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结核病药物研发:新兴耐药性出现后的进展和未来干预措施。

Tuberculosis drug discovery: Progression and future interventions in the wake of emerging resistance.

机构信息

Infectious Diseases Division, CSIR- Indian Institute of Integrative Medicine, Jammu, 180001, India; Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, 201002, India.

Infectious Diseases Division, CSIR- Indian Institute of Integrative Medicine, Jammu, 180001, India; Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, 201002, India.

出版信息

Eur J Med Chem. 2022 Feb 5;229:114066. doi: 10.1016/j.ejmech.2021.114066. Epub 2021 Dec 26.

Abstract

The emergence of drug resistance continues to afflict TB control where drug resistant strains have become a global health concern. Contrary to drug-sensitive TB, the treatment of MDR/XDR-TB is more complicated requiring the administration of second-line drugs that are inefficient than the first line drugs and are associated with greater side effects. The emergence of drug resistant Mtb strains had coincided with an innovation void in the field of drug discovery of anti-mycobacterials. However, the approval of bedaquiline and delamanid recently for use in MDR/XDR-TB has given an impetus to the TB drug discovery. The review discusses the drug discovery efforts in the field of tuberculosis with a focus on the strategies adopted and challenges confronted by TB research community. Here, we discuss the diverse clinical candidates in the current TB drug discovery pipeline. There is an urgent need to combat the current TB menace through multidisciplinary approaches and strategies making use of the recent advances in understanding the molecular biology and pathogenesis of Mtb. The review highlights the recent advances in drug discovery, with the host directed therapeutics and nanoparticles-drug delivery coming up as important tools to fight tuberculosis in the future.

摘要

耐药性的出现继续困扰着结核病控制,耐药菌株已成为全球关注的健康问题。与敏感型结核病不同,耐多药/广泛耐药结核病的治疗更为复杂,需要使用二线药物,这些药物的效果不如一线药物,而且副作用更大。耐药性结核分枝杆菌菌株的出现恰逢抗分枝杆菌药物发现领域的创新空白。然而,最近批准贝达喹啉和德拉马尼用于耐多药/广泛耐药结核病的治疗,为结核病药物发现带来了动力。本文综述了结核病药物发现领域的努力,重点讨论了结核病研究界所采用的策略和面临的挑战。在这里,我们讨论了当前结核病药物发现管道中的多种临床候选药物。迫切需要通过多学科方法和策略来对抗当前的结核病威胁,利用对结核分枝杆菌分子生物学和发病机制的最新认识。本文综述了药物发现的最新进展,宿主导向治疗和纳米颗粒-药物输送成为未来治疗结核病的重要工具。

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