宿主导向的抗结核药物靶点研究进展

Research progress in host-directed anti-tuberculosis drug targets

结核病是一种严重的人兽共患传染病,全球每年增加约1000万新发结核病例。目前结核分枝杆菌各种耐药菌株的出现是结核病防控面临的重要挑战,因此迫切需要开发新的抗结核药物来治疗耐药结核病并缩短治疗时间,而药物作用靶点的发现是新抗结核药物开发的瓶颈。目前广泛报道的结核药物靶点,主要包括参与结核分枝杆菌组分生物合成、免疫代谢途径相关的新靶点等。另外,近年来靶向宿主免疫系统的宿主导向治疗(Host-Directed Therapies,HDT)成为研究热点,辅助宿主导向治疗可以通过影响肉芽肿形成、自噬效应、宿主免疫代谢和细胞内的杀伤机制调控肺部炎症,增强结核病治疗效果,缩短治疗时间。这些新靶点的发现为未来研发安全、有效的新型抗结核药物提供了新思路。

Tuberculosis is a serious zoonotic disease causing approximately 10 million new cases worldwide every year.The emergence of various drug-resistant strains of Mycobacterium tuberculosis is currently an important challenge intuberculosisprevention and control,and an urgent need exists to develop new anti-tuberculosis drugs to treat drug-resistant tuberculosis and shorten the treatment time.The discovery of drug targets is a bottleneck inthe development of new anti-tuberculosis drugs.At present,the widely reported drug targets for tuberculosis include primarily new targets related to the biosynthesis of Mycobacterium tuberculosis components and immune metabolic pathways.In addition,host-directed therapiestargeting the host immune system have become a research hotspot in recent years.Adjuvant host-directed therapies can enhance the therapeutic effect of tuberculosis and shorten treatment times by affecting granuloma formation,autophagy,host immune metabolism and the intracellular killing mechanism,as well as regulating pulmonary inflammation.The discovery of these new targets provides new ideas for the future development of safe and effective new anti-tuberculosis drugs.