Screening approaches and therapeutic targets: The two driving wheels of tuberculosis drug discovery

[Display omitted] Tuberculosis (TB) is an infectious disease, infecting a quarter of world’s population. Drug resistant TB further exacerbates the grim scenario of the drying TB drug discovery pipeline. The limited arsenal to fight TB presses the need for thorough efforts for identifying promising hits to combat the disease. The review highlights the efforts in the field of tuberculosis drug discovery, with an emphasis on massive drug screening campaigns for identifying novel hits against Mtb in both industry and academia. As an intracellular pathogen, mycobacteria reside in a complicated intracellular environment with multiple factors at play. Here, we outline various strategies employed in an effort to mimic the intracellular milieu for bringing the screening models closer to the actual settings. The review also focuses on the novel targets and pathways that could aid in target-based drug discovery in TB. The recent high throughput screening efforts resulting in the identification of potent hits against Mtb has been summarized in this article. There is a pressing need for effective screening strategies and approaches employing innovative tools and recent technologies; including nanotechnology, gene-editing tools such as CRISPR–cas system, host-directed bacterial killing and high content screening to augment the TB drug discovery pipeline with safer and shorter drug regimens.