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从新型冠状病毒 S 蛋白与 ACE2 的亲和力看药物筛选与开发。

Drug screening and development from the affinity of S protein of new coronavirus with ACE2.

机构信息

College of Basic Medical Science, Zhejiang Chinese Medical University, Hangzhou, 310058, China.

Department of gynecology, Heilongjiang University of Chinese Medicine, Harbin, 150040, China.

出版信息

Eur J Clin Microbiol Infect Dis. 2021 Apr;40(4):715-723. doi: 10.1007/s10096-020-04048-7. Epub 2020 Oct 9.

Abstract

Recently, various studies have shown that angiotensin-converting enzyme 2 (ACE2) acts as the "doorknob" that can be bound by the spike protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which conduces to its entrance to the host cells, and plays an important role in corona virus disease 2019 (COVID-19). This paper aims to collect and sorts out the existing drugs, which exert the ability to block the binding of S protein and ACE2 so as to provide directions for the later drug development. By reviewing the existing literature, we expound the pathogenesis of SARS-CoV-2 from the perspective of S protein and ACE2 binding, and summarize the drugs and compounds that can interfere with the interaction of spike protein and ACE2 receptor from different ways. We summarized five kinds of substances, including peptide P6, griffithsin, hr2p analogs, EK1, vaccine, monoclonal antibody, cholesterol-depleting agents, and extracts from traditional Chinese medicine. They can fight SARS-CoV-2 by specifically binding to ACE2 receptor, S protein, or blocking membrane fusion between the host and virus. ACE2 is the key point for SARS-CoV-2 to enter the cells, and it is also the focus of drug intervention. Our drug summary on this pathomechanism is expected to provide ideas for the drug research on SARS-CoV-2 and help to develop anti-coronavirus drugs of broad spectrum for future epidemics.

摘要

最近,各种研究表明血管紧张素转换酶 2(ACE2)充当“门把手”,可以与严重急性呼吸综合征冠状病毒 2(SARS-CoV-2)的刺突蛋白结合,从而使其进入宿主细胞,并在 2019 冠状病毒病(COVID-19)中发挥重要作用。本文旨在收集和整理现有的能够阻断 S 蛋白与 ACE2 结合的药物,为后期药物开发提供方向。通过回顾现有文献,我们从 S 蛋白和 ACE2 结合的角度阐述了 SARS-CoV-2 的发病机制,并从不同途径总结了能够干扰刺突蛋白和 ACE2 受体相互作用的药物和化合物。我们总结了五种物质,包括肽 P6、格氏血兰素、hr2p 类似物、EK1、疫苗、单克隆抗体、胆固醇耗竭剂和中药提取物。它们可以通过特异性结合 ACE2 受体、S 蛋白或阻断宿主与病毒之间的膜融合来抵抗 SARS-CoV-2。ACE2 是 SARS-CoV-2 进入细胞的关键,也是药物干预的重点。我们对该发病机制的药物总结有望为 SARS-CoV-2 的药物研究提供思路,并有助于为未来的流行疫情开发广谱抗冠状病毒药物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/68cc/7545154/23c01b609af4/10096_2020_4048_Fig1_HTML.jpg

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