Discovery of potential FDA-approved SARS-CoV-2 Papain-like protease inhibitors: A multi-phase in silico approach
Ahmed M Metwaly, Eslam B Elkaeed, Mohamed M Khalifa, Aisha A Alsfouk, Fatma G Amin, Ibrahim M Ibrahim, Ibrahim H Eissa
Journal of Chemical Research, doi:10.1177/17475198241298547
Papain-like protease (PLpro) is a crucial enzyme for SARS-CoV-2 replication and immune evasion. Inhibiting PLpro could be a promising strategy to fight against COVID-19. This study aimed to identify potent inhibitors of PLpro among FDAapproved drugs using an in silico approach. The study also aimed to examine and confirm the binding of the selected compounds to the active pocket of PLpro using a multi-phased in silico approach, involving the screening of 3009 FDAapproved drugs to pinpoint the most similar compounds to, TTT, the co-crystallized ligand TTT of PLpro. The selected compounds were subjected to further analysis, including molecular docking, molecular dynamics simulations, MM-GPSA (molecular mechanics generalized Born surface area), and PLIP (Protein-Ligand Interaction Profiler) studies, to examine and confirm their binding to the active pocket of PLpro. Seven candidates (Vismodegib, Celecoxib, Ketoprofen, Indomethacin, Naphazoline, Valdecoxib, and Eslicarbazepine) showed promising in silico activities against the PLpro. The computational analysis confirmed the binding of Celecoxib to the active pocket of PLpro, suggesting its potential in the fight against COVID-19. This study identified seven FDA-approved drugs as potential inhibitors of PLpro, providing a feasible approach for drug repurposing against COVID-19. The results obtained from the in silico approach hold promise, but further in vitro and in vivo studies are warranted to validate the potential of these compounds.
Author contributions
Declaration of conflicting interests The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
ORCID iD Ahmed M Metwaly https://orcid.org/0000-0001-8566-1980
Supplemental material Supplemental material for this article is available online.
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'abstract': '<jats:p> Papain-like protease (PLpro) is a crucial enzyme for SARS-CoV-2 replication and '
'immune evasion. Inhibiting PLpro could be a promising strategy to fight against COVID-19. '
'This study aimed to identify potent inhibitors of PLpro among FDA-approved drugs using an in '
'silico approach. The study also aimed to examine and confirm the binding of the selected '
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