Please use this identifier to cite or link to this item: https://hdl.handle.net/11000/30649
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dc.contributor.authorEncinar, José Antonio-
dc.contributor.authorMENÉNDEZ MENÉNDEZ, JAVIER ABEL-
dc.contributor.otherDepartamentos de la UMH::Bioquímica y Biología Moleculares_ES
dc.date.accessioned2024-01-26T08:56:21Z-
dc.date.available2024-01-26T08:56:21Z-
dc.date.created2020-05-08-
dc.identifier.citationViruses 2020, 12(5), 525es_ES
dc.identifier.issn1999-4915-
dc.identifier.urihttps://hdl.handle.net/11000/30649-
dc.description.abstractThe severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) causing the COVID-19 respiratory disease pandemic utilizes unique 20-O-methyltransferase (20-O-MTase) capping machinery to camouflage its RNA from innate immune recognition. The nsp16 catalytic subunit of the 20-O-MTase is unusual in its requirement for a stimulatory subunit (nsp10) to catalyze the ribose 20-O-methylation of the viral RNA cap. Here we provide a computational basis for drug repositioning or de novo drug development based on three di erential traits of the intermolecular interactions of the SARS-CoV-2-specific nsp16/nsp10 heterodimer, namely: (1) the S-adenosyl-l-methionine-binding pocket of nsp16, (2) the unique “activating surface” between nsp16 and nsp10, and (3) the RNA-binding groove of nsp16. We employed 9000 U.S. Food and Drug Administration (FDA)-approved investigational and experimental drugs from the DrugBank repository for docking virtual screening. After molecular dynamics calculations of the stability of the binding modes of high-scoring nsp16/nsp10–drug complexes, we considered their pharmacological overlapping with functional modules of the virus–host interactome that is relevant to the viral lifecycle, and to the clinical features of COVID-19. Some of the predicted drugs (e.g., tegobuvir, sonidegib, siramesine, antrafenine, bemcentinib, itacitinib, or phthalocyanine) might be suitable for repurposing to pharmacologically reactivate innate immune restriction and antagonism of SARS-CoV-2 RNAs lacking 20-O-methylation.es_ES
dc.formatapplication/pdfes_ES
dc.format.extent25es_ES
dc.language.isoenges_ES
dc.publisherMDPIes_ES
dc.rightsinfo:eu-repo/semantics/openAccesses_ES
dc.rightsAttribution-NonCommercial-NoDerivatives 4.0 Internacional*
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/*
dc.subjectCOVID-19es_ES
dc.subjectdrug repurposinges_ES
dc.subjectmethylationes_ES
dc.subjectmethyltransferaseses_ES
dc.subjectcomputational screeninges_ES
dc.subjectmolecular dockinges_ES
dc.subjectmolecular dynamicses_ES
dc.subject.classificationBioquímica y Biología Moleculares_ES
dc.subject.otherCDU::5 - Ciencias puras y naturales::57 - Biología::577 - Bioquímica. Biología molecular. Biofísicaes_ES
dc.titlePotential Drugs Targeting Early Innate Immune Evasion of SARS-Coronavirus 2 via 2’-O-Methylation of Viral RNAes_ES
dc.typeinfo:eu-repo/semantics/articlees_ES
dc.relation.publisherversionhttps://doi.org/10.3390/v12050525es_ES
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Artículos Bioquímica y Biología Molecular


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