Search for Novel Potent Inhibitors of the SARS-CoV-2 Papain-like Enzyme: A Computational Biochemistry Approach
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Fecha
2022-08
Profesor/a Guía
Facultad/escuela
Idioma
en
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Título del volumen
Editor
MDPI
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Licencia CC
CC BY 4.0 DEED
Attribution 4.0 International
Licencia CC
https://creativecommons.org/licenses/by/4.0/
Resumen
The 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.
Notas
Indexación: Scopus.
Palabras clave
Binding free energy, Molecular dynamics simulation, Papain-like protease of SARS-CoV-2, Virtual screening
Citación
Pharmaceuticals, Volume 15, Issue 8, August 2022, Article number 986
DOI
10.3390/ph15080986