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.

In silico and in vitro screening of FDA-approved drugs for potential repurposing against tuberculosis

“…Several drugs, including, fluroquinolones, clofazimine, meropenem and clavulanate were primarily used for other clinical conditions and now repurposed successfully for treatment of drug resistant forms of TB (Palomino and Martin 2013;Maitra et al, 2015). In addition, several more drugs, to name a few, verapamil (Adams et al, 2011, Gupta et al, 2013and Adams et al, 2014, statins, (Skerry et al, 2014, Parihar et al, 2014and Lobato et al, 2014 and metformin (Singhal et al, 2014) have been reported to have potential use in the treatment of TB.…”

New agents for the treatment of drug-resistant Mycobacterium tuberculosis

“…Repurposing existing antibiotics such as β-lactams (faropenem, meropenem), oxazolidiones (linezolid), and fluoroquinolones (moxifloxacin) is another productive strategy to identify new MDR-TB treatment options [5, 132]. Linezolid is the prototypical example in terms of MDR-TB treatment [80].…”

Early diagnosis and effective treatment regimens are the keys to tackle antimicrobial resistance in tuberculosis (TB): A report from Euroscicon's international TB Summit 2016

“…[145][146][147] Dr Bhakta and his research group reported the common, over-the-counter non-steroidal anti-inflammatory drugs (NSAIDs), ibuprofen and carprofen to be antitubercular specific. 131,148,149 They were found to be active against drug resistant strains and stationary phase mycobacteria. The endogenous mechanism of action of these drugs is still under debate, however, transcriptomic analyses reveal that the drugs may have pleiotropic effects on the pathogen.…”