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Halting Tuberculosis in Its Tracks: Advances and Strategies for Discovering Therapeutic Targets in Mycobacterium
Ayushi Sharma1,2, Gyanendra Singh3, Rahul Shrivastava1
1Department of Biotechnology and Bioinformatics, Jaypee University of Information Technology, Waknaghat, Solan, Himachal Pradesh, India.
Abstract:
Tuberculosis is a global emergency. Despite two decades of intense research to understand and cure the disease, biological uncertainties prevail and hamper the therapeutic progress. Increasing incidences of multidrug-resistant (MDR) and extensively drug resistant (XDR) Mycobacterium tuberculosis strains further complicate tuberculosis control. Modern research, therefore, focuses on development of new antitubercular drugs to treat drug-resistant tuberculosis and shorten the duration of the standard chemotherapy. Fortunately, the recent accelerated approval of delamanid and bedaquiline for use in MDR and XDR tuberculosis has reinvigorated antitubercular research. Although progresses in tuberculosis drug discovery are being made following the availability of M. tuberculosis genome and progressions in molecular biology, novel drug targets and leads are continuously required to strengthen the tuberculosis therapeutic pipeline. Discovery of new targets has eventually promoted tuberculosis therapy, and will keep paving the foundation for generating the future wave of tuberculosis drug leads. This review summarizes important M. tuberculosis drug targets such as F1/F0 ATP synthase, isocitrate lyase, β-ketoacyl-ACP synthases KasA and KasB, QcrB, and mycobactin biosynthesis enzymes MbtA and MbtI, and drugs under preclinical and clinical development stages that aim at making drug discovery breakthroughs. It also discusses the strategies that entail discovery of new mycobacterial therapeutic determinants and provide ideas for development of more efficient drugs. The article comprehensively provides a better understanding of M. tuberculosis drug targets, along with opening new ventures for tuberculosis control and treatment.
Insights
Tuberculosis drug discovery faces challenges from resistant strains. This review highlights key Mycobacterium tuberculosis targets and emerging drugs to combat drug-resistant tuberculosis and improve treatment outcomes.
Area of Science:
- Microbiology
- Drug Discovery
- Infectious Diseases
Background:
- Tuberculosis (TB) remains a global health emergency, complicated by rising multidrug-resistant (MDR) and extensively drug-resistant (XDR) Mycobacterium tuberculosis strains.
- Existing chemotherapy durations are long, and therapeutic progress is hampered by biological uncertainties, necessitating new drug development.
Purpose of the Study:
- To review critical Mycobacterium tuberculosis drug targets and novel antitubercular agents in preclinical and clinical development.
- To discuss strategies for discovering new therapeutic determinants and developing more effective TB drugs.
Main Methods:
- Literature review of current tuberculosis research, focusing on drug targets and development pipelines.
- Analysis of key M. tuberculosis targets including F1/F0 ATP synthase, isocitrate lyase, KasA, KasB, QcrB, MbtA, and MbtI.
- Examination of drugs in preclinical and clinical stages targeting these pathways.
Main Results:
- Identified essential M. tuberculosis drug targets crucial for bacterial survival and virulence.
- Highlighted several novel drug candidates and strategies aimed at overcoming drug resistance.
- Noted the recent approval of delamanid and bedaquiline, signaling renewed progress in TB drug research.
Conclusions:
- Continued discovery of novel drug targets and leads is essential to strengthen the tuberculosis therapeutic pipeline.
- Understanding M. tuberculosis drug targets and development strategies is vital for advancing tuberculosis control and treatment.
- New drugs are needed to combat MDR and XDR tuberculosis and shorten treatment durations.
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