Host-Directed FDA-Approved Drugs with Antiviral Activity against SARS-CoV-2 Identified by Hierarchical In Silico/In Vitro Screening Methods

The unprecedent situation generated by the COVID-19 global emergency has prompted us to actively work to fight against this pandemic by searching for repurposable agents among FDA approved drugs to shed light into immediate opportunities for the treatment of COVID-19 patients. In the attempt to proc...

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Autores: Ginex, Tiziana, Garaigorta, Urtzi, Ramírez, David, Castro, Victoria, Nozal, Vanesa, Maestro, Inés, Garcia-Carceles, Javier, Campillo, Nuria E., Martínez Gil, Ana, Gastaminza, Pablo, Gil, Carmen
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2021
País:España
Institución:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/241077
Acceso en línea:http://hdl.handle.net/10261/241077
Access Level:acceso abierto
Palabra clave:SARS-CoV-2 evaluation
COVID-19
Drug repurposing
Host-based targets
Virtual screening
Entry inhibitors
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spelling Host-Directed FDA-Approved Drugs with Antiviral Activity against SARS-CoV-2 Identified by Hierarchical In Silico/In Vitro Screening MethodsGinex, TizianaGaraigorta, UrtziRamírez, DavidCastro, VictoriaNozal, VanesaMaestro, InésGarcia-Carceles, JavierCampillo, Nuria E.Martínez Gil, AnaGastaminza, PabloGil, CarmenSARS-CoV-2 evaluationCOVID-19Drug repurposingHost-based targetsVirtual screeningEntry inhibitorsThe unprecedent situation generated by the COVID-19 global emergency has prompted us to actively work to fight against this pandemic by searching for repurposable agents among FDA approved drugs to shed light into immediate opportunities for the treatment of COVID-19 patients. In the attempt to proceed toward a proper rationalization of the search for new antivirals among approved drugs, we carried out a hierarchical in silico/in vitro protocol which successfully combines virtual and biological screening to speed up the identification of host-directed therapies against COVID-19 in an effective way. To this end a multi-target virtual screening approach focused on host-based targets related to viral entry, followed by the experimental evaluation of the antiviral activity of selected compounds, has been carried out. As a result, five different potentially repurposable drugs interfering with viral entry—cepharantine, clofazimine, metergoline, imatinib and efloxate—have been identifiedThis research was funded by CSIC (201980E024, 202020E103 and PIE-RD-COVID-19 ref. E202020E079), EVA (European Virus Archive; grant agreement No 871029), ANID (Agencia Nacional de Investigación y Desarrollo de Chile, grant No COVID0199), and CONICYT-PCI (Comisión Nacional de Investigación Científica y Tecnológica de Chile—Programa de Cooperación Internacional, grant No REDES190074). I.M. was funded by H2020-MSCA-ITN-2017 (grant no. 765912) and V.N. holds a pre-doctoral FPU grant (FPU16/04466)Peer reviewedMolecular Diversity Preservation InternationalConsejo Superior de Investigaciones Científicas (España)Agencia Nacional de Investigación y Desarrollo (Chile)Comisión Nacional de Investigación Científica y Tecnológica (Chile)European CommissionMinisterio de Educación, Cultura y Deporte (España)Ginex, Tiziana [0000-0002-5739-8713]Garaigorta, Urtzi [0000-0002-0683-5725]Ramírez, David [0000-0003-0002-1189]Castro, Victoria [0000-0001-9151-5138]Nozal, Vanesa [0000-0001-5260-5683]Maestro, Inés [0000-0002-5026-5803]Garcia-Carceles, Javier [0000-0003-4614-9639]Martínez, Ana [0000-0002-2707-8110]Gil, Carmen [0000-0002-3882-6081]Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]202120212021info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501Publisher's versioninfo:eu-repo/semantics/publishedVersionhttp://hdl.handle.net/10261/241077reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)Inglés#PLACEHOLDER_PARENT_METADATA_VALUE#info:eu-repo/grantAgreement/EC/H2020/765912https://doi.org/10.3390/ph14040332Síinfo:eu-repo/semantics/openAccessoai:digital.csic.es:10261/2410772026-05-22T06:33:51Z
dc.title.none.fl_str_mv Host-Directed FDA-Approved Drugs with Antiviral Activity against SARS-CoV-2 Identified by Hierarchical In Silico/In Vitro Screening Methods
title Host-Directed FDA-Approved Drugs with Antiviral Activity against SARS-CoV-2 Identified by Hierarchical In Silico/In Vitro Screening Methods
spellingShingle Host-Directed FDA-Approved Drugs with Antiviral Activity against SARS-CoV-2 Identified by Hierarchical In Silico/In Vitro Screening Methods
Ginex, Tiziana
SARS-CoV-2 evaluation
COVID-19
Drug repurposing
Host-based targets
Virtual screening
Entry inhibitors
title_short Host-Directed FDA-Approved Drugs with Antiviral Activity against SARS-CoV-2 Identified by Hierarchical In Silico/In Vitro Screening Methods
title_full Host-Directed FDA-Approved Drugs with Antiviral Activity against SARS-CoV-2 Identified by Hierarchical In Silico/In Vitro Screening Methods
title_fullStr Host-Directed FDA-Approved Drugs with Antiviral Activity against SARS-CoV-2 Identified by Hierarchical In Silico/In Vitro Screening Methods
title_full_unstemmed Host-Directed FDA-Approved Drugs with Antiviral Activity against SARS-CoV-2 Identified by Hierarchical In Silico/In Vitro Screening Methods
title_sort Host-Directed FDA-Approved Drugs with Antiviral Activity against SARS-CoV-2 Identified by Hierarchical In Silico/In Vitro Screening Methods
dc.creator.none.fl_str_mv Ginex, Tiziana
Garaigorta, Urtzi
Ramírez, David
Castro, Victoria
Nozal, Vanesa
Maestro, Inés
Garcia-Carceles, Javier
Campillo, Nuria E.
Martínez Gil, Ana
Gastaminza, Pablo
Gil, Carmen
author Ginex, Tiziana
author_facet Ginex, Tiziana
Garaigorta, Urtzi
Ramírez, David
Castro, Victoria
Nozal, Vanesa
Maestro, Inés
Garcia-Carceles, Javier
Campillo, Nuria E.
Martínez Gil, Ana
Gastaminza, Pablo
Gil, Carmen
author_role author
author2 Garaigorta, Urtzi
Ramírez, David
Castro, Victoria
Nozal, Vanesa
Maestro, Inés
Garcia-Carceles, Javier
Campillo, Nuria E.
Martínez Gil, Ana
Gastaminza, Pablo
Gil, Carmen
author2_role author
author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Consejo Superior de Investigaciones Científicas (España)
Agencia Nacional de Investigación y Desarrollo (Chile)
Comisión Nacional de Investigación Científica y Tecnológica (Chile)
European Commission
Ministerio de Educación, Cultura y Deporte (España)
Ginex, Tiziana [0000-0002-5739-8713]
Garaigorta, Urtzi [0000-0002-0683-5725]
Ramírez, David [0000-0003-0002-1189]
Castro, Victoria [0000-0001-9151-5138]
Nozal, Vanesa [0000-0001-5260-5683]
Maestro, Inés [0000-0002-5026-5803]
Garcia-Carceles, Javier [0000-0003-4614-9639]
Martínez, Ana [0000-0002-2707-8110]
Gil, Carmen [0000-0002-3882-6081]
Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]
dc.subject.none.fl_str_mv SARS-CoV-2 evaluation
COVID-19
Drug repurposing
Host-based targets
Virtual screening
Entry inhibitors
topic SARS-CoV-2 evaluation
COVID-19
Drug repurposing
Host-based targets
Virtual screening
Entry inhibitors
description The unprecedent situation generated by the COVID-19 global emergency has prompted us to actively work to fight against this pandemic by searching for repurposable agents among FDA approved drugs to shed light into immediate opportunities for the treatment of COVID-19 patients. In the attempt to proceed toward a proper rationalization of the search for new antivirals among approved drugs, we carried out a hierarchical in silico/in vitro protocol which successfully combines virtual and biological screening to speed up the identification of host-directed therapies against COVID-19 in an effective way. To this end a multi-target virtual screening approach focused on host-based targets related to viral entry, followed by the experimental evaluation of the antiviral activity of selected compounds, has been carried out. As a result, five different potentially repurposable drugs interfering with viral entry—cepharantine, clofazimine, metergoline, imatinib and efloxate—have been identified
publishDate 2021
dc.date.none.fl_str_mv 2021
2021
2021
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
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10261/241077
url http://hdl.handle.net/10261/241077
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv #PLACEHOLDER_PARENT_METADATA_VALUE#
info:eu-repo/grantAgreement/EC/H2020/765912
https://doi.org/10.3390/ph14040332
Sí
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv Molecular Diversity Preservation International
publisher.none.fl_str_mv Molecular Diversity Preservation International
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
collection DIGITAL.CSIC. Repositorio Institucional del CSIC
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15.812429

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