Universidad Peruana Cayetano Heredia

Comprehensive virtual screening of 4.8 k flavonoids reveals novel insights into allosteric inhibition of SARS-CoV-2 M-PRO

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dc.contributor.author Jimenez-Avalos, Gabriel
dc.contributor.author Paula Vargas-Ruiz, A.
dc.contributor.author Delgado-Pease, Nicolas E.
dc.contributor.author Olivos-Ramirez, Gustavo E.
dc.contributor.author Sheen Cortavarria, Patricia
dc.contributor.author Fernandez-Diaz, Manolo
dc.contributor.author Quiliano, Miguel
dc.contributor.author Zimic-Peralta, Mirko Juan
dc.contributor.author COVID-19 Working Grp Peru
dc.date.accessioned 2021-10-04T23:00:56Z
dc.date.available 2021-10-04T23:00:56Z
dc.date.issued 2021
dc.date.issued 2021
dc.identifier.uri https://hdl.handle.net/20.500.12866/9801
dc.description.abstract SARS-CoV-2 main protease is a common target for inhibition assays due to its high conservation among coronaviruses. Since flavonoids show antiviral activity, several in silico works have proposed them as potential SARS-CoV-2 main protease inhibitors. Nonetheless, there is reason to doubt certain results given the lack of consideration for flavonoid promiscuity or main protease plasticity, usage of short library sizes, absence of control molecules and/or the limitation of the methodology to a single target site. Here, we report a virtual screening study where dorsilurin E, euchrenone a11, sanggenol O and CHEMBL2171598 are proposed to inhibit main protease through different pathways. Remarkably, novel structural mechanisms were observed after sanggenol O and CHEMBL2171598 bound to experimentally proven allosteric sites. The former drastically affected the active site, while the latter triggered a hinge movement which has been previously reported for an inactive SARS-CoV main protease mutant. The use of a curated database of 4.8 k flavonoids, combining two well-known docking software (AutoDock Vina and AutoDock4.2), molecular dynamics and MMPBSA, guaranteed an adequate analysis and robust interpretation. These criteria can be considered for future screening campaigns against SARS-CoV-2 main protease en_US
dc.language.iso eng
dc.publisher Springer Nature
dc.relation.ispartofseries Scientific Reports
dc.relation.ispartofseries Scientific Reports
dc.rights info:eu-repo/semantics/restrictedAccess
dc.rights info:eu-repo/semantics/restrictedAccess
dc.rights.uri https://creativecommons.org/licenses/by-nc-nd/4.0/deed.es
dc.rights.uri https://creativecommons.org/licenses/by-nc-nd/4.0/deed.es
dc.subject Computational biology and bioinformatics en_US
dc.subject Drug discovery en_US
dc.subject Structural biology en_US
dc.title Comprehensive virtual screening of 4.8 k flavonoids reveals novel insights into allosteric inhibition of SARS-CoV-2 M-PRO en_US
dc.type info:eu-repo/semantics/article
dc.type info:eu-repo/semantics/article
dc.identifier.doi https://doi.org/10.1038/s41598-021-94951-6
dc.identifier.doi https://doi.org/10.1038/s41598-021-94951-6
dc.relation.issn 2045-2322


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