Cell
Volume 181, Issue 2, 16 April 2020, Pages 271-280.e8
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Article
SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor

https://doi.org/10.1016/j.cell.2020.02.052Get rights and content
open access

Highlights

  • SARS-CoV-2 uses the SARS-CoV receptor ACE2 for host cell entry

  • The spike protein of SARS-CoV-2 is primed by TMPRSS2

  • Antibodies against SARS-CoV spike may offer some protection against SARS-CoV-2

Summary

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.

Keywords

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

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13

These authors contributed equally

14

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