ArticleAntimicrobial agents and chemotherapy2011
Comparative study of the genetic barriers and pathways towards resistance of selective inhibitors of hepatitis C virus replication.
Article in Antimicrobial agents and chemotherapy, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 57 citations in OpenAlex.
- In vitro antiviral activity and preclinical and clinical resistance profile of miravirsen, a novel anti-hepatitis C virus therapeutic targeting the human factor miR-122.Antimicrobial agents and chemotherapy · 2015Trial
- Nanobody-based bioPROTAC for viral protein degradation provides an antiviral strategy for porcine arterivirus.Journal of nanobiotechnology · 2026Article
- Functionally-informed fine-mapping identifies genetic variants linking increased CHD1L expression and HIV restriction in monocytes.Scientific reports · 2025Article
- Influenza A virus resistance to 4'-fluorouridine coincides with viral attenuation in vitro and in vivo.PLoS pathogens · 2024Article
- Therapeutic strategies and promising vaccine for hepatitis C virus infection.Immunity, inflammation and disease · 2023Review
- Review
- Discovery and Optimization of a 4-Aminopiperidine Scaffold for Inhibition of Hepatitis C Virus Assembly.Journal of medicinal chemistry · 2021Article
- A Cyclic Phosphoramidate Prodrug of 2'-Deoxy-2'-Fluoro-2'-Antimicrobial agents and chemotherapy · 2020Article
- Modulation of Lipid Droplet Metabolism-A Potential Target for Therapeutic Intervention inFrontiers in microbiology · 2017Review
- Selective Inhibitor of Nuclear Export (SINE) Compounds Alter New World Alphavirus Capsid Localization and Reduce Viral Replication in Mammalian Cells.PLoS neglected tropical diseases · 2016Article
- Molecular and Dynamic Mechanism Underlying Drug Resistance in Genotype 3 Hepatitis C NS3/4A Protease.Journal of the American Chemical Society · 2016Article
- Review
- Cross-genotypic examination of hepatitis C virus polymerase inhibitors reveals a novel mechanism of action for thumb binders.Antimicrobial agents and chemotherapy · 2014Article
- Inhibitors of the tick-borne, hemorrhagic fever-associated flaviviruses.Antimicrobial agents and chemotherapy · 2014Article
- West Nile virus drug discovery.Viruses · 2013Review
- The viral polymerase inhibitor 2'-C-methylcytidine inhibits Norwalk virus replication and protects against norovirus-induced diarrhea and mortality in a mouse model.Journal of virology · 2013Article
- Cyclophilin A as a New Therapeutic Target for Hepatitis C Virus-induced Hepatocellular Carcinoma.The Korean journal of physiology & pharmacology : official journal of the Korean Physiological Society and the Korean Society of Pharmacology · 2013Review
- Cyclophilins as modulators of viral replication.Viruses · 2013Review
- Curing a viral infection by targeting the host: the example of cyclophilin inhibitors.Antiviral research · 2013Review
- Evaluation of phosphatidylinositol-4-kinase IIIα as a hepatitis C virus drug target.Journal of virology · 2012Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Hepatitis C virus (HCV) inhibitors include direct-acting antivirals (DAAs) such as NS3 serine protease inhibitors, nucleoside and nonnucleoside polymerase inhibitors, and host-targeting antivirals (HTAs) such as cyclophilin inhibitors that have been developed in recent years. Drug-resistant HCV variants have been reported both in vitro and in the clinical setting for most classes of drugs. We report a comparative study in which the genetic barrier to drug resistance of a representative selection of these inhibitors is evaluated employing a number of resistance selection protocols. The NS3 protease inhibitors VX-950 and BILN 2061, the nucleoside polymerase inhibitor 2'-C-methylcytidine, three nonnucleoside polymerase inhibitors (thiophene carboxylic acid, benzimidazole, and benzothiadiazine), and DEB025 were included. For each drug and passage in the selection process, the phenotype and genotype of the drug-resistant replicon were determined. For a number of molecules (BILN 2061 and nonnucleoside inhibitors), drug-resistant variants were readily selected when wild-type replicon-containing cells were directly cultured in the presence of high concentrations of the inhibitor. Resistance to DEB025 could be selected only following a lengthy stepwise selection procedure. For some DAAs, the signature mutations that emerged under inhibitor pressure differed depending on the selection protocol that was employed. Replication fitness of resistant mutants revealed that the C445F mutation in the RNA-dependent RNA polymerase can restore loss of fitness caused by a number of unfit resistance mutations. These data provide important insights into the various pathways leading to drug resistance and allow a direct comparison of the genetic barriers of various HCV drugs.
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