Development of Potent SARS-CoV 3CL Protease Inhibitors: In silico Analogues Designing of Darunavir, Molecular Modelling and Molecular Dynamic Simulation

ABSTRACT

COVID pandemic initiated in early 2019 and the origin from where it initiated was Wuhan city of China. It changed the whole world. A huge population died due to COVID-19 in spite of taking precautions. New treatments and vaccines are introduced for the treatment and prevention. Among successful treatments, antivirals were found effective against COVID-19. But there is a need to find derivatives, which could be more effective for the treatment of COVID-19. The current research is focused on computational studies on one of the antiviral, darunavir. A computational strategy, molecular docking and molecular dynamic simulation techniques is presented to discover the potent analogues of darunavir for inhibiting protease 3CLpro of SARS-CoV2. The newly discovered X-ray structure (PDB ID 6LU7) was selected for docking study and generated analogues were docked. The docking results showed that the compounds were bound in the active site of receptor with good binding affinity. It was concluded that compounds D8 and D15 were have good binding affinity value of -9.85 and -8.95 kcal/mol, respectively and these compounds were selected for molecular dynamic simulation (MDS) study to check their stability in pocket of receptor. © 2022 Chemical Publishing Co.. All rights reserved.