SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor
SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor
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DOI：
10.1016/j.cell.2020.02.052
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发表时间：
2020-04-16
期刊：
影响因子：
64.5
通讯作者：
Poehlmann, Stefan
中科院分区：
文献类型：
--
作者：
Hoffmann, Markus;Kleine-Weber, Hannah;Poehlmann, Stefan
新型致病性SARS冠状病毒2（SARS-CoV-2）最近在中国的出现及其在国内和国际上的快速传播构成了全球卫生紧急情况。冠状病毒的细胞进入依赖于病毒刺突（S）蛋白与细胞受体的结合以及宿主细胞蛋白酶对S蛋白的引发。解开SARS-CoV-2使用哪些细胞因子进入可能会提供对病毒传播的见解并揭示治疗靶点。在这里，我们证明了SARS-CoV-2使用SARS-CoV受体ACE 2进入和丝氨酸蛋白酶TMPRSS 2 S蛋白引发。批准用于临床使用的TMPRSS 2抑制剂阻止了进入，并可能构成一种治疗选择。最后，我们表明，从恢复期SARS患者的血清交叉中和SARS-2-S驱动的进入。我们的研究结果揭示了SARS-CoV-2和SARS-CoV感染之间的重要共性，并确定了抗病毒干预的潜在靶点。
The recent emergence of the novel, pathogenic SARS-coronavirus 2 (SARS-CoV-2) in China and its rapid national and international spread pose a global health emergency. Cell entry of coronaviruses depends on binding of the viral spike (S) proteins to cellular receptors and on S protein priming by host cell proteases. Unravelling which cellular factors are used by SARS-CoV-2 for entry might provide insights into viral transmission and reveal therapeutic targets. Here, we demonstrate that SARS-CoV-2 uses the SARS-CoV receptor ACE2 for entry and the serine protease TMPRSS2 for S protein priming. A TMPRSS2 inhibitor approved for clinical use blocked entry and might constitute a treatment option. Finally, we show that the sera from convalescent SARS patients cross-neutralized SARS-2-S-driven entry. Our results reveal important commonalities between SARS-CoV-2 and SARS-CoV infection and identify a potential target for antiviral intervention.