Lethal Mutagenesis of Hepatitis C Virus Induced by Favipiravir
de Ávila, Ana Isabel (Consejo Superior de Investigaciones Científicas)
Gallego, Isabel (Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas)
Soria, Maria Eugenia (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Gregori i Font, Josep (Roche Diagnostics (Sant Cugat))
Quer, Josep 1963- (Universitat Autònoma de Barcelona)
Esteban Mur, Juan Ignacio (Universitat Autònoma de Barcelona)
Rice, Charles M. (The Rockefeller University)
Domingo, Esteban (Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas)
Perales Viejo, Celia (Hospital Universitari Vall d'Hebron. Institut de Recerca)

Date:	2016
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 (CC). 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.
Grants:	Ministerio de Ciencia e Innovación BFU-2011-23604 Ministerio de Economía y Competitividad SAF-2014-52400-R Instituto de Salud Carlos III PI13-00456 Instituto de Salud Carlos III PI15-00829 Instituto de Salud Carlos III CP14/00121
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Published in:	PloS one, Vol. 11 (october 2016) , ISSN 1932-6203

DOI: 10.1371/journal.pone.0164691
PMID: 27755573

19 p, 2.2 MB

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Articles > Research articles
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