Molecular docking and molecular dynamic simulation-based phytoconstituents against SARS-CoV-2 with dual inhibition of the primary protease targets

Abstract

A novel coronavirus has caused major health problems and is spreading globally. The main protease enzyme plays a significant role in the number of copies of ss-RNA produced during the proteolytic cleavage of polypeptides. This work aims to find possible dual inhibitors of the 3-Chymotrypsin-like proteases PDB-6W63 and 6LU7 which increase efficiency and faster inhibition activity. By using an in-silico technique, polyphenols are molecularly docked against these targets to inhibit protease enzymes. Some polyphenols, such as pelargonidin and naringin, have significant dual inhibition characteristics with remarkable binding affinities with active scaffolds of both proteins, which have important ADMET parameters. These organic molecules are strongly bonded with amino acids of protein via mostly hydrogen bonding. These polyphenols also have outstanding docking scores and MMGBSA energies. The validity of the docking score was evaluated using a molecular dynamics simulation that assessed the stability of the complex. With the aid of computer-aided drug design, we hypothesise that the dual inhibition of compounds pelargonidin and naringin could effectively and potentially oppose SARS-CoV-2.