Lethal Mutagenesis of Hepatitis C Virus Induced by Favipiravir. Academic Article uri icon

Overview

abstract

  • Lethal mutagenesis is an antiviral approach that consists in extinguishing a virus by an excess of mutations acquired during replication in the presence of a mutagen. Here we show that favipiravir (T-705) is a potent mutagenic agent for hepatitis C virus (HCV) during its replication in human hepatoma cells. T-705 leads to an excess of G → A and C → U transitions in the mutant spectrum of preextinction HCV populations. Infectivity decreased significantly in the presence of concentrations of T-705 which are 2- to 8-fold lower than its cytotoxic concentration 50 (CC50). Passaging the virus five times in the presence of 400 μM T-705 resulted in virus extinction. Since T-705 has undergone advanced clinical trials for approval for human use, the results open a new approach based on lethal mutagenesis to treat hepatitis C virus infections. If proven effective for HCV in vivo, this new anti-HCV agent may be useful in patient groups that fail current therapeutic regimens.

publication date

  • October 18, 2016

Research

keywords

  • Amides
  • Antiviral Agents
  • Hepacivirus
  • Pyrazines

Identity

PubMed Central ID

  • PMC5068784

Scopus Document Identifier

  • 84992111855

Digital Object Identifier (DOI)

  • 10.1371/journal.pmed.1001967

PubMed ID

  • 27755573

Additional Document Info

volume

  • 11

issue

  • 10