ABSTRACT
The challenges posed by COVID-19's emergence have led to a search for its therapies. There is no cure for COVID-19 infection yet, but there is significant progress in vaccine formulation for prophylaxis and drug development (such as Paxlovid) for high-risk patients. As a contribution to the ongoing quest for solutions, this study shows potent phytocompounds identification as inhibitors of SARS-CoV-2 targets using in silico methods. We used virtual screening, molecular docking, and molecular dynamics (MD) simulations to investigate the interaction of some phytochemicals with 3CLpro, ACE2, and PLpro proteins crucial to the SARS-CoV-2 viral cycle. The predicted docking scores range from -5.5 to -9.4 kcal/mol, denoting appreciable binding of these compounds to the SARS-CoV-2 proteins and presenting a multitarget inhibition for COVID-19. Some phytocompounds interact favorably at non-active sites of the enzymes. For instance, MD simulation shows that an identified site on PLpro is stable and likely an allosteric region for inhibitor binding and modulation. These phytocompounds could be developed into effective therapy against COVID-19 and probed as potential multitarget-directed ligands and drug candidates against the SARS-CoV-2 virus. The study unveils drug repurposing, selectivity, allosteric site targeting, and multitarget-directed ligand in one piece. These concepts are three distinct approaches in the drug design and discovery pipeline.