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

Corresponding authors: Markus Hoffmann, Stefan Pöhlmann

Affiliations: Infection Biology Unit, German Primate Center - Leibniz Institute for Primate Research, Göttingen, Germany; Infection Biology Unit, German Primate Center - Leibniz Institute for Primate Research, Göttingen, Germany; Faculty of Biology and Psychology, University Göttingen, Göttingen, Germany; 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; Institute of Virology, University of Veterinary Medicine Hannover, Hannover, Germany; Research Center for Emerging Infections and Zoonoses, University of Veterinary Medicine Hannover, Hannover, Germany; BG Unfallklinik Murnau, Murnau, Germany; Institute for Biomechanics, BG Unfallklinik Murnau, Murnau, Germany; Institute for Biomechanics, Paracelsus Medical University Salzburg, Salzburg, Austria; Biobank of the Department of General, Visceral, and Transplant Surgery, Ludwig-Maximilians-University Munich, Munich, Germany; Institute of Virology, University of Veterinary Medicine Hannover, Hannover, Germany; Robert Koch Institute, ZBS 1 Highly Pathogenic Viruses, WHO Collaborating Centre for Emerging Infections and Biological Threats, Berlin, Germany; 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; Infection Biology Unit, German Primate Center - Leibniz Institute for Primate Research, Göttingen, Germany; Faculty of Biology and Psychology, University Göttingen, Göttingen, Germany.

Publication date: this article was published online on March 5, 2020

DOI: https://doi.org/10.1016/j.cell.2020.02.052

Highlights

The SARS-S/ACE2 interface has been elucidated at the atomic level, and the efficiency of ACE2 usage was found to be a key determinant of SARS-CoV transmissibility. SARS-S and SARS-2-S share ∼76% amino acid identity. However, it is unknown whether SARS-2-S like SARS-S employs ACE2 and TMPRSS2 for host cell entry. In this article, the researchers provided evidence that host cell entry of SARS-CoV-2 depends on the SARS-CoV receptor ACE2 and can be blocked by a clinically proven inhibitor of the cellular serine protease TMPRSS2, which is employed by SARS-CoV-2 for S protein priming. Moreover, it suggests that antibody responses raised against SARS-CoV could at least partially protect against SARS-CoV-2 infection.

Nomination Reasons

This study revealed important commonalities between SARS-CoV-2 and SARS-CoV infection, provided key insights into the first step of SARS-CoV-2 infection, viral entry into cells, and defined potential targets for antiviral intervention. 

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