The spread of SARS-CoV-2 has affected human health globally. Hence, it is necessary to rapidly find the drug-candidates that can be used to treat the
infection. Since the main
protease (Mpro) is the key
protein in the virus's life cycle, Mpro is served as one of the critical targets of
antiviral treatment. We employed virtual screening tools to search for new inhibitors to accelerate the drug discovery process. The hit compounds were subsequently docked into the active site of
SARS-CoV-2 main protease and ranked by their binding energy. Furthermore, in-silico ADME studies were performed to probe for adoption with the standard ranges. Finally, molecular dynamics simulations were applied to study the
protein-drug complex's fluctuation over time in an aqueous medium. This study indicates that the interaction energy of the top ten retrieved compounds with
COVID-19 main
protease is much higher than the interaction energy of some currently in use
protease drugs such as
ML188,
nelfinavir,
lopinavir,
ritonavir, and α-ketoamide. Among the discovered compounds, Pubchem44326934 showed druglike properties and was further analyzed by MD and MM/
PBSA approaches. Besides, the constant binding free energy over MD trajectories suggests a probable drug possessing
antiviral properties. MD simulations demonstrate that GLU166 and GLN189 are the most important residues of Mpro, which interact with inhibitors.