The Potential of Stilbene Compounds to Inhibit M pro Protease as a Natural Treatment Strategy for Coronavirus Disease-2019.

COVID-19 disease has had a global impact on human health with increased levels of morbidity and mortality. There is an unmet need to design and produce effective antivirals to treat COVID-19. This study aimed to explore the potential ability of natural stilbenes to inhibit the M pro protease, an acute respiratory syndrome coronavirus-2 (SARS-CoV-2) enzyme involved in viral replication. The binding affinities of stilbene compounds against M pro were scrutinized using molecular docking, prime molecular mechanics-generalized Born surface area (MM-GBSA) energy calculations, and molecular dynamic simulations. Seven stilbene molecules were docked with M pro and compared with GC376 and N3, antivirals with demonstrated efficacy against M pro . Ligand binding efficiencies and polar and non-polar interactions between stilbene compounds and M pro were analyzed. The binding affinities of astringin, isorhapontin, and piceatannol were -9.319, -8.166, and -6.291 kcal/mol, respectively, and higher than either GC376 or N3 at -6.976 and -6.345 kcal/mol, respectively. Prime MM-GBSA revealed that these stilbene compounds exhibited useful ligand efficacy and binding affinity to M pro . Molecular dynamic simulation studies of astringin, isorhapontin, and piceatannol showed their stability at 300 K throughout the simulation time. Collectively, these results suggest that stilbenes such as astringin, isorhapontin, and piceatannol could provide useful natural inhibitors of M pro and thereby act as novel treatments to limit SARS-CoV-2 replication.