02285nas a2200265   4500000000100000008004100001260001200042653001800054653001700072653001500089653002700104653001900131653002000150653002100170653002700191653001200218653002600230653002900256100001200285700001200297700001200309245008100321520160300402022001402005       2024                            d  c01/202410a3M mechanisms10aBuruli ulcer10atratamento10aMycobacterium ulcerans10aPKS inhibitors10aantituberculars10aDrug repurposing10aefflux pump inhibitors10aleprosy10amycolactone analogues10amycolactone biosynthesis1 aShyam M1 aKumar S1 aSingh V00aUnlocking Opportunities for Mycobacterium leprae and Mycobacterium ulcerans.3 a<p>In the recent decade, scientific communities have toiled to tackle the emerging burden of drug-resistant tuberculosis (DR-TB) and rapidly growing opportunistic nontuberculous mycobacteria (NTM). Among these, two neglected mycobacteria species of the Acinetobacter family, and , are the etiological agents of leprosy and Buruli ulcer infections, respectively, and fall under the broad umbrella of neglected tropical diseases (NTDs). Unfortunately, lackluster drug discovery efforts have been made against these pathogenic bacteria in the recent decade, resulting in the discovery of only a few countable hits and majorly repurposing anti-TB drug candidates such as telacebec (Q203), P218, and TB47 for current therapeutic interventions. Major ignorance in drug candidate identification might aggravate the dramatic consequences of rapidly spreading mycobacterial NTDs in the coming days. Therefore, this Review focuses on an up-to-date account of drug discovery efforts targeting selected druggable targets from both bacilli, including the accompanying challenges that have been identified and are responsible for the slow drug discovery. Furthermore, a succinct discussion of the all-new possibilities that could be alternative solutions to mitigate the neglected mycobacterial NTD burden and subsequently accelerate the drug discovery effort is also included. We anticipate that the state-of-the-art strategies discussed here may attract major attention from the scientific community to navigate and expand the roadmap for the discovery of next-generation therapeutics against these NTDs.</p>
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