Roles of host proteases in the entry of SARS-CoV-2.
Roles of host proteases in the entry of SARS-CoV-2.
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DOI：
10.1186/s44149-023-00075-x
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发表时间：
2023
期刊：
影响因子：
--
通讯作者：
中科院分区：
文献类型：
--
作者：
SARS-CoV-2的刺突蛋白（spike protein， S）负责病毒附着和进入，是影响宿主易感性、组织趋向性、毒力和致病性的主要因素。S区分为S1区和S2区，S1区包含受体结合域（receptor-binding domain， RBD）， S2区包含进入宿主细胞的疏水融合域。许多宿主蛋白酶通过不同的裂解位点参与了sars - cov - 2s的激活。本文综述了在SARS-CoV-2活化过程中的宿主蛋白酶，包括furin、胰蛋白酶、跨膜蛋白酶丝氨酸2 （TMPRSS2）和组织蛋白酶。包括SARS-CoV-2在内的许多乙型冠状病毒在S1/S2位点有多碱基残基，可被furin切割。S1/S2的切割促进了受体ACE2更可评估的RBD，并且结合引发了进一步的构象变化和S2位点暴露于蛋白酶，如II型跨膜丝氨酸蛋白酶（ttpr），包括TMPRSS2。在靶细胞上存在TMPRSS2的情况下，SARS-CoV-2可以通过病毒包膜与细胞膜融合的方式直接进入细胞。在缺乏TMPRSS2的情况下，SARS-CoV-2通过内体进入靶细胞，在内体中多个组织蛋白酶切割S以成功进入。我们还讨论了参与S裂解的其他宿主蛋白酶。本文还包括对组织蛋白酶L具有抑制活性的3c样蛋白酶抑制剂在SARS-CoV-2侵入中的作用，并讨论了此类抑制剂在病毒复制中的双重作用。
The spike protein (S) of SARS-CoV-2 is responsible for viral attachment and entry, thus a major factor for host susceptibility, tissue tropism, virulence and pathogenicity. The S is divided with S1 and S2 region, and the S1 contains the receptor-binding domain (RBD), while the S2 contains the hydrophobic fusion domain for the entry into the host cell. Numerous host proteases have been implicated in the activation of SARS-CoV-2 S through various cleavage sites. In this article, we review host proteases including furin, trypsin, transmembrane protease serine 2 (TMPRSS2) and cathepsins in the activation of SARS-CoV-2 S. Many betacoronaviruses including SARS-CoV-2 have polybasic residues at the S1/S2 site which is subjected to the cleavage by furin. The S1/S2 cleavage facilitates more assessable RBD to the receptor ACE2, and the binding triggers further conformational changes and exposure of the S2’ site to proteases such as type II transmembrane serine proteases (TTPRs) including TMPRSS2. In the presence of TMPRSS2 on the target cells, SARS-CoV-2 can utilize a direct entry route by fusion of the viral envelope to the cellular membrane. In the absence of TMPRSS2, SARS-CoV-2 enter target cells via endosomes where multiple cathepsins cleave the S for the successful entry. Additional host proteases involved in the cleavage of the S were discussed. This article also includes roles of 3C-like protease inhibitors which have inhibitory activity against cathepsin L in the entry of SARS-CoV-2, and discussed the dual roles of such inhibitors in virus replication.
普罗蛋白转化酶在严重急性呼吸综合征冠状病毒的加工和传播中的影响。
DOI：
10.1016/j.bbrc.2004.11.063
发表时间：
2005-01-21
影响因子：
3.1
作者：
Bergeron E;Vincent MJ;Wickham L;Hamelin J;Basak A;Nichol ST;Chrétien M;Seidah NG
通讯作者：
Seidah NG
影响因子：
3.7
作者：
Shiryaev SA;Chernov AV;Golubkov VS;Thomsen ER;Chudin E;Chee MS;Kozlov IA;Strongin AY;Cieplak P
通讯作者：
Cieplak P