Chile | Artículo
dc.creatorOsorio, Manuel I.
dc.creatorYáñez, Osvaldo
dc.creatorGallardo, Mauricio
dc.creatorZuñiga Bustos, Matías
dc.creatorMulia Rodríguez, Jorge
dc.creatorLópez Rendón, Roberto
dc.creatorGarcía Beltrán, Olimpo
dc.creatorGonzález Nilo, Fernando
dc.creatorPérez Donoso, José M.
dc.date.accessioned2023-09-29T20:16:38Z
dc.date.accessioned2024-05-02T15:15:32Z
dc.date.available2023-09-29T20:16:38Z
dc.date.available2024-05-02T15:15:32Z
dc.date.created2023-09-29T20:16:38Z
dc.date.issued2022-08
dc.identifierPharmaceuticals, Volume 15, Issue 8, August 2022, Article number 986
dc.identifier1424-8247
dc.identifierhttps://repositorio.unab.cl/xmlui/handle/ria/53383
dc.identifier10.3390/ph15080986
dc.identifier.urihttps://repositorioslatinoamericanos.uchile.cl/handle/2250/9264374
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.
dc.languageen
dc.publisherMDPI
dc.rightshttps://creativecommons.org/licenses/by/4.0/
dc.rightsCC BY 4.0 DEED Attribution 4.0 International
dc.subjectBinding free energy
dc.subjectMolecular dynamics simulation
dc.subjectPapain-like protease of SARS-CoV-2
dc.subjectVirtual screening
dc.titleSearch for Novel Potent Inhibitors of the SARS-CoV-2 Papain-like Enzyme: A Computational Biochemistry Approach
dc.typeArtículo


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