R.

    2010-01-01

    Background: The hurdle of cost effectiveness for the selection and reimbursement of drugs in Australia limits access to new medicines based on an assessment of cost relative to clinical benefit. Those drugs that are expensive and provide modest benefits will be less likely to receive a government price subsidy. There is concern that the cost-effectiveness hurdle will limit access to new cancer treatments because of their high costs and modest benefits. Objective: To test the hypothesis that C...

  4. Antiviral Polymer Therapeutics

    DEFF Research Database (Denmark)

    Smith, Anton Allen Abbotsford

    2014-01-01

    and the drug which increased the potency of the conjugates significantly. A different approach to drug delivery is that of surface mediated drug delivery. Hydrogels of poly(vinyl alcohol) has shown great promise in this regard. The chemical opportunities of this polymer are explored through the virtues...... of reversible-addition-fragmentation chain transfer polymerization, which not only controls the size of polymer, but also allows the introduction of a terminal amine on the polymer which can be used for further conjugation. This has allowed for not only fluorescent labeling of the polymer, but also protein......The field of drug delivery is in essence an exercise in engineered pharmacokinetics. Methods of doing so have been developed through the introduction of a vehicle carrying the drug, either by encapsulation or covalent attachment. The emergence of polymer therapeutics in anticancer therapy has...

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

    Science.gov (United States)

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

    1999-06-01

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

  6. Exploiting Genetic Interference for Antiviral Therapy.

    Science.gov (United States)

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

    2016-05-01

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

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

    Science.gov (United States)

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

    2015-01-01

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

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

    Science.gov (United States)

    Litterman, Nadia; Lipinski, Christopher; Ekins, Sean

    2015-01-01

    The recent outbreak of the Ebola virus in West Africa has highlighted the clear shortage of broad-spectrum antiviral drugs for emerging viruses. There are numerous FDA approved drugs and other small molecules described in the literature that could be further evaluated for their potential as antiviral compounds. These molecules are in addition to the few new antivirals that have been tested in Ebola patients but were not originally developed against the Ebola virus, and may play an important role as we await an effective vaccine. The balance between using FDA approved drugs versus novel antivirals with minimal safety and no efficacy data in humans should be considered. We have evaluated 55 molecules from the perspective of an experienced medicinal chemist as well as using simple molecular properties and have highlighted 16 compounds that have desirable qualities as well as those that may be less desirable. In addition we propose that a collaborative database for sharing such published and novel information on small molecules is needed for the research community studying the Ebola virus. PMID:25713700

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

    Science.gov (United States)

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

    2016-01-01

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

  10. Liposomal Systems as Nanocarriers for the Antiviral Agent Ivermectin

    Directory of Open Access Journals (Sweden)

    Romina Croci

    2016-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Akram Astani

    2014-06-01

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

  12. Drug: D07441 [KEGG MEDICUS

    Lifescience Database Archive (English)

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

  13. 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.

  14. 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.

  15. 76 FR 44017 - Risk Communication Advisory Committee; Notice of Meeting

    Science.gov (United States)

    2011-07-22

    ... HUMAN SERVICES Food and Drug Administration Risk Communication Advisory Committee; Notice of Meeting... the public. Name of Committee: Risk Communication Advisory Committee. General Function of the... Person: Lee L. Zwanziger, Office of Policy, Planning and Budget, Food and Drug Administration, 10903...

  16. 75 FR 74735 - Food Advisory Committee; Notice of Meeting

    Science.gov (United States)

    2010-12-01

    ...'s consumption of synthetic color additives in food and adverse effects on behavior. FDA intends to... HUMAN SERVICES Food and Drug Administration Food Advisory Committee; Notice of Meeting AGENCY: Food and... advisory committee of the Food and Drug Administration (FDA). The meeting will be open to the public....

  17. 75 FR 65640 - Cellular, Tissue and Gene Therapies Advisory Committee; Notice of Meeting

    Science.gov (United States)

    2010-10-26

    ... HUMAN SERVICES Food and Drug Administration Cellular, Tissue and Gene Therapies Advisory Committee... and Gene Therapies Advisory Committee. General Function of the Committee: To provide advice and... Tumor Vaccines and Biotechnology Branch, Office of Cellular, Tissue and Gene Therapies, Center...

  18. 77 FR 73472 - Cellular, Tissue and Gene Therapies Advisory Committee; Notice of Meeting

    Science.gov (United States)

    2012-12-10

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration Cellular, Tissue and Gene Therapies Advisory Committee... and Gene Therapies Advisory Committee. General Function of the Committee: To provide advice...

  19. 78 FR 12068 - Device Good Manufacturing Practice Advisory Committee; Notice of Meeting

    Science.gov (United States)

    2013-02-21

    ... HUMAN SERVICES Food and Drug Administration Device Good Manufacturing Practice Advisory Committee... meeting will be open to the public. Name of Committee: Device Good Manufacturing Practice Advisory... effects of extreme weather and natural disasters on medical device manufacturing chain processes...

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

    Directory of Open Access Journals (Sweden)

    Malihe Farahani

    2013-08-01

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

  1. Drug: D00333 [KEGG MEDICUS

    Lifescience Database Archive (English)

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

  2. Drug: D03256 [KEGG MEDICUS

    Lifescience Database Archive (English)

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

  3. 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.

  4. Advisory Committees.

    Science.gov (United States)

    ERIC Clearinghouse on Educational Management, Eugene, OR.

    This chapter of "The Best of the Best of ERIC," Volume 2, contains 14 summaries of documents and journal articles on citizen advisory committees, all of which are indexed in either "Resources in Education" or "Current Index to Journals in Education." The materials included deal with various aspects of this topic, such as the role of the school…

  5. Liposomal Systems as Nanocarriers for the Antiviral Agent Ivermectin

    OpenAIRE

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

    2016-01-01

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

  6. Effects of nerve block combined with antiviral drug on patients with herpes zoster pain and sleep quality%神经阻滞联合抗病毒药物对带状疱疹患者疼痛及睡眠质量影响

    Institute of Scientific and Technical Information of China (English)

    陈慧

    2015-01-01

    Objective To explore the nerve block combined with antiviral drug on patients with herpes zoster treatment effect,and provide the basis for clinical pain relief and improve the quality of sleep.Methods The 90 cases of herpes zoster patients in our hospital in the Department of Dermatology for treatment,30 cases were randomly divided into a,B,C 30 cases 30 cases,group A with simple antiviral therapy,group B with antiviral joint pain relieving antiphlogistic drug therapy,group C treated with nerve block combined with antiviral therapy,recording three groups of visual score (VAS) and sleep quality score (QS),analysis and improvement in three groups of pain and sleep quality.Results The pain scores before and after treatment,in group A had no obvious change for the better,after 2 weeks,will be obviously significant differences (t =4.329,5.424,P < 0.05),C B two groups in 1 weeks after treatment there were significant differences (P < 0.05).In sleep quality,sleep quality has not improved significantly in group A (P >0.05),after 1 weeks,the sleep quality improvement (P < 0.05) before and after treatment in the two groups of ethylene and propylene,there was significant difference (P < 0.05),ethylene propylene no obvious differences between the two groups (P > 0.05).Conclusions The nerve block combined with antiviral drug with good pain relief and improve the role of sleep in patients with herpes zoster,can be used in clinical treatment.%目的 探究神经阻滞联合抗病毒药物对带状疱疹患者治疗效果,为临床疼痛缓解和改善睡眠质量提供依据.方法 选用来我院神经内科就诊带状疱疹患者90例,随机分为甲30例、乙30例、丙30例,甲组采用单纯抗病毒治疗,乙组采用抗病毒联合镇痛消炎药治疗,丙组采用神经阻滞联合抗病毒治疗,记录三组视觉评分(VAS)和睡眠质量评分(QS),分析三组疼痛和睡眠质量改善情况.结果 疼痛评分上,甲组治疗前后未见明显好转,2

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

    Science.gov (United States)

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

    2016-06-01

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

  8. Antiviral Strategies Against Chikungunya Virus.

    Science.gov (United States)

    Abdelnabi, Rana; Neyts, Johan; Delang, Leen

    2016-01-01

    In the last few decades the Chikungunya virus (CHIKV) has evolved from a geographically isolated pathogen to a virus that is widespread in many parts of Africa, Asia and recently also in Central- and South-America. Although CHIKV infections are rarely fatal, the disease can evolve into a chronic stage, which is characterized by persisting polyarthralgia and joint stiffness. This chronic CHIKV infection can severely incapacitate patients for weeks up to several years after the initial infection. Despite the burden of CHIKV infections, no vaccine or antivirals are available yet. The current therapy is therefore only symptomatic and consists of the administration of analgesics, antipyretics, and anti-inflammatory agents. Recently several molecules with various viral or host targets have been identified as CHIKV inhibitors. In this chapter, we summarize the current status of the development of antiviral strategies against CHIKV infections. PMID:27233277

  9. Drug: D10518 [KEGG MEDICUS

    Lifescience Database Archive (English)

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

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

    OpenAIRE

    Arinaminpathy, N.; McLean, A. R.

    2007-01-01

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

  11. Antiviral therapy for hepatitis B virus associated hepatic failure

    Institute of Scientific and Technical Information of China (English)

    Yu-Ming Wang; Ying-Zi Tang

    2009-01-01

    BACKGROUND: Chronic hepatitis B virus (HBV) infection remains a major global health issue, and the prognosis of patients with HBV-associated fulminant hepatic failure is extremely poor. The application of antiviral therapies has led to signiifcant improvements in patient outcomes. This article aimed to review the current strategies in antiviral treatment of HBV-associated fulminant hepatic failure. DATA SOURCES: Literature search was conducted using PubMed on the related subjects. Part of the data was from the most recent work of the authors' laboratory. RESULTS: Hepatitis B immunoglobulin in prevention of recurrent HBV infection after orthotopic liver transplantation (OLT) has been proven effective. However, its cost is high, and signiifcant side effects have been found to induce viral mutations. Lamivudine has a potent suppression for HBV replication and an excellent safety proifle in decompensated cirrhotic patients, but its major drawback is the high rate of drug-resistance. Adefovir is effective for lamivudine-resistance strains in the post-OLT situation, and its drug-resistance rate is relatively low. Combination therapies such as hepatitis B immunoglobulin combined with lamivudine and lamivudine combined with adefovir have been widely adopted for prophylaxis against HBV recurrence of infection after OLT. Entecavir, telbivudine, tenofovir and other newer agents have been widely used in antiviral therapy. CONCLUSIONS: The prognosis of HBV-associated ful-minant hepatic failure is being transformed by developments in antiviral therapy. However, it should be noticed that HBV is controlled but never eliminated, and drug-resistance still remains a major issue. Hopefully, newer strategies may help to solve these problems.

  12. Antifungal and antiviral products of marine organisms.

    Science.gov (United States)

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

    2014-04-01

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

  13. 76 FR 12973 - Neurological Devices Panel of the Medical Devices Advisory Committee; Amendment of Notice

    Science.gov (United States)

    2011-03-09

    ... HUMAN SERVICES Food and Drug Administration Neurological Devices Panel of the Medical Devices Advisory... Medical Devices Advisory Committee. This meeting was announced in the Federal Register of February 7, 2011... meeting of the Neurological Devices Panel of the Medical Devices Advisory Committee would be held on...

  14. 75 FR 58414 - Dental Products Panel of the Medical Devices Advisory Committee; Amendment of Notice

    Science.gov (United States)

    2010-09-24

    ... HUMAN SERVICES Food and Drug Administration Dental Products Panel of the Medical Devices Advisory... Medical Devices Advisory Committee. This meeting was announced in the Federal Register of June 11, 2010... announced that a meeting of the Dental Products Panel of the Medical Devices Advisory Committee would...

  15. 76 FR 80949 - Request for Nominations for Voting Members on Public Advisory Panels or Committees

    Science.gov (United States)

    2011-12-27

    ... include experience in medical practice, teaching, and/or research relevant to the field of activity of the... Manufacturing Practice Advisory Committee, certain device panels of the Medical Devices Advisory Committee, and... Device Good Manufacturing and Radiological Health, Food and Drug Practice Advisory...

  16. ANTIVIRAL POTENTIAL OF MEDICINAL PLANTS: AN OVERVIEW

    Directory of Open Access Journals (Sweden)

    Ruwali Pushpa

    2013-06-01

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

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

    Directory of Open Access Journals (Sweden)

    Yasuhara-Bell Jarred

    2010-08-01

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

  18. 21 CFR 14.155 - Fees and compensation pertaining to a color additive advisory committee.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 1 2010-04-01 2010-04-01 false Fees and compensation pertaining to a color additive advisory committee. 14.155 Section 14.155 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL PUBLIC HEARING BEFORE A PUBLIC ADVISORY COMMITTEE Color...

  19. Drug: D04008 [KEGG MEDICUS

    Lifescience Database Archive (English)

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

  20. Drug: D08775 [KEGG MEDICUS

    Lifescience Database Archive (English)

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

  1. Drug: D03690 [KEGG MEDICUS

    Lifescience Database Archive (English)

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

  2. 75 FR 65641 - Risk Communication Advisory Committee; Amendment of Notice

    Science.gov (United States)

    2010-10-26

    ... HUMAN SERVICES Food and Drug Administration Risk Communication Advisory Committee; Amendment of Notice... announcing an amendment to the notice of meeting of the Risk Communication Advisory Committee. This meeting was announced in the Federal Register of September 20, 2010 (75 FR 57279). The amendment is being...

  3. 78 FR 42087 - Risk Communications Advisory Committee; Notice of Meeting

    Science.gov (United States)

    2013-07-15

    ... the White Oak Campus must enter through Building 1. Contact Person: Luis G. Bravo, Risk Communication... HUMAN SERVICES Food and Drug Administration Risk Communications Advisory Committee; Notice of Meeting... the public. Name of Committee: Risk Communications Advisory Committee. General Function of...

  4. 75 FR 20608 - Risk Communication Advisory Committee; Notice of Meeting

    Science.gov (United States)

    2010-04-20

    ... HUMAN SERVICES Food and Drug Administration Risk Communication Advisory Committee; Notice of Meeting... the public. Name of Committee: Risk Communication Advisory Committee. General Function of the... current research in a range of fields relevant to improving risk communication at FDA, and...

  5. 78 FR 33423 - Arthritis Advisory Committee; Notice of Meeting

    Science.gov (United States)

    2013-06-04

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration Arthritis Advisory Committee; Notice of Meeting AGENCY: Food... of Committee: Arthritis Advisory Committee. General Function of the Committee: To provide advice...

  6. 77 FR 14529 - Arthritis Advisory Committee; Notice of Meeting

    Science.gov (United States)

    2012-03-12

    ... HUMAN SERVICES Food and Drug Administration Arthritis Advisory Committee; Notice of Meeting AGENCY: Food... of Committee: Arthritis Advisory Committee. General Function of the Committee: To provide advice and... moderately to severely active rheumatoid arthritis who have had an inadequate response to one or more...

  7. 76 FR 42715 - Arthritis Advisory Committee; Notice of Meeting

    Science.gov (United States)

    2011-07-19

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration Arthritis Advisory Committee; Notice of Meeting AGENCY: Food... of Committee: Arthritis Advisory Committee. General Function of the Committee: To provide advice...

  8. 76 FR 29767 - Arthritis Advisory Committee; Notice of Meeting

    Science.gov (United States)

    2011-05-23

    ... HUMAN SERVICES Food and Drug Administration Arthritis Advisory Committee; Notice of Meeting AGENCY: Food... of Committee: Arthritis Advisory Committee. General Function of the Committee: To provide advice and... arthritis attacks. ILARIS has also been shown to extend the time to the next attack and reduce the...

  9. 75 FR 55805 - Arthritis Advisory Committee; Notice of Meeting

    Science.gov (United States)

    2010-09-14

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration Arthritis Advisory Committee; Notice of Meeting AGENCY: Food... of Committee: Arthritis Advisory Committee. General Function of the Committee: To provide advice...

  10. 77 FR 64524 - Arthritis Advisory Committee; Notice of Meeting

    Science.gov (United States)

    2012-10-22

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration Arthritis Advisory Committee; Notice of Meeting AGENCY: Food... of Committee: Arthritis Advisory Committee. General Function of the Committee: To provide advice...

  11. 78 FR 32403 - Arthritis Advisory Committee; Notice of Meeting

    Science.gov (United States)

    2013-05-30

    ... HUMAN SERVICES Food and Drug Administration Arthritis Advisory Committee; Notice of Meeting AGENCY: Food... of Committee: Arthritis Advisory Committee. General Function of the Committee: To provide advice and... meeting. Agenda: On July 22, 2013, the committee will discuss the Assessment of...

  12. 77 FR 1697 - Arthritis Advisory Committee; Notice of Meeting

    Science.gov (United States)

    2012-01-11

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration Arthritis Advisory Committee; Notice of Meeting AGENCY: Food... of Committee: Arthritis Advisory Committee. General Function of the Committee: To provide advice...

  13. 75 FR 4576 - Veterinary Medicine Advisory Committee; Notice of Meeting

    Science.gov (United States)

    2010-01-28

    ... HUMAN SERVICES Food and Drug Administration Veterinary Medicine Advisory Committee; Notice of Meeting... the public. Name of Committee: Veterinary Medicine Advisory Committee. General Function of the... PROHEART 6 (NADA 141-189), the subsequent safety data collected under the Center for Veterinary...

  14. Drug: D02764 [KEGG MEDICUS

    Lifescience Database Archive (English)

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

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

    Directory of Open Access Journals (Sweden)

    A. V. Rudakova

    2016-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Seyed M Moghadas

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

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

    OpenAIRE

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

    2015-01-01

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

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

    NARCIS (Netherlands)

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

    2015-01-01

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

  19. 21 CFR 861.38 - Standards advisory committees.

    Science.gov (United States)

    2010-04-01

    ... Development and Publication § 861.38 Standards advisory committees. (a) The Food and Drug Administration will... the proposed regulation which requires the exercise of scientific judgment if: (1) The Food and...

  20. Drug: D00317 [KEGG MEDICUS

    Lifescience Database Archive (English)

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

  1. Drug: D06478 [KEGG MEDICUS

    Lifescience Database Archive (English)

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

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

    Science.gov (United States)

    Oh, Ding Y; Hurt, Aeron C

    2016-01-01

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

  3. 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.

  4. Antiviral active peptide from oyster

    Science.gov (United States)

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

    2008-08-01

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

  5. Antiviral active peptide from oyster

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

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

  6. Antiviral Perspectives for Chikungunya Virus

    Directory of Open Access Journals (Sweden)

    Deepti Parashar

    2014-01-01

    Full Text Available Chikungunya virus (CHIKV is a mosquito-borne pathogen that has a major health impact in humans and causes acute febrile illness in humans accompanied by joint pains and, in many cases, persistent arthralgia lasting for weeks to years. CHIKV reemerged in 2005-2006 in several parts of the Indian Ocean islands and India after a gap of 32 years, causing millions of cases. The re-emergence of CHIKV has also resulted in numerous outbreaks in several countries in the eastern hemisphere, with a threat to further expand in the near future. However, there is no vaccine against CHIKV infection licensed for human use, and therapy for CHIKV infection is still mainly limited to supportive care as antiviral agents are yet in different stages of testing or development. In this review we explore the different perspectives for chikungunya treatment and the effectiveness of these treatment regimens and discuss the scope for future directions.

  7. Drug: D07896 [KEGG MEDICUS

    Lifescience Database Archive (English)

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

  8. Drug: D10081 [KEGG MEDICUS

    Lifescience Database Archive (English)

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

  9. Drug: D02737 [KEGG MEDICUS

    Lifescience Database Archive (English)

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

  10. 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.

  11. Drug: D00579 [KEGG MEDICUS

    Lifescience Database Archive (English)

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

  12. Drug: D02124 [KEGG MEDICUS

    Lifescience Database Archive (English)

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

  13. Drug: D02495 [KEGG MEDICUS

    Lifescience Database Archive (English)

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

  14. Drug: D05407 [KEGG MEDICUS

    Lifescience Database Archive (English)

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

  15. Drug: D04301 [KEGG MEDICUS

    Lifescience Database Archive (English)

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

  16. 75 FR 65497 - Science Board Advisory Committee; Notice of Meeting

    Science.gov (United States)

    2010-10-25

    ... HUMAN SERVICES Food and Drug Administration Science Board Advisory Committee; Notice of Meeting AGENCY: Food and Drug Administration, HHS. ACTION: Notice of meeting. This notice announces a forthcoming... Science Board to the Food and Drug Administration and provide an overview of its strategic plan....

  17. 78 FR 66942 - Orthopaedic and Rehabilitation Devices Panel of the Medical Devices Advisory Committee; Notice of...

    Science.gov (United States)

    2013-11-07

    ... HUMAN SERVICES Food and Drug Administration Orthopaedic and Rehabilitation Devices Panel of the Medical Devices 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...

  18. 76 FR 17422 - Orthopaedic and Rehabilitation Devices Panel of the Medical Devices Advisory Committee; Notice of...

    Science.gov (United States)

    2011-03-29

    ... HUMAN SERVICES Food and Drug Administration Orthopaedic and Rehabilitation Devices Panel of the Medical Devices 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...

  19. 75 FR 36660 - Orthopaedic and Rehabilitation Devices Panel of the Medical Devices Advisory Committee; Notice of...

    Science.gov (United States)

    2010-06-28

    ... HUMAN SERVICES Food and Drug Administration Orthopaedic and Rehabilitation Devices Panel of the Medical Devices 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...

  20. [Interferon : antiviral mechanisms and viral escape].

    Science.gov (United States)

    Espert, Lucile; Gongora, Céline; Mechti, Nadir

    2003-02-01

    15 % of human cancers have virus origin, meaning that viruses are the second cause of cancers after tabagism. The knowledge of antiviral mechanisms is essential for treatment and prevention of infection evolution towards cancers. Interferons (IFNs) are a large family of multifunctional cytokines. They are involved in regulation of cell growth and modulation of immune response. But, all these functions seem to converge toward the most important of them : the antiviral activity. IFN secretion is the first event induced by viral infection, and will act on specific receptors on neighbour cells and prevent their infection by inducing numbers of antiviral genes. Although few of them are well known like the PKR, the 2-5OAS/RNase L pathway and the Mx proteins, many others need extensive studies to understand the wide range of IFN effect. Viruses have evolved to circumvent the IFN antiviral activity, and are able not only to divert the cellular machinery but also to lure the antiviral mechanisms of the host cell. The purpose of this review is to describe the many antiviral pathways and proteins induced by IFNs and to summarize the strategies of viral escape. PMID:12660132

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

    Science.gov (United States)

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

    2013-07-11

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

  2. 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.

  3. Antiviral effect of ranpirnase against Ebola virus.

    Science.gov (United States)

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

    2016-08-01

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

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

    Science.gov (United States)

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

    2015-12-01

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

  5. 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.

  6. Containing pandemic influenza with antiviral agents.

    Science.gov (United States)

    Longini, Ira M; Halloran, M Elizabeth; Nizam, Azhar; Yang, Yang

    2004-04-01

    For the first wave of pandemic influenza or a bioterrorist influenza attack, antiviral agents would be one of the few options to contain the epidemic in the United States until adequate supplies of vaccine were available. The authors use stochastic epidemic simulations to investigate the effectiveness of targeted antiviral prophylaxis to contain influenza. In this strategy, close contacts of suspected index influenza cases take antiviral agents prophylactically. The authors compare targeted antiviral prophylaxis with vaccination strategies. They model an influenza pandemic or bioterrorist attack for an agent similar to influenza A virus (H2N2) that caused the Asian influenza pandemic of 1957-1958. In the absence of intervention, the model predicts an influenza illness attack rate of 33% of the population (95% confidence interval (CI): 30, 37) and an influenza death rate of 0.58 deaths/1,000 persons (95% Cl: 0.4, 0.8). With the use of targeted antiviral prophylaxis, if 80% of the exposed persons maintained prophylaxis for up to 8 weeks, the epidemic would be contained, and the model predicts a reduction to an illness attack rate of 2% (95% Cl: 0.2, 16) and a death rate of 0.04 deaths/1,000 persons (95% CI: 0.0003, 0.25). Such antiviral prophylaxis is nearly as effective as vaccinating 80% of the population. Vaccinating 80% of the children aged less than 19 years is almost as effective as vaccinating 80% of the population. Targeted antiviral prophylaxis has potential as an effective measure for containing influenza until adequate quantities of vaccine are available.

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

    Science.gov (United States)

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

    2014-01-01

    Enterovirus 71 (EV71) is the predominant cause of hand, foot and mouth disease (HFMD). The antiviral activity of hederasaponin B from Hedera helix against EV71 subgenotypes C3 and C4a was evaluated in vero cells. In the current study, the antiviral activity of hederasaponin B against EV71 C3 and C4a was determined by cytopathic effect (CPE) reduction method and western blot assay. Our results demonstrated that hederasaponin B and 30% ethanol extract of Hedera helix containing hederasaponin B showed significant antiviral activity against EV71 subgenotypes C3 and C4a by reducing the formation of a visible CPE. Hederasaponin B also inhibited the viral VP2 protein expression, suggesting the inhibition of viral capsid protein synthesis.These results suggest that hederasaponin B and Hedera helix extract containing hederasaponin B can be novel drug candidates with broad-spectrum antiviral activity against various subgenotypes of EV71. PMID:24596620

  8. 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 BACKGROUND: 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. METHODS AND FINDINGS: 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

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

    International Nuclear Information System (INIS)

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

  10. A fresh look at an antiviral helicase

    Institute of Scientific and Technical Information of China (English)

    Leonid Gitlin; Marco Colonna

    2007-01-01

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

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

    Science.gov (United States)

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

    2013-11-01

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

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

    Science.gov (United States)

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

    2013-11-01

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

  13. Drug: D06298 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available D06298 Drug Vidarabine (JAN); Vidarabine anhydrous; ARA-A; Armes (TN) C10H13N5O4 26...gents against pathologic organisms and parasites 62 Chemotherapeutics 625 Antivirals 6250 Antivirals D06298 Vida...eosides and nucleotides excl. reverse transcriptase inhibitors J05AB03 Vidarabine D06298 Vidarabine (JAN) S ...SENSORY ORGANS S01 OPHTHALMOLOGICALS S01A ANTIINFECTIVES S01AD Antivirals S01AD06 Vidarabine D06298 Vidarabi...ibitor Pyrimidine analogue Vidarabine [ATC:J05AB03 S01AD06] D06298 Vidarabine (JAN) CAS: 5536-17-4 PubChem:

  14. Drug: D05776 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available D05776 Drug Rupintrivir (USAN/INN) C31H39FN4O7 598.2803 598.6624 D05776.gif Antivir...al intended for use in the treatment of the common cold [human rhinovirus 3C protease inhibitor] human rhinoviru...s (HRV) 3C protease inhibitor Antiinfectives [BR:br08307] Antivirals Others Anti-HRV agent HRV 3C protease inhibitor Ru...pintrivir D05776 Rupintrivir (USAN/INN) CAS: 223537-30-2 PubChem:

  15. Drug: D00222 [KEGG MEDICUS

    Lifescience Database Archive (English)

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

  16. Antiviral activity of constituents of Tamus communis.

    Science.gov (United States)

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

    1991-10-01

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

  17. Emerging antiviral strategies to interfere with influenza virus entry.

    Science.gov (United States)

    Vanderlinden, Evelien; Naesens, Lieve

    2014-03-01

    Influenza A and B viruses are highly contagious respiratory pathogens with a considerable medical and socioeconomical burden and known pandemic potential. Current influenza vaccines require annual updating and provide only partial protection in some risk groups. Due to the global spread of viruses with resistance to the M2 proton channel inhibitor amantadine or the neuraminidase inhibitor oseltamivir, novel antiviral agents with an original mode of action are urgently needed. We here focus on emerging options to interfere with the influenza virus entry process, which consists of the following steps: attachment of the viral hemagglutinin to the sialylated host cell receptors, endocytosis, M2-mediated uncoating, low pH-induced membrane fusion, and, finally, import of the viral ribonucleoprotein into the nucleus. We review the current functional and structural insights in the viral and cellular components of this entry process, and the diverse antiviral strategies that are being explored. This encompasses small molecule inhibitors as well as macromolecules such as therapeutic antibodies. There is optimism that at least some of these innovative concepts to block influenza virus entry will proceed from the proof of concept to a more advanced stage. Special attention is therefore given to the challenging issues of influenza virus (sub)type-dependent activity or potential drug resistance. PMID:23801557

  18. 76 FR 18757 - Monthly Public Meetings of the Local Government Advisory Committee's Small Community Advisory...

    Science.gov (United States)

    2011-04-05

    ... AGENCY Monthly Public Meetings of the Local Government Advisory Committee's Small Community Advisory... Advisory Committee Act, the U.S. Environmental Protection Agency's Local Government Advisory Committee's... the Local Government Advisory Committee. BILLING CODE 6560-50-P...

  19. 77 FR 71591 - Meetings of the Local Government Advisory Committee and the Small Communities Advisory Subcommittee

    Science.gov (United States)

    2012-12-03

    ... AGENCY Meetings of the Local Government Advisory Committee and the Small Communities Advisory... environmental issues affecting small communities. The Local Government Advisory Committee (LGAC) will meet in... INFORMATION CONTACT: Local Government Advisory Committee (LGAC) and Small Communities Advisory...

  20. Drug: D00398 [KEGG MEDICUS

    Lifescience Database Archive (English)

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

  1. Citizens Advisory Committees.

    Science.gov (United States)

    Stemnock, Suzanne K.

    1968-01-01

    This document contains the results of a national survey designed to determine the composition and location of permanent citizens advisory committees operating within the nation's school districts. The 52 district-wide, continuing citizens advisory bodies identified by 290 responding school systems are listed alphabetically by State. The following…

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

    Science.gov (United States)

    McKimm-Breschkin, Jennifer L; Fry, Alicia M

    2016-05-01

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

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

    Directory of Open Access Journals (Sweden)

    Amy L Caroline

    2014-04-01

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

  4. DMPD: Antiviral innate immunity pathways. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 16474426 Antiviral innate immunity pathways. Seth RB, Sun L, Chen ZJ. Cell Res. 200...6 Feb;16(2):141-7. (.png) (.svg) (.html) (.csml) Show Antiviral innate immunity pathways. PubmedID 16474426 ...Title Antiviral innate immunity pathways. Authors Seth RB, Sun L, Chen ZJ. Publication Cell Res. 2006 Feb;16

  5. 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.

  6. The IKK Kinases: Operators of Antiviral Signaling

    Directory of Open Access Journals (Sweden)

    Alissa M. Pham

    2010-01-01

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

  7. Drug: D08664 [KEGG MEDICUS

    Lifescience Database Archive (English)

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

  8. Antiviral treatment in patients with cytomegalovirus positive ulcerative colitis

    Institute of Scientific and Technical Information of China (English)

    Kadir; Ozturk

    2014-01-01

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

  9. Antiviral effect of cationic compounds on bacteriophages

    Directory of Open Access Journals (Sweden)

    Mai Huong eChatain-Ly

    2013-03-01

    Full Text Available The antiviral activity of several cationic compounds - cetytrimethylammonium (CTAB, chitosan, nisin and lysozyme - was investigated on the bacteriophage c2 (DNA head and non-contractile tail infecting Lactococcus strains and the bacteriophage MS2 (F-specific RNA infecting E.coli. Firstly, these activities were evaluated in a phosphate buffer pH 7- 10 mM. The CTAB had a virucidal effect on the Lactococcus bacteriophages, but not on the MS2. After 1 min of contact with 0.125 mM CTAB, the c2 population was reduced from 6 log(pfu/mL to 1,5 log(pfu/mL and completely deactivated at 1 mM. On the contrary, chitosan inhibited the MS2 more than it did the bacteriophages c2. No antiviral effect was observed for the nisin or the lysozyme on bacteriophages after 1 min of treatment. A 1 and 2.5 log reduction was respectively observed for nisin and lysozyme when the treatment time increased (5 or 10 min. These results showed that the antiviral effect depended both on the virus and structure of the antimicrobial compounds. The antiviral activity of these compounds was also evaluated in different physico-chemical conditions and in complex matrices. The antiviral activity of CTAB was impaired in acid pH and with an increase of the ionic strength. These results might be explained by the electrostatic interactions between cationic compounds and negatively charged particles such as bacteriophages or other compounds in a matrix. Milk proved to be protective suggesting the components of food could interfere with antimicrobial compounds.

  10. 76 FR 8715 - Technology Advisory Committee

    Science.gov (United States)

    2011-02-15

    ... COMMISSION Technology Advisory Committee AGENCY: Commodity Futures Trading Commission (``CFTC''). ACTION: Notice of meeting of Technology Advisory Committee. SUMMARY: The Technology Advisory Committee will hold...: Office of the Secretary. Please use the title ``Technology Advisory Committee'' in any written...

  11. 75 FR 17929 - Vaccines and Related Biological Products Advisory Committee; Notice of Meeting

    Science.gov (United States)

    2010-04-08

    ... will review and discuss available data regarding the unexpected finding of DNA originating from porcine... HUMAN SERVICES Food and Drug Administration Vaccines and Related Biological Products Advisory Committee... be open to the public. Name of Committee: Vaccines and Related Biological Products Advisory...

  12. 77 FR 65693 - Cellular, Tissue and Gene Therapies Advisory Committee; Amendment of Notice

    Science.gov (United States)

    2012-10-30

    ... HUMAN SERVICES Food and Drug Administration Cellular, Tissue and Gene Therapies Advisory Committee... Therapies Advisory Committee. This meeting was announced in the Federal Register of October 17, 2012 (77 FR... Register of October 17, 2012, FDA announced that a meeting of the Cellular, Tissue and Gene...

  13. 75 FR 66381 - Cellular, Tissue and Gene Therapies Advisory Committee; Notice of Meeting

    Science.gov (United States)

    2010-10-28

    ... HUMAN SERVICES Food and Drug Administration Cellular, Tissue and Gene Therapies Advisory Committee... be open to the public. Name of Committee: Cellular, Tissue and Gene Therapies Advisory Committee... Lentiviral Vector Based Gene Therapy Products. FDA intends to make background material available to...

  14. 77 FR 63840 - Cellular, Tissue and Gene Therapies Advisory Committee; Notice of Meeting

    Science.gov (United States)

    2012-10-17

    ... HUMAN SERVICES Food and Drug Administration Cellular, Tissue and Gene Therapies Advisory Committee..., Tissue and Gene Therapies Advisory Committee. General Function of the Committee: To provide advice and..., Office of Cellular, Tissue and Gene Therapies, Center for Biologics Evaluation and Research, and...

  15. 78 FR 44133 - Cellular, Tissue and Gene Therapies Advisory Committee; Notice of Meeting

    Science.gov (United States)

    2013-07-23

    ... HUMAN SERVICES Food and Drug Administration Cellular, Tissue and Gene Therapies Advisory Committee... be open to the public. Name of Committee: Cellular, Tissue and Gene Therapies Advisory Committee... on guidance documents issued from the Office of Cellular, Tissue and Gene Therapies, Center...

  16. 76 FR 49774 - Cellular, Tissue and Gene Therapies Advisory Committee; Notice of Meeting

    Science.gov (United States)

    2011-08-11

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration Cellular, Tissue and Gene Therapies Advisory Committee... be open to the public. Name of Committee: Cellular, Tissue and Gene Therapies Advisory...

  17. 78 FR 79699 - Cellular, Tissue, and Gene Therapies Advisory Committee; Notice of Meeting

    Science.gov (United States)

    2013-12-31

    ... HUMAN SERVICES Food and Drug Administration Cellular, Tissue, and Gene Therapies Advisory Committee... be open to the public. Name of Committee: Cellular, Tissue, and Gene Therapies Advisory Committee..., Tissue, and Gene Therapies, Center for Biologics Evaluation and Research (CBER), FDA. On February...

  18. 78 FR 15726 - Cellular, Tissue and Gene Therapies Advisory Committee; Notice of Meeting

    Science.gov (United States)

    2013-03-12

    ... HUMAN SERVICES Food and Drug Administration Cellular, Tissue and Gene Therapies Advisory Committee... portion of the meeting will be closed to the public. Name of Committee: Cellular, Tissue and Gene Therapies Advisory Committee. General Function of the Committee: To provide advice and recommendations...

  19. 76 FR 18768 - Cellular, Tissue, and Gene Therapies Advisory Committee; Notice of Meeting

    Science.gov (United States)

    2011-04-05

    ... HUMAN SERVICES Food and Drug Administration Cellular, Tissue, and Gene Therapies Advisory Committee... portion of the meeting will be closed to the public. Name of Committee: Cellular, Tissue, and Gene Therapies Advisory Committee. General Function of the Committee: To provide advice and recommendations...

  20. 76 FR 81513 - Cellular, Tissue, and Gene Therapies Advisory Committee; Notice of Meeting

    Science.gov (United States)

    2011-12-28

    ... HUMAN SERVICES Food and Drug Administration Cellular, Tissue, and Gene Therapies Advisory Committee..., Tissue, and Gene Therapies Advisory Committee. General Function of the Committee: To provide advice and... Gene Therapies, Center for Biologics Evaluation and Research, FDA. FDA intends to make...

  1. 76 FR 64951 - Cellular, Tissue and Gene Therapies Advisory Committee; Notice of Meeting

    Science.gov (United States)

    2011-10-19

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration Cellular, Tissue and Gene Therapies Advisory Committee... be open to the public. Name of Committee: Cellular, Tissue and Gene Therapies Advisory...

  2. 76 FR 22405 - Cellular, Tissue and Gene Therapies Advisory Committee; Notice of Meeting

    Science.gov (United States)

    2011-04-21

    ... HUMAN SERVICES Food and Drug Administration Cellular, Tissue and Gene Therapies Advisory Committee... be open to the public. Name of Committee: Cellular, Tissue and Gene Therapies Advisory Committee... gene therapy products for the treatment of retinal disorders. Topics to be considered include...

  3. 78 FR 48438 - Pediatric Ethics Subcommittee of the Pediatric Advisory Committee; Notice of Meeting

    Science.gov (United States)

    2013-08-08

    ... HUMAN SERVICES Food and Drug Administration Pediatric Ethics Subcommittee of the Pediatric Advisory... Administration (FDA). The meeting will be open to the public. Name of Subcommittee: Pediatric Ethics Subcommittee... recommendations to the Pediatric Advisory Committee on pediatric ethical issues. Date and Time: The meeting...

  4. 78 FR 77688 - Ophthalmic Devices Panel of the Medical Devices Advisory Committee; Notice of Meeting

    Science.gov (United States)

    2013-12-24

    ... HUMAN SERVICES Food and Drug Administration Ophthalmic Devices Panel of the Medical Devices Advisory...). The meeting will be open to the public. Name of Committee: Ophthalmic Devices Panel of the Medical Devices Advisory Committee. General Function of the Committee: To provide advice and recommendations...

  5. 76 FR 6625 - Neurological Devices Panel of the Medical Devices Advisory Committee; Notice of Meeting

    Science.gov (United States)

    2011-02-07

    ... HUMAN SERVICES Food and Drug Administration Neurological Devices Panel of the Medical Devices Advisory... Devices Advisory Committee. General Function of the Committee: To provide advice and recommendations to... Embolization Device (PED), sponsored by Chestnut Medical. The PED is indicated for the endovascular...

  6. 78 FR 13350 - Ophthalmic Devices Panel of the Medical Devices Advisory Committee; Notice of Meeting

    Science.gov (United States)

    2013-02-27

    ... HUMAN SERVICES Food and Drug Administration Ophthalmic Devices Panel of the Medical Devices Advisory...). The meeting will be open to the public. Name of Committee: Ophthalmic Devices Panel of the Medical Devices Advisory Committee. General Function of the Committee: To provide advice and recommendations...

  7. 75 FR 44273 - Radiological Devices Panel of the Medical Devices Advisory Committee; Notice of Meeting

    Science.gov (United States)

    2010-07-28

    ... HUMAN SERVICES Food and Drug Administration Radiological Devices Panel of the Medical Devices Advisory...). The meeting will be open to the public. Name of Committee: Radiological Devices Panel of the Medical Devices Advisory Committee. General Function of the Committee: To provide advice and recommendations...

  8. 77 FR 73034 - Neurological Devices Panel of the Medical Devices Advisory Committee; Notice of Meeting

    Science.gov (United States)

    2012-12-07

    ... HUMAN SERVICES Food and Drug Administration Neurological Devices Panel of the Medical Devices Advisory...). The meeting will be open to the public. Name of Committee: Neurological Devices Panel of the Medical Devices Advisory Committee. General Function of the Committee: To provide advice and recommendations...

  9. 75 FR 35495 - Ophthalmic Devices Panel of the Medical Devices Advisory Committee; Notice of Meeting

    Science.gov (United States)

    2010-06-22

    ... HUMAN SERVICES Food and Drug Administration Ophthalmic Devices Panel of the Medical Devices Advisory...). The meeting will be open to the public. Name of Committee: Ophthalmic Devices Panel of the Medical Devices Advisory Committee. General Function of the Committee: To provide advice and recommendations...

  10. 76 FR 3639 - Vaccines and Related Biological Products Advisory Committee; Notice of Meeting

    Science.gov (United States)

    2011-01-20

    ... HUMAN SERVICES Food and Drug Administration Vaccines and Related Biological Products Advisory Committee... be open to the public. Name of Committee: Vaccines and Related Biological Products Advisory Committee... selection of strains to be included in the influenza virus vaccine for the 2011-2012 influenza season....

  11. 75 FR 2876 - Vaccines and Related Biological Products Advisory Committee; Notice of Meeting

    Science.gov (United States)

    2010-01-19

    ... HUMAN SERVICES Food and Drug Administration Vaccines and Related Biological Products Advisory Committee... be open to the public. Name of Committee: Vaccines and Related Biological Products Advisory Committee... selection of strains to be included in the influenza virus vaccine for the 2010 - 2011 influenza season....

  12. 78 FR 5465 - Vaccines and Related Biological Products Advisory Committee; Notice of Meeting

    Science.gov (United States)

    2013-01-25

    ... HUMAN SERVICES Food and Drug Administration Vaccines and Related Biological Products Advisory Committee... be open to the public. Name of Committee: Vaccines and Related Biological Products Advisory Committee... strains to be included in the influenza virus vaccine for the 2013- 2014 influenza season. FDA intends...

  13. 76 FR 52334 - Arthritis Advisory Committee; Notice of Postponement of Meeting

    Science.gov (United States)

    2011-08-22

    ... Administration (FDA) is postponing the Arthritis Advisory Committee meeting scheduled for September 13, 2011. This meeting was announced in the Federal Register of July 19, 2011 (76 FR 42715). The postponement is... HUMAN SERVICES Food and Drug Administration Arthritis Advisory Committee; Notice of Postponement...

  14. 77 FR 14769 - Meeting of the Uniform Formulary Beneficiary Advisory Panel

    Science.gov (United States)

    2012-03-13

    ... Department of Defense (DoD) announces the following Federal Advisory Committee meeting of the Uniform... Formulary Beneficiary Advisory Panel, 4130 Stanley Road, Suite 208, Building 1000, San Antonio, TX 78234...: Dipeptidyl Peptidase--4(DPP-4) Inhibitors. d. Designated Newly Approved Drugs in Already-Reviewed Classes....

  15. Drug: D05362 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available D05362 Drug Rubella virus vaccine live (USP); Meruvax (TN) Immunizing agent [active... [BR:br08302] Immunological Agents Vaccines Rubella Virus Vaccine D05362 Rubella virus vaccine live (USP) PubChem: 17398291 ... ...] Component of Biavax (TN), M-M-R II (TN), M-R-Vax II (TN) map07044 Antiviral agents USP drug classification

  16. Drug: D06806 [KEGG MEDICUS

    Lifescience Database Archive (English)

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

  17. The antiviral effect of jiadifenoic acids C against coxsackievirus B3

    Directory of Open Access Journals (Sweden)

    Miao Ge

    2014-08-01

    Full Text Available Coxsackievirus B type 3 (CVB3 is one of the major causative pathogens associated with viral meningitis and myocarditis, which are widespread in the human population and especially prevalent in neonates and children. These infections can result in dilated cardiomyopathy (DCM and other severe clinical complications. There are no vaccines or drugs approved for the prevention or therapy of CVB3-induced diseases. During screening for anti-CVB3 candidates in our previous studies, we found that jiadifenoic acids C exhibited strong antiviral activities against CVB3 as well as other strains of Coxsackie B viruses (CVBs. The present studies were carried out to evaluate the antiviral activities of jiadifenoic acids C. Results showed that jiadifenoic acids C could reduce CVB3 RNA and proteins synthesis in a dose-dependent manner. Jiadifenoic acids C also had a similar antiviral effect on the pleconaril-resistant variant of CVB3. We further examined the impact of jiadifenoic acids C on the synthesis of viral structural and non-structural proteins, finding that jiadifenoic acids C could reduce VP1 and 3D protein production. A time-course study with Vero cells showed that jiadifenoic acids C displayed significant antiviral activities at 0–6 h after CVB3 inoculation, indicating that jiadifenoic acids C functioned at an early step of CVB3 replication. However, jiadifenoic acids C had no prophylactic effect against CVB3. Taken together, we show that jiadifenoic acids C exhibit strong antiviral activities against all strains of CVB, including the pleconaril-resistant variant. Our study could provide a significant lead for anti-CVB3 drug development.

  18. Chemical derivatives of a small molecule deubiquitinase inhibitor have antiviral activity against several RNA viruses.

    Directory of Open Access Journals (Sweden)

    Marta J Gonzalez-Hernandez

    Full Text Available Most antiviral treatment options target the invading pathogen and unavoidably encounter loss of efficacy as the pathogen mutates to overcome replication restrictions. A good strategy for circumventing drug resistance, or for pathogens without treatment options, is to target host cell proteins that are utilized by viruses during infection. The small molecule WP1130 is a selective deubiquitinase inhibitor shown previously to successfully reduce replication of noroviruses and some other RNA viruses. In this study, we screened a library of 31 small molecule derivatives of WP1130 to identify compounds that retained the broad-spectrum antiviral activity of the parent compound in vitro but exhibited improved drug-like properties, particularly increased aqueous solubility. Seventeen compounds significantly reduced murine norovirus infection in murine macrophage RAW 264.7 cells, with four causing decreases in viral titers that were similar or slightly better than WP1130 (1.9 to 2.6 log scale. Antiviral activity was observed following pre-treatment and up to 1 hour postinfection in RAW 264.7 cells as well as in primary bone marrow-derived macrophages. Treatment of the human norovirus replicon system cell line with the same four compounds also decreased levels of Norwalk virus RNA. No significant cytotoxicity was observed at the working concentration of 5 µM for all compounds tested. In addition, the WP1130 derivatives maintained their broad-spectrum antiviral activity against other RNA viruses, Sindbis virus, LaCrosse virus, encephalomyocarditis virus, and Tulane virus. Thus, altering structural characteristics of WP1130 can maintain effective broad-spectrum antiviral activity while increasing aqueous solubility.

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

    OpenAIRE

    Acosta, EP; Kimberlin, DW

    2010-01-01

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

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

    OpenAIRE

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

    2014-01-01

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

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

    Institute of Scientific and Technical Information of China (English)

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

    2009-01-01

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

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

    Directory of Open Access Journals (Sweden)

    V. V. Vysochinskayа

    2012-01-01

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

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

    OpenAIRE

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

    2014-01-01

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

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

    OpenAIRE

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

    2016-01-01

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

  5. 76 FR 14980 - National Institute on Alcohol Abuse and Alcoholism; National Institute on Drug Abuse; Notice of...

    Science.gov (United States)

    2011-03-18

    ... HUMAN SERVICES National Institutes of Health National Institute on Alcohol Abuse and Alcoholism... Council on Alcohol Abuse and Alcoholism and the National Advisory Council on Drug Abuse. The meeting will...: National Advisory Council on Alcohol Abuse and Alcoholism and National Advisory Council on Drug Abuse....

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

    Institute of Scientific and Technical Information of China (English)

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

    2007-01-01

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

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

    Science.gov (United States)

    Wang, Lingyan; Li, Wenjun; Li, Shitao

    2016-01-01

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

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

    Science.gov (United States)

    Wang, Lingyan; Li, Wenjun; Li, Shitao

    2016-01-01

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

  9. 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.

    into four cationic and six anionic isoenzymes using the polybuffer e x changers 118 and 94, respectively. Their p I values ranged from 5.4 to 9.2. On electrophoresis, the testis GSTs showed identical subunit pattern to that of brain, i.e. Yc, Yb, Y b... and in various organs like liver, kidney, intestine, brain and testis. They occur in the cytoplasm, membranes of mitochondria, micr o somes and nuclei 3 . Each organ possesses a unique profile of GSTs, the liver and testis having the high GST activity in r...

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

    OpenAIRE

    Cox, Manon M. J.

    2005-01-01

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

  11. An antiviral furanoquinone from Paulownia tomentosa Steud.

    Science.gov (United States)

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

    1999-11-01

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

  12. Antiviral and Immunostimulant Activities of Andrographis paniculata

    OpenAIRE

    Churiyah; Olivia Bunga Pongtuluran; Elrade Rofaani; Tarwadi,

    2015-01-01

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

  13. 76 FR 38668 - Advisory Committee for Pharmaceutical Science and Clinical Pharmacology; Notice of Meeting

    Science.gov (United States)

    2011-07-01

    ... Pharmacology; Notice of Meeting AGENCY: Food and Drug Administration, HHS. ACTION: Notice. This notice... Science and Clinical Pharmacology. General Function of the Committee: To provide advice and... April 13, 2010, Advisory Committee for Pharmaceutical Science and Clinical Pharmacology...

  14. 78 FR 104 - Advisory Committees; Tentative Schedule of Meetings for 2013

    Science.gov (United States)

    2013-01-02

    ... dates to be determined. Cardiovascular and Renal Drugs Advisory April 17 and other date(s) to Committee.... Ophthalmic Devices Panel June 14, August 23. Orthopaedic and Rehabilitation Devices April 5, September...

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

    OpenAIRE

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

    2013-01-01

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

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

    Directory of Open Access Journals (Sweden)

    P Mehrbod

    2009-08-01

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

  17. 75 FR 30002 - Federal Advisory Committee; Threat Reduction Advisory Committee

    Science.gov (United States)

    2010-05-28

    ... Office of the Secretary Federal Advisory Committee; Threat Reduction Advisory Committee AGENCY... the charter for the Threat Reduction Advisory Committee (hereafter referred to as the Committee). FOR... Acquisition, Technology and Logistics and the Director of the Defense Threat Reduction Agency on the...

  18. 75 FR 60430 - Federal Advisory Committee; Threat Reduction Advisory Committee

    Science.gov (United States)

    2010-09-30

    ... of the Secretary Federal Advisory Committee; Threat Reduction Advisory Committee AGENCY: Office of... announces a meeting of the Threat Reduction Advisory Committee (hereafter referred to as ``the Committee..., October 21, 2010, from 9 a.m. to 5 p.m. ADDRESSES: The meeting will be held at the Heritage...

  19. Drug: D02734 [KEGG MEDICUS

    Lifescience Database Archive (English)

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

  20. Drug: D07057 [KEGG MEDICUS

    Lifescience Database Archive (English)

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

  1. Drug: D03656 [KEGG MEDICUS

    Lifescience Database Archive (English)

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

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

    Science.gov (United States)

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

    2015-12-01

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

  3. 76 FR 53901 - The President's Management Advisory Board (PMAB); Notification of Upcoming Public Advisory Meeting

    Science.gov (United States)

    2011-08-30

    ... management, SES leadership development, and SES performance appraisal systems. The meeting minutes will be... ADMINISTRATION The President's Management Advisory Board (PMAB); Notification of Upcoming Public Advisory Meeting.... SUMMARY: The President's Management Advisory Board (PMAB), a Federal Advisory Committee established...

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

    Science.gov (United States)

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

    1995-10-01

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

  5. Replicative Homeostasis III: implications for antiviral therapy and mechanisms of response and non-response

    Directory of Open Access Journals (Sweden)

    Sallie Richard

    2007-03-01

    Full Text Available Abstract While improved drug regimens have greatly enhanced outcomes for patients with chronic viral infection, antiviral therapy is still not ideal due to drug toxicities, treatment costs, primary drug failure and emergent resistance. New antiviral agents, alternative treatment strategies and a better understanding of viral pathobiology, host responses and drug action are desperately needed. Interferon (IFN and ribavirin, are effective drugs used to treat hepatitis C (HCV, but the mechanism(s of their action are uncertain. Error catastrophe (EC, or precipitous loss of replicative fitness caused by genomic mutation, is postulated to mediate ribavirin action, but is a deeply flawed hypothesis lacking empirical confirmation. Paradoxically ribavirin, a proven RNA mutagen, has no impact on HCV viraemia long term, suggesting real viruses, replicating in-vitro, as opposed to mathematical models, replicating in-silico, are likely to resist EC by highly selective replication of fit (~consensus sequence genomes mediated, in part, by replicative homeostasis (RH, an epicyclic mechanism that dynamically links RNApol fidelity and processivity and other viral protein functions. Replicative homeostasis provides a rational explanation for the various responses seen during treatment of HCV, including genotype-specific and viral load-dependent differential response rates, as well as otherwise unexplained phenomena like the transient inhibition and rebound of HCV viraemia seen during ribavirin monotherapy. Replicative homeostasis also suggests a primarily non-immunological mechanism that mediates increased immune responsiveness during treatment with ribavirin (and other nucleos(tide analogues, explicating the enhanced second-phase clearance of HCV ribavirin promotes and, thus, the apparent immunomodulatory action of ribavirin. More importantly, RH suggests specific new antiviral therapeutic strategies.

  6. Systems biology: A tool for charting the antiviral landscape.

    Science.gov (United States)

    Bowen, James R; Ferris, Martin T; Suthar, Mehul S

    2016-06-15

    The host antiviral programs that are initiated following viral infection form a dynamic and complex web of responses that we have collectively termed as "the antiviral landscape". Conventional approaches to studying antiviral responses have primarily used reductionist systems to assess the function of a single or a limited subset of molecules. Systems biology is a holistic approach that considers the entire system as a whole, rather than individual components or molecules. Systems biology based approaches facilitate an unbiased and comprehensive analysis of the antiviral landscape, while allowing for the discovery of emergent properties that are missed by conventional approaches. The antiviral landscape can be viewed as a hierarchy of complexity, beginning at the whole organism level and progressing downward to isolated tissues, populations of cells, and single cells. In this review, we will discuss how systems biology has been applied to better understand the antiviral landscape at each of these layers. At the organismal level, the Collaborative Cross is an invaluable genetic resource for assessing how genetic diversity influences the antiviral response. Whole tissue and isolated bulk cell transcriptomics serves as a critical tool for the comprehensive analysis of antiviral responses at both the tissue and cellular levels of complexity. Finally, new techniques in single cell analysis are emerging tools that will revolutionize our understanding of how individual cells within a bulk infected cell population contribute to the overall antiviral landscape.

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

    Science.gov (United States)

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

    2016-04-28

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

  8. 78 FR 20328 - Orthopaedic and Rehabilitation Devices Panel of the Medical Devices Advisory Committee: Notice of...

    Science.gov (United States)

    2013-04-04

    ... HUMAN SERVICES Food and Drug Administration Orthopaedic and Rehabilitation Devices Panel of the Medical Devices Advisory Committee: Notice of Postponement of Meeting AGENCY: Food and Drug Administration, HHS. ACTION: Notice. SUMMARY: The Food and Drug Administration (FDA) is postponing the meeting of...

  9. 75 FR 42100 - National Institute on Drug Abuse; Notice of Meeting

    Science.gov (United States)

    2010-07-20

    ... HUMAN SERVICES National Institutes of Health National Institute on Drug Abuse; Notice of Meeting... hereby given of a meeting of the National Advisory Council on Drug Abuse. The meeting will be open to the... unwarranted invasion of personal privacy. Name of Committee: National Advisory Council on Drug Abuse....

  10. 76 FR 2697 - National Institute on Drug Abuse; Notice of Meeting

    Science.gov (United States)

    2011-01-14

    ... HUMAN SERVICES National Institutes of Health National Institute on Drug Abuse; Notice of Meeting... ] hereby given of a meeting of the National Advisory Council on Drug Abuse. The meeting will be open to the... unwarranted invasion of personal privacy. Name of Committee: National Advisory Council on Drug Abuse....

  11. 76 FR 81952 - National Institute on Drug Abuse; Notice of Meeting

    Science.gov (United States)

    2011-12-29

    ... HUMAN SERVICES National Institutes of Health National Institute on Drug Abuse; Notice of Meeting... hereby given of a meeting of the National Advisory Council on Drug Abuse. The meeting will be open to the... unwarranted invasion of personal privacy. Name of Committee: National Advisory Council on Drug Abuse....

  12. 77 FR 52752 - National Institute on Drug Abuse; Notice of Meeting

    Science.gov (United States)

    2012-08-30

    ... HUMAN SERVICES National Institutes of Health National Institute on Drug Abuse; Notice of Meeting... hereby given of a meeting of the National Advisory Council on Drug Abuse. The meeting will be open to the... unwarranted invasion of personal privacy. Name of Committee: National Advisory Council on Drug Abuse....

  13. 77 FR 22581 - National Institute on Drug Abuse; Notice of Meeting

    Science.gov (United States)

    2012-04-16

    ... HUMAN SERVICES National Institutes of Health National Institute on Drug Abuse; Notice of Meeting... hereby given of a meeting of the National Advisory Council on Drug Abuse. The meeting will be open to the... unwarranted invasion of personal privacy. Name of Committee: National Advisory Council on Drug Abuse....

  14. 76 FR 51381 - National Institute on Drug Abuse; Notice of Meeting

    Science.gov (United States)

    2011-08-18

    ... HUMAN SERVICES National Institutes of Health National Institute on Drug Abuse; Notice of Meeting... hereby given of a meeting of the National Advisory Council on Drug Abuse. The meeting will be open to the... unwarranted invasion of personal privacy. Name of Committee: National Advisory Council on Drug Abuse....

  15. 75 FR 14176 - National Institute on Drug Abuse; Notice of Meeting

    Science.gov (United States)

    2010-03-24

    ... HUMAN SERVICES National Institutes of Health National Institute on Drug Abuse; Notice of Meeting... hereby given of a meeting of the National Advisory Council on Drug Abuse. The meeting will be open to the... unwarranted invasion of personal privacy. Name of Committee: National Advisory Council on Drug Abuse....

  16. 78 FR 45252 - National Institute on Drug Abuse; Notice of Meeting

    Science.gov (United States)

    2013-07-26

    ... HUMAN SERVICES National Institutes of Health National Institute on Drug Abuse; Notice of Meeting... hereby given of a meeting of the National Advisory Council on Drug Abuse. The meeting will be open to the... unwarranted invasion of personal privacy. Name of Committee: National Advisory Council on Drug Abuse....

  17. 77 FR 72365 - National Institute on Drug Abuse; Notice of Meeting

    Science.gov (United States)

    2012-12-05

    ... HUMAN SERVICES National Institutes of Health National Institute on Drug Abuse; Notice of Meeting... hereby given of a meeting of the National Advisory Council on Drug Abuse. The meeting will be open to the... unwarranted invasion of personal privacy. Name of Committee: National Advisory Council on Drug Abuse....

  18. Antiviral and Immunostimulant Activities of Andrographis paniculata

    Directory of Open Access Journals (Sweden)

    Churiyah

    2015-04-01

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

  19. New antiviral targets for innovative treatment concepts for hepatitis B virus and hepatitis delta virus.

    Science.gov (United States)

    Durantel, David; Zoulim, Fabien

    2016-04-01

    Current therapies of chronic hepatitis B (CHB) remain limited to pegylated-interferon-alpha (PegIFN-α) or any of the five approved nucleos(t)ide analogues (NUC) treatments. While viral suppression can be achieved in the majority of patients with the high-barrier-to-resistance new-generation of NUC, i.e. entecavir and tenofovir, HBsAg loss is achieved by PegIFN-α and/or NUC in only 10% of patients, after a 5-year follow-up. Attempts to improve the response by administering two different NUC or a combination of NUC and PegIFN-α have not provided a dramatic increase in the rate of functional cure. Because of this and the need of long-term NUC administration, there is a renewed interest regarding the understanding of various steps of the HBV replication cycle, as well as specific virus-host cell interactions, in order to define new targets and develop new antiviral drugs. This includes a direct inhibition of viral replication with entry inhibitors, drugs targeting cccDNA, siRNA targeting viral transcripts, capsid assembly modulators, and approaches targeting the secretion of viral envelope proteins. Restoration of immune responses is a complementary approach. The restoration of innate immunity against HBV can be achieved, with TLR agonists or specific antiviral cytokine delivery. Restoration of adaptive immunity may be achieved with inhibitors of negative checkpoint regulators, therapeutic vaccines, or autologous transfer of engineered HBV-specific T cells. Novel targets and compounds will readily be evaluated using both relevant and novel in vitro and in vivo models of HBV infection. The addition of one or several new drugs to current therapies should offer the prospect of a markedly improved response to treatments and an increased rate of functional cure. This should lead to a reduced risk of antiviral drug resistance, and to a decreased incidence of cirrhosis and hepatocellular carcinoma (HCC).

  20. 76 FR 42713 - General and Plastic Surgery Devices Panel of the Medical Devices Advisory Committee; Amendment of...

    Science.gov (United States)

    2011-07-19

    ... HUMAN SERVICES Food and Drug Administration General and Plastic Surgery Devices Panel of the Medical... General and Plastic Surgery Devices Panel of the Medical Devices Advisory Committee. This meeting was... of the General and Plastic Surgery Devices Panel of the Medical Devices Advisory Committee would...

  1. Use of Cough and Cold Medications in Severe Bronchiolitis Before and After a Health Advisory Warning against Their Use

    Science.gov (United States)

    O’Donnell, Katherine; Mansbach, Jonathan M.; LoVecchio, Frank; Cheng, John; Piedra, Pedro A.; Clark, Sunday; Sullivan, Ashley F.; Camargo, Carlos A.

    2015-01-01

    We compared the use of cough and cold medications in two multicenter studies of young children hospitalized with bronchiolitis before and after the 2008 Food and Drug Administration cough and cold medications advisory. Although cough and cold medications use decreased after the advisory, nearly 20% of children age 12–23.9 months with severe bronchiolitis received cough and cold medications. PMID:25888349

  2. Antiviral Treatment among Pregnant Women with Chronic Hepatitis B

    Directory of Open Access Journals (Sweden)

    Lin Fan

    2014-01-01

    Full Text Available Objective. To describe the antiviral treatment patterns for chronic hepatitis B (CHB among pregnant and nonpregnant women. Methods. Using 2011 MarketScan claims, we calculated the rates of antiviral treatment among women (aged 10–50 years with CHB. We described the pattern of antiviral treatment during pregnancy and ≥1 month after delivery. Results. We identified 6274 women with CHB during 2011. Among these, 64 of 507 (12.6% pregnant women and 1151 of 5767 (20.0% nonpregnant women received antiviral treatment (P < 0.01. Pregnant women were most commonly prescribed tenofovir (73.4% and lamivudine (21.9%; nonpregnant women were most commonly prescribed tenofovir (50.2% and entecavir (41.3% (P < 0.01. Among 48 treated pregnant women with an identifiable delivery date, 16 (33.3% were prescribed an antiviral before pregnancy and continued treatment for at least one month after delivery; 14 (29.2% started treatment during the third trimester and continued at least one month after delivery. Conclusion. Among this insured population, pregnant women with CHB received an antiviral significantly less often than nonpregnant women. The most common antiviral prescribed for pregnant women was tenofovir. These data provide a baseline for assessing changes in treatment patterns with anticipated increased use of antivirals to prevent breakthrough perinatal hepatitis B virus infection.

  3. Antiviral Treatment among Pregnant Women with Chronic Hepatitis B

    Science.gov (United States)

    Fan, Lin; Owusu-Edusei, Kwame; Schillie, Sarah F.; Murphy, Trudy V.

    2014-01-01

    Objective. To describe the antiviral treatment patterns for chronic hepatitis B (CHB) among pregnant and nonpregnant women. Methods. Using 2011 MarketScan claims, we calculated the rates of antiviral treatment among women (aged 10–50 years) with CHB. We described the pattern of antiviral treatment during pregnancy and ≥1 month after delivery. Results. We identified 6274 women with CHB during 2011. Among these, 64 of 507 (12.6%) pregnant women and 1151 of 5767 (20.0%) nonpregnant women received antiviral treatment (P < 0.01). Pregnant women were most commonly prescribed tenofovir (73.4%) and lamivudine (21.9%); nonpregnant women were most commonly prescribed tenofovir (50.2%) and entecavir (41.3%) (P < 0.01). Among 48 treated pregnant women with an identifiable delivery date, 16 (33.3%) were prescribed an antiviral before pregnancy and continued treatment for at least one month after delivery; 14 (29.2%) started treatment during the third trimester and continued at least one month after delivery. Conclusion. Among this insured population, pregnant women with CHB received an antiviral significantly less often than nonpregnant women. The most common antiviral prescribed for pregnant women was tenofovir. These data provide a baseline for assessing changes in treatment patterns with anticipated increased use of antivirals to prevent breakthrough perinatal hepatitis B virus infection. PMID:25548510

  4. Beyond RNAi: antiviral defense strategies in Drosophila and mosquito

    NARCIS (Netherlands)

    Merkling, S.H.; Rij, R.P. van

    2013-01-01

    Virus transmission and spread by arthropods is a major economic and public health concern. The ongoing dissemination of arthropod-borne viruses by blood-feeding insects is an important incentive to study antiviral immunity in these animals. RNA interference is a major mechanism for antiviral defense

  5. Induction and suppression of the innate antiviral responses by picornaviruses

    NARCIS (Netherlands)

    Feng, Q.

    2014-01-01

    On the front line of innate antiviral immune reactions is the type I interferon (IFN-α/β) system. IFN-α/β are small signaling molecules that can be produced by virtually all nucleated cells in our body upon virus infections, and induce a so-called “antiviral state” in neighboring cells by activating

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

    DEFF Research Database (Denmark)

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

    2015-01-01

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

  7. Innate Antiviral Defenses Independent of Inducible IFNα/β Production.

    Science.gov (United States)

    Paludan, Søren R

    2016-09-01

    The type I interferons (IFNs) (IFNα and IFNβ) not only have potent antiviral activities, but also have pathological functions if produced at high levels or over a long time. Recent articles have described antiviral immune mechanisms that are activated in response to virus infection at epithelial surfaces independently of IFNα and IFNβ. This may allow the host to exert rapid local antiviral activity and only induce a full-blown, and potentially pathological, type I IFN response in situations where stronger protective immunity is needed. Here, I describe the emerging understanding of early antiviral defenses, which are independent of type I IFN responses, and also discuss how this enables tissues to exert rapid antiviral activities and to limit type I IFN production. PMID:27345728

  8. 78 FR 50040 - Technology Advisory Committee

    Science.gov (United States)

    2013-08-16

    ... COMMISSION Technology Advisory Committee AGENCY: Commodity Futures Trading Commission. ACTION: Notice of Meeting of Technology Advisory Committee. SUMMARY: The Commodity Futures Trading Commission (CFTC) announces that on September 12, 2013, the CFTC's Technology Advisory Committee (TAC) will hold a...

  9. 76 FR 776 - Technology Advisory Committee

    Science.gov (United States)

    2011-01-06

    ... COMMISSION Technology Advisory Committee AGENCY: Commodity Futures Trading Commission (``CFTC''). ACTION: Notice of meeting of Technology Advisory Committee. SUMMARY: The Technology Advisory Committee will hold...., Washington, DC 20581, attention: Office of the Secretary. Please use the title ``Technology...

  10. 75 FR 58367 - Technology Advisory Committee Meeting

    Science.gov (United States)

    2010-09-24

    ... COMMISSION Technology Advisory Committee Meeting AGENCY: Commodity Futures Trading Commission (``CFTC''). ACTION: Notice of meeting of Technology Advisory Committee. SUMMARY: The Technology Advisory Committee...., Washington, DC 20581, attention: Office of the Secretary. Please use the title ``Technology...

  11. 75 FR 28542 - Superior Resource Advisory Committee

    Science.gov (United States)

    2010-05-21

    ... orient the new Superior Resource Advisory Committee members on their roles and responsibilities. DATES... of the roles and responsibilities of the Superior Resource Advisory Committee members; Election of... Forest Service Superior Resource Advisory Committee AGENCY: Forest Service, USDA. ACTION: Notice...

  12. 77 FR 36250 - Recreation Resource Advisory Committees

    Science.gov (United States)

    2012-06-18

    ... Forest Service Recreation Resource Advisory Committees AGENCY: Forest Service, USDA. ACTION: Call for nominations for the Pacific Northwest Recreation Resource Advisory Committee. SUMMARY: The Secretary of Agriculture has established the Pacific Northwest Recreation Resource Advisory Committee (Recreation...

  13. Drug: D03210 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available D03210 Drug Ancriviroc (USAN/INN) C28H37BrN4O3 556.2049 557.5224 D03210.gif Antiviral; Treatment of autoimmu...ne conditions [CCR5 antagonist] chemokine receptor 5 (CCR5) antagonist [HSA:1234] [

  14. Drug: D09012 [KEGG MEDICUS

    Lifescience Database Archive (English)

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

  15. Drug: D02747 [KEGG MEDICUS

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

  16. Drug: D04553 [KEGG MEDICUS

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

  17. Drug: D00423 [KEGG MEDICUS

    Lifescience Database Archive (English)

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

  18. Drug: D03001 [KEGG MEDICUS

    Lifescience Database Archive (English)

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

  19. Drug: D07989 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available D07989 Drug Fomivirsen (INN) C204H243N63O114P20S20 6657.4321 6662.2412 Antisense antiviral used in the thera...py of cytomegalovirus retinitis [DS:H00368] ATC code: S01AD08 Antisense oligonucleo

  20. Citizen Advisory Committees.

    Science.gov (United States)

    Miller, Leann R.

    This guide, describing community involvement through citizen advisory committees, is a summary of the literature on such committees. Its main concern is district committees created by school boards. Citations in the bibliography contain all points of view on committees and present many alternatives on most of the topics covered in the guide.…

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

    Science.gov (United States)

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

    2016-06-01

    Arctigenin (ACT) is a phenylpropanoid dibenzylbutyrolactone lignan extracted from the traditional herb Arctium lappa L. (Compositae) with anti-viral and anti-inflammatory effects. Here, we investigated the antiviral activity of ACT found in traditional Chinese medicine on porcine circovirus type 2 (PCV2) in vitro and in vivo. Results showed that dosing of 15.6-62.5μg/mL ACT could significantly inhibit the PCV2 proliferation in PK-15 cells (P<0.01). Dosing of 62.5μg/mL ACT 0, 4 or 8h after challenge inoculation significantly inhibited the proliferation of 1MOI and 10MOI in PK-15 cells (P<0.01), and the inhibitory effect of ACT dosing 4h or 8h post-inoculation was greater than 0h after dosing (P<0.01). In vivo test with mice challenge against PCV2 infection demonstrated that intraperitoneal injection of 200μg/kg ACT significantly inhibited PCV2 proliferation in the lungs, spleens and inguinal lymph nodes, with an effect similar to ribavirin, demonstrating the effectiveness of ACT as an antiviral agent against PCV2 in vitro and in vivo. This compound, therefore, may have the potential to serve as a drug for protection of pigs against the infection of PCV2. PMID:27234554

  2. 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.

  3. 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.

  4. Hepatitis C virus cell-cell transmission and resistance to direct-acting antiviral agents.

    Directory of Open Access Journals (Sweden)

    Fei Xiao

    2014-05-01

    Full Text Available Hepatitis C virus (HCV is transmitted between hepatocytes via classical cell entry but also uses direct cell-cell transfer to infect neighboring hepatocytes. Viral cell-cell transmission has been shown to play an important role in viral persistence allowing evasion from neutralizing antibodies. In contrast, the role of HCV cell-cell transmission for antiviral resistance is unknown. Aiming to address this question we investigated the phenotype of HCV strains exhibiting resistance to direct-acting antivirals (DAAs in state-of-the-art model systems for cell-cell transmission and spread. Using HCV genotype 2 as a model virus, we show that cell-cell transmission is the main route of viral spread of DAA-resistant HCV. Cell-cell transmission of DAA-resistant viruses results in viral persistence and thus hampers viral eradication. We also show that blocking cell-cell transmission using host-targeting entry inhibitors (HTEIs was highly effective in inhibiting viral dissemination of resistant genotype 2 viruses. Combining HTEIs with DAAs prevented antiviral resistance and led to rapid elimination of the virus in cell culture model. In conclusion, our work provides evidence that cell-cell transmission plays an important role in dissemination and maintenance of resistant variants in cell culture models. Blocking virus cell-cell transmission prevents emergence of drug resistance in persistent viral infection including resistance to HCV DAAs.

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

    Science.gov (United States)

    Silva, Débora Scopel e; de Castro, Clarissa Caetano; Silva, Fábio da Silva e; Sant’anna, Voltaire; Vargas, Gilberto D’Avila; de Lima, Marcelo; Fischer, Geferson; Brandelli, Adriano; da Motta, Amanda de Souza; Hübner, Silvia de Oliveira

    2014-01-01

    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 104.5 TCID50 to 102.75 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. PMID:25477947

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

    Directory of Open Access Journals (Sweden)

    Débora Scopel e Silva

    2014-09-01

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

  7. Immunomodulating and antiviral therapy in herpes zoster.

    Science.gov (United States)

    Topciu, V; Mihăilescu, R

    1996-01-01

    Two groups of patients with herpes zoster were followed up. The first group was subjected, beside a symptomatic therapy, to an immunological and antiviral treatment. The control group was treated only symptomatically. The immunological preparations used were: the immunostimulant SRE (Corynebacterium parvum), which stimulated the lymphocytes and macrophages, Moroxidin (Virustat-Paris) and Antiherpin (interferon inductor), which acted by blocking the virus replication. The preparations were indigenous and atoxic. A significant difference between the courses of disease in the two groups was observed, namely, the severity and duration of subjective and objective symptoms were more than double and followed by persistent neurological sequelae in the control group in comparison with the patients of the experimental group. PMID:9495784

  8. Novel concept on antiviral strategies to dengue.

    Science.gov (United States)

    Lo, Yu-Chih; Perng, Guey Chuen

    2016-06-01

    Recent evidence has revealed that asymptomatic and/or persistent dengue virus (DENV) infections play a role in the cycling pattern of dengue outbreaks. These findings add a new dimension to the continually evolving search for effective prevention strategies in dengue. Disappointing outcomes of clinical trials in anti-dengue modalities have become commonplace. These failures may result from confounding variables and/or unresolved scientific issues that surround dengue, including the replication cycle of DENV in a natural setting, the target cells and reservoir for viral replication in vivo, and the effect of asymptomatic/persistent carriers in the dissemination of dengue. This article sets forth to address these issues using the most updated information available in the literature and to propose a novel antiviral strategy for the prevention and control of dengue. PMID:27284691

  9. RNAi:antiviral therapy against dengue virus

    Institute of Scientific and Technical Information of China (English)

    Sobia Idrees; Usman A Ashfaq

    2013-01-01

    Dengue virus infection has become a global threat affecting around 100 countries in the world. Currently, there is no licensed antiviral agent available against dengue. Thus, there is a strong need to develop therapeutic strategies that can tackle this life threatening disease. RNA interference is an important and effective gene silencing process which degrades targeted RNA by a sequence specific process. Several studies have been conducted during the last decade to evaluate the efficiency of siRNA in inhibiting dengue virus replication. This review summarizes siRNAs as a therapeutic approach against dengue virus serotypes and concludes that siRNAs against virus and host genes can be next generation treatment of dengue virus infection.

  10. Antiviral therapy in hepatitis C virus cirrhotic patients in compensated and decompensated condition

    Institute of Scientific and Technical Information of China (English)

    Angelo Iacobellis; Antonio Ippolito; Angelo Andriulli

    2008-01-01

    The main goals of treating cirrhotic patients with antiviral therapy are to attain sustained viral clearance (SVR), halt disease progression, and prevent re-infection of the liver graft. However, while the medical need is great, the use of interferon and ribavirin might expose these patients to severe treated-related side effects as a large proportion of them have pre-existing hematological cytopenias. We have reviewed potential benefits and risks associated with antiviral drugs in patients with liver cirrhosis, due to hepatitis C virus (HCV) infection. In cases presenting with bridging fibrosis or cirrhosis, current regimens of antiviral therapy have attained a 44%-48% rate of SVR. In cirrhotic patients with portal hypertension, the SVR rate was 22% overall, 12.5% in patients with genotype 1, and 66.7% in those with genotypes 2 and 3 following therapy with low doses of either Peg-IFN alpha-2b and of ribavirin. In patients with decompensated cirrhosis, full dosages of Peg-IFN alpha-2b and of ribavirin produced a SVR rate of 35% overall, 16% in patients with genotype 1 and 4, and 59% in those with genotype 2 and 3. Use of hematological cytokines will either ensure full course of treatment to be accomplished with and prevent development of treatment-associated side effects. Major benefits after HCV eradication were partial recovery of liver metabolic activity, prevention of hepatitis C recurrence after transplantation, and removal of some patients from the waiting list for liver transplant. Several observations highlighted that therapy is inadvisable for individuals with poor hepatic reserve (ChUd-Pugh-Turcotte score ≥ 10). Although SVR rates are low in decompensated cirrhotics due to hepatitis C, these patients have the most to gain as successful antiviral therapy is potentially lifesaving. C 2008 The W.1G Press. All dghts reserved.

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

    Science.gov (United States)

    McKimm‐Breschkin, Jennifer L.

    2012-01-01

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

  12. Antiviral Activity of Chloroquine against Human Coronavirus OC43 Infection in Newborn Mice▿

    OpenAIRE

    Keyaerts, Els; Li, Sandra; Vijgen, Leen; Rysman, Evelien; Verbeeck, Jannick; Van Ranst, Marc; Maes, Piet

    2009-01-01

    Until recently, human coronaviruses (HCoVs), such as HCoV strain OC43 (HCoV-OC43), were mainly known to cause 15 to 30% of mild upper respiratory tract infections. In recent years, the identification of new HCoVs, including severe acute respiratory syndrome coronavirus, revealed that HCoVs can be highly pathogenic and can cause more severe upper and lower respiratory tract infections, including bronchiolitis and pneumonia. To date, no specific antiviral drugs to prevent or treat HCoV infectio...

  13. [Antiviral activity of plant components. 1st communication: Flavonoids (author's transl)].

    Science.gov (United States)

    Wacker, A; Eilmes, H G

    1978-01-01

    Some drugs effective against influenza contain flavonoids. We therefore examined the antiviral effect of hesperidin, hesperidinmethylchalcon, trihydroxyethylrutin, catechol, quercitrin, rutin and aurantiin against vesicular stromatitis virus (VSV) action on mouse fibroblasts and that of hesperidin against influenza virus in HeLa cells system by means of dye uptake measurements (Finter) and by plaque reduction test, respectively. Preincubation of the cells with the flavonoids 6--8 h before virus addition was inevitable. Protection of cells against virus action persisted for about 24 h and it abruptly disappeared after an addition of hyaluronidase. Maximal inhibition of virus action was achieved with a concentration of 200 microgram/ml flavonoid.

  14. Molecular Sleds and More: Novel Antiviral Agents via Single-Molecule Biology (441st Brookhaven Lecture)

    Energy Technology Data Exchange (ETDEWEB)

    Mangel, Wally (Ph.D., Biology Department)

    2008-10-15

    Vaccines are effective against viruses such as polio and measles, but vaccines against other important viruses, such as HIV and flu viruses, may be impossible to obtain. These viruses change their genetic makeup each time they replicate so that the immune system cannot recognize all their variations. Hence it is important to develop new antiviral agents that inhibit virus replication. During this lecture, Dr. Mangel will discuss his group's work with a model system, the human adenovirus, which causes, among other ailments, pink eye, blindness and obesity. Mangel's team has developed a promising drug candidate that works by inihibiting adenovirus proteinase, an enzyme necessary for viral replication.

  15. Characterization of Antiviral Activity of Benzamide Derivative AH0109 against HIV-1 Infection

    OpenAIRE

    Chen, Liyu; Ao, Zhujun; Jayappa, Kallesh Danappa; Kobinger, Gary; Liu, ShuiPing; Wu, Guojun; Wainberg, Mark A.; Yao, Xiaojian

    2013-01-01

    In the absence of an effective vaccine against HIV-1 infection, anti-HIV-1 strategies play a major role in disease control. However, the rapid emergence of drug resistance against all currently used anti-HIV-1 molecules necessitates the development of new antiviral molecules and/or strategies against HIV-1 infection. In this study, we have identified a benzamide derivative named AH0109 that exhibits potent anti-HIV-1 activity at an 50% effective concentration of 0.7 μM in HIV-1-susceptible CD...

  16. Drug: D00891 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available D00891 Drug Abacavir sulfate (JAN/USAN); Ziagen (TN) (C14H18N6O)2. H2SO4 670.2758 6...ersensitivity reaction to Abacavir RNA-directed DNA polymerase inhibitor Genomic ...ls 6250 Antivirals D00891 Abacavir sulfate (JAN/USAN) Anatomical Therapeutic Chem...A DIRECT ACTING ANTIVIRALS J05AF Nucleoside and nucleotide reverse transcriptase inhibitors J05AF06 Abacavir D00891 Abacavir...ls Anti-HIV Agents, Nucleoside and Nucleotide Reverse Transcriptase Inhibitors (NRTI)v Abacavir D00891 Abacavir

  17. Drug: D00777 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available 28 187.7096 D00777.gif Antiviral, Antiparkinsonian [DS:H00057 H00398] Same as: C07939 Therapeutic category: ...ansporter: SLC22A2 [HSA:6582] map07044 Antiviral agents map07057 Antiparkinsonian agents map07235 N-Metyl-D-...rvous system and sensory organs 11 Agents affecting central nervous system 116 Antiparkins...ation [BR:br08302] Antiparkinson Agents Antiparkinson Agents, Other Amantadine D0...04BB Adamantane derivatives N04BB01 Amantadine D00777 Amantadine hydrochloride (JP16/USP) USP drug classific

  18. 76 FR 62419 - General and Plastic Surgery Devices Panel of the Medical Devices Advisory Committee; Notice of...

    Science.gov (United States)

    2011-10-07

    ..., Salons A, B, C and D, 620 Perry Pkwy., Gaithersburg, MD. Contact Person: Avena Russell, Food and Drug... Spring, MD 20993-0002, 301-796-3805, Avena.Russell@fda.hhs.gov , or FDA Advisory Committee...

  19. HIV-1 Antiretroviral Drug Therapy

    OpenAIRE

    Arts, Eric J.; Hazuda, Daria J.

    2012-01-01

    The most significant advance in the medical management of HIV-1 infection has been the treatment of patients with antiviral drugs, which can suppress HIV-1 replication to undetectable levels. The discovery of HIV-1 as the causative agent of AIDS together with an ever-increasing understanding of the virus replication cycle have been instrumental in this effort by providing researchers with the knowledge and tools required to prosecute drug discovery efforts focused on targeted inhibition with ...

  20. Antiviral Treatment among Pregnant Women with Chronic Hepatitis B

    OpenAIRE

    Lin Fan; Kwame Owusu-Edusei; Schillie, Sarah F.; Murphy, Trudy V.

    2014-01-01

    Objective. To describe the antiviral treatment patterns for chronic hepatitis B (CHB) among pregnant and nonpregnant women. Methods. Using 2011 MarketScan claims, we calculated the rates of antiviral treatment among women (aged 10–50 years) with CHB. We described the pattern of antiviral treatment during pregnancy and ≥1 month after delivery. Results. We identified 6274 women with CHB during 2011. Among these, 64 of 507 (12.6%) pregnant women and 1151 of 5767 (20.0%) nonpregnant women receiv...

  1. Evaluation antiviral effect of leaf extract of Rosmarinus officinalis against Herpes simplex virus type 1 in cell cultur

    OpenAIRE

    G Yousefi Kordestani; M Parsania

    2015-01-01

    Introduction Herpes simplex virus type I belongs to herpesviridae. Several studies are ongoing for achieve a drug with good effectiveness and lower side effects, because the incidence of infections caused by this virus is increasing and there is some HSV resistance in the world. In this study, anti-viral effects of rosemary extract against of HSV was evaluated in cell culture. Material and methods: At first the rosemary extract toxicity on Hela cells with trypan blue and MTT methods has been ...

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

    International Nuclear Information System (INIS)

    Highlights: • Screening of 50,000 compounds and subsequent lead optimization identified WV970. • WV970 has antiviral effects against influenza A, B and highly pathogenic viral strains. • WV970 inhibits viral genome replication and transcription. • A target database search suggests that WV970 may bind to a number of kinases. • KINOMEscan screening revealed that WV970 has inhibitory effects on 15 kinases. - Abstract: Neuraminidase inhibitors are the only currently available influenza treatment, although resistant viruses to these drugs have already been reported. Thus, new antiviral drugs with novel mechanisms of action are urgently required. In this study, we identified a novel antiviral compound, WV970, through cell-based screening of a 50,000 compound library and subsequent lead optimization. This compound exhibited potent antiviral activity with nanomolar IC50 values against both influenza A and B viruses but not non-influenza RNA viruses. Time-of-addition and indirect immunofluorescence assays indicated that WV970 acted at an early stage of the influenza life cycle, but likely after nuclear entry of viral ribonucleoprotein (vRNP). Further analyses of viral RNA expression and viral polymerase activity indicated that WV970 inhibited vRNP-mediated viral genome replication and transcription. Finally, structure-based virtual screening and comprehensive human kinome screening were used to demonstrate that WV970 acts as a multiple kinase inhibitor, many of which are associated with influenza virus replication. Collectively, these results strongly suggest that WV970 is a promising anti-influenza drug candidate and that several kinases associated with viral replication are promising drug targets

  3. Genetically Engineered Protein Modules: Development and Applications in Anti-Viral Agent Screening and Cancer Marker Detection

    OpenAIRE

    Biswas, Payal

    2010-01-01

    ABSTRACT OF THE DISSERTATION Genetically Engineered Protein Modules: Development and Applications in Anti-Viral Agent Screening and Cancer Marker Detection byPayal BiswasDoctor of Philosophy Cell Molecular and Developmental Biology Graduate ProgramUniversity of California, Riverside, August 2010Dr. Wilfred Chen, ChairpersonOne of the most critical aspects in drug discovery is the bioactivity screening assay, by which compounds that most effectively inhibit the target are identified. During t...

  4. 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.

  5. Antiviral therapy with nucleotide/nucleoside analogues in chronic hepatitis B: A meta-analysis of prospective randomized trials.

    Science.gov (United States)

    Bedre, Renesh H; Raj, Utkarsh; Misra, Sri Prakash; Varadwaj, Pritish Kumar

    2016-03-01

    Nucleotide/nucleoside analogues (antiviral therapy) are used in the therapy of HBeAg positive and HBeAg negative chronic hepatitis B. We analyzed ten selected randomized controlled with 2557 patients to estimate the effect of antiviral drugs in chronic hepatitis B with compared to placebo. Virological response, biochemical response, histological response, seroconversion of HBeAg, and loss of HBeAg were estimated as primary efficacy measures. The included studies were subjected for heterogeneity and publication bias. The heterogeneity was assessed with χ2 and I(2) statistics. Publication bias was assessed by funnel plot. Greater rates of improvement obtained in antiviral group for virological response [43.96 % vs. 3.15 %, RR = 0.57, 95 % CI = 0.54-0.61, p-value pharyngitis [22.22 % vs. 18.23 %, OR = 1.12, 95 % CI = 0.86-1.45, p-value = 0.40]. Excluding adverse events, all primary efficacy measures shown statistical significant result for chronic hepatitis treatment (p-value <0.05). Antiviral therapy provided significant benefit for the treatment of chronic hepatitis B with no measurable adverse effects. PMID:27083430

  6. Drug: D10066 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available D10066 Drug Dolutegravir (USAN) C20H19F2N3O5 419.1293 419.3788 D10066.gif Treatment...R SYSTEMIC USE J05A DIRECT ACTING ANTIVIRALS J05AX Other antivirals J05AX12 Dolutegravir D100...e Inhibitors (INSTI) Dolutegravir D10066 Dolutegravir (USAN) Antiinfectives [BR:br08307] Antivirals Anti-HIV... agent Ohters HIV-1 integrase inhibitor Dolutegravir D10066 Dolutegravir (USAN) C...AS: 1051375-16-6 PubChem: 135626786 PDB-CCD: DLU LigandBox: D10066 ATOM 30 1 C8y C 17.0100 -20.8600 2 N4y N 17.0100

  7. The Prevalence and Trends of Antiviral Medication Use during Pregnancy in the U.S. A population-based study of 664,297 deliveries in 2001-2007

    Science.gov (United States)

    Avalos, Lyndsay A.; Chen, Hong; Yang, Chunmei; Andrade, Susan E.; Cooper, William O.; Cheetham, Craig T.; Davis, Robert L.; Dublin, Sascha; Hammad, Tarek A.; Kaplan, Sigal; Pawloski, Pamala A.; Raebel, Marsha A.; Scott, Pamela E.; Smith, David H.; Toh, Sengwee; Li, De-Kun

    2013-01-01

    Objectives To evaluate the prevalence, trends, timing and duration of exposure to antiviral medications during pregnancy within a US cohort of pregnant women and to evaluate the proportion of deliveries with a viral infection diagnosis among women given antiviral medication during pregnancy. Methods Live-born deliveries between 2001 and 2007, to women aged 15 to 45 years, were included from the Medication Exposure in Pregnancy Risk Evaluation Program (MEPREP), a collaborative research program between the U.S. Food and Drug Administration and eleven health plans. They were evaluated for prevalence, timing, duration, and temporal trends of exposure to antiviral medications during pregnancy. We also calculated the proportion of deliveries with a viral infection diagnosis among those exposed to antiviral medications. Results Among 664,297 live births, the overall prevalence of antiviral exposure during pregnancy was 4% (n=25,155). Between 2001 and 2007, antiviral medication exposure during pregnancy doubled from 2.5% to 5%. The most commonly used antiviral medication was acyclovir, with 3% of the deliveries being exposed and most of the exposure occurring after the 1st trimester. Most deliveries exposed to antiviral medications were exposed for less than 30 days (2% of all live births). Forty percent of the women delivering an infant exposed to antiviral medications had a herpes diagnosis. Conclusions Our findings highlight the increased prevalence of women delivering an infant exposed to antiviral medications over time. These findings support the need for large, well-designed studies to assess the safety and effectiveness of these medications during pregnancy. PMID:23420306

  8. Atmospheric release advisory capability

    International Nuclear Information System (INIS)

    The ARAC system (Atmospheric Release Advisory Capability) is described. The system is a collection of people, computers, computer models, topographic data and meteorological input data that together permits a calculation of, in a quasi-predictive sense, where effluent from an accident will migrate through the atmosphere, where it will be deposited on the ground, and what instantaneous and integrated dose an exposed individual would receive

  9. The antiviral response to gamma interferon.

    Science.gov (United States)

    Costa-Pereira, Ana P; Williams, Timothy M; Strobl, Birgit; Watling, Diane; Briscoe, James; Kerr, Ian M

    2002-09-01

    A role for alpha/beta interferon (IFN-alpha/beta) in the IFN-gamma antiviral response has long been suggested. Accordingly, possible roles for autocrine or double-stranded-RNA (dsRNA)-induced IFN-alpha/beta in the IFN-gamma response were investigated. Use was made of wild-type and a variety of mutant human fibrosarcoma cell lines, including mutant U5A cells, which lack a functional IFN-alpha/beta receptor and hence an IFN-alpha/beta response. IFN-gamma did not induce detectable levels of IFN-alpha/beta in any of the cell lines, nor was the IFN-gamma response per se dependent on autocrine IFN-alpha/beta. On the other hand, a number of responses to dsRNA [poly(I). poly(C)] and encephalomyocarditis virus were greatly enhanced by IFN-gamma pretreatment (priming) of wild-type cells or of mutant cells lacking an IFN-alpha/beta response; these include the primary induction of dsRNA-inducible mRNAs, including IFN-beta mRNA, and, to a lesser extent, the dsRNA-mediated activation of the p38 mitogen-activated protein (MAP) kinase(s). IFN-gamma priming of mRNA induction by dsRNA is dependent on JAK1 and shows biphasic kinetics, with an initial rapid (<30-min) response being followed by a more substantial effect on overnight incubation. The IFN-gamma-primed dsRNA responses appear to be subject to modulation through the p38, phosphatidylinositol 3-kinase, and ERK1/ERK2 MAP kinase pathways. It can be concluded that despite efficient priming of IFN-beta production, the IFN-alpha/beta pathways play no significant role in the primary IFN-gamma antiviral response in these cell-virus systems. The observed IFN-gamma priming of dsRNA responses, on the other hand, will likely play a significant role in combating virus infection in vivo.

  10. Multiplex Liquid Chromatography-Tandem Mass Spectrometry Assay for Simultaneous Therapeutic Drug Monitoring of Ribavirin, Boceprevir, and Telaprevir

    OpenAIRE

    Aouri, Manel; Moradpour, Darius; Cavassini, Matthias; Mercier, Thomas; Buclin, Thierry; Csajka, Chantal; Telenti, Amalio; Rauch, Andri; Decosterd, Laurent A.

    2013-01-01

    New directly acting antivirals (DAAs) that inhibit hepatitis C virus (HCV) replication are increasingly used for the treatment of chronic hepatitis C. A marked pharmacokinetic variability and a high potential for drug-drug interactions between DAAs and numerous drug classes have been identified. In addition, ribavirin (RBV), commonly associated with hemolytic anemia, often requires dose adjustment, advocating for therapeutic drug monitoring (TDM) in patients under combined antiviral therapy. ...

  11. Dengue Virus Entry as Target for Antiviral Therapy

    Directory of Open Access Journals (Sweden)

    Marijke M. F. Alen

    2012-01-01

    Full Text Available Dengue virus (DENV infections are expanding worldwide and, because of the lack of a vaccine, the search for antiviral products is imperative. Four serotypes of DENV are described and they all cause a similar disease outcome. It would be interesting to develop an antiviral product that can interact with all four serotypes, prevent host cell infection and subsequent immune activation. DENV entry is thus an interesting target for antiviral therapy. DENV enters the host cell through receptor-mediated endocytosis. Several cellular receptors have been proposed, and DC-SIGN, present on dendritic cells, is considered as the most important DENV receptor until now. Because DENV entry is a target for antiviral therapy, various classes of compounds have been investigated to inhibit this process. In this paper, an overview is given of all the putative DENV receptors, and the most promising DENV entry inhibitors are discussed.

  12. STUDY OF ANTIVIRAL ACTIVITY OF SOME HYDRAZONE PINOSTROBIN DERIVATIVES

    Directory of Open Access Journals (Sweden)

    G. K. Mukusheva

    2014-01-01

    Full Text Available New derivatives on the basis of hydrazone pinostrobin molecule were synthesized. Significant antiviral activity of received samples of new hydrazone pinstrobin derivatives was identified.

  13. Regulation of antiviral innate immunity by deubiquitinase CYLD

    Institute of Scientific and Technical Information of China (English)

    Minying Zhang; Andrew J Lee; Xuefeng Wu; Shao-Cong Sun

    2011-01-01

    An antiviral innate immune response involves induction of type Ⅰ interferons (IFNs) and their subsequent autocrine and paracrine actions,but the underlying regulatory mechanisms are incompletely understood.Here we report that CYLD,a deubiquitinase that specifically digests lysine 63-1inked ubiquitin chains,is required for antiviral host defense.Loss of CYLD renders mice considerably more susceptible to infection by vesicular stomatitis virus (VSV).Consistently,CYLD-deficient dendritic cells are more sensitive to VSV infection.This functional defect was not due to lack of type I IFN production but rather because of attenuated IFN receptor signaling.In the absence of CYLD,IFN-β is ineffective in the induction of antiviral genes and protection of cells from viral infection.These findings establish CYLD as a novel regulator of antiviral innate immunity and suggest a role for CYLD in regulating IFN receptor signaling.

  14. Dendrimers in drug research

    DEFF Research Database (Denmark)

    Boas, Ulrik; Heegaard, Peter M. H.

    2004-01-01

    and in vivo cytotoxicity, as well as biopermeability, biostability and immunogenicity. The review deals with numerous applications of dendrimers as tools for efficient multivalent presentation of biological ligands in biospecific recognition, inhibition and targeting. Dendrimers may be used as drugs...... for antibacterial and antiviral treatment and have found use as antitumor agents. The review highlights the use of dendrimers as drug or gene delivery devices in e.g. anticancer therapy, and the design of different host-guest binding motifs directed towards medical applications is described. Other specific examples...

  15. The SARS-coronavirus papain-like protease: structure, function and inhibition by designed antiviral compounds.

    Science.gov (United States)

    Báez-Santos, Yahira M; St John, Sarah E; Mesecar, Andrew D

    2015-03-01

    Over 10 years have passed since the deadly human coronavirus that causes severe acute respiratory syndrome (SARS-CoV) emerged from the Guangdong Province of China. Despite the fact that the SARS-CoV pandemic infected over 8500 individuals, claimed over 800 lives and cost billions of dollars in economic loss worldwide, there still are no clinically approved antiviral drugs, vaccines or monoclonal antibody therapies to treat SARS-CoV infections. The recent emergence of the deadly human coronavirus that causes Middle East respiratory syndrome (MERS-CoV) is a sobering reminder that new and deadly coronaviruses can emerge at any time with the potential to become pandemics. Therefore, the continued development of therapeutic and prophylactic countermeasures to potentially deadly coronaviruses is warranted. The coronaviral proteases, papain-like protease (PLpro) and 3C-like protease (3CLpro), are attractive antiviral drug targets because they are essential for coronaviral replication. Although the primary function of PLpro and 3CLpro are to process the viral polyprotein in a coordinated manner, PLpro has the additional function of stripping ubiquitin and ISG15 from host-cell proteins to aid coronaviruses in their evasion of the host innate immune responses. Therefore, targeting PLpro with antiviral drugs may have an advantage in not only inhibiting viral replication but also inhibiting the dysregulation of signaling cascades in infected cells that may lead to cell death in surrounding, uninfected cells. This review provides an up-to-date discussion on the SARS-CoV papain-like protease including a brief overview of the SARS-CoV genome and replication followed by a more in-depth discussion on the structure and catalytic mechanism of SARS-CoV PLpro, the multiple cellular functions of SARS-CoV PLpro, the inhibition of SARS-CoV PLpro by small molecule inhibitors, and the prospect of inhibiting papain-like protease from other coronaviruses. This paper forms part of a series of

  16. 77 FR 25183 - Circulatory System Devices Panel of the Medical Devices Advisory Committee; Notice of Meeting

    Science.gov (United States)

    2012-04-27

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration Circulatory System Devices Panel of the Medical Devices Advisory Committee; Notice of Meeting AGENCY: Food and Drug Administration, HHS. ACTION: Notice. This notice announces a forthcoming meeting of a...

  17. 77 FR 71195 - Orthopaedic and Rehabilitation Devices Panel of the Medical Devices Advisory Committee; Notice of...

    Science.gov (United States)

    2012-11-29

    ... From the Federal Register Online via the Government Publishing Office ] DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration Orthopaedic and Rehabilitation Devices Panel of the Medical Devices Advisory Committee; Notice of Meeting AGENCY: Food and Drug Administration, HHS. ACTION: Notice. This notice announces a...

  18. 76 FR 55398 - Immunology Devices Panel of the Medical Devices Advisory Committee: Notice of Postponement of...

    Science.gov (United States)

    2011-09-07

    ... in the Federal Register of August 9, 2011 (76 FR 48871). The meeting is postponed so that FDA can... HUMAN SERVICES Food and Drug Administration Immunology Devices Panel of the Medical Devices Advisory.... SUMMARY: The Food and Drug Administration (FDA) is postponing the meeting of the Immunology Devices...

  19. 76 FR 60848 - National Mammography Quality Assurance Advisory Committee; Notice of Meeting

    Science.gov (United States)

    2011-09-30

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration National Mammography Quality Assurance Advisory Committee; Notice of Meeting AGENCY: Food and Drug Administration, HHS. ACTION: Notice. This notice announces a forthcoming meeting of a public...

  20. 21 CFR 20.84 - Disclosure to consultants, advisory committees, State and local government officials commissioned...

    Science.gov (United States)

    2010-04-01

    ..., State and local government officials commissioned pursuant to 21 U.S.C. 372(a), and other special government employees. 20.84 Section 20.84 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH... consultants, advisory committees, State and local government officials commissioned pursuant to 21 U.S.C....

  1. 77 FR 50701 - Radiological Devices Panel of the Medical Devices Advisory Committee; Notice of Meeting

    Science.gov (United States)

    2012-08-22

    .... The Selenia Dimensions 3D System is currently approved for breast cancer screening and diagnosis. The... HUMAN SERVICES Food and Drug Administration Radiological Devices Panel of the Medical Devices Advisory Committee; Notice of Meeting AGENCY: Food and Drug Administration, HHS. ] ACTION: Notice. This...

  2. 78 FR 70317 - Invasive Species Advisory Committee

    Science.gov (United States)

    2013-11-25

    ... Office of the Secretary Invasive Species Advisory Committee AGENCY: Office of the Secretary, Interior. ACTION: Notice of Public Meeting (via Teleconference) of the Invasive Species Advisory Committee. SUMMARY... Invasive Species Advisory Committee. The purpose of the Advisory Committee is to provide advice to...

  3. 76 FR 55079 - Homeland Security Advisory Council

    Science.gov (United States)

    2011-09-06

    ... SECURITY Homeland Security Advisory Council AGENCY: The Office of Policy, DHS. ACTION: Notice of Open Teleconference Federal Advisory Committee Meeting. SUMMARY: The Homeland Security Advisory Council (HSAC) will... subject line of the message. Fax: (202) 282-9207. Mail: Homeland Security Advisory Council, Department...

  4. 77 FR 26774 - Homeland Security Advisory Council

    Science.gov (United States)

    2012-05-07

    ... SECURITY Homeland Security Advisory Council AGENCY: The Office of Policy, DHS. ACTION: Notice of partially closed federal advisory committee meeting. SUMMARY: The Homeland Security Advisory Council (HSAC) will... number in the subject line of the message. Fax: (202) 282-9207. Mail: Homeland Security Advisory...

  5. 76 FR 58813 - Homeland Security Advisory Council

    Science.gov (United States)

    2011-09-22

    ... SECURITY Homeland Security Advisory Council AGENCY: The Office of Policy, DHS. ACTION: Notice of open teleconference Federal Advisory Committee meeting. SUMMARY: The Homeland Security Advisory Council (HSAC) will... message. Fax: (202) 282-9207 Mail: Homeland Security Advisory Council, Department of Homeland...

  6. 77 FR 59627 - Homeland Security Advisory Council

    Science.gov (United States)

    2012-09-28

    ... SECURITY Homeland Security Advisory Council AGENCY: The Office of Policy, DHS. ACTION: Notice of open teleconference federal advisory committee meeting. SUMMARY: The Homeland Security Advisory Council (HSAC) will... line of the message. Fax: (202) 282-9207. Mail: Homeland Security Advisory Council, Department...

  7. 75 FR 26782 - Homeland Security Advisory Council

    Science.gov (United States)

    2010-05-12

    ... SECURITY Homeland Security Advisory Council AGENCY: The Office of Policy, DHS. ACTION: Notice of Open Teleconference Federal Advisory Committee Meeting. SUMMARY: The Homeland Security Advisory Council (HSAC) will... (Homeland Security) Review Advisory Committee. DATE: The HSAC conference call will take place from 4 p.m....

  8. 75 FR 53707 - Homeland Security Advisory Council

    Science.gov (United States)

    2010-09-01

    ... SECURITY Homeland Security Advisory Council AGENCY: The Office of Policy, DHS. ACTION: Notice of Open Teleconference Federal Advisory Committee Meeting. SUMMARY: The Homeland Security Advisory Council (HSAC) will...: Homeland Security Advisory Council, Department of Homeland Security, Mailstop 0850, 245 Murray Lane,...

  9. 75 FR 59278 - Homeland Security Advisory Council

    Science.gov (United States)

    2010-09-27

    ... SECURITY Homeland Security Advisory Council AGENCY: The Office of Policy, DHS. ACTION: Notice of Closed Federal Advisory Committee Meeting. SUMMARY: The Homeland Security Advisory Council (HSAC) will meet on... message. Fax: (202) 282-9207. Mail: Homeland Security Advisory Council, Department of Homeland...

  10. 78 FR 77443 - Electricity Advisory Committee

    Science.gov (United States)

    2013-12-23

    ... Electricity Advisory Committee AGENCY: Office of Electricity Delivery and Energy Reliability, Department of... Electricity Advisory Committee (EAC). The Federal Advisory Committee Act (Pub. L. 92-463, 86 Stat. 770.../oe/services/electricity-advisory-committee-eac . FOR FURTHER INFORMATION CONTACT: Matthew...

  11. Budesonide and formoterol reduce early innate anti-viral immune responses in vitro.

    Directory of Open Access Journals (Sweden)

    Janet M Davies

    Full Text Available Asthma is a chronic inflammatory airways disease in which respiratory viral infections frequently trigger exacerbations. Current treatment of asthma with combinations of inhaled corticosteroids and long acting beta2 agonists improves asthma control and reduces exacerbations but what impact this might have on innate anti-viral immunity is unclear. We investigated the in vitro effects of asthma drugs on innate anti-viral immunity. Peripheral blood mononuclear cells (PBMC from healthy and asthmatic donors were cultured for 24 hours with the Toll-like receptor 7 agonist, imiquimod, or rhinovirus 16 (RV16 in the presence of budesonide and/or formoterol. Production of proinflammatory cytokines and expression of anti-viral intracellular signalling molecules were measured by ELISA and RT-PCR respectively. In PBMC from healthy donors, budesonide alone inhibited IP-10 and IL-6 production induced by imiquimod in a concentration-dependent manner and the degree of inhibition was amplified when budesonide and formoterol were used in combination. Formoterol alone had little effect on these parameters, except at high concentrations (10⁻⁶ M when IL-6 production increased. In RV16 stimulated PBMC, the combination of budesonide and formoterol inhibited IFNα and IP-10 production in asthmatic as well as healthy donors. Combination of budesonide and formoterol also inhibited RV16-stimulated expression of the type I IFN induced genes myxovirus protein A and 2', 5' oligoadenylate synthetise. Notably, RV16 stimulated lower levels of type Myxovirus A and oligoadenylate synthase in PBMC of asthmatics than control donors. These in vitro studies demonstrate that combinations of drugs commonly used in asthma therapy inhibit both early pro-inflammatory cytokines and key aspects of the type I IFN pathway. These findings suggest that budesonide and formoterol curtail excessive inflammation induced by rhinovirus infections in patients with asthma, but whether this inhibits

  12. Diagnosis and antiviral intervention strategies for mitigating an influenza epidemic.

    Directory of Open Access Journals (Sweden)

    Robert Moss

    Full Text Available BACKGROUND: Many countries have amassed antiviral stockpiles for pandemic preparedness. Despite extensive trial data and modelling studies, it remains unclear how to make optimal use of antiviral stockpiles within the constraints of healthcare infrastructure. Modelling studies informed recommendations for liberal antiviral distribution in the pandemic phase, primarily to prevent infection, but failed to account for logistical constraints clearly evident during the 2009 H1N1 outbreaks. Here we identify optimal delivery strategies for antiviral interventions accounting for logistical constraints, and so determine how to improve a strategy's impact. METHODS AND FINDINGS: We extend an existing SEIR model to incorporate finite diagnostic and antiviral distribution capacities. We evaluate the impact of using different diagnostic strategies to decide to whom antivirals are delivered. We then determine what additional capacity is required to achieve optimal impact. We identify the importance of sensitive and specific case ascertainment in the early phase of a pandemic response, when the proportion of false-positive presentations may be high. Once a substantial percentage of ILI presentations are caused by the pandemic strain, identification of cases for treatment on syndromic grounds alone results in a greater potential impact than a laboratory-dependent strategy. Our findings reinforce the need for a decentralised system capable of providing timely prophylaxis. CONCLUSIONS: We address specific real-world issues that must be considered in order to improve pandemic preparedness policy in a practical and methodologically sound way. Provision of antivirals on the scale proposed for an effective response is infeasible using traditional public health outbreak management and contact tracing approaches. The results indicate to change the transmission dynamics of an influenza epidemic with an antiviral intervention, a decentralised system is required for

  13. RNA interference: Antiviral weapon and beyond

    Institute of Scientific and Technical Information of China (English)

    Quan-Chu Wang; Qing-He Nie; Zhi-Hua Feng

    2003-01-01

    RNA interference (RNAi) is a remarkable type of gene regulation based on sequence-specific targeting and degradation of RNA. The term encompasses related pathways found in a broad range of eukaryotic organisms, including fungi, plants, and animals. RNA interference is part of a sophisticated network of interconnected pathways for cellular defense, RNA surveillance, and development and it may become a powerful tool to manipulate gene expression experimentally. RNAi technology is currently being evaluated not only as an extremely powerful instrument for functional genomic analyses, but also as a potentially useful method to develop specific dsRNA based gene-silencing therapeutics.Several laboratories have been interested in using RNAi to control viral infection and many reports in Nature and in Cell show that short interfering (si) RNAs can inhibit infection by HIV-1, polio and hepatitis C viruses in a sequence-specific manner. RNA-based strategies for gene inhibition in mammalian cells have recently been described, which offer the promise of antiviral therapy.

  14. Antiviral Warrior-APOBEC3G

    Institute of Scientific and Technical Information of China (English)

    WU Xiao-xia; MA Yi-cai

    2005-01-01

    This paper is to further understand how APOBEC3G can defend the retroviruses and to find new approaches to AIDs (acquired immure deficiency syndrome).The viral infectivity factor (Vif) induces rapid degradation of APOBEC3G by ubiquitination, which is a proteosome-dependent pathway. Precisely speaking, only in the virus-producing cell Vif expression is necessary; in its absence, infection of a subsequent target cell terminates at a postentry step through the action of the human APOBEC3G antiviral mechanism. Vif protein has two domains: one binds to APOBEC3G and the other regulates the degradation of APOBEC3G by a conserved sequence, SLQ (Y/F) LA motif. Recently, the research on Vif has also revealed APOBEC3G is a novel component of innate immune system. In fact, APOBEC3G not only acts in DNA editing to block the replication of retroviruses such as HIV-1, but also is able to defend a wide spectrum of distantly related retroviruses and interferes with HBV through a different mechanism from HIV.

  15. Ribozymes:an anti-viral agent

    Institute of Scientific and Technical Information of China (English)

    Asad U.Khan; Shahper N.Khan

    2008-01-01

    The discovery that RNA can act as an enzyme led Thomas Cech to win the Nobel Prize in Chemistry and led immediately to the next wave of attempts to find an effective RNA-based therapy.The tantalizing idea that RNA enzymes called trans-cleaving ribozymes enables them to act as potential antiviral and powerful tool for functional genomic studies.The efficacy of ribozyme function in a complex intracellular environment is depend-ent on the intracellular fate of the RNA that is being targeted.Recently,ribozymes have been used successfully to inhibit gene expression in a variety of biological systems in vitro and in vivo.Ribozyme has also been used successfully to combat many cases of viral infection,as clinical trial.Despite it needs to be investigated and explored as far as its structural and functional aspects are concern.In view of the significance of ribozyme in modern medicine,we reviewed the recent literature on general approach to control viral infection.

  16. Natural Products as Source of Potential Dengue Antivirals

    Directory of Open Access Journals (Sweden)

    Róbson Ricardo Teixeira

    2014-06-01

    Full Text Available Dengue is a neglected disease responsible for 22,000 deaths each year in areas where it is endemic. To date, there is no clinically approved dengue vaccine or antiviral for human beings, even though there have been great efforts to accomplish these goals. Several approaches have been used in the search for dengue antivirals such as screening of compounds against dengue virus enzymes and structure-based computational discovery. During the last decades, researchers have turned their attention to nature, trying to identify compounds that can be used as dengue antivirals. Nature represents a vast reservoir of substances that can be explored with the aim of discovering new leads that can be either used directly as pharmaceuticals or can serve as lead structures that can be optimized towards the development of new antiviral agents against dengue. In this review we describe an assortment of natural products that have been reported as possessing dengue antiviral activity. The natural products are organized into classes of substances. When appropriate, structure-activity relationships are outlined. The biological assays used to assess antiviral activity are briefly described.

  17. 77 FR 2277 - Federal Advisory Committee; Defense Intelligence Agency (DIA) Advisory Board; Closed Meeting

    Science.gov (United States)

    2012-01-17

    ... of the Secretary Federal Advisory Committee; Defense Intelligence Agency (DIA) Advisory Board; Closed... discussions of classified information relating to DIA's intelligence operations including its support to... Advisory Board to discuss DIA operations and capabilities in support of current intelligence...

  18. 78 FR 295 - Federal Advisory Committee; Defense Intelligence Agency (DIA) Advisory Board; Closed Meeting

    Science.gov (United States)

    2013-01-03

    ... of the Secretary Federal Advisory Committee; Defense Intelligence Agency (DIA) Advisory Board; Closed... discussions of classified information relating to DIA's intelligence operations including its support to... the Advisory Board to discuss DIA operations and capabilities in support of current...

  19. 77 FR 62222 - Federal Advisory Committee; Defense Intelligence Agency (DIA) Advisory Board; Closed Meeting

    Science.gov (United States)

    2012-10-12

    ... of the Secretary Federal Advisory Committee; Defense Intelligence Agency (DIA) Advisory Board; Closed... discussions of classified information relating to DIA's intelligence operations including its support to... the Advisory Board to discuss DIA operations and capabilities in support of current...

  20. 76 FR 70425 - Federal Advisory Committee; Defense Intelligence Agency (DIA) Advisory Board; Closed Meeting

    Science.gov (United States)

    2011-11-14

    ... Office of the Secretary Federal Advisory Committee; Defense Intelligence Agency (DIA) Advisory Board... discussions of classified information relating to DIA's intelligence operations including its support to... Advisory Board to discuss DIA operations and capabilities in support of current intelligence...