Identification of Lead Moiety to Treat Polycystic Ovarian Syndrome from Ganoderma lucidum: A Computational Approach

Polycystic ovarian syndrome (PCOS) is characterized by gynecological, endocrine, and metabolic abnormalities in women of reproductive ages. Symptoms include hypergonadotropism, amenorrhea, oligomenorrhea, multiple cysts in ovaries, hirsutism, obesity, and commonly associated with infertility. Presently the standard treatment for PCOS includes lifestyle modifications, pharmacological treatments, and surgical procedures. However, these treatments are not promising for the complete elimination of PCOS. Therefore, natural sources have been a highly valued source of medicine and help improve and manage PCOS conditions. Ganoderma lucidum (G.lucidum) is an oriental fungus possessing a wide range of medicinal properties. Ganoderic acids (GAs) have been reported to show antioxidant, anti-cancer, anti-diabetic, anti-inflammatory, anti-hyperlipidemic, immunomodulatory, and antiandrogenic effects. Molecular docking studies for 22 GAs and clomiphene with human androgen receptor (PDB ID: 1E3G) were carried out using AutoDock Vina and PyRx 0.8 tool. ADMET analysis was carried out for the top 5GAs using pkCSM to predict small molecule pharmacokinetic and toxicity properties. The stability of protein-ligand complex GAA-1E3G was analyzed using DESMOND. The binding affinity of Ganoderma triterpenes with 1E3G ranged from -6.9 to -8.7 kcal mol-1. Ganoderic acid A showed a maximum affinity with a score of -8.7, unlike standard drugs with a score of -6. The in silico predicted pharmacokinetic properties of the top 5 ganoderic acids were better when compared to standard drugs with minimum toxicity. The stability of GAA at 1E3G binding pockets was validated using molecular dynamics. Hence, GAA can be further evaluated for the successful treatment of PCOS.