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Lethal Mutagenesis of Hepatitis C Virus Induced by Favipiravir.

Lethal Mutagenesis of Hepatitis C Virus Induced by Favipiravir.
Author Information (click to view)

de Ávila AI, Gallego I, Soria ME, Gregori J, Quer J, Esteban JI, Rice CM, Domingo E, Perales C,


de Ávila AI, Gallego I, Soria ME, Gregori J, Quer J, Esteban JI, Rice CM, Domingo E, Perales C, (click to view)

de Ávila AI, Gallego I, Soria ME, Gregori J, Quer J, Esteban JI, Rice CM, Domingo E, Perales C,

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PloS one 2016 Oct 1811(10) e0164691 doi 10.1371/journal.pone.0164691
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.

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