Impact of Target-Based Drug Design in Anti-bacterial Drug Discovery for the Treatment of Tuberculosis

Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis (Mtb) and is a major public health concern. According to the 2017 WHO report, global burden of TB infection was 10.4 million people causing the mortality rate of ~1.6 million. The rapid emergence of multidrug-resistant (MDR) and extensively drug-resistant (XDR) TB is of major concern in anti-TB drug discovery. There are different druggable targets and its pathways involved in the virulence, which include Mtb cell wall, replication and transcription, regulatory, protein synthesis, membrane transport, and energy production which need to be explored for efficient killing of the bacteria. The ability of the tubercle bacilli to remain within the host intracellular compartment is of other major concern in TB therapy. Thus, to tackle the TB drug resistance, potent inhibitors with novel mechanism of action of different Mtb druggable targets need to be discovered. Three-dimensional structure of different Mtb target was solved for structure-based drug design. The current chapter focuses on some of the key druggable targets in Mtb and also the recent advances in target-based drug designing in the area of anti-tubercular drug discovery.