Search for Novel Potent Inhibitors of the SARS-CoV-2 Papain-like Enzyme: A Computational Biochemistry Approach

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dc.contributor.authorOsorio, Manuel I.
dc.contributor.authorYáñez, Osvaldo
dc.contributor.authorGallardo, Mauricio
dc.contributor.authorZuñiga Bustos, Matías
dc.contributor.authorMulia Rodríguez, Jorge
dc.contributor.authorLópez Rendón, Roberto
dc.contributor.authorGarcía Beltrán, Olimpo
dc.contributor.authorGonzález Nilo, Fernando
dc.contributor.authorPérez Donoso, José M.
dc.date.accessioned2023-09-29T20:16:38Z
dc.date.available2023-09-29T20:16:38Z
dc.date.issued2022-08
dc.descriptionIndexación: Scopus.es
dc.description.abstractThe rapid emergence and spread of new variants of coronavirus type 2, as well as the emergence of zoonotic viruses, highlights the need for methodologies that contribute to the search for new pharmacological treatments. In the present work, we searched for new SARS-CoV-2 papain-like protease inhibitors in the PubChem database, which has more than 100 million compounds. Based on the ligand efficacy index obtained by molecular docking, 500 compounds with higher affinity than another experimentally tested inhibitor were selected. Finally, the seven compounds with ADME parameters within the acceptable range for such a drug were selected. Next, molecular dynamics simulation studies at 200 ns, ΔG calculations using molecular mechanics with generalized Born and surface solvation, and quantum mechanical calculations were performed with the selected compounds. Using this in silico protocol, seven papain-like protease inhibitors are proposed: three compounds with similar free energy (D28, D04, and D59) and three compounds with higher binding free energy (D60, D99, and D06) than the experimentally tested inhibitor, plus one compound (D24) that could bind to the ubiquitin-binding region and reduce the effect on the host immune system. The proposed compounds could be used in in vitro assays, and the described protocol could be used for smart drug design. © 2022 by the authors.es
dc.description.urihttps://www.mdpi.com/1424-8247/15/8/986
dc.identifier.citationPharmaceuticals, Volume 15, Issue 8, August 2022, Article number 986es
dc.identifier.doi10.3390/ph15080986
dc.identifier.issn1424-8247
dc.identifier.urihttps://repositorio.unab.cl/xmlui/handle/ria/53383
dc.language.isoenes
dc.publisherMDPIes
dc.rights.licenseCC BY 4.0 DEED Attribution 4.0 International
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.subjectBinding free energyes
dc.subjectMolecular dynamics simulationes
dc.subjectPapain-like protease of SARS-CoV-2es
dc.subjectVirtual screeninges
dc.titleSearch for Novel Potent Inhibitors of the SARS-CoV-2 Papain-like Enzyme: A Computational Biochemistry Approaches
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