Efficacy decrease of antiviral agents when administered to ongoing hepatitis C virus infections in cell culture

We report a quantification of the decrease of effectiveness of antiviral agents directed to hepatitis C virus, when the agents are added during an ongoing infection in cell culture vs. when they are added at the beginning of the infection. Major determinants of the decrease of inhibitory activity ar...

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Detalles Bibliográficos
Autores: García-Crespo, Carlos, Vázquez-Sirvent, Lucía, Somovilla, Pilar, Soria, María Eugenia, Gallego, Isabel, Ávila, Ana Isabel de, Martínez-González, Brenda, Durán-Pastor, Antoni, Domingo, Esteban, Perales, Celia
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2022
País:España
Institución:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/304782
Acceso en línea:http://hdl.handle.net/10261/304782
Access Level:acceso abierto
Palabra clave:Daclatasvir
Sofosbuvir
Favipiravir
Ribavirin
Direct acting antivirals
Viral fitness
Delayed drug administration
Lethal mutagenesis
Descripción
Sumario:We report a quantification of the decrease of effectiveness of antiviral agents directed to hepatitis C virus, when the agents are added during an ongoing infection in cell culture vs. when they are added at the beginning of the infection. Major determinants of the decrease of inhibitory activity are the time post-infection of inhibitor administration and viral replicative fitness. The efficacy decrease has been documented with antiviral assays involving the combination of the direct-acting antiviral agents, daclatasvir and sofosbuvir, and with the combination of the lethal mutagens, favipiravir and ribavirin. The results suggest that strict antiviral effectiveness assays in preclinical trials may involve the use of high fitness viral populations and the delayed administration of the agents, relative to infection onset.