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针对 COVID-19 的药物再利用筛选的一年进展与困境。

Progress and pitfalls of a year of drug repurposing screens against COVID-19.

机构信息

Institute for Biomedical Sciences, Georgia State University, Atlanta, GA, United States.

Institute for Biomedical Sciences, Georgia State University, Atlanta, GA, United States.

出版信息

Curr Opin Virol. 2021 Aug;49:183-193. doi: 10.1016/j.coviro.2021.06.004. Epub 2021 Jun 19.

Abstract

Near the end of 2019, a new betacoronavirus started to efficiently transmit between humans, resulting in the current COVID-19 pandemic. Unprecedented worldwide efforts were made to identify and repurpose antiviral therapeutics from collections of approved drugs and known bioactive compounds. Typical pitfalls of this approach (promiscuous/cytotoxic compounds leading to false positives), combined with bypassing antiviral drug development parameters due to urgency have resulted in often disappointing outcomes. A flood of publications, press-releases, and media posts, created confusion in the general public and sometime mobilized precious resources for clinical trials with minimal prospect of success. Breakthroughs have been made, not in the laboratory but in the clinic, resulting from the empiric identification of mitigators of clinical signs such as the discovery of improved disease management through immunomodulators. This opinion piece will aim to capture some of the lessons that we believe the COVID-19 pandemic has taught about drug repurposing screens.

摘要

2019 年末,一种新型β冠状病毒开始在人与人之间高效传播,导致目前的 COVID-19 大流行。为了从已批准药物和已知生物活性化合物的收藏中识别和重新利用抗病毒治疗药物,全世界都做出了前所未有的努力。这种方法的典型陷阱(广谱/细胞毒性化合物导致假阳性),再加上由于紧急情况而绕过抗病毒药物开发参数,导致结果往往令人失望。大量的出版物、新闻稿和媒体帖子在普通公众中造成了混乱,有时还为临床试验调动了宝贵的资源,而这些临床试验成功的前景微乎其微。突破不是在实验室,而是在临床上取得的,这是通过经验性地确定临床症状的缓解剂(如通过免疫调节剂发现改善疾病管理)实现的。这篇观点文章旨在总结我们认为 COVID-19 大流行在药物再利用筛选方面所带来的一些经验教训。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/52ce/8214175/df9587aeae88/gr1_lrg.jpg

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