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Antiviral drugs targeting endosomal membrane proteins inhibit distant animal and human pathogenic viruses

The endocytic pathway is a common strategy that several highly pathogenic viruses use to enter into the cell. To demonstrate the usefulness of this pathway as a common target for the development of broad-spectrum antivirals, the inhibitory effect of drug compounds targeting endosomal membrane protei...

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Autores principales: Galindo, I., Garaigorta, U., Lasala, F., Cuesta-Geijo, M.A., Bueno, P., Gil, C., Delgado, R., Gastaminza, P., Alonso, C.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Author(s). Published by Elsevier B.V. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7690281/
https://www.ncbi.nlm.nih.gov/pubmed/33249093
http://dx.doi.org/10.1016/j.antiviral.2020.104990
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author Galindo, I.
Garaigorta, U.
Lasala, F.
Cuesta-Geijo, M.A.
Bueno, P.
Gil, C.
Delgado, R.
Gastaminza, P.
Alonso, C.
author_facet Galindo, I.
Garaigorta, U.
Lasala, F.
Cuesta-Geijo, M.A.
Bueno, P.
Gil, C.
Delgado, R.
Gastaminza, P.
Alonso, C.
author_sort Galindo, I.
collection PubMed
description The endocytic pathway is a common strategy that several highly pathogenic viruses use to enter into the cell. To demonstrate the usefulness of this pathway as a common target for the development of broad-spectrum antivirals, the inhibitory effect of drug compounds targeting endosomal membrane proteins were investigated. This study entailed direct comparison of drug effectiveness against animal and human pathogenic viruses, namely Ebola (EBOV), African swine fever virus (ASFV), and the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). A panel of experimental and FDA-approved compounds targeting calcium channels and PIKfyve at the endosomal membrane caused potent reductions of entry up to 90% in SARS-CoV-2 S-protein pseudotyped retrovirus. Similar inhibition was observed against transduced EBOV glycoprotein pseudovirus and ASFV. SARS-CoV-2 infection was potently inhibited by selective estrogen receptor modulators in cells transduced with pseudovirus, among them Raloxifen inhibited ASFV with very low 50% inhibitory concentration. Finally, the mechanism of the inhibition caused by the latter in ASFV infection was analyzed. Overall, this work shows that cellular proteins related to the endocytic pathway can constitute suitable cellular targets for broad range antiviral compounds.
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spelling pubmed-76902812020-11-27 Antiviral drugs targeting endosomal membrane proteins inhibit distant animal and human pathogenic viruses Galindo, I. Garaigorta, U. Lasala, F. Cuesta-Geijo, M.A. Bueno, P. Gil, C. Delgado, R. Gastaminza, P. Alonso, C. Antiviral Res Article The endocytic pathway is a common strategy that several highly pathogenic viruses use to enter into the cell. To demonstrate the usefulness of this pathway as a common target for the development of broad-spectrum antivirals, the inhibitory effect of drug compounds targeting endosomal membrane proteins were investigated. This study entailed direct comparison of drug effectiveness against animal and human pathogenic viruses, namely Ebola (EBOV), African swine fever virus (ASFV), and the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). A panel of experimental and FDA-approved compounds targeting calcium channels and PIKfyve at the endosomal membrane caused potent reductions of entry up to 90% in SARS-CoV-2 S-protein pseudotyped retrovirus. Similar inhibition was observed against transduced EBOV glycoprotein pseudovirus and ASFV. SARS-CoV-2 infection was potently inhibited by selective estrogen receptor modulators in cells transduced with pseudovirus, among them Raloxifen inhibited ASFV with very low 50% inhibitory concentration. Finally, the mechanism of the inhibition caused by the latter in ASFV infection was analyzed. Overall, this work shows that cellular proteins related to the endocytic pathway can constitute suitable cellular targets for broad range antiviral compounds. The Author(s). Published by Elsevier B.V. 2021-02 2020-11-26 /pmc/articles/PMC7690281/ /pubmed/33249093 http://dx.doi.org/10.1016/j.antiviral.2020.104990 Text en © 2020 The Author(s) Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.
spellingShingle Article
Galindo, I.
Garaigorta, U.
Lasala, F.
Cuesta-Geijo, M.A.
Bueno, P.
Gil, C.
Delgado, R.
Gastaminza, P.
Alonso, C.
Antiviral drugs targeting endosomal membrane proteins inhibit distant animal and human pathogenic viruses
title Antiviral drugs targeting endosomal membrane proteins inhibit distant animal and human pathogenic viruses
title_full Antiviral drugs targeting endosomal membrane proteins inhibit distant animal and human pathogenic viruses
title_fullStr Antiviral drugs targeting endosomal membrane proteins inhibit distant animal and human pathogenic viruses
title_full_unstemmed Antiviral drugs targeting endosomal membrane proteins inhibit distant animal and human pathogenic viruses
title_short Antiviral drugs targeting endosomal membrane proteins inhibit distant animal and human pathogenic viruses
title_sort antiviral drugs targeting endosomal membrane proteins inhibit distant animal and human pathogenic viruses
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7690281/
https://www.ncbi.nlm.nih.gov/pubmed/33249093
http://dx.doi.org/10.1016/j.antiviral.2020.104990
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