In-silico Investigation and ADMET Prediction of Potential Antifungal Phytochemicals against Lanosterol 14-Alpha Demethylase Inhibitors

Abstract

Mycosis is a chronic infectious disorder caused by various fungi affecting about 5% of the worldwide population. Pathogenesis involves the primary contact or inhalational roué for transmission. The infection is caused by to encoding of CYP450 enzyme Lanosterol 14-alpha demethylase. Numerous inhibitors are already used in clinical settings as therapeutic targets. A human lanosterol protein target (PDB ID: 6UEZ) and phytochemicals ligand library were used in a molecular docking simulation to perform docking simulation and ADMET studies on selected phytochemicals against human lanosterol protein receptor for drug discovery against lanosterol 14-alpha demethylase. The protein's crystal structure was retrieved and developed from the protein data repository with the aid of Biovia Discovery Studio. The phytochemicals' chemical structures were generated using Open Babel and VConf software after being downloaded from the NCBI PubChem database. PyRx was used to do molecular docking on Autodock Vina. SwissADME and pkCSM web servers were used to compute the best-performing compounds' ADMET characteristics. The findings demonstrated that taraxasterol exhibits a greater binding affinity. According to the findings, these compounds may be able to create anti-fungal activity, have decreased toxicity, and have easy absorbability at the tissue site, according to an ADME analysis. As a result, these substances can be examined in more in vitro research and could play a key role in developing a potential medicine to treat fungus infections.