Phytochemicals as potential inhibitors for COVID-19 revealed by molecular docking, molecular dynamic simulation and DFT studies

The COVID-19 pandemic outbreak demands the designing of potential drugs as there is no specific treatment available. Thanks to their safety and effectiveness, phytochemicals have been used to treat various diseases, including antiviral therapeutics. Molecular docking is a simple, quick, and effective way to screen a variety of molecules for structure-based drug design. Here, we investigate molecular docking experiments on compounds present in plant species, Cocculus hirsutus and Rhodiola rosea and show their potential for the treatment of COVID-19. Almost all the components showed higher binding affinity than the built-in ligand, and those with significantly higher binding affinity were explored further. Molecular mechanics-based generalized born surface area calculations were used to re-rank the top candidates, rhodionidin and cocsoline, and their stability in association with viral protease was confirmed. Density functional theory was used for detailed investigations of the geometries, and electrical properties of rhodionidin and cocsoline. Using the frontier molecular orbitals method, the charge transfer within the molecule was calculated. Chemical reactivity and intermolecular interactions were studied using molecular electrostatic potential maps. These in silico discoveries will simulate the identification of powerful COVID-19 inhibitors, and similar research is likely to make a significant contribution to antiviral drug discovery. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s11224-022-01982-4.