Repurposing of FDA-approved drugs as potential inhibitors of the SARS-CoV-2 main protease: Molecular insights into improved therapeutic discovery.
Binding free energy
FDA-Approved drugs
Main protease
Molecular dynamics
SARS-CoV-2
Journal
Computers in biology and medicine
ISSN: 1879-0534
Titre abrégé: Comput Biol Med
Pays: United States
ID NLM: 1250250
Informations de publication
Date de publication:
03 2022
03 2022
Historique:
received:
06
10
2021
revised:
26
12
2021
accepted:
26
12
2021
pubmed:
6
1
2022
medline:
17
2
2022
entrez:
5
1
2022
Statut:
ppublish
Résumé
With numerous infections and fatalities, COVID-19 has wreaked havoc around the globe. The main protease (Mpro), which cleaves the polyprotein to form non-structural proteins, thereby helping in the replication of SARS-CoV-2, appears as an attractive target for antiviral therapeutics. As FDA-approved drugs have shown effectiveness in targeting Mpro in previous SARS-CoV(s), molecular docking and virtual screening of existing antiviral, antimalarial, and protease inhibitor drugs were carried out against SARS-CoV-2 Mpro. Among 53 shortlisted drugs with binding energies lower than that of the crystal-bound inhibitor α-ketoamide 13 b (-6.7 kcal/mol), velpatasvir, glecaprevir, grazoprevir, baloxavir marboxil, danoprevir, nelfinavir, and indinavir (-9.1 to -7.5 kcal/mol) were the most significant on the list (hereafter referred to as the 53-list). Molecular dynamics (MD) simulations confirmed the stability of their Mpro complexes, with the MMPBSA binding free energy (ΔG
Identifiants
pubmed: 34986429
pii: S0010-4825(21)00977-X
doi: 10.1016/j.compbiomed.2021.105183
pmc: PMC8714248
pii:
doi:
Substances chimiques
Pharmaceutical Preparations
0
Protease Inhibitors
0
3C-like proteinase, SARS-CoV-2
EC 3.4.22.-
Coronavirus 3C Proteases
EC 3.4.22.28
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
105183Informations de copyright
Copyright © 2021 Elsevier Ltd. All rights reserved.
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