ArticlePloS one2013
Extinction of hepatitis C virus by ribavirin in hepatoma cells involves lethal mutagenesis.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed.
- Mutations Identified in the Hepatitis C Virus (HCV) Polymerase of Patients with Chronic HCV Treated with Ribavirin Cause Resistance and Affect Viral Replication Fidelity.Antimicrobial agents and chemotherapy · 2020Trial
- Synergistic antiviral effects of structure-guided peptides and a mutagenic base analog on SARS-CoV-2 replication.Antimicrobial agents and chemotherapy · 2026Article
- Viral Quasispecies Inference from Single Observations-Mutagens as Accelerators of Quasispecies Evolution.Microorganisms · 2025Article
- Quasispecies theory and emerging viruses: challenges and applications.Npj viruses · 2024Review
- In-Host HEV Quasispecies Evolution Shows the Limits of Mutagenic Antiviral Treatments.International journal of molecular sciences · 2023Article
- Atypical Mutational Spectrum of SARS-CoV-2 Replicating in the Presence of Ribavirin.Antimicrobial agents and chemotherapy · 2023Article
- Ribavirin inhibits the replication of infectious bursal disease virus predominantly through depletion of cellular guanosine pool.Frontiers in veterinary science · 2023Article
- Lethal Mutagenesis of RNA Viruses and Approved Drugs with Antiviral Mutagenic Activity.Viruses · 2022Review
- Favipiravir Inhibits Hepatitis A Virus Infection in Human Hepatocytes.International journal of molecular sciences · 2022Article
- Efficacy decrease of antiviral agents when administered to ongoing hepatitis C virus infections in cell culture.Frontiers in microbiology · 2022Article
- Guanosine inhibits hepatitis C virus replication and increases indel frequencies, associated with altered intracellular nucleotide pools.PLoS pathogens · 2022Article
- Controversies' clarification regarding ribavirin efficacy in measles and coronaviruses: Comprehensive therapeutic approach strictly tailored to COVID-19 disease stages.World journal of clinical cases · 2021Article
- Review
- Inhibition of viral RNA-dependent RNA polymerases with clinically relevant nucleotide analogs.The Enzymes · 2021Article
- Antiviral and Antimicrobial Nucleoside Derivatives: Structural Features and Mechanisms of Action.Molecular biology · 2021Article
- Strategy, Progress, and Challenges of Drug Repurposing for Efficient Antiviral Discovery.Frontiers in pharmacology · 2021Review
- Current pharmacological modalities for management of novel coronavirus disease 2019 (COVID-19) and the rationale for their utilization: A review.Reviews in medical virology · 2020Review
- Synergistic lethal mutagenesis of hepatitis C virus.Antimicrobial agents and chemotherapy · 2019Article
- Lethal Mutagenesis of Rift Valley Fever Virus Induced by Favipiravir.Antimicrobial agents and chemotherapy · 2019Article
- Review
Corrections and comments
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Authors and funding
9 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Lethal mutagenesis, or virus extinction produced by enhanced mutation rates, is under investigation as an antiviral strategy that aims at counteracting the adaptive capacity of viral quasispecies, and avoiding selection of antiviral-escape mutants. To explore lethal mutagenesis of hepatitis C virus (HCV), it is important to establish whether ribavirin, the purine nucleoside analogue used in anti-HCV therapy, acts as a mutagenic agent during virus replication in cell culture. Here we report the effect of ribavirin during serial passages of HCV in human hepatoma Huh-7.5 cells, regarding viral progeny production and complexity of mutant spectra. Ribavirin produced an increase of mutant spectrum complexity and of the transition types associated with ribavirin mutagenesis, resulting in HCV extinction. Ribavirin-mediated depletion of intracellular GTP was not the major contributory factor to mutagenesis since mycophenolic acid evoked a similar decrease in GTP without an increase in mutant spectrum complexity. The intracellular concentration of the other nucleoside-triphosphates was elevated as a result of ribavirin treatment. Mycophenolic acid extinguished HCV without an intervening mutagenic activity. Ribavirin-mediated, but not mycophenolic acid-mediated, extinction of HCV occurred via a decrease of specific infectivity, a feature typical of lethal mutagenesis. We discuss some possibilities to explain disparate results on ribavirin mutagenesis of HCV.
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