Structure-based docking, pharmacokinetic evaluation, and molecular dynamics-guided evaluation of traditional formulation against SARS-CoV-2 spike protein receptor bind domain and ACE2 receptor complex

There is an urgent need for reliable cure and preventive measures in this hour of the outbreak of SARS-CoV-2. Siddha- and Ayurvedic-based classical formulations have antiviral properties and great potential therapeutic choice in this pandemic situation. In the current study, in silico-based analysis for the binding potential of phytoconstituents from the classical formulations suggested by the Ministry of Ayush (Kabasura Kudineer, Shwas Kuthar Rasa with Kantakari and pippali churna, Talisadi churna) to the interface domain of the SARS-CoV-2 receptor-binding domain and angiotensin-converting enzyme 2 was performed. Maestro software from Schrodinger and tools like Glide Docking, induced fit docking, MM-GBSA, molecular dynamics (MD) simulation, and thermal MM-GBSA was used to analyze the binding of protein PDB ID:6VW1 and the selected 133 ligands in comparison with drug molecules like favipiravir and ribavirin. QikProp-based ADMET evaluation of all the phytoconstituents found them nontoxic and with drug-like properties. Selection of top ten ligands was made based on docking score for further MM-GBSA analysis. After performing IFD of top five molecules iso-chlorogenic acid, taxiphyllin, vasicine, catechin and caffeic acid, MD simulation and thermal MM-GBSA were done. Iso-chlorogenic acid had formed more stable interaction with key residue among all phytoconstituents. Computational-based study has highlighted the potential of the many constituents of traditional medicine to interact with the SARS-CoV-2 RBD and ACE2, which might stop the viral entry into the cell. However, in vivo experiments and clinical trials are necessary for supporting this claim. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s11696-021-01917-z.