[PDF][PDF] SARS-CoV-2 cell entry depends on ACE2 and TMPRSS2 and is blocked by a clinically proven protease inhibitor

M Hoffmann, H Kleine-Weber, S Schroeder, N Krüger… - cell, 2020 - cell.com
M Hoffmann, H Kleine-Weber, S Schroeder, N Krüger, T Herrler, S Erichsen, TS Schiergens…
cell, 2020cell.com
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 …
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.
cell.com