Rutaretin1'-(6″-sinapoylglucoside): promising inhibitor of COVID 19 m catalytic dyad from the leaves of miq (Pittosporaceae).

SARS CoV2 is a novel strain of coronavirus, first reported in Wuhan of China, in 2019 and drugs specific to COVID-19 treatment are still lacking. The main protease (3CL) present in the new coronavirus strain is considered a potential drug target due to its role in viral replications. The plant Miq. is a medicinal plant reported to have prominent antimicrobial including antibacterial and antifungal activity. In this study, 12 natural compounds were selected on the basis of major peaks observed in the LC-HRMS analysis of aqueous leaves extract (AQLE). The pharmacological properties of the selected compounds against 3CLpro were investigated through studies along with the standard antiviral drugs Lopinavir and Nelfinavir. The molecular docking study was done using Autodock 4.2 tool and visualized using Pymol (1.7.4.5 Edu). The docking analysis revealed that three compounds showed a better binding affinity than the standard drug Lopinavir. To validate the docking interactions, behaviour and stability of protein- ligand complex, molecular dynamics (100 ns) simulations were performed with the four best-ranked bioactive compounds identified through molecular docking analysis namely; Leptinidine, Rutaretin1'-(6″-sinapoylglucoside), Kalambroside A, and 5,7-dimethoxy', 4'methylenedioxyflavanone. The stability of the docking conformation was studied in depth by calculating the binding free energy using MM-PBSA method. Our findings on molecular docking, MD simulations and binding energy calculations suggest that Rutaretin1'-(6''-sinapoylglucoside) could be a potential inhibitor of COVID-19 3CLpro. However, considering the current pandemic situation of COVID-19, further research is required to experimentally validate their potential medicinal use against COVID-19 3CLpro both in vitro and in vivo along with clinical practices. Communicated by Ramaswamy H. Sarma.