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关于冠状病毒刺突蛋白通过血管紧张素转换酶-2 和弗林蛋白酶进行裂解激活的综述。

A review on the cleavage priming of the spike protein on coronavirus by angiotensin-converting enzyme-2 and furin.

机构信息

Department of Mechanical and Industrial Engineering, College of Engineering, Qatar University, Doha, Qatar.

Biomedical Research Center, Qatar University, Doha, Qatar.

出版信息

J Biomol Struct Dyn. 2021 May;39(8):3025-3033. doi: 10.1080/07391102.2020.1754293. Epub 2020 Apr 22.

Abstract

The widespread antigenic changes lead to the emergence of a new type of coronavirus (CoV) called as severe acute respiratory syndrome (SARS)-CoV-2 that is immunologically different from the previous circulating species. Angiotensin-converting enzyme-2 (ACE-2) is one of the most important receptors on the cell membrane of the host cells (HCs) which its interaction with spike protein (SP) with a furin-cleavage site results in the SARS-CoV-2 invasion. Hence, in this review, we presented an overview on the interaction of ACE-2 and furin with SP. As several kinds of CoVs, from various genera, have at their S1/S2 binding site a preserved site, we further surveyed the role of furin cleavage site (FCS) on the life cycle of the CoV. Furthermore, we discussed that the small molecular inhibitors can limit the interaction of ACE-2 and furin with SP and can be used as potential therapeutic platforms to combat the spreading CoV epidemic. Finally, some ongoing challenges and future prospects for the development of potential drugs to promote targeting specific activities of the CoV were reviewed. In conclusion, this review may pave the way for providing useful information about different compounds involved in improving the effectiveness of CoV vaccine or drugs with minimum toxicity against human health.Communicated by Ramaswamy H. Sarma.

摘要

广泛的抗原变化导致了一种新型冠状病毒(CoV)的出现,称为严重急性呼吸系统综合症(SARS)-CoV-2,它在免疫学上与以前流行的物种不同。血管紧张素转换酶-2(ACE-2)是宿主细胞(HCs)细胞膜上最重要的受体之一,其与刺突蛋白(SP)的相互作用带有一个弗林切割位点,导致 SARS-CoV-2 的入侵。因此,在这篇综述中,我们介绍了 ACE-2 和弗林与 SP 的相互作用概述。由于几种来自不同属的 CoVs 在其 S1/S2 结合位点具有保守位点,我们进一步研究了弗林切割位点(FCS)在 CoV 生命周期中的作用。此外,我们讨论了小分子抑制剂可以限制 ACE-2 和弗林与 SP 的相互作用,并可以作为潜在的治疗平台来对抗 CoV 的传播。最后,对开发针对 CoV 特定活性的潜在药物的一些当前挑战和未来前景进行了综述。总之,本综述可能为提供有关改善 CoV 疫苗效果或对人类健康毒性最小的化合物的不同信息铺平道路。由 Ramaswamy H. Sarma 传达。

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