ArticleAntimicrobial agents and chemotherapy2012
Hepatitis C virus RNA elimination and development of resistance in replicon cells treated with BMS-790052.
Article in Antimicrobial agents and chemotherapy, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
What it found
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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
20 citing papers in PubMed, 52 citations in OpenAlex.
- Efficacy and safety of daclatasvir plus pegylated-interferon alfa 2a and ribavirin in previously untreated HCV subjects coinfected with HIV and HCV genotype-1: a Phase III, open-label study.Hepatology international · 2017Trial
- Article
- Article
- Resistance to DAAs: When to Look and When It Matters.Current HIV/AIDS reports · 2017Review
- Prevalence of hepatitis C virus-resistant association substitutions to direct-acting antiviral agents in treatment-naïve hepatitis C genotype 1b-infected patients in western China.Infection and drug resistance · 2017Article
- Global prevalence of pre-existing HCV variants resistant to direct-acting antiviral agents (DAAs): mining the GenBank HCV genome data.Scientific reports · 2016Article
- Complex Pattern of Resistance-Associated Substitutions of Hepatitis C Virus after Daclatasvir/Asunaprevir Treatment Failure.PloS one · 2016Article
- Article
- Synergistic Activity of Combined NS5A Inhibitors.Antimicrobial agents and chemotherapy · 2015Article
- Comparison of daclatasvir resistance barriers on NS5A from hepatitis C virus genotypes 1 to 6: implications for cross-genotype activity.Antimicrobial agents and chemotherapy · 2014Article
- In vitro activity and resistance profile of samatasvir, a novel NS5A replication inhibitor of hepatitis C virus.Antimicrobial agents and chemotherapy · 2014Article
- Antiviral treatment of hepatitis C.BMJ (Clinical research ed.) · 2014Review
- 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
- A quantitative high-resolution genetic profile rapidly identifies sequence determinants of hepatitis C viral fitness and drug sensitivity.PLoS pathogens · 2014Article
- Finally sofosbuvir: an oral anti-HCV drug with wide performance capability.Pharmacogenomics and personalized medicine · 2014Review
- Persistence of resistant variants in hepatitis C virus-infected patients treated with the NS5A replication complex inhibitor daclatasvir.Antimicrobial agents and chemotherapy · 2013Article
- Combinations of lambda interferon with direct-acting antiviral agents are highly efficient in suppressing hepatitis C virus replication.Antimicrobial agents and chemotherapy · 2013Article
- Combination treatment with hepatitis C virus protease and NS5A inhibitors is effective against recombinant genotype 1a, 2a, and 3a viruses.Antimicrobial agents and chemotherapy · 2013Article
- In vitro activity of daclatasvir on hepatitis C virus genotype 3 NS5A.Antimicrobial agents and chemotherapy · 2013Article
- Daclatasvir: potential role in hepatitis C.Drug design, development and therapy · 2013Review
Corrections and comments
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Authors and funding
12 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
BMS-790052, a first-in-class hepatitis C virus (HCV) replication complex inhibitor, targeting nonstructural protein 5A (NS5A), displays picomolar to nanomolar potency against genotypes 1 to 5. This exceptional potency translated into robust anti-HCV activity in clinical studies with HCV genotype 1-infected subjects. To date, all BMS-790052-associated resistance mutations have mapped to the N-terminal region of NS5A. To further characterize the antiviral activity of BMS-790052, HCV replicon elimination and colony formation assays were performed. Replicon was cleared from genotype 1a and 1b replicon cells in a time- and dose-dependent manner. Elimination of the genotype 1a replicon required longer treatment durations and higher concentrations of BMS-790052 than those for the genotype1b replicon. Single amino acid substitutions that conferred relatively low levels of resistance were observed at early time points and at low doses. Higher doses and longer treatment durations yielded mutations that conferred greater levels of resistance, including linked amino acid substitutions. Replicon cells that survived inhibitor treatment remained fully sensitivity to pegylated alpha interferon (pegIFN-α) and other HCV inhibitors. Moreover, genotype 1a replicon elimination was markedly enhanced when pegIFN-α and BMS-790052 were combined. Resistant variants observed in this study were very similar to those observed in a multiple ascending dose (MAD) monotherapy trial of BMS-790052, validating replicon elimination studies as a model to predict clinical resistance. Insights gained from the in vitro anti-HCV activity and resistance profiles of BMS-790052 will be used to help guide the clinical development of this novel HCV inhibitor.
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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.