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

Hoffmann Markus M, Kleine-Weber Hannah H, Schroeder Simon S, Krüger Nadine N, Herrler Tanja T, Erichsen Sandra S,

Open AccessDOI:




Published:2020 Mar 04

Created at:–

Last revised:2020-03-06

Source:Cell (Cell), volume , issue , 2020, ISSN: 1097-4172

Publication Country:United States

Publication Type:Journal Article

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

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.