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 (M pro ). 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 M pro 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 M pro . 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. Communicated by Ramaswamy H. Sarma.
Keywords: COVID-19; SARS-CoV-2 main protease; drug repurposing; in-silico drug discovery; molecular dynamics.
【저자키워드】 COVID-19, Drug repurposing, molecular dynamics, SARS-CoV-2 main protease, in-silico drug discovery, 【초록키워드】 Drug repurposing, SARS-CoV-2, molecular docking, clinical trials, drug, molecular dynamics, protease, database, SARS-CoV-2 main protease, MD simulations, binding affinity, Cobicistat, binding energy, stability, Accuracy, amino acids, molecular, in-silico, Amino acid, Hydrogen bond, Analysis, darunavir, followed by, active site, hydrogen, surface area, docking scores, M pro, potency, DrugBank database, docking score, potentiality, highlight, essential amino acids, approved, conducted, exhibited, demonstrated, much lower, 【제목키워드】 molecular, inhibitor,