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Title

Lethal mutagenesis of hepatitis C virus induced by favipiravir

AuthorsÁvila Lucas, Ana Isabel de ; Gallego, Isabel ; Soria, María Eugenia; Gregori, Josep Maria; Quer, Josep; Esteban, Juan Ignacio; Rice, Charles M.; Domingo, Esteban ; Perales, Celia
Issue Date18-Oct-2016
PublisherPublic Library of Science
CitationPLoS ONE 11 (2016)
AbstractLethal 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.
URIhttp://hdl.handle.net/10261/151677
DOIhttp://dx.doi.org/10.1371/journal.pone.0164691
Identifiersdoi: 10.1371/journal.pone.0164691
issn: 1932-6203
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