Tetrandrine, an Effective Inhibitor of COVID-19 Main Protease (Mpro); Insights from Molecular Docking and Dynamics Simulations

Background: Natural products emerged as potential lead molecules in the drug discovery paradigm. During COVID-19 pandemic, researchers explored several natural agents with antiviral activity. The objective of the present study is to predict inhibitors of important COVID-19 targets from a set of potential candidates belonging to natural origin using molecular docking and dynamic simulation. Materials and Methods: Important target, main protease (Mpro) (PDB ID: 6M03) was selected for this purpose. Twenty natural agents were selected for molecular docking (Auto Dock vina 4.2). Molecular dynamic studies were performed using GROMACS. Results and Discussion: Among the selected natural products, tetrandrine, an isoquinoline alkaloid (-8.9 kcal/mol), and etoposide, a podophyllotoxin (-8.4kcal/mol) showed excellent binding affinity compared to remdesivir (-7.1kcal/mol) with Mpro. Further, the stability of the complex formed between Mpro and tetrandrine was confirmed in molecular dynamic studies at 100ns. Conclusion: The present in silico investigation could lead to the development of tetrandrine as a potent COVID-19 inhibitor