Screening Balanites aegyptiaca for inhibitors against putative drug targets in Microsporum gypseum - Subtractive proteome, docking and simulation approach

Abstract

Microsporum gypseum is a keratinophilic fungi grouped under dermatophytes infecting skin, hair and nail portions in human and animals causing tinea corporis, tinea facei and tinea capitis. As both human and fungi are eukaryotes, the available drugs for treating dermatophytes produce some side effects due to drug interaction with human also. Apart from this, the gut microbiota has a very big role in the health of human which should not be affected by the drugs. Hence this study focused on finding a target which is unique and essential to M. gypseum and non-homologous to human and gut microbiota, non-homologous to human domain architecture, highly interacting with other proteins, sub-cellular localization of proteins and non-druggability analysis of the targets using subtractive proteomics approach which resulted with 3 novel drug targets from M. gypseum which were modeled using I-TASSER, refined by ModRefiner and validated by PROCHECK. Further these targets were docked with compounds identified through LC-MS of fractioned methanol extract of B. aegyptiaca fruit pulp using Glide module and the stability of the docked complex was analyzed by molecular dynamics simulation using Desmond module of Schrodinger. Cyanidin-3-O-rhamnoside had better interaction with all the targets and Taurocholic acid had better result with ECCP which suggests the multi-targeting potency of these two compounds against M. gypseum which has to be confirmed by in vitro and in vivo studies.

Keywords: Docking; Drug target; Gut microbiota; MD simulation; Microsporum gypseum; Protein network; Proteome.