SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor

被引：12171

作者：

Hoffmann, Markus ^{[1
]}

Kleine-Weber, Hannah ^{[1
,2
]}

Schroeder, Simon ^{[3
,4
,5
,6
,7
]}

Krueger, Nadine ^{[8
,9
]}

Herrler, Tanja ^{[10
]}

Erichsen, Sandra ^{[11
,12
]}

Schiergens, Tobias S. ^{[13
]}

Herrler, Georg ^{[8
]}

Wu, Nai-Huei ^{[8
]}

Nitsche, Andreas ^{[14
]}

Mueller, Marcel A. ^{[3
,4
,5
,6
,7
,15
]}

Drosten, Christian ^{[3
,4
,5
,6
,7
]}

Poehlmann, Stefan ^{[1
,2
]}

机构：

[1] Leibniz Inst Primate Res, German Primate Ctr, Infect Biol Unit, Gottingen, Germany

[2] Univ Gottingen, Fac Biol & Psychol, Gottingen, Germany

[3] Charite Univ Med Berlin, Berlin, Germany

[4] Free Univ Berlin, Berlin, Germany

[5] Humboldt Univ, Berlin, Germany

[6] Berlin Inst Hlth, Inst Virol, Berlin, Germany

[7] German Ctr Infect Res, Associated Partner Charite, Berlin, Germany

[8] Univ Vet Med Hannover, Inst Virol, Hannover, Germany

[9] Univ Vet Med Hannover, Res Ctr Emerging Infect & Zoonoses, Hannover, Germany

[10] BG Unfallklin Murnau, Murnau, Germany

[11] BG Unfallklin Murnau, Inst Biomech, Murnau, Germany

[12] Paracelsus Med Univ Salzburg, Inst Biomech, Salzburg, Austria

[13] Ludwig Maximilians Univ Munchen, Dept Gen Visceral & Transplant Surg, Biobank, Munich, Germany

[14] Robert Koch Inst, WHO Collaborating Ctr Emerging Infect & Biol Thre, ZBS Highly Pathogen Viruses 1, Berlin, Germany

[15] Sechenov Univ, Martsinovsky Inst Med Parasitol Trop & Vector Bor, Moscow, Russia

来源：

CELL | 2020年 / 181卷 / 02期

关键词：

ACUTE RESPIRATORY SYNDROME; ANGIOTENSIN-CONVERTING ENZYME-2; SARS-ASSOCIATED CORONAVIRUS; TO-HUMAN TRANSMISSION; SPIKE PROTEIN; FUNCTIONAL RECEPTOR; S-PROTEIN; VIRUS; INFECTION; LUNG;

D O I：

10.1016/j.cell.2020.02.052

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页码：271 / +

页数：18

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