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

[tetano]

Cell. 2020 Mar 4. pii: S0092-8674(20)30229-4. doi: 10.1016/j.cell.2020.02.052. [Epub ahead of print] SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor.

Hoffmann M¹, Kleine-Weber H², Schroeder S³, Kr?ger N⁴, Herrler T⁵, Erichsen S⁶, Schiergens TS⁷, Herrler G⁸, Wu NH⁸, Nitsche A⁹, M?ller MA¹⁰, Drosten C³, P?hlmann S¹¹.
Author information

Abstract

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.
Copyright ? 2020 Elsevier Inc. All rights reserved.


KEYWORDS:

ACE2; COVID-19; SARS-CoV-2; TMPRSS2; coronavirus; entry; neutralization; priming; spike

PMID: 32142651 DOI: 10.1016/j.cell.2020.02.052