ArticleAntimicrobial agents and chemotherapy2014
Comparison of daclatasvir resistance barriers on NS5A from hepatitis C virus genotypes 1 to 6: implications for cross-genotype activity.
Article in Antimicrobial agents and chemotherapy, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed.
- Integrated Resistance Analysis of CERTAIN-1 and CERTAIN-2 Studies in Hepatitis C Virus-Infected Patients Receiving Glecaprevir and Pibrentasvir in Japan.Antimicrobial agents and chemotherapy · 2018Trial
- Treatment-Resistant Hepatitis C Viral Infection: A Case Report and Literature Review.Case reports in hepatology · 2022Article
- The Role of RASs /RVs in the Current Management of HCV.Viruses · 2021Review
- Real-Life Effectiveness and Safety of Glecaprevir/Pibrentasvir for Korean Patients with Chronic Hepatitis C at a Single Institution.Gut and liver · 2021Observational
- Impact of Preexisting Hepatitis C Virus Genotype 6 NS3, NS5A, and NS5B Polymorphisms on theAntimicrobial agents and chemotherapy · 2019Article
- Resistance detection and re-treatment options in hepatitis C virus-related chronic liver diseases after DAA-treatment failure.Infection · 2018Review
- Challenge to overcome: Nonstructural protein 5A-P32 deletion in direct-acting antiviral-based therapy for hepatitis C virus.World journal of gastroenterology · 2018Article
- Article
- HA1077 displays synergistic activity with daclatasvir against hepatitis C virus and suppresses the emergence of NS5A resistance-associated substitutions in mice.Scientific reports · 2018Article
- Efficacy and safety of sofosbuvir plus daclatasvir with or without ribavirin: large real-life results of patients with chronic hepatitis C genotype 4.Hepatology international · 2018Article
- Article
- Article
- Preclinical Pharmacokinetics and First-in-Human Pharmacokinetics, Safety, and Tolerability of Velpatasvir, a Pangenotypic Hepatitis C Virus NS5A Inhibitor, in Healthy Subjects.Antimicrobial agents and chemotherapy · 2017Article
- Daclatasvir: A Review in Chronic Hepatitis C.Drugs · 2016Review
- Interferon-Free Treatments for Chronic Hepatitis C Genotype 1 Infection.Journal of clinical and translational hepatology · 2016Review
- State of the Art, Unresolved Issues, and Future Research Directions in the Fight against Hepatitis C Virus: Perspectives for Screening, Diagnostics of Resistances, and Immunization.Journal of immunology research · 2016Review
- Synergistic Activity of Combined NS5A Inhibitors.Antimicrobial agents and chemotherapy · 2015Article
- Virologic Tools for HCV Drug Resistance Testing.Viruses · 2015Review
- Hepatitis C Virus Treatment: Is It Possible To Cure All Hepatitis C Virus Patients?Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association · 2015Review
- Daclatasvir: a review of its use in adult patients with chronic hepatitis C virus infection.Drugs · 2015Review
Corrections and comments
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Authors and funding
12 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
A comparison of the daclatasvir (DCV [BMS-790052]) resistance barrier on authentic or hybrid replicons containing NS5A from hepatitis C virus (HCV) genotypes 1 to 6 (GT-1 to -6) was completed using a replicon elimination assay. The data indicated that genotype 1b (GT-1b) has the highest relative resistance barrier and genotype 2a (GT-2a M31) has the lowest. The rank order of resistance barriers to DCV was 1b>4a≥5a>6a≅1a>2a JFH>3a>2a M31. Importantly, DCV in combination with a protease inhibitor (PI) eliminated GT-2a M31 replicon RNA at a clinically relevant concentration. Previously, we reported the antiviral activity and resistance profiles of DCV on HCV genotypes 1 to 4 evaluated in the replicon system. Here, we report the antiviral activity and resistance profiles of DCV against hybrid replicons with NS5A sequences derived from HCV GT-5a and GT-6a clinical isolates. DCV was effective against both GT-5a and -6a hybrid replicon cell lines (50% effective concentrations [EC50s] ranging from 3 to 7 pM for GT-5a, and 74 pM for GT-6a). Resistance selection identified amino acid substitutions in the N-terminal domain of NS5A. For GT-5a, L31F and L31V, alone or in combination with K56R, were the major resistance variants (EC50s ranging from 2 to 40 nM). In GT-6a, Q24H, L31M, P32L/S, and T58A/S were identified as resistance variants (EC50s ranging from 2 to 250 nM). The in vitro data suggest that DCV has the potential to be an effective agent for HCV genotypes 1 to 6 when used in combination therapy.
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