Mechanisms of SARS-CoV-2 entry into cells.

Mechanisms of SARS-CoV-2 entry into cells.
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DOI:
10.1038/s41580-021-00418-x
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发表时间:
2022-01
期刊:
Nature reviews. Molecular cell biology
影响因子:
--
通讯作者:
Choe H
Choe H
中科院分区:
其他
文献类型:
--
作者:
Jackson CB;Farzan M;Chen B;Choe H

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由严重急性呼吸系统综合征冠状病毒2型(SARS-CoV-2)感染引起的COVID-19大流行对公共卫生和经济造成了前所未有的影响,科学界也做出了同样前所未有的反应。这种反应主要集中在SARS-CoV-2进入宿主细胞的机制上,特别是刺突(S)蛋白与其受体血管紧张素转换酶2(ACE 2)的结合以及随后的膜融合。本文综述了SARS-CoV-2进入细胞的结构和细胞基础,包括S蛋白的合成、S蛋白的结构、S蛋白与ACE 2结合所需的构象转换、S蛋白受体结合域与ACE 2的结合、S蛋白的蛋白水解激活、胞吞作用和膜融合。我们定义了弗林蛋白酶样蛋白酶,跨膜蛋白酶,丝氨酸2(TMPRSS 2)和组织蛋白酶L在这些过程中的作用,并描绘了水库动物物种和S蛋白的适应,促进有效的人类传播ACE 2直系同源物的功能。我们还研究了针对SARS-CoV-2进入机制的疫苗,抗体和其他潜在治疗方法的效用。最后,我们提出了与这一关键过程相关的关键未决问题。SARS-CoV-2进入宿主细胞是通过病毒刺突蛋白与其受体血管紧张素转换酶2之间的相互作用介导的,随后是病毒-细胞膜融合。全球的研究工作在结构和细胞水平上提供了对这一过程的详细了解,从而成功开发了快速应对COVID-19大流行的疫苗。
The unprecedented public health and economic impact of the COVID-19 pandemic caused by infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been met with an equally unprecedented scientific response. Much of this response has focused, appropriately, on the mechanisms of SARS-CoV-2 entry into host cells, and in particular the binding of the spike (S) protein to its receptor, angiotensin-converting enzyme 2 (ACE2), and subsequent membrane fusion. This Review provides the structural and cellular foundations for understanding the multistep SARS-CoV-2 entry process, including S protein synthesis, S protein structure, conformational transitions necessary for association of the S protein with ACE2, engagement of the receptor-binding domain of the S protein with ACE2, proteolytic activation of the S protein, endocytosis and membrane fusion. We define the roles of furin-like proteases, transmembrane protease, serine 2 (TMPRSS2) and cathepsin L in these processes, and delineate the features of ACE2 orthologues in reservoir animal species and S protein adaptations that facilitate efficient human transmission. We also examine the utility of vaccines, antibodies and other potential therapeutics targeting SARS-CoV-2 entry mechanisms. Finally, we present key outstanding questions associated with this critical process. Entry of SARS-CoV-2 into host cells is mediated by the interaction between the viral spike protein and its receptor angiotensin-converting enzyme 2, followed by virus–cell membrane fusion. Worldwide research efforts have provided a detailed understanding of this process at the structural and cellular levels, enabling successful vaccine development for a rapid response to the COVID-19 pandemic.
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发表时间: 2008-09-01
影响因子: 5.4
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期刊: AGING CELL
影响因子: 7.8
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