Saul Sirle, Einav Shirit
Department of Medicine, Division of Infectious Diseases and Geographic Medicine, and Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford University, 300 Pasteur Drive, Lane Building, Rm L127, Stanford, California 94305, United States.
ACS Infect Dis. 2020 Sep 11;6(9):2304-2318. doi: 10.1021/acsinfecdis.0c00343. Epub 2020 Aug 10.
There is a large global unmet need for effective countermeasures to combat severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19). The development of novel antiviral drugs is expensive and too slow to meet the immediate need. The repurposing of drugs that are approved or are under advanced clinical investigation provides a cost- and time-effective therapeutic solution. This review summarizes the major repurposed approaches that have been proposed or are already being studied in clinical trials for COVID-19. Among these approaches are drugs that aim to reduce SARS-CoV-2 replication by targeting either viral enzymatic functions or cellular factors required for the viral life cycle. Drugs that modulate the host immune response to SARS-CoV-2 infection by boosting it to enhance viral clearance or by suppressing it to prevent excessive inflammation and tissue injury represent another category. Lastly, we discuss means to discover repurposed drugs and the ongoing challenges associated with the off-label use of existing drugs in the context of the COVID-19 outbreak.
对于抗击2019冠状病毒病(COVID-19)的病原体——严重急性呼吸综合征冠状病毒2(SARS-CoV-2),全球存在着对有效应对措施的巨大未满足需求。新型抗病毒药物的研发成本高昂且速度过慢,无法满足当下的需求。对已获批或正在进行晚期临床研究的药物进行重新利用,提供了一种具有成本效益和时间效益的治疗解决方案。本综述总结了已被提出或正在针对COVID-19进行临床试验研究的主要重新利用方法。在这些方法中,有些药物旨在通过靶向病毒酶功能或病毒生命周期所需的细胞因子来减少SARS-CoV-2的复制。另一类药物则是通过增强宿主对SARS-CoV-2感染的免疫反应以提高病毒清除率,或通过抑制免疫反应来防止过度炎症和组织损伤。最后,我们讨论了发现重新利用药物的方法以及在COVID-19疫情背景下与现有药物的标签外使用相关的持续挑战。