Computational Assessment of the Chemical Components of Swertia chirayita Roxb. ex Fleming Targeting NSP13 of SARS-CoV-2

Due to the effectiveness and relatively lower toxicity at high dose levels, natural products have been practiced in different medicine systems since ancient times. It plays a vital role in prophylactics and therapeutics of many maladies and has been an accessible and affordable choice to modern medicines. For a possible treatment option for the current pandemic caused by SARS-CoV-2, various chemical components of Swertia chirayita Roxb. ex Fleming plant were explored by computational methods. The phytochemicals present in the plant, amaroswerin, amarogentin, mangiferin, oleanolic acid, syringaresinol, swertiamarin, and sweroside were proposed as the top candidates with probable inhibition capabilities determined in terms of docking scores/binding affinities against non-structural protein 13 (PDB ID: 5RMM) calculated from flexible receptor molecular docking. The values calculated were −17.2, −15.7, −14.9, −13.0, −13.6, −13.0, and −13.3 kcal/mol, respectively and were better than those calculated for some FDA approved drugs and a native ligand which showed values from −12.9 to −8.9 kcal/mol. From the 200 ns long molecular dynamics simulations of different protein-ligand adducts, it was found that oleanolic acid RMSD was less than 5 Å and snapshots at multiple instances displayed that it nearly retained the docked position with moderately smooth nature of the curve. These geometrical results implied acceptable structural stability of the protein-ligand adduct. The binding free energy change of protein-oleanolic acid complex (−32.72±4.65 kcal/mol) was the best among the test cases. This thermodynamic parameter hinted at the spontaneous nature of the reaction and its frame-by-frame analysis complemented the geometrical results. The ADMET prediction revealed lipophilic nature and some toxicity end-points of the hit molecule, oleanolic acid. The results point towards the need for further extensive characterization of oleanolic acid by in vitro and in vivo methods in the development of anti COVID-19 drug from readily available plant with ethnobotanical values.