About this Research Topic
Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb), claims about 1.4 million lives annually and the global number of TB cases is continuously rising fuelled by poverty, the HIV/AIDS pandemic, the emergence of multidrug-resistant (MDR) and extremely drug-resistant (XDR) strains of Mtb. Additionally, the drug-drug interaction issue with antiretrovirals and antidiabetics is a growing concern. The expanding threat of drug-resistance has prompted urgent calls for new approaches to TB control, including the implementation of new modes of drug-susceptibility testing, use of alternative (shorter) therapeutic regimens aimed at expediting diagnosis and treatment, and most importantly to discover compounds (and regimens) with novel mechanisms of action (MOAs).
A lead compound for MDR-TB must satisfy at least three essential criteria: (i) it should possess an MOA distinct from existing anti-TB drugs; (ii) it should exhibit a pharmacological profile which suggests the capacity for good tissue penetration, with minimal liabilities in terms of host toxicity; and (iii) it should preferably act synergistically with – but at the very least should not antagonize – existing front- and second-line anti-TB agents. For TB drug discovery and development, each of these poses its own challenges from both a microbiological and a pharmacological perspective; however, it is critical these are addressed if new anti-TB drugs are to overcome the major obstacles to final approval for clinical use. While considerable progress has been made on establishing a TB drug pipeline, the high attrition rate in clinical development reinforces the need to continually replenish the pipeline with high-quality leads that act through inhibition of novel targets.
The Research Topic aims to address the current knowledge, research trends, and the future directions of TB drug discovery and development. We welcome the submission of Original Research, Review, Mini-Review, Perspective, and Brief Research Report articles that address one or more of the following themes:
1. Novel drug targets with proven potential
2. Old targets with a novel mechanism of actions
3. New chemical matter targeting novel drug targets, including the novel chemical scaffolds with a potential of targeting novel drug targets
4. New approaches covering the compound library screening, synergy/combination in both in vitro and in vivo systems; New in vitro or in vivo models;
5. Alternative approaches like host-directed therapy
6. Methods/Approaches/compounds/targets addressing drug resistance to existing anti-tubercular drugs
Keywords: Mycobacterium tuberculosis, Drug Discovery, mechanisms of action (MOAs)
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