ArticleAntimicrobial agents and chemotherapy2015
In vitro activity and resistance profile of dasabuvir, a nonnucleoside hepatitis C virus polymerase inhibitor.
Article in Antimicrobial agents and chemotherapy, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers.
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Who cites it
54 citing papers in PubMed, 119 citations in OpenAlex.
- Daclatasvir, sofosbuvir, and ribavirin for hepatitis C virus genotype 3 and advanced liver disease: A randomized phase III study (ALLY-3+).Hepatology (Baltimore, Md.) · 2016Trial
- Randomized phase 3 trial of ombitasvir/paritaprevir/ritonavir for hepatitis C virus genotype 1b-infected Japanese patients with or without cirrhosis.Hepatology (Baltimore, Md.) · 2015Trial
- Positive-Strand RNA Viral RdRps: From Structure Conservation and Activity Assay to Drug Development.Molecules (Basel, Switzerland) · 2026Review
- Crystallographic Fragment Screening of the Dengue Virus Polymerase Reveals Multiple Binding Sites for the Development of Non-nucleoside Antiflavivirals.Journal of medicinal chemistry · 2025Article
- 3D conformation and crystal interaction insights into drug development challenges for HCV drug analogues via molecular simulations.Communications chemistry · 2025Article
- Article
- Computational design of potent dimeric phenylthiazole NS5A inhibitors for hepatitis C virus.Scientific reports · 2024Article
- Repurposing of approved antivirals against dengue virus serotypes: an in silico and in vitro mechanistic study.Molecular diversity · 2024Article
- Antiviral Agents: Structural Basis of Action and Rational Design.Sub-cellular biochemistry · 2024Review
- Study of drug resistance-associated genetic mutations, and phylo-genetic analysis of HCV in the Province of Sindh, Pakistan.Scientific reports · 2023Article
- ABT-333 (Dasabuvir) Increases Action Potential Duration and Provokes Early Afterdepolarizations in Canine Left Ventricular Cells via Inhibition of IPharmaceuticals (Basel, Switzerland) · 2023Article
- Breakthroughs in hepatitis C research: from discovery to cure.Nature reviews. Gastroenterology & hepatology · 2022Review
- Combination of dasabuvir and PSI-6206 for the treatment of coxsackievirus B3 infection.Journal of virus eradication · 2022Article
- Review
- Hepatitis C Viral Replication Complex.Viruses · 2021Review
- RNA-dependent RNA polymerase (RdRp) inhibitors: The current landscape and repurposing for the COVID-19 pandemic.European journal of medicinal chemistry · 2021Review
- Targeting the RdRp of Emerging RNA Viruses: The Structure-Based Drug Design Challenge.Molecules (Basel, Switzerland) · 2020Review
- Amide Bond Bioisosteres: Strategies, Synthesis, and Successes.Journal of medicinal chemistry · 2020Review
- Benzannulation of isobenzopyryliums with electron-rich alkynes: a modular access to β-functionalized naphthalenes.Chemical science · 2020Article
- FDA-Approved Drugs Efavirenz, Tipranavir, and Dasabuvir Inhibit Replication of Multiple Flaviviruses in Vero Cells.Microorganisms · 2020Article
Corrections and comments
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Authors and funding
12 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Dasabuvir (ABT-333) is a nonnucleoside inhibitor of the RNA-dependent RNA polymerase encoded by the hepatitis C virus (HCV) NS5B gene. Dasabuvir inhibited recombinant NS5B polymerases derived from HCV genotype 1a and 1b clinical isolates, with 50% inhibitory concentration (IC50) values between 2.2 and 10.7 nM, and was at least 7,000-fold selective for the inhibition of HCV genotype 1 polymerases over human/mammalian polymerases. In the HCV subgenomic replicon system, dasabuvir inhibited genotype 1a (strain H77) and 1b (strain Con1) replicons with 50% effective concentration (EC50) values of 7.7 and 1.8 nM, respectively, with a 13-fold decrease in inhibitory activity in the presence of 40% human plasma. This level of activity was retained against a panel of chimeric subgenomic replicons that contained HCV NS5B genes from 22 genotype 1 clinical isolates from treatment-naive patients, with EC50s ranging between 0.15 and 8.57 nM. Maintenance of replicon-containing cells in medium containing dasabuvir at concentrations 10-fold or 100-fold greater than the EC50 resulted in selection of resistant replicon clones. Sequencing of the NS5B coding regions from these clones revealed the presence of variants, including C316Y, M414T, Y448C, Y448H, and S556G, that are consistent with binding to the palm I site of HCV polymerase. Consequently, dasabuvir retained full activity against replicons known to confer resistance to other polymerase inhibitors, including the S282T variant in the nucleoside binding site and the M423T, P495A, P495S, and V499A single variants in the thumb domain. The use of dasabuvir in combination with inhibitors targeting HCV NS3/NS4A protease (ABT-450 with ritonavir) and NS5A (ombitasvir) is in development for the treatment of HCV genotype 1 infections.
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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.