In-Silico Identification of MurX as a Novel Drug Target in Mycobacterium tuberculosis and Molecular Docking Analysis of Bergenin
TL;DR
Findings support MurX as a viable therapeutic target and Bergenin as a promising candidate for further anti-TB drug development, and lays the foundation for subsequent experimental validation and the design of novel therapeutics targeting resistant strains of Mtb.
Abstract
Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb), remains a leading global health concern, exacerbated by the rise of multidrug-resistant (MDR) strains that compromise current treatment regimens. This study employed an integrated in-silico approach to identify and validate novel drug targets involved in Mtb cell wall biosynthesis, a pathway critical for bacterial survival and absent in humans. Through comparative genomic analysis and protein–protein interaction (PPI) network construction, MurX, a key enzyme in peptidoglycan biosynthesis, was identified as an essential, nonhomologous drug target. The three-dimensional structure of MurX was modeled using homology-based methods and validated using ERRAT and Ramachandran plot analysis, confirming high structural integrity. A set of ten phytochemicals with reported anti-TB activity were subjected to molecular docking using Molegro Virtual Docker. Among them, Bergenin exhibited the strongest binding affinity to MurX, with favorable docking scores and hydrogen bonding interactions, indicating its potential as a lead compound. These findings support MurX as a viable therapeutic target and Bergenin as a promising candidate for further anti-TB drug development. This study lays the foundation for subsequent experimental validation and the design of novel therapeutics targeting resistant strains of Mtb.