ArticleNature communications2023
Direct-acting antiviral resistance of Hepatitis C virus is promoted by epistasis.
Article in Nature communications, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 20 citations in OpenAlex.
- A Novel Host-Based Immunotherapy for the Suppression of HBV and HCV Replication: Heat-KilledCells · 2026Article
- Selection Estimation from Genetic Time-Series Data: Effects of Limited Sampling and Genetic Drift.Molecular biology and evolution · 2025Article
- Rapid simultaneous self-testing of HIV and HCV viral loads with integrated RNA extraction and multiplex RT-PCR in under 1 hour.Biosensors & bioelectronics · 2025Article
- Silent mutations in coding regions of Hepatitis C virus affect patterns of HCV RNA structures and attenuate viral replication and pathogenesis.Genome biology · 2025Article
- Health Care Resource Utilization and Costs Associated with US Medicaid Sobriety Restrictions on Direct-Acting Antivirals for Hepatitis C Virus: A Retrospective Claims Database Analysis.PharmacoEconomics · 2025Article
- Article
- Sofalcone Suppresses Dengue Virus Replication by Activating Heme Oxygenase-1-Mediated Antiviral Interferon Responses.International journal of molecular sciences · 2025Article
- Strategies and efforts in circumventing the emergence of antiviral resistance against conventional antivirals.npj antimicrobials and resistance · 2025Review
- Hepatitis C virus care continuum: integrating point of care RNA assay and direct acting antivirals.EXCLI journal · 2025Article
- Viral Hepatitis: Host Immune Interaction, Pathogenesis and New Therapeutic Strategies.Pathogens (Basel, Switzerland) · 2024Review
- Advancements in Antiviral Drug Development: Comprehensive Insights into Design Strategies and Mechanisms Targeting Key Viral Proteins.Journal of microbiology and biotechnology · 2024Review
- Review
- Article
- HCV E1 influences the fitness landscape of E2 and may enhance escape from E2-specific antibodies.Virus evolution · 2023Article
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Direct-acting antiviral agents (DAAs) provide efficacious therapeutic treatments for chronic Hepatitis C virus (HCV) infection. However, emergence of drug resistance mutations (DRMs) can greatly affect treatment outcomes and impede virological cure. While multiple DRMs have been observed for all currently used DAAs, the evolutionary determinants of such mutations are not currently well understood. Here, by considering DAAs targeting the nonstructural 3 (NS3) protein of HCV, we present results suggesting that epistasis plays an important role in the evolution of DRMs. Employing a sequence-based fitness landscape model whose predictions correlate highly with experimental data, we identify specific DRMs that are associated with strong epistatic interactions, and these are found to be enriched in multiple NS3-specific DAAs. Evolutionary modelling further supports that the identified DRMs involve compensatory mutational interactions that facilitate relatively easy escape from drug-induced selection pressures. Our results indicate that accounting for epistasis is important for designing future HCV NS3-targeting DAAs.
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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.