In silico evaluation of Philippine Natural Products against SARS-CoV-2 Main Protease

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of COVID-19, is a novel strain of coronavirus first reported in December 2019 which rapidly spread throughout the world and was subsequently declared a pandemic by the World Health Organization (WHO) in March 2020. Although vaccines, as well as treatments, have been rapidly developed and deployed, these are still spread thin, especially in the developing world. There is also a continuing threat of the emergence of mutated variants which may not be as responsive to available vaccines and drugs. Accessible and affordable sources of antiviral drugs against SARS-CoV-2 offer wider options for the clinical treatment of populations at risk for severe COVID-19. Using in silico methods, this study identified potential inhibitors against the SARS-CoV-2 main protease (Mpro), the protease directly responsible for the activation of the viral replication enzyme, from a consolidated database of 1516 Philippine natural products. Molecular docking experiments, along with in silico ADME predictions, determined top ligands from this database with the highest potential inhibitory effects against Mpro. Molecular dynamic trajectories of the apo and diosmetin-7-O-b-D-glucopyranoside (DG) in complex with the protein predicted potential mechanisms of action for the ligand—by separating the Cys145–His41 catalytic dyad and by influencing the protein network through key intra-signaling residues within the Mpro binding site. These findings show the inhibitory potential of DG against the SARS-CoV-2 Mpro, and further validation is recommended through in vitro or in vivo experimentation. GRAPHICAL ABSTRACT: [Image: see text] SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s00894-022-05334-1.