title: Repurposing-a ray of hope in tackling extensively drug resistance in tuberculosis.
abstract: Tuberculosis (TB) remains a serious concern more than two decades on from when the World Health Organization declared it a global health emergency. The alarming rise of antibiotic resistance in Mycobacterium tuberculosis, the etiological agent of TB, has made it exceedingly difficult to control the disease with the existing portfolio of anti-TB chemotherapy. The development of effective drugs with novel mechanism(s) of action is thus of paramount importance to tackle drug resistance. The development of novel chemical entities requires more than 10 years of research, requiring high-risk investment to become commercially available. Repurposing pre-existing drugs offers a solution to circumvent this mammoth investment in time and funds. In this context, several drugs with known safety and toxicity profiles have been evaluated against the TB pathogen and found to be efficacious against its different physiological states. As the endogenous targets of these drugs in the TB bacillus are most likely to be novel, there is minimal chance of cross-resistance with front-line anti-TB drugs. Also, reports that some of these drugs may potentially have multiple targets means that the possibility of the development of resistance against them is minimal. Thus repurposing existing molecules offers immense promise to tackle extensively drug-resistant TB infections.
authors: Mycobacteria Research Laboratory, Institute of Structural and Molecular Biology, Department of Biological Sciences, Birkbeck, University of London, London, UK.
authors: Arundhati
authors: A
authors: Maitra
authors: Mycobacteria Research Laboratory, Institute of Structural and Molecular Biology, Department of Biological Sciences, Birkbeck, University of London, London, UK.
authors: Sadé
authors: S
authors: Bates
authors: Mycobacteria Research Laboratory, Institute of Structural and Molecular Biology, Department of Biological Sciences, Birkbeck, University of London, London, UK.
authors: Trupti
authors: T
authors: Kolvekar
authors: Department of Pharmaceutical Sciences and Technology, Institute of Chemical Technology, N. P. Marg, Matunga, Mumbai, India.
authors: Padma V
authors: PV
authors: Devarajan
authors: Departamento de Química y Biología, División de Ciencias Básicas, Universidad del Norte, Barranquilla, Colombia.
authors: Juan D
authors: JD
authors: Guzman
authors: Mycobacteria Research Laboratory, Institute of Structural and Molecular Biology, Department of Biological Sciences, Birkbeck, University of London, London, UK. Electronic address: s.bhakta@bbk.ac.uk.
authors: Sanjib
authors: S
authors: Bhakta
mesh_terms: D000995:Antitubercular Agents / Q000627:therapeutic use*; D058492:Drug Repositioning; D054908:Extensively Drug-Resistant Tuberculosis / Q000188:drug therapy*; D006801:Humans; D009169:Mycobacterium tuberculosis / Q000187:drug effects
chemical_list: D000995:Antitubercular Agents
keywords: Antibiotic resistance; Mycobacterium tuberculosis; Repositioning; Repurposing; Tuberculosis (TB); Whole-cell phenotypic screening