Rapid prediction of possible inhibitors for SARS-CoV-2 main protease using docking and FPL simulations

• Published in: RSC advances Vol. 1; no. 53; pp. 31991 - 31996
• Main Authors: Pham, Minh Quan, Vu, Khanh B, Han Pham, T. Ngoc, Thuy Huong, Le Thi, Tran, Linh Hoang, Tung, Nguyen Thanh, Vu, Van V, Nguyen, Trung Hai, Ngo, Son Tung
• Format: Journal Article
• Language: English
• Published: England Royal Society of Chemistry 28.08.2020; The Royal Society of Chemistry
• Subjects: Chemistry; China; computer simulation; Coronavirus infections; correlation; Correlation coefficients; glycyrrhizin; lead; Ligands; Molecular docking; prediction; Protease; Protease inhibitors; proteinases; Severe acute respiratory syndrome coronavirus 2; Simulation; therapeutics; China
• ISSN: 2046-2069; 2046-2069
• DOI: 10.1039/d0ra06212j

Originating for the first time in Wuhan, China, the outbreak of SARS-CoV-2 has caused a serious global health issue. An effective treatment for SARS-CoV-2 is still unavailable. Therefore, in this study, we have tried to predict a list of potential inhibitors for SARS-CoV-2 main protease (Mpro) using a combination of molecular docking and fast pulling of ligand (FPL) simulations. The approaches were initially validated over a set of eleven available inhibitors. Both Autodock Vina and FPL calculations produced consistent results with the experiments with correlation coefficients of R Dock = 0.72 ± 0.14 and R W = −0.76 ± 0.10, respectively. The combined approaches were then utilized to predict possible inhibitors that were selected from a ZINC15 sub-database for SARS-CoV-2 Mpro. Twenty compounds were suggested to be able to bind well to SARS-CoV-2 Mpro. Among them, five top-leads are periandrin V , penimocycline , cis-p-Coumaroylcorosolic acid , glycyrrhizin , and uralsaponin B . The obtained results could probably lead to enhance the COVID-19 therapy. A combination of Autodock Vina and FPL calculations suggested that periandrin V , penimocycline , cis-p-Coumaroylcorosolic acid , glycyrrhizin , and uralsaponin B are able to bind well to SARS-CoV-2 Mpro.