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结核病:治疗与药物研发研究的过去、现在与未来

Tuberculosis: Past, present and future of the treatment and drug discovery research.

作者信息

Bendre Ameya D, Peters Peter J, Kumar Janesh

机构信息

Laboratory of Membrane Protein Biology, National Centre for Cell Science, NCCS Complex, S. P. Pune University, Maharashtra, Pune, 411007, India.

The Maastricht Multimodal Molecular Imaging Institute (M4I), Division of Nanoscopy, Maastricht University, Maastricht, the Netherlands.

出版信息

Curr Res Pharmacol Drug Discov. 2021 May 27;2:100037. doi: 10.1016/j.crphar.2021.100037. eCollection 2021.

Abstract

Tuberculosis (TB) is an infectious disease caused by the bacterium . Despite decades of research driving advancements in drug development and discovery against TB, it still leads among the causes of deaths due to infectious diseases. We are yet to develop an effective treatment course or a vaccine that could help us eradicate TB. Some key issues being prolonged treatment courses, inadequate drug intake, and the high dropout rate of patients during the treatment course. Hence, we require drugs that could accelerate the elimination of bacteria, shortening the treatment duration. It is high time we evaluate the probable lacunas in research holding us back in coming up with a treatment regime and/or a vaccine that would help control TB spread. Years of dedicated and focused research provide us with a lead molecule that goes through several tests, trials, and modifications to transform into a 'drug'. The transformation from lead molecule to 'drug' is governed by several factors determining its success or failure. In the present review, we have discussed drugs that are part of the currently approved treatment regimen, their limitations, vaccine candidates under trials, and current issues in research that need to be addressed. While we are waiting for the path-breaking treatment for TB, these factors should be considered during the ongoing quest for novel yet effective anti-tubercular. If these issues are addressed, we could hope to develop a more effective treatment that would cure multi/extremely drug-resistant TB and help us meet the WHO's targets for controlling the global TB pandemic within the prescribed timeline.

摘要

结核病(TB)是由细菌引起的一种传染病。尽管数十年来的研究推动了抗结核药物研发方面的进展,但它仍是传染病致死原因之首。我们尚未开发出能帮助根除结核病的有效治疗方案或疫苗。一些关键问题包括治疗疗程延长、药物摄入不足以及患者在治疗过程中的高辍学率。因此,我们需要能加速细菌清除、缩短治疗时长的药物。现在是时候评估研究中阻碍我们提出有助于控制结核病传播的治疗方案和/或疫苗的潜在缺陷了。多年专注的研究为我们提供了一种先导分子,该分子要经过多次测试、试验和改进才能转化为“药物”。从先导分子到“药物”的转化受多种决定其成败的因素支配。在本综述中,我们讨论了目前已批准治疗方案中的药物、它们的局限性、正在试验的候选疫苗以及研究中需要解决的当前问题。在等待结核病突破性治疗方法的同时,在持续探索新型且有效的抗结核药物的过程中应考虑这些因素。如果这些问题得到解决,我们有望开发出一种更有效的治疗方法,治愈多重/极度耐药结核病,并帮助我们在规定时间内实现世界卫生组织控制全球结核病疫情的目标。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aa7f/8663960/a2fc01790b36/ga1.jpg

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