Dietary stigmastane-type saponins as promising dual-target directed inhibitors of SARS-CoV-2 proteases: a structure-based screening

Abstract

with the highest binding tendency for the active sites of S-3CLpro and S-PLpro. In an optimized docking analysis, the FSS were further docked against four equilibrated conformers of the S-3CLpro and S-PLpro. Three stigmastane-type steroidal saponins (vernonioside A2, vernonioside A4 and vernonioside D2) were revealed as the lead compounds. These compounds interacted with the catalytic residues of both S-3CLpro and S-PLpro, thereby exhibiting dual inhibitory potential against these SARS-CoV-2 cysteine proteases. The binding free energy calculations further corroborated the static and optimized docking analysis. The complexed proteases with these promising phytochemicals were stable during a full atomistic MD simulation while the phytochemicals exhibited favourable physicochemical and ADMET properties, hence, recommended as promising inhibitors of SARS-CoV-2 cysteine proteases.