Repurposing Anthocyanins into Potential Inhibitors of the SARS-CoV-2 Main Protease (Mpro): an In Silico Approach

Drug repurposing for SARS-CoV-2 has been actively probed since the onset of the global pandemic. Drugs and other compounds with antiviral activities are investigated for their probable role in suppressing the pathogenesis of the novel coronavirus. Phytochemicals like anthocyanins are natural and powerful antioxidants reported to exhibit antiviral activities. This study investigated the repurposing of anthocyanins as potential blockers of the SARS-CoV-2 main protease (M-Pro) via in silica techniques. The monoglycoside derivatives of the six most common anthocyanidins were evaluated for their docking affinities to M-pro in Autodock Vina. The pharmacophore profile of the best ligand was inspected using PhannaGist. CABS-flex was employed for the molecular dynamics simulation (MDS) of the native and ligand-bound complex. The druglikeness and toxicity properties of the anthocyanins were systematically evaluated using the ADMETlab platform. Petunidin 3-O-glucoside (PTG) afforded the best binding affinity to M-pro (-8.6 kcal/mol) compared to the protease inhibitor drug lopinavir (-8.3 kcal/mol). Chrysanthemin, peonidin 3-O-glucoside, and oenin afforded equal affinities (-8.5 kcal/mol) while callistephin and myrtillin produced the lowest scores in the group (-8.3 kcal/mol). MDS showed minimal PIG-induced conformational changes in the protein with RMSF confirming stability. PTG also revealed promising druglikeness characteristics. This study suggests that PIG may be an inhibitor of Mpro and can potentially be an antiviral candidate for SARS-CoV-2.