Please use this identifier to cite or link to this item: http://hdl.handle.net/10261/224797
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Title

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

AuthorsGalindo Estrada, Ignacio; Garaigorta, Urtzi ; Lasala, Fátima; Cuesta-Geijo, Miguel Ángel CSIC ORCID; Bueno, P.; Gil, Carmen CSIC ORCID ; Delgado, Rafael; Gastaminza, Pablo CSIC ORCID; Alonso, C. CSIC ORCID
KeywordsSARS-CoV-2
EBOV
ASFV
Antivirals
PIKfyve
Calcium channels
Issue Date26-Nov-2020
PublisherElsevier BV
CitationAntiviral Research 104990 (2020)
AbstractThe 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.
Publisher version (URL)https://doi.org/10.1016/j.antiviral.2020.104990
URIhttp://hdl.handle.net/10261/224797
DOI10.1016/j.antiviral.2020.104990
ISSN0166-3542
Appears in Collections:(PTI Salud Global) Colección Especial COVID-19
(CNB) Artículos
(CIB) Artículos
(INIA) Artículos

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