Proteolytic activation of the SARS-coronavirus spike protein: cutting enzymes at the cutting edge of antiviral research.

Proteolytic activation of the SARS-coronavirus spike protein: cutting enzymes at the cutting edge of antiviral research.
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SARS 冠状病毒刺突蛋白的蛋白水解激活:抗病毒研究前沿的切割酶。

DOI:
10.1016/j.antiviral.2013.09.028
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发表时间:
2013-12
期刊:
影响因子:
7.6
通讯作者:
Poehlmann, Stefan
Poehlmann, Stefan
中科院分区:
医学2区
文献类型:
--
作者:
Simmons, Graham;Zmora, Pawel;Gierer, Stefanie;Heurich, Adeline;Poehlmann, Stefan

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宿主细胞蛋白酶激活 SARS 冠状病毒的刺突蛋白。激活对于病毒感染性至关重要,也是潜在的干预目标。组织蛋白酶 L 激活宿主细胞内体中的刺突蛋白。 TMPRSS2 激活质膜上的刺突蛋白。 SARS 和 MERS 冠状病毒利用相同的蛋白酶进行激活。严重急性呼吸综合征(SARS)大流行表明,动物冠状病毒(CoV)向人类的人畜共患传播对公众健康构成重大威胁,需要进行监测和制定对策。宿主细胞蛋白酶的活性可裂解并激活 SARS-CoV 刺突 (S) 蛋白,对于病毒感染性至关重要,也是干预的目标。然而,所涉及的蛋白酶的身份尚不清楚。先驱研究发现组织蛋白酶和 II 型跨膜丝氨酸蛋白酶是 SARS-CoV 的细胞激活剂,并证明几种新兴病毒可能利用这些酶来促进其传播。在这里,我们将回顾 SARS-CoV 劫持的 S 蛋白激活蛋白水解系统,讨论它们对病毒在宿主体内传播的贡献,并概述针对这些酶的抗病毒策略。本文是《抗病毒研究》系列特邀文章的一部分,主题为“从 SARS 到 MERS:高致病性人类冠状病毒的 10 年研究”。
Host cell proteases activate the spike protein of the SARS-coronavirus. Activation is essential for viral infectivity and a potential target for intervention. Cathepsin L activates the spike protein in host cell endosomes. TMPRSS2 activates the spike protein at the plasma membrane. SARS- and MERS-coronavirus exploit the same proteases for activation. The severe acute respiratory syndrome (SARS) pandemic revealed that zoonotic transmission of animal coronaviruses (CoV) to humans poses a significant threat to public health and warrants surveillance and the development of countermeasures. The activity of host cell proteases, which cleave and activate the SARS-CoV spike (S) protein, is essential for viral infectivity and constitutes a target for intervention. However, the identities of the proteases involved have been unclear. Pioneer studies identified cathepsins and type II transmembrane serine proteases as cellular activators of SARS-CoV and demonstrated that several emerging viruses might exploit these enzymes to promote their spread. Here, we will review the proteolytic systems hijacked by SARS-CoV for S protein activation, we will discuss their contribution to viral spread in the host and we will outline antiviral strategies targeting these enzymes. This paper forms part of a series of invited articles in Antiviral Research on “From SARS to MERS: 10 years of research on highly pathogenic human coronaviruses.’’
DOI: 10.1074/jbc.m110.103275
发表时间: 2010-07-23
期刊: The Journal of biological chemistry
影响因子: --
作者:
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影响因子: 5.4
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发表时间: 2011-05-01
影响因子: 5.4
作者:
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