Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is a pandemic cause of Corona Virus Disease (COVID-19), that has claimed numerous human lives across the globe. Main protease being the active protein of SARS-CoV-2 requires urgent mitigating effect against the spread of the virus. The therapeutic roles of the active compounds present in ten typical African medicinal plants were investigated in this study. Five active compounds Curcuma longa (Curcumin and Bisdethoxy curcumin), Garcinia kola (kolaviron), Zingiber officinale (Gingerol) and Vernonia amygdalina (Artemisinin) were selected and docked against Main protease through receptor grid generation, protein ligand docking, receptor ligand complex pharmacophore and binding free energy. The results obtained revealed Curcumin had the highest binding score of −8.628 kcal/mol while artermisinin presented the least with −4.123 kcal/mol. The outcome of the pharmacokinetic prediction in this study revealed high transport capacity across the gastrointestinal tract and high blood brain barrier permeability for curcumin, bisdemethoxy curcumin, gingerol and artemisinin. The exemption is gingerol with low LD50 value (250 mg/kg), the LD50 of all active compounds ranged from 2000 to 4228 mg/kg. Adsorption, distribution, metabolism, excretion and toxicity (ADMET) properties exhibited by all compounds portrayed them as non-hepatotoxic, non-cytotoxic, non-mutagenic and non-carcinogenic. The active compounds exhibited drug-likeness features against Main protease of Covid-19.
