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

Authors:
Markus Hoffmann  1 , Hannah Kleine-Weber  2 , Simon Schroeder  3 , Nadine Krüger  4 , Tanja Herrler  5 , Sandra Erichsen  6 , Tobias S Schiergens  7 , Georg Herrler  8 , Nai-Huei Wu  8 , Andreas Nitsche  9 , Marcel A Müller  10 , Christian Drosten  3 , Stefan Pöhlmann  11             
In:
Source: Cell
Publication Date: (2020)
Issue: 1: 1
Research Area:
Cancer Research/Cell Biology
Immunotherapy / Hematology
Respiratory Research
Cells used in publication:
MRC-5
Species: human
Tissue Origin: lung
Vero
Species: monkey
Tissue Origin: kidney
HuH7
Species: human
Tissue Origin: liver
293T
Species: human
Tissue Origin: kidney
Experiment


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.