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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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
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network_acronym_str ES
network_name_str España
repository_id_str
dc.title.none.fl_str_mv Efficacy decrease of antiviral agents when administered to ongoing hepatitis C virus infections in cell culture
title Efficacy decrease of antiviral agents when administered to ongoing hepatitis C virus infections in cell culture
spellingShingle Efficacy decrease of antiviral agents when administered to ongoing hepatitis C virus infections in cell culture
García-Crespo, Carlos
Daclatasvir
Sofosbuvir
Favipiravir
Ribavirin
Direct acting antivirals
Viral fitness
Delayed drug administration
Lethal mutagenesis
title_short Efficacy decrease of antiviral agents when administered to ongoing hepatitis C virus infections in cell culture
title_full Efficacy decrease of antiviral agents when administered to ongoing hepatitis C virus infections in cell culture
title_fullStr Efficacy decrease of antiviral agents when administered to ongoing hepatitis C virus infections in cell culture
title_full_unstemmed Efficacy decrease of antiviral agents when administered to ongoing hepatitis C virus infections in cell culture
title_sort Efficacy decrease of antiviral agents when administered to ongoing hepatitis C virus infections in cell culture
dc.creator.none.fl_str_mv 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
author García-Crespo, Carlos
author_facet 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
author_role author
author2 Vázquez-Sirvent, Lucía
Somovilla, Pilar
Soria, María Eugenia
Gallego, Isabel
Ávila, Ana Isabel de
Martínez-González, Brenda
Durán-Pastor, Antoni
Domingo, Esteban
Perales, Celia
author2_role author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Instituto de Salud Carlos III
Ministerio de Ciencia e Innovación (España)
Consejo Superior de Investigaciones Científicas (España)
Fundació La Marató de TV3
Ministerio de Ciencia, Innovación y Universidades (España)
Agencia Estatal de Investigación (España)
Comunidad de Madrid
European Commission
Centro de Investigación Biomédica en Red Enfermedades Hepáticas y Digestivas (España)
Fundación Ramón Areces
Banco Santander
Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]
dc.subject.none.fl_str_mv Daclatasvir
Sofosbuvir
Favipiravir
Ribavirin
Direct acting antivirals
Viral fitness
Delayed drug administration
Lethal mutagenesis
topic Daclatasvir
Sofosbuvir
Favipiravir
Ribavirin
Direct acting antivirals
Viral fitness
Delayed drug administration
Lethal mutagenesis
description 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.
publishDate 2022
dc.date.none.fl_str_mv 2022
2023
2023
2023
dc.type.none.fl_str_mv info:eu-repo/semantics/article
http://purl.org/coar/resource_type/c_6501
Publisher's version
info:eu-repo/semantics/publishedVersion
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status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10261/304782
url http://hdl.handle.net/10261/304782
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
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info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/PID2020-113888RB-I00
info:eu-repo/grantAgreement/AEI//BFU2017-91384-EXP
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info:eu-repo/grantAgreement/AEI/BFU2017-91384-EXP/
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info:eu-repo/grantAgreement/AEI//PRE2018-083422
http://dx.doi.org/10.3389/fmicb.2022.960676
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dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
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dc.publisher.none.fl_str_mv Frontiers Media
publisher.none.fl_str_mv Frontiers Media
dc.source.none.fl_str_mv reponame:DIGITAL.CSIC. Repositorio Institucional del CSIC
instname:Consejo Superior de Investigaciones Científicas (CSIC)
instname_str Consejo Superior de Investigaciones Científicas (CSIC)
reponame_str DIGITAL.CSIC. Repositorio Institucional del CSIC
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spelling Efficacy decrease of antiviral agents when administered to ongoing hepatitis C virus infections in cell cultureGarcía-Crespo, CarlosVázquez-Sirvent, LucíaSomovilla, PilarSoria, María EugeniaGallego, IsabelÁvila, Ana Isabel deMartínez-González, BrendaDurán-Pastor, AntoniDomingo, EstebanPerales, CeliaDaclatasvirSofosbuvirFavipiravirRibavirinDirect acting antiviralsViral fitnessDelayed drug administrationLethal mutagenesisWe 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.This work was supported by Instituto de Salud Carlos III, Spanish Ministry of Science and Innovation (COVID-19 Research Call COV20/00181) and cofinanced by European Development Regional Fund A way to achieve Europe and grants CSIC-COV19-014 from Consejo Superior de Investigaciones Científicas (CSIC), project 525/C/2021 from Fundació La Marató de TV3, PID2020-113888RB-I00 from Ministerio de Ciencia e Innovación, BFU2017-91384-EXP from Ministerio de Ciencia, Innovación y Universidades (MCIU), PI18/00210 and PI21/00139 from Instituto de Salud Carlos III, and S2018/BAA-4370 (PLATESA2 from Comunidad de Madrid/FEDER). This research work was also funded by the European Commission NextGenerationEU (Regulation EU 2020/2094), through the CSIC's Global Health Platform (PTI Salud Global). CP was supported by the Miguel Servet Program of the Instituto de Salud Carlos III (CP14/00121 and CPII19/00001), cofinanced by the European Regional Development Fund (ERDF). Centro de Investigación en Red de Enfermedades Hepáticas y Digestivas (CIBERehd) is funded by Instituto de Salud Carlos III. Institutional grants from the Fundación Ramón Areces and Banco Santander to the CBMSO are also acknowledged. The team at CBMSO belongs to the Global Virus Network (GVN). CG-C was supported by predoctoral contract PRE2018-083422 from MCIU. PS was supported by postdoctoral contract Margarita Salas CA1/RSUE/2021 from MCIU. BM-G was supported by predoctoral contract PFIS FI19/00119 from ISCIII, cofinanced by Fondo Social Europeo (FSE).Peer reviewedFrontiers MediaInstituto de Salud Carlos IIIMinisterio de Ciencia e Innovación (España)Consejo Superior de Investigaciones Científicas (España)Fundació La Marató de TV3Ministerio de Ciencia, Innovación y Universidades (España)Agencia Estatal de Investigación (España)Comunidad de MadridEuropean CommissionCentro de Investigación Biomédica en Red Enfermedades Hepáticas y Digestivas (España)Fundación Ramón ArecesBanco SantanderConsejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]2023202320222023info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501Publisher's versioninfo:eu-repo/semantics/publishedVersionapplication/pdfhttp://hdl.handle.net/10261/304782reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)Inglés#PLACEHOLDER_PARENT_METADATA_VALUE##PLACEHOLDER_PARENT_METADATA_VALUE##PLACEHOLDER_PARENT_METADATA_VALUE##PLACEHOLDER_PARENT_METADATA_VALUE##PLACEHOLDER_PARENT_METADATA_VALUE##PLACEHOLDER_PARENT_METADATA_VALUE#info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/PID2020-113888RB-I00info:eu-repo/grantAgreement/AEI//BFU2017-91384-EXPinfo:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/PID2020-113888RB-I00info:eu-repo/grantAgreement/AEI/BFU2017-91384-EXP/S2018/BAA-4370/PLATESA2info:eu-repo/grantAgreement/AEI//PRE2018-083422http://dx.doi.org/10.3389/fmicb.2022.960676Síinfo:eu-repo/semantics/openAccessoai:digital.csic.es:10261/3047822026-05-22T06:33:51Z
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