Screening of bioactive compounds from selected mushroom species against putative drug targets in Mycobacterium tuberculosis: a multi-target approach

Abstract

Mycobacterium tuberculosis (Mtb) is a notorious pathogen that causes one of the highest mortalities globally. Due to a pressing demand to identify novel therapeutic alternatives, the present study aims to focus on screening the putative drug targets and prioritizing their role in antibacterial drug development. The most vital proteins involved in the Biotin biosynthesis pathway and the Lipoarabinomannan (LAM) pathway such as biotin synthase (bioB) and alpha-(1->6)-mannopyranosyltransferase A (mptA) respectively, along with other essential virulence proteins of Mtb were selected as drug targets. Among these, the ones without native structures were modelled and validated using standard bioinformatics tools. Further, the interactions were performed with naturally available lead molecules present in selected mushroom species such as Agaricus bisporus, Pleurotus djamor, Hypsizygus ulmarius. Through Gas Chromatography-Mass Spectrometry (GC-MS), 15 bioactive compounds from the methanolic extract of mushrooms were identified. Further, 4 were selected based on drug-likeness and pharmacokinetic screening for molecular docking analysis against our prioritized targets wherein Benz[e]azulene from Pleurotus djamor illustrated a good binding affinity with a LF rank score of −9.036 kcal mol −1 against nuoM (NADH quinone oxidoreductase subunit M) and could be used as a prospective candidate in order to combat Tuberculosis (TB). Furthermore, the stability of the complex are validated using MD Simulations and subsequently, the binding free energy was calculated using MM-GBSA analysis. Thus, the current in silico analysis suggests a promising role of compounds extracted from mushrooms in tackling the TB burden. Communicated by Ramaswamy H. Sarma