Abstract
This study utilized a comprehensive computational approach to identify multi-targeted drug molecules against prominent SARS-CoV-2 druggable proteins. This is considered imperative as the damaging effects of the virus still lingers as a global threat and because of the increasing awareness of the enhanced therapeutic efficacy of multi-target drug. Thus, we investigated and identified novel therapeutic interventions for SARS-CoV-2 from an array of previously reported natural antiviral compounds. The systematic virtual screening was achieved by predicting the interaction potential of the selected natural lead molecules with important SARS-CoV-2 target proteins and comparing their binding energies with that of currently approved COVID-19 drugs, some of which are also the target proteins' co-crystallized ligands. Out of the 22 selected compounds, Acteoside (Act) was identified as the most promising, as it exhibited remarkable molecular interactions with docking scores of - 11.68, - 9.81, - 8.64, - 10.38, - 11.75 and - 6.68 kcal/mol with SARS-CoV-2 Mpro, TMPRSS2, Cath L, RdRp, Sgp, and hACE2, respectively. The one-compound-multi-target prospect of Act was also demonstrated by its strong hydrogen bonding interactions with the active sites residues of the proteins. Furthermore, the stability of Act in the protein binding pockets were demonstrated by the binding free energies of - 76.7491, - 53.3057, - 54.4685, and - 45.7573 kcal/mol recorded for the 7BQY-Act, 7MEQ- Act, 5MQY-Act, 7BV2-Act complexes respectively; all which competed more favourably than the co-crystallized ligands during the 200 ns simulation. All our findings suggest Act as a potent multi-target anti-SARS-CoV-2 agent that can serve as the lead for the development of effective therapeutics against the virus.