Prediction of SARS-CoV-2 main protease inhibitors in medicinal plant-derived compounds by molecular docking approach

Coronaviruses are endemic in humans and infections typically mild, such as the common cold. Still, the cross-species transmission has produced some unusually virulent strains which now causing viral pneumonia, in severe cases, even acute respiratory distress syndrome and death. SARS-CoV-2 is the most threatening issue which leads the world to an uncertainty alongside thousands of regular death scenes. An effective vaccine to cure this virus is not yet available, so it requires concerted efforts at various scales. The viral Main Protease controls coronavirus replication and is a proven drug discovery target for SARS-CoV-2. Comprehensive computational study e.g., molecular docking and ADMET (absorption, distribution, metabolism and excretion) profiling were employed to predict the efficacy of medicinal plant-based bioactive compounds against SARS-CoV-2 MPP. Paritaprevir and lopinavir-previously approved viral main protease inhibitors were used as standards for comparison. MPP was docked with 90 phytochemical compounds, and the screening revealed that four compounds (azadirachtin, -12.5 kcal/mol; rutin, -9 kcal/mol; theaflavin, -9 kcal/mol; astragalin, -8.8 kcal/mol) showed the highest binding affinity than the controls paritaprevir and lopinavir (-8.7 and -7.9 kcal/mol, respectively). Comparative structural analysis of protein-inhibitor complexes revealed that the compounds have intense interaction with the vital catalytic residue His-41 and Cys-145. Furthermore, the pharmaco-kinetics and drug-likeness properties of the antiviral phytochemicals suggested that the compounds do not have any considerable detrimental effects and can be considered potential drug candidates against SARS-CoV-2. These compounds can be further explored for in vitro experimental validation against SARS-CoV-2.