Computational Study on Inhibitory Potential of Natural Compounds against SARS-CoV-۲ Main Protease

Small molecules from natural origin, particularly compounds extracted from honeybee pollen, possess good biological potential. Bear this in mind; this study utilized a molecular docking protocol to explore the antiviral potential of ۱۰۰ natural compounds extracted from honeybee pollen, from various botanical origins from throughout the world, targeting the SARS-CoV-۲ main protease (Mpro). The docking analysis identified six natural compounds-Luteolin-۷-glucuronide, Narigenin, Genistin, Selagin, ۱-p-tolyl-anthraquinon, and Resveratrol-with the strongest binding energies to the viral protease. Subsequent investigations delved into the pharmacokinetic characteristics of these compounds. Notably, all six natural compounds were found to bind to the catalytic pocket through hydrogen bonding and hydrophobic interactions with the Cys-His catalytic dyad (Cys۱۴۵ and His۴۱). These interactions could impede substrate binding in the catalytic pocket, disrupting the catalytic function of the viral receptor by blocking the nucleophilic attack of Cys۱۴۵ on the substrate. Furthermore, pharmacokinetic assessments indicated that two natural compounds, Narigenin and Selagin, exhibited excellent pharmacological properties, demonstrated low to moderate toxicity, and were capable of crossing the blood-brain barrier- a crucial factor for accessing the viral protease. In light of these findings, it can be inferred that Narigenin and Selagin may possess high potential for inhibiting the enzymatic activities of the SARS-CoV-۲ Mpro. Consequently, further studies are warranted to validate their antiviral efficacy.