Identification of potential COVID-19 Mpro inhibitors through covalent drug docking, molecular dynamics simulation, and MMGBSA calculation

• Published in: Scientific reports Vol. 15; no. 1; pp. 20500 - 14
• Main Authors: Abadi, Mohammad Hossein Haghir Ebrahim, Bayani, Fatemeh, Sefidbakht, Yahya
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.07.2025; Nature Portfolio
• Subjects: 631/45; 631/45/468; 631/535/1267; 631/57/2272; 692/699/255; Antiviral Agents - chemistry; Antiviral Agents - pharmacology; Computational drug design; Coronavirus 3C Proteases - antagonists & inhibitors; Coronavirus 3C Proteases - chemistry; Coronavirus 3C Proteases - metabolism; Covalent drug design; COVID-19; COVID-19 - virology; COVID-19 Drug Treatment; Humanities and Social Sciences; Humans; Ligands; Main protease (Mpro); MMGBSA; Molecular Docking Simulation; Molecular Dynamics Simulation; multidisciplinary; Protease Inhibitors - chemistry; Protease Inhibitors - pharmacology; SARS-CoV-2 - drug effects; SARS-CoV-2 - enzymology; Science; Science (multidisciplinary); COVID-19; Covalent drug design; Computational drug design; MMGBSA; Main protease (Mpro)

The viral main protease is a critical drug target due to its role in the SARS-CoV-2 life cycle. In this study, we evaluated 2,000 potential Mpro inhibitors recommended by the FragRep server, with a focus on interactions with the CYS145 residue. Six top candidates were selected for each of the 7JKV a...