Protein targets in Mycobacterium tuberculosis and their inhibitors for therapeutic implications: A narrative review

Advancement in the area of anti-tubercular drug development has been full-fledged, yet, a very less number of drug molecules have reached phase II clinical trials, and therefore “End-TB” is still a global challenge. Inhibitors to specific metabolic pathways of Mycobacterium tuberculosis (Mtb) gain importance in strategizing anti-tuberculosis drug discovery. The lead compounds that target DNA replication, protein synthesis, cell wall biosynthesis, bacterial virulence and energy metabolism are emerging as potential chemotherapeutic options against Mtb growth and survival within the host. In recent times, the in silico approaches have become most promising tools in the identification of suitable inhibitors for specific protein targets of Mtb. An update in the fundamental understanding of these inhibitors and the mechanism of interaction may bring hope to future perspectives in novel drug development and delivery approaches. This review provides a collective impression of the small molecules with potential antimycobacterial activities and their target pathways in Mtb such as cell wall biosynthesis, DNA replication, transcription and translation, efflux pumps, antivirulence pathways and general metabolism. The mechanism of interaction of specific inhibitor with their respective protein targets has been discussed. The comprehensive knowledge of such an impactful area of research would essentially reflect in the discovery of novel drug molecules and effective delivery approaches. This narrative review encompasses the knowledge of emerging targets and promising chemical inhibitors that could potentially translate in to the anti-TB-drug discovery.