IN SILICO EVALUATION OF ANTI-HYPERCHOLESTEROLEMIC POTENTIAL OF COMMIPHORA WIGHTII PHYTOCONSTITUENTS AGAINST PCSK9 USING MOLECULAR DOCKING

Sandeep Kumar*, Priyanshu Kumar

Hypercholesterolemia is a major risk factor for cardiovascular diseases and Pro Protein Convertase Subtilisin/Kexin Type 9(PCSK9) has emerged as an important therapeutic target due to its role in promoting low-density lipoprotein receptor (LDLR) degradation, leading to elevated plasma LDL cholesterol levels. The present study aimed to investigate the anti-hypercholesterolemic potential of selected phytoconstituents from Commiphora wightii through an in silico molecular docking approach targeting PCSK9. Nine bioactive compounds were subjected to high-throughput virtual screening using AutoDock Vina with optimized and validated grid parameters, followed by refined molecular docking of the top-performing compounds. Protein-ligand interaction were further analysed using BIOVIA Discovery Studio Visualizer to identify key binding residues within the active site. High-throughput virtual screening identified Z-Guggulsterone (-8.64kcal/mol), E-Guggulsterone (-8.45 kcal/mol) and Myrrhanol A (-8.12 kcal/mol) as the most promising phytoconstituents. Refined docking further improved their binding affinities to -8.82, -8.61 and -8.25 kcal/mol, respectively. These compounds established a stable interaction with critical PCSK9 residues, particularly Asp374 and Arg194, suggesting their potential to interfere with the PCSK9-LDLR interaction. Overall, the findings demonstrate that Commiphora wightii contains promising natural compounds with significant affinity towards PCSK9 and Highlight Z-Guggulsterone, E-Guggulsterone and Myrrhanol A as potential lead molecules for the development of novel anti-hypercholesterolemic agent. Further experimental and clinical investigations are warranted to validate their therapeutic potential.