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Lethal Mutagenesis of Hepatitis C Virus Induced by Favipiravir

Ana I de Ávila1, Isabel Gallego1,2, Maria Eugenia Soria3

  • 1Centro de Biología Molecular "Severo Ochoa" (CSIC-UAM), Consejo Superior de Investigaciones Científicas (CSIC), Campus de Cantoblanco, 28049, Madrid, Spain.

Plos One
|October 19, 2016
PubMed

Insights

Favipiravir (T-705) acts as a potent mutagen, inducing lethal mutagenesis in hepatitis C virus (HCV). This antiviral strategy led to significant infectivity reduction and eventual virus extinction in laboratory studies.

Area of Science:

  • Virology
  • Antiviral Therapy
  • Molecular Biology

Background:

  • Lethal mutagenesis is an antiviral strategy aiming to eliminate viruses through excessive mutations during replication.
  • Hepatitis C virus (HCV) remains a significant global health concern, necessitating novel therapeutic approaches.

Purpose of the Study:

  • To investigate favipiravir (T-705) as a mutagenic agent against hepatitis C virus (HCV) replication.
  • To evaluate the potential of lethal mutagenesis as a treatment strategy for HCV infections.

Main Methods:

  • HCV replication in human hepatoma cells was studied in the presence of favipiravir (T-705).
  • Mutation spectrum analysis (G → A and C → U transitions) and infectivity assays were performed.
  • Virus extinction was assessed after serial passaging in the presence of T-705.

Main Results:

  • Favipiravir (T-705) induced a significant excess of G → A and C → U mutations in HCV populations.
  • HCV infectivity decreased substantially at T-705 concentrations 2- to 8-fold below its cytotoxic concentration (CC50).
  • Five passages with 400 μM T-705 led to complete HCV extinction in vitro.

Conclusions:

  • Favipiravir (T-705) is a potent mutagen for HCV, supporting lethal mutagenesis as a viable antiviral mechanism.
  • The findings suggest T-705 as a potential new therapeutic agent for HCV, particularly for treatment-resistant cases.
  • Further in vivo studies are warranted to confirm the efficacy of T-705 for treating hepatitis C virus infections.

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