Navigating tuberculosis drug discovery with target-based screening

Area of Science:

• Microbiology
• Drug Discovery
• Genomics

Background:

• Mycobacterium tuberculosis is a leading bacterial pathogen causing significant mortality.
• There is a critical need for novel drugs to treat drug-resistant and latent tuberculosis and to shorten treatment durations.
• Genomic insights into M. tuberculosis have enabled detailed mapping of pathogen traits for targeted therapeutic development.

Purpose of the Study:

• To review the discovery of current and candidate tuberculosis drugs.
• To outline recent advancements in selecting molecular targets for novel anti-mycobacterial agents.
• To assess screening techniques integrating target knowledge and explore future methodologies.

Main Methods:

• Review of current clinical and candidate tuberculosis drug discovery.
• Examination of molecular target selection for anti-mycobacterial agents.
• Appraisal of screening techniques including in silico, in vitro enzyme-based, differential antisense sensitivity, and gene expression systems.

Main Results:

• Targeted screening methods have identified several M. tuberculosis inhibitors in preclinical development.
• Traditional random screening has historically yielded current tuberculosis drugs and will likely remain important.
• Advancements in targeted screening technologies are poised to increase their adoption.

Conclusions:

• A combined approach of targeted and random screening is anticipated for tuberculosis drug discovery.
• Targeted screening is increasingly contributing to the development pipeline for new tuberculosis therapies.
• Continued innovation in targeted screening promises to enhance the discovery of novel anti-mycobacterial drugs.