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

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.

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Affiliated Institutions

• Freie Universität Berlin DE
• Paracelsus Medical University AT
• Sechenov University RU
• Charité - Universitätsmedizin Berlin DE
• Berufsgenossenschaftliche Unfallklinik Murnau DE
• Humboldt-Universität zu Berlin DE
• German Center for Infection Research DE
• Robert Koch Institute DE
• German Primate Center DE
• Ludwig-Maximilians-Universität München DE
• University of Göttingen DE
• University of Veterinary Medicine Hannover, Foundation DE

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