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Structure, Function, and Antigenicity of the SARS-CoV-2 Spike Glycoprotein

Identifieur interne : 000020 ( France/Analysis ); précédent : 000019; suivant : 000021

Structure, Function, and Antigenicity of the SARS-CoV-2 Spike Glycoprotein

Auteurs : Alexandra C. Walls [États-Unis] ; Young-Jun Park [États-Unis] ; M. Alejandra Tortorici [États-Unis, France] ; Abigail Wall [États-Unis] ; Andrew T. Mcguire [États-Unis] ; David Veesler [États-Unis]

Source :

RBID : PMC:7102599

Abstract

Summary

The emergence of SARS-CoV-2 has resulted in >90,000 infections and >3,000 deaths. Coronavirus spike (S) glycoproteins promote entry into cells and are the main target of antibodies. We show that SARS-CoV-2 S uses ACE2 to enter cells and that the receptor-binding domains of SARS-CoV-2 S and SARS-CoV S bind with similar affinities to human ACE2, correlating with the efficient spread of SARS-CoV-2 among humans. We found that the SARS-CoV-2 S glycoprotein harbors a furin cleavage site at the boundary between the S1/S2 subunits, which is processed during biogenesis and sets this virus apart from SARS-CoV and SARS-related CoVs. We determined cryo-EM structures of the SARS-CoV-2 S ectodomain trimer, providing a blueprint for the design of vaccines and inhibitors of viral entry. Finally, we demonstrate that SARS-CoV S murine polyclonal antibodies potently inhibited SARS-CoV-2 S mediated entry into cells, indicating that cross-neutralizing antibodies targeting conserved S epitopes can be elicited upon vaccination.


Url:
DOI: 10.1016/j.cell.2020.02.058
PubMed: 32155444
PubMed Central: 7102599


Affiliations:


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PMC:7102599

Le document en format XML

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<p>The emergence of SARS-CoV-2 has resulted in >90,000 infections and >3,000 deaths. Coronavirus spike (S) glycoproteins promote entry into cells and are the main target of antibodies. We show that SARS-CoV-2 S uses ACE2 to enter cells and that the receptor-binding domains of SARS-CoV-2 S and SARS-CoV S bind with similar affinities to human ACE2, correlating with the efficient spread of SARS-CoV-2 among humans. We found that the SARS-CoV-2 S glycoprotein harbors a furin cleavage site at the boundary between the S
<sub>1</sub>
/S
<sub>2</sub>
subunits, which is processed during biogenesis and sets this virus apart from SARS-CoV and SARS-related CoVs. We determined cryo-EM structures of the SARS-CoV-2 S ectodomain trimer, providing a blueprint for the design of vaccines and inhibitors of viral entry. Finally, we demonstrate that SARS-CoV S murine polyclonal antibodies potently inhibited SARS-CoV-2 S mediated entry into cells, indicating that cross-neutralizing antibodies targeting conserved S epitopes can be elicited upon vaccination.</p>
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</listBibl>
</div1>
</back>
</TEI>
<affiliations>
<list>
<country>
<li>France</li>
<li>États-Unis</li>
</country>
<region>
<li>Washington (État)</li>
<li>Île-de-France</li>
</region>
<settlement>
<li>Seattle</li>
</settlement>
<orgName>
<li>Université de Washington</li>
</orgName>
</list>
<tree>
<country name="États-Unis">
<region name="Washington (État)">
<name sortKey="Walls, Alexandra C" sort="Walls, Alexandra C" uniqKey="Walls A" first="Alexandra C." last="Walls">Alexandra C. Walls</name>
</region>
<name sortKey="Mcguire, Andrew T" sort="Mcguire, Andrew T" uniqKey="Mcguire A" first="Andrew T." last="Mcguire">Andrew T. Mcguire</name>
<name sortKey="Mcguire, Andrew T" sort="Mcguire, Andrew T" uniqKey="Mcguire A" first="Andrew T." last="Mcguire">Andrew T. Mcguire</name>
<name sortKey="Park, Young Jun" sort="Park, Young Jun" uniqKey="Park Y" first="Young-Jun" last="Park">Young-Jun Park</name>
<name sortKey="Tortorici, M Alejandra" sort="Tortorici, M Alejandra" uniqKey="Tortorici M" first="M. Alejandra" last="Tortorici">M. Alejandra Tortorici</name>
<name sortKey="Veesler, David" sort="Veesler, David" uniqKey="Veesler D" first="David" last="Veesler">David Veesler</name>
<name sortKey="Wall, Abigail" sort="Wall, Abigail" uniqKey="Wall A" first="Abigail" last="Wall">Abigail Wall</name>
</country>
<country name="France">
<region name="Île-de-France">
<name sortKey="Tortorici, M Alejandra" sort="Tortorici, M Alejandra" uniqKey="Tortorici M" first="M. Alejandra" last="Tortorici">M. Alejandra Tortorici</name>
</region>
</country>
</tree>
</affiliations>
</record>

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