Exploring the potent inhibitor β-stigmasterol from Pittosporum dasycaulon Miq. leaves against snake venom phospholipase A2 protein through in vitro and molecular dynamics behavior approach

Abstract β-Stigmasterol, responsible for antivenom activity against abundant PLA2 protein of Viper (Daboia russelii) and Cobra (Naja naja) venom, was identified, characterized, and isolated from Pittosporum dasycaulon leaves extract. The compound purity was checked by RP-HPLC analysis, and structure was elucidated by FTIR and NMR analysis, followed by in-vitro as well as in-silico studies. The structural stability of the docked complexes was evaluated by molecular dynamic simulation, and the binding free energies were calculated by MM-PBSA analysis. The in-vitro analysis revealed that the isolated compound β-SS is effective against D. russelii PLA2 (IC50 40.903 ± 0.479 μg/mL) than N. naja venom PLA2 (42.340 ± 0.11 μg/mL). The in-silico approaches helps to conclude that the β-SS-PLA2 D. russelii complex showed a stable conformation with a reduced degree of flexibility throughout the dynamics simulation time period with high-affinity docking energy −10.60 kcal/mol than β-SS-PLA2 N. naja complex, which observed docking energy of −10.39 kcal/mol.