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基于蛋白酶抑制剂的宿主导向疗法以控制结核与HIV合并感染。

Host-Directed Therapies Based on Protease Inhibitors to Control and HIV Coinfection.

作者信息

Mandal Manoj, Pires David, Azevedo-Pereira José Miguel, Anes Elsa

机构信息

Host-Pathogen Interactions Unit, Research Institute for Medicines, iMed.ULisboa, Faculty of Pharmacy, Universidade de Lisboa, Av. Prof. Gama Pinto, 1649-003 Lisboa, Portugal.

Center for Interdisciplinary Research in Health, Católica Medical School, Universidade Católica Portuguesa, Estrada Octávio Pato, 2635-631 Rio de Mouro, Portugal.

出版信息

Microorganisms. 2025 Apr 30;13(5):1040. doi: 10.3390/microorganisms13051040.

Abstract

Despite continuous and extensive global efforts in the fight against tuberculosis (TB), this infectious disease continues to exert a tremendous burden on public health concerns and deaths worldwide. TB, caused by the bacterial species , is highly frequent in people living with HIV. The continuing epidemics of both chronic infections and the emergence of antimicrobial resistance, as well as the lack of effective diagnostic tools and drug-drug interactions, pose major challenges in the fight against these pathogens. Developing a wide range of host-directed therapies may improve treatment outcomes, helping alleviate the morbidity and mortality associated with both infections. In this review, we discuss the identification and development of new host-directed strategies based on protease inhibitors and their clinical relevance as adjunctive treatment. In the context of therapeutic agents with novel mechanisms, selective protease inhibitors, including saquinavir (SQV) and cystatins (CstC and CstF), are valuable targets that may provide effective therapeutic solutions for controlling Mtb and HIV coinfection.

摘要

尽管全球在抗击结核病(TB)方面持续做出了广泛努力,但这种传染病仍然给全球公共卫生问题和死亡带来巨大负担。由结核分枝杆菌引起的结核病在艾滋病毒感染者中极为常见。慢性感染的持续流行、抗菌药物耐药性的出现,以及缺乏有效的诊断工具和药物相互作用,在对抗这些病原体的斗争中构成了重大挑战。开发多种宿主导向疗法可能会改善治疗效果,有助于减轻与这两种感染相关的发病率和死亡率。在本综述中,我们讨论基于蛋白酶抑制剂的新型宿主导向策略的识别与开发及其作为辅助治疗的临床相关性。在具有新机制的治疗药物背景下,包括沙奎那韦(SQV)和胱抑素(CstC和CstF)在内的选择性蛋白酶抑制剂是有价值的靶点,可能为控制结核分枝杆菌和艾滋病毒合并感染提供有效的治疗方案。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f6d7/12113826/5ae82f26ba64/microorganisms-13-01040-g001.jpg

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