In-silico drug repurposing and molecular dynamics puzzled out potential SARS-CoV-2 main protease inhibitors

Mahmoud A. A. Ibrahim, Alaa H. M. Abdelrahman, Mohamed-Elamir F. Hegazy

10.1080/07391102.2020.1791958

Research curated

Abstract

Herein, the DrugBank database which contains 10,036 approved and investigational drugs was explored deeply for potential drugs that target SARS-CoV-2 main protease (Mpro). Filtration process of the database was conducted using three levels of accuracy for molecular docking calculations. The top 35 drugs with docking scores > −11.0 kcal/mol were then subjected to 10 ns molecular dynamics (MD) simulations followed by molecular mechanics–generalized Born surface area (MM-GBSA) binding energy calculations. The results showed that DB02388 and Cobicistat (DB09065) exhibited potential binding affinities towards Mpro over 100 ns MD simulations, with binding energy values of −49.67 and −46.60 kcal/mol, respectively. Binding energy and structural analyses demonstrated the higher stability of DB02388 over Cobicistat. The potency of DB02388 and Cobicistat is attributed to their abilities to form several hydrogen bonds with the essential amino acids inside the active site of Mpro. Compared to DB02388 and Cobicistat, Darunavir showed a much lower binding affinity of −34.83 kcal/mol. The present study highlights the potentiality of DB02388 and Cobicistat as anti-COVID-19 drugs for clinical trials.

Source: PubMed

Related molecules

Name	Synonyms	Genes
Cyclohexyl-{4-[5-(3,4-Dichlorophenyl)-2-Piperidin-4-Yl-3-Propyl-3h-Imidazol-4-Yl]-Pyrimidin-2-Yl}Amine
Cobicistat
3C-like protease	3CLpro, Mpro, SARS coronavirus main peptidase, 3CLpro-SARS-CoV-2	rep, ORF1a-1b

Related interactions

Target	Drug	Type	Result
3C-like protease	Cyclohexyl-{4-[5-(3,4-Dichlorophenyl)-2-Piperidin-4-Yl-3-Propyl-3h-Imidazol-4-Yl]-Pyrimidin-2-Yl}Amine	Computational	positive
3C-like protease	Cobicistat	Computational	positive