Multitargeting: An Alternative Approach to Tackle Multidrug Resistance in Tuberculosis.

Area of Science:

• Microbiology and Infectious Diseases
• Drug Discovery and Development
• Computational Chemistry

Background:

• Rising global prevalence of drug-resistant organisms, particularly in tuberculosis (TB).
• Need for multitargeting therapeutic regimens against Mycobacterium tuberculosis (Mtb) due to co-morbidity and rapid resistance emergence.
• Limitations of current in silico approaches in developing effective multitargeting TB drugs.

Approach:

• Focus on underexplored exotic targets within crucial Mtb survival pathways.
• Investigation of promiscuous compounds from natural products and repurposed drugs for novel Mtb inhibition.
• Exploration of host-directed therapies as a complementary strategy for multidrug-resistant TB.

Key Points:

• Novel multitargeting compounds show promise but face challenges in clinical efficacy.
• Exploiting less-understood Mtb targets and drug promiscuity offers new therapeutic avenues.
• Host-directed therapies present a potentially fruitful addition to existing TB treatment regimens.

Conclusions:

• A holistic approach is outlined to address drawbacks in drug discovery for drug-resistant TB.
• Future therapeutic solutions for TB necessitate a focus on emerging trends in multitargeting strategies.
• Development of 'smart drugs' with improved safety/efficacy profiles is crucial for advancing TB therapeutics.