<br>释放麻风分枝杆菌和溃疡分枝杆菌的机会,ACS Infectious Diseases

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释放麻风分枝杆菌和溃疡分枝杆菌的机会
ACS Infectious Diseases ( IF 4.0 ) Pub Date : 2024-01-31 , DOI: 10.1021/acsinfecdis.3c00371
Mousumi Shyam ₁ , Sumit Kumar ₂ , Vinayak Singh _{2,

3,

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Affiliation

近十年来，科学界一直在努力应对耐药结核病 (DR-TB) 和迅速增长的机会性非结核分枝杆菌 (NTM) 带来的新负担。其中，不动杆菌家族的两种被忽视的分枝杆菌，麻风分枝杆菌和溃疡分枝杆菌，分别是麻风病和布鲁里溃疡感染的病原体，属于被忽视的热带病（NTD）的范畴。不幸的是，近十年来，针对这些病原菌的药物发现工作乏善可陈，导致仅发现了少数几个有效药物，并且主要重新利用了抗结核候选药物，例如 Telacebec (Q203)、P218 和 TB47，用于当前的治疗干预措施。对候选药物识别的严重忽视可能会加剧未来几天分枝杆菌 NTD 迅速传播的严重后果。因此，本综述重点关注针对两种杆菌中选定的可成药靶点的药物发现工作的最新说明，包括已确定的伴随的挑战以及导致药物发现缓慢的原因。此外，还包括对全新可能性的简要讨论，这些可能性可能是减轻被忽视的分枝杆菌 NTD 负担并随后加速药物发现工作的替代解决方案。我们预计，这里讨论的最先进的策略可能会吸引科学界的主要关注，以引导和扩展发现针对这些 NTD 的下一代疗法的路线图。

"点击查看英文标题和摘要"

Unlocking Opportunities for Mycobacterium leprae and Mycobacterium ulcerans

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, Mycobacterium leprae and Mycobacterium ulcerans, 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.

更新日期：2024-01-31

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