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SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor
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...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier Inc.
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7102627/ https://www.ncbi.nlm.nih.gov/pubmed/32142651 http://dx.doi.org/10.1016/j.cell.2020.02.052 |
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author | Hoffmann, Markus Kleine-Weber, Hannah Schroeder, Simon Krüger, Nadine Herrler, Tanja Erichsen, Sandra Schiergens, Tobias S. Herrler, Georg Wu, Nai-Huei Nitsche, Andreas Müller, Marcel A. Drosten, Christian Pöhlmann, Stefan |
author_facet | Hoffmann, Markus Kleine-Weber, Hannah Schroeder, Simon Krüger, Nadine Herrler, Tanja Erichsen, Sandra Schiergens, Tobias S. Herrler, Georg Wu, Nai-Huei Nitsche, Andreas Müller, Marcel A. Drosten, Christian Pöhlmann, Stefan |
author_sort | Hoffmann, Markus |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-7102627 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Elsevier Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-71026272020-03-31 SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor Hoffmann, Markus Kleine-Weber, Hannah Schroeder, Simon Krüger, Nadine Herrler, Tanja Erichsen, Sandra Schiergens, Tobias S. Herrler, Georg Wu, Nai-Huei Nitsche, Andreas Müller, Marcel A. Drosten, Christian Pöhlmann, Stefan Cell Article 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. Elsevier Inc. 2020-04-16 2020-03-05 /pmc/articles/PMC7102627/ /pubmed/32142651 http://dx.doi.org/10.1016/j.cell.2020.02.052 Text en © 2020 Elsevier Inc. Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active. |
spellingShingle | Article Hoffmann, Markus Kleine-Weber, Hannah Schroeder, Simon Krüger, Nadine Herrler, Tanja Erichsen, Sandra Schiergens, Tobias S. Herrler, Georg Wu, Nai-Huei Nitsche, Andreas Müller, Marcel A. Drosten, Christian Pöhlmann, Stefan SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor |
title | SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor |
title_full | SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor |
title_fullStr | SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor |
title_full_unstemmed | SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor |
title_short | SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor |
title_sort | sars-cov-2 cell entry depends on ace2 and tmprss2 and is blocked by a clinically proven protease inhibitor |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7102627/ https://www.ncbi.nlm.nih.gov/pubmed/32142651 http://dx.doi.org/10.1016/j.cell.2020.02.052 |
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