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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 principales: Ginex, Tiziana, Garaigorta, Urtzi, Ramírez, David, Castro, Victoria, Nozal, Vanesa, Maestro, Inés, García-Cárceles, Javier, Campillo, Nuria E., Martinez, Ana, Gastaminza, Pablo, Gil, Carmen
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8067418/
https://www.ncbi.nlm.nih.gov/pubmed/33917313
http://dx.doi.org/10.3390/ph14040332
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author Ginex, Tiziana
Garaigorta, Urtzi
Ramírez, David
Castro, Victoria
Nozal, Vanesa
Maestro, Inés
García-Cárceles, Javier
Campillo, Nuria E.
Martinez, Ana
Gastaminza, Pablo
Gil, Carmen
author_facet Ginex, Tiziana
Garaigorta, Urtzi
Ramírez, David
Castro, Victoria
Nozal, Vanesa
Maestro, Inés
García-Cárceles, Javier
Campillo, Nuria E.
Martinez, Ana
Gastaminza, Pablo
Gil, Carmen
author_sort Ginex, Tiziana
collection PubMed
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.
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spelling pubmed-80674182021-04-25 Host-Directed FDA-Approved Drugs with Antiviral Activity against SARS-CoV-2 Identified by Hierarchical In Silico/In Vitro Screening Methods Ginex, Tiziana Garaigorta, Urtzi Ramírez, David Castro, Victoria Nozal, Vanesa Maestro, Inés García-Cárceles, Javier Campillo, Nuria E. Martinez, Ana Gastaminza, Pablo Gil, Carmen Pharmaceuticals (Basel) Article 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. MDPI 2021-04-06 /pmc/articles/PMC8067418/ /pubmed/33917313 http://dx.doi.org/10.3390/ph14040332 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Ginex, Tiziana
Garaigorta, Urtzi
Ramírez, David
Castro, Victoria
Nozal, Vanesa
Maestro, Inés
García-Cárceles, Javier
Campillo, Nuria E.
Martinez, Ana
Gastaminza, Pablo
Gil, Carmen
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
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_short 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
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8067418/
https://www.ncbi.nlm.nih.gov/pubmed/33917313
http://dx.doi.org/10.3390/ph14040332
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