Título:
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Lethal Mutagenesis of Hepatitis C Virus Induced by Favipiravir
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Autor/a:
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de Ávila, Ana Isabel; Gallego, Isabel; Soria, Maria Eugenia; Gregori i Font, Josep; Quer, Josep; Esteban Mur, Juan Ignacio; Rice, Charles M.; Domingo, Esteban; Perales Viejo, Celia
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Abstract:
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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 |
Derechos:
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open access
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Uri:
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https://ddd.uab.cat/record/254248
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