Bioactive metabolites of edible mushrooms efficacious against androgenic alopecia: Targeting SRD5A2 using computational approach

Abstract

IntroductionAndrogenic alopecia (AGA), scalp hair loss, occurs due to the hyperactivity of steroid 5α-reductase2 (SRD5A2), which metabolizes testosterone into 5α-dihydroxytestosterone. Finasteride, an FDA-approved drug producing many side effects, is a commonly used competitive inhibitor for SRD5A2 to treat AGA. As a number of mushroom species have been used to treat patients having hair loss problems since ancient times, in the present paper, the bioactive metabolites in mushrooms were computationally screened to assess SRD5A2 inhibitory properties and compared with Finasteride. MethodologyA virtual screening approach in conjunction with molecular dynamics simulation and MMPBSA methods has been applied to identify potential inhibitors against SRD5A2. SwissADME tool and AutoDock Vina were used to screen the library of 152 bioactive mushroom metabolites. All MD simulations were carried out using GROMACS 5.1.4 suite and GROMOS96 43a1 force field. The stability of SRD5A-ligand complexes was determined in terms of RMSD, RMSF, Rg, SASA, and hydrogen bonding. The binding energy of complexes was calculated using MMPBSA. Results and ConclusionVirtual screening and MD simulation studies revealed that out of the 152 metabolites, three bioactives, i.e., Zhankuic acid A (−11.5 kcal/mol), Sterenin M (−10.4 kcal/mol), Melleolide K (−10.2 kcal/mol), and drug Finasteride having the least binding energy are the potential inhibitors of SRD5A2. These molecules also exhibited stable interaction with SRD5A2 during MD simulation. This study will pave the way for the experimental evaluation and validation of the medicinal potentials of screened mushroom compounds to treat androgenic alopecia.