Schor Stanford, Einav Shirit
Department of Medicine, Division of Infectious Diseases and Geographic Medicine, and Department of Microbiology and Immunology, School of Medicine, Stanford University , 300 Pasteur Drive, Lane Building Rm L127, Stanford, California 94305, United States.
ACS Infect Dis. 2018 Feb 9;4(2):88-92. doi: 10.1021/acsinfecdis.7b00268. Epub 2018 Jan 3.
There is a large, global unmet need for the development of countermeasures to combat intracellular pathogens. The development of novel antimicrobials is expensive and slow and typically focuses on selective inhibition of proteins encoded by a single pathogen, thereby providing a narrow spectrum of coverage. The repurposing of approved drugs targeting host functions required for microbial infections represents a promising alternative. This review summarizes progress and challenges in the repurposing of approved drugs as host-targeted broad-spectrum agents for the treatment of intracellular pathogens. These strategies include targeting both cellular factors required for infection by various viruses, intracellular bacteria, and/or protozoa as well as factors that modulate the host immune response to these microbial infections. The repurposed approach offers complementary means to develop therapeutics against existing and emerging intracellular microbial threats.
开发对抗细胞内病原体的对策存在巨大的全球未满足需求。新型抗菌药物的开发成本高昂且进展缓慢,通常侧重于选择性抑制单一病原体编码的蛋白质,因此覆盖范围狭窄。重新利用已批准的针对微生物感染所需宿主功能的药物是一种有前景的替代方法。本综述总结了将已批准药物重新用作靶向宿主的广谱药物以治疗细胞内病原体方面的进展和挑战。这些策略包括针对各种病毒、细胞内细菌和/或原生动物感染所需的细胞因子,以及调节宿主对这些微生物感染免疫反应的因子。重新利用药物的方法为开发针对现有和新出现的细胞内微生物威胁的治疗方法提供了补充手段。