Stiftung Tierärztliche Hochschule Hannover (TiHo)

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

Affiliation
Infection Biology Unit, German Primate Center - Leibniz Institute for Primate Research, Göttingen, Germany. Electronic address: mhoffmann@dpz.eu.
Hoffmann, Markus;
Affiliation
Infection Biology Unit, German Primate Center - Leibniz Institute for Primate Research, Göttingen, Germany; Faculty of Biology and Psychology, University Göttingen, Göttingen, Germany.
Kleine-Weber, Hannah;
Affiliation
Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Institute of Virology, Berlin, Germany; German Centre for Infection Research, associated partner Charité, Berlin, Germany.
Schroeder, Simon;
ORCID
0000-0002-4413-8699
Affiliation
Institute of Virology, University of Veterinary Medicine Hannover, Hannover, Germany; Research Center for Emerging Infections and Zoonoses, University of Veterinary Medicine Hannover, Hannover, Germany.
Krüger, Nadine;
Affiliation
BG Unfallklinik Murnau, Murnau, Germany.
Herrler, Tanja;
Affiliation
Institute for Biomechanics, BG Unfallklinik Murnau, Murnau, Germany; Institute for Biomechanics, Paracelsus Medical University Salzburg, Salzburg, Austria.
Erichsen, Sandra;
Affiliation
Biobank of the Department of General, Visceral, and Transplant Surgery, Ludwig-Maximilians-University Munich, Munich, Germany.
Schiergens, Tobias S;
GND
14152877X
ORCID
0000-0002-5827-0957
Affiliation
Institute of Virology, University of Veterinary Medicine Hannover, Hannover, Germany.
Herrler, Georg;
Affiliation
Institute of Virology, University of Veterinary Medicine Hannover, Hannover, Germany.
Wu, Nai-Huei;
Affiliation
Robert Koch Institute, ZBS 1 Highly Pathogenic Viruses, WHO Collaborating Centre for Emerging Infections and Biological Threats, Berlin, Germany.
Nitsche, Andreas;
Affiliation
Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Institute of Virology, Berlin, Germany; German Centre for Infection Research, associated partner Charité, Berlin, Germany; Martsinovsky Institute of Medical Parasitology, Tropical and Vector Borne Diseases, Sechenov University, Moscow, Russia.
Müller, Marcel A;
Affiliation
Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Institute of Virology, Berlin, Germany; German Centre for Infection Research, associated partner Charité, Berlin, Germany.
Drosten, Christian;
Affiliation
Infection Biology Unit, German Primate Center - Leibniz Institute for Primate Research, Göttingen, Germany; Faculty of Biology and Psychology, University Göttingen, Göttingen, Germany. Electronic address: spoehlmann@dpz.eu.
Pöhlmann, Stefan

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.

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