Molecular Docking and In Vitro Evaluation of Selected Nigerian Medicinal Plant Compounds as Potential Inhibitors of SARS-CoV-2 Main Protease

The COVID-19 pandemic underscored the critical need for expanded antiviral drug discovery pipelines, including systematic evaluation of bioactive compounds from African medicinal plants. The SARS-CoV-2 main protease (Mpro) is a validated therapeutic target with no known human homolog, making it an ideal candidate for structure-based drug design. This study investigates the potential of ten Nigerian medicinal plant-derived compounds as Mpro inhibitors using molecular docking simulation and in vitro biochemical validation. Compounds selected included quercetin, luteolin, naringenin, cryptolepine, kolaviron, andrographolide, vitexin, nobiletin, oleanolic acid, and betulinic acid, chosen based on structural diversity and prior broad-spectrum antiviral literature. Molecular docking was performed using AutoDock Vina with the crystal structure of Mpro (PDB: 6LU7). The three highest-scoring compounds were evaluated in a fluorometric FRET-based Mpro enzyme inhibition assay. Quercetin and kolaviron exhibited the strongest binding affinities at -9.1 and -8.8 kcal/mol respectively, with binding interactions in the catalytic dyad region. In vitro Mpro inhibition IC50 values were 14.2 uM for quercetin and 21.7 uM for kolaviron. Cryptolepine showed moderate binding affinity but superior enzyme inhibition. These findings identify Nigerian phytochemical scaffolds as viable starting points for anti-SARS-CoV-2 drug development and recommend further cell-based antiviral evaluation. Keywords: SARS-CoV-2, Mpro inhibitor, molecular docking, kolaviron, Nigerian medicinal plants