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

Identifieur interne : 000282 ( Main/Exploration ); précédent : 000281; suivant : 000283

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

Auteurs : Markus Hoffmann [Allemagne] ; Hannah Kleine-Weber [Allemagne] ; Simon Schroeder [Allemagne] ; Nadine Krüger [Allemagne] ; Tanja Herrler [Allemagne] ; Sandra Erichsen [Autriche] ; Tobias S. Schiergens [Allemagne] ; Georg Herrler [Allemagne] ; Nai-Huei Wu [Allemagne] ; Andreas Nitsche [Allemagne] ; Marcel A. Müller [Russie] ; Christian Drosten [Allemagne] ; Stefan Pöhlmann [Allemagne]

Source :

RBID : pubmed:32142651

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.

DOI: 10.1016/j.cell.2020.02.052
PubMed: 32142651


Affiliations:


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<div type="abstract" xml:lang="en">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.</div>
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<li>Bavière</li>
<li>Berlin</li>
<li>District de Haute-Bavière</li>
<li>District fédéral central</li>
</region>
<settlement>
<li>Berlin</li>
<li>Göttingen</li>
<li>Hanovre</li>
<li>Moscou</li>
<li>Munich</li>
</settlement>
</list>
<tree>
<country name="Allemagne">
<region name="Basse-Saxe">
<name sortKey="Hoffmann, Markus" sort="Hoffmann, Markus" uniqKey="Hoffmann M" first="Markus" last="Hoffmann">Markus Hoffmann</name>
</region>
<name sortKey="Drosten, Christian" sort="Drosten, Christian" uniqKey="Drosten C" first="Christian" last="Drosten">Christian Drosten</name>
<name sortKey="Herrler, Georg" sort="Herrler, Georg" uniqKey="Herrler G" first="Georg" last="Herrler">Georg Herrler</name>
<name sortKey="Herrler, Tanja" sort="Herrler, Tanja" uniqKey="Herrler T" first="Tanja" last="Herrler">Tanja Herrler</name>
<name sortKey="Kleine Weber, Hannah" sort="Kleine Weber, Hannah" uniqKey="Kleine Weber H" first="Hannah" last="Kleine-Weber">Hannah Kleine-Weber</name>
<name sortKey="Kruger, Nadine" sort="Kruger, Nadine" uniqKey="Kruger N" first="Nadine" last="Krüger">Nadine Krüger</name>
<name sortKey="Nitsche, Andreas" sort="Nitsche, Andreas" uniqKey="Nitsche A" first="Andreas" last="Nitsche">Andreas Nitsche</name>
<name sortKey="Pohlmann, Stefan" sort="Pohlmann, Stefan" uniqKey="Pohlmann S" first="Stefan" last="Pöhlmann">Stefan Pöhlmann</name>
<name sortKey="Schiergens, Tobias S" sort="Schiergens, Tobias S" uniqKey="Schiergens T" first="Tobias S" last="Schiergens">Tobias S. Schiergens</name>
<name sortKey="Schroeder, Simon" sort="Schroeder, Simon" uniqKey="Schroeder S" first="Simon" last="Schroeder">Simon Schroeder</name>
<name sortKey="Wu, Nai Huei" sort="Wu, Nai Huei" uniqKey="Wu N" first="Nai-Huei" last="Wu">Nai-Huei Wu</name>
</country>
<country name="Autriche">
<noRegion>
<name sortKey="Erichsen, Sandra" sort="Erichsen, Sandra" uniqKey="Erichsen S" first="Sandra" last="Erichsen">Sandra Erichsen</name>
</noRegion>
</country>
<country name="Russie">
<region name="District fédéral central">
<name sortKey="Muller, Marcel A" sort="Muller, Marcel A" uniqKey="Muller M" first="Marcel A" last="Müller">Marcel A. Müller</name>
</region>
</country>
</tree>
</affiliations>
</record>

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