ArticleAntimicrobial agents and chemotherapy2009
Robust antiviral efficacy upon administration of a nucleoside analog to hepatitis C virus-infected chimpanzees.
Article in Antimicrobial agents and chemotherapy, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
34 citing papers in PubMed, 91 citations in OpenAlex.
- NS5-targeting nucleoside analogs inhibit dengue virus and other flaviviruses.PLoS pathogens · 2026Article
- Competing interests during the keyFrontiers in chemistry · 2023Article
- A nanoluciferase SARS-CoV-2 for rapid neutralization testing and screening of anti-infective drugs for COVID-19.Nature communications · 2020Article
- Animal Models to Study Hepatitis C Virus Infection.Frontiers in immunology · 2018Review
- The Chimpanzee Model of Viral Hepatitis: Advances in Understanding the Immune Response and Treatment of Viral Hepatitis.ILAR journal · 2017Review
- Pyrrolo[2,3-d]pyrimidine (7-deazapurine) as a privileged scaffold in design of antitumor and antiviral nucleosides.Medicinal research reviews · 2017Review
- Antiviral screening identifies adenosine analogs targeting the endogenous dsRNA Leishmania RNA virus 1 (LRV1) pathogenicity factor.Proceedings of the National Academy of Sciences of the United States of America · 2017Article
- My Cousin, My Enemy: quasispecies suppression of drug resistance.Current opinion in virology · 2016Review
- Review
- Persistent hepatitis C viral replication despite priming of functional CD8+ T cells by combined therapy with a vaccine and a direct-acting antiviral.Hepatology (Baltimore, Md.) · 2016Article
- Role of Mitochondrial RNA Polymerase in the Toxicity of Nucleotide Inhibitors of Hepatitis C Virus.Antimicrobial agents and chemotherapy · 2016Article
- Nucleoside inhibitors of tick-borne encephalitis virus.Antimicrobial agents and chemotherapy · 2015Article
- Inhibition of viral RNA polymerases by nucleoside and nucleotide analogs: therapeutic applications against positive-strand RNA viruses beyond hepatitis C virus.Current opinion in virology · 2014Review
- T-cell immunity and hepatitis C virus reinfection after cure of chronic hepatitis C with an interferon-free antiviral regimen in a chimpanzee.Hepatology (Baltimore, Md.) · 2014Article
- Kinetic analyses reveal potent and early blockade of hepatitis C virus assembly by NS5A inhibitors.Gastroenterology · 2014Article
- Direct-acting antiviral agents and the path to interferon independence.Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association · 2014Review
- Finally sofosbuvir: an oral anti-HCV drug with wide performance capability.Pharmacogenomics and personalized medicine · 2014Review
- Preclinical characterization of GSK2336805, a novel inhibitor of hepatitis C virus replication that selects for resistance in NS5A.Antimicrobial agents and chemotherapy · 2014Article
- Inhibition of hepatitis C virus replication by GS-6620, a potent C-nucleoside monophosphate prodrug.Antimicrobial agents and chemotherapy · 2014Article
- Modeling HCV disease in animals: virology, immunology and pathogenesis of HCV and GBV-B infections.Frontiers in microbiology · 2014Review
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Hepatitis C virus (HCV) infects an estimated 170 million individuals worldwide and is associated with an increased incidence of liver fibrosis, cirrhosis, and hepatocellular carcinoma. Currently approved therapies to treat HCV infection consist of combinations of pegylated alpha interferon and ribavirin which result in a sustained viral response in 40 to 60% of patients. Efforts to develop improved therapies include the development of direct inhibitors of virally encoded enzymes such as the viral RNA-dependent RNA polymerase. A nucleoside analog, 2'-C-methyl-7-deaza-adenosine (MK-0608), has been shown to inhibit viral RNA replication in the subgenomic HCV genotype 1b replicon, with a 50% effective concentration (EC(50)) of 0.3 microM (EC(90) = 1.3 microM). To determine efficacy in vivo, MK-0608 was administered to HCV-infected chimpanzees, resulting in dose- and time-dependent decreases in plasma viral loads. In separate experiments, chimpanzees dosed for 7 days with MK-0608 at 0.2 and 2 mg per kg of body weight per day by intravenous administration experienced average reductions in viral load of 1.0 and >5 log(10) IU/ml, respectively. Two other HCV-infected chimpanzees received daily doses of 1 mg MK-0608 per kg via oral administration. After 37 days of oral dosing, one chimpanzee with a high starting viral load experienced a reduction in viral load of 4.6 log(10), and the viral load in the other chimpanzee fell below the limit of quantification (LOQ) of the HCV TaqMan assay (20 IU/ml). Importantly, viral load remained below the LOQ throughout the duration of dosing and for at least 12 days after dosing ended. The results demonstrate a robust antiviral effect on the administration of MK-0608 to HCV-infected chimpanzees.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.