Molecular Docking and Dynamics Simulations Study of Selected Phytoconstituents of "Pangi" (Pangium edule Reinw) Leaf as Anti-SARS-CoV-2.

Herbal plants are often used as alternative medicine because they contain active compounds for the treatment of diseases and disorders with minimal side effects, and are easily obtained from the surrounding environment. Some of them have antiviral activity. This study aimed to analyze the potential of phytochemical compounds in the leaf of "pangi" (Pangium edule Reinw) as anti- SARS-CoV-2 using molecular docking study. The drug- and lead-likeness properties of the selected compounds were obtained from the Swiss ADME and admetSAR online server tools. Molecular dynamics (MD) simulation of the selected ligand was carried out to validate the stability of the interaction. The results suggested that pangi leaves contain three compounds with remarkable binding affinities with Mpro (main protease) and RBD (receptor binding domain) were (5.beta.) pregnane-3,20.beta.-diol, 14.alpha.,18.alpha.-[4-methyl-3-oxo-(1-oxa-4-azabutane-1,4-diyl)]-, diacetate (PD), ethyl cholate (EC), and bis(3,5,5-trimethylhexyl) phthalate. Because EC will be metabolized in the body into cholic acid (Cho), this compound was then docked and validated using MD simulation. The compound has the best free binding energy (ΔG) with SARS-CoV-2 (-7.1 kcal/ mol with Mpro and -6.0 kcal/mol with RBD). Moreover, the compound is bound strongly to the active cavity of Mpro on Thr24, Thr26, His41, and Cys145 residues. The MM-GBSA calculation showed that the interaction of Cho with Mpro was higher than with RBD. According to the RMSD (root mean square deviation), RMSF (root mean square fluctuation), the radius of gyration (Rg), and intermolecular hydrogen bond (H-bond) analysis obtained from 50 ns MD simulations, Cho formed stable interactions with Mpro and RBD. The finding of this study indicated that Cho showed good anti-SARS-CoV-2 activity. The potential of the compound to inhibit the virus can serve as a starting point in the process of developing COVID-19 therapeutic natural medicine. [ABSTRACT FROM AUTHOR]