Neutralizing antibody 5-7 defines a distinct site of vulnerability in SARS-CoV-2 spike N-terminal domain

Summary: Antibodies that potently neutralize SARS-CoV-2 target mainly the receptor-binding domain or the N-terminal domain (NTD). Over a dozen potently neutralizing NTD-directed antibodies have been studied structurally, and all target a single antigenic supersite in NTD (site 1). Here, we report th...

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Autores principales:	Gabriele Cerutti, Yicheng Guo, Pengfei Wang, Manoj S. Nair, Maple Wang, Yaoxing Huang, Jian Yu, Lihong Liu, Phinikoula S. Katsamba, Fabiana Bahna, Eswar R. Reddem, Peter D. Kwong, David D. Ho, Zizhang Sheng, Lawrence Shapiro
Formato:	article
Lenguaje:	EN
Publicado:	Elsevier 2021
Materias:	COVID-19 cryo-EM neutralizing antibody N-terminal domain NTD antigenic supersite Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/119804b01c4646e6825cbbdee4f5658b
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spelling	oai:doaj.org-article:119804b01c4646e6825cbbdee4f5658b2021-11-04T04:29:17ZNeutralizing antibody 5-7 defines a distinct site of vulnerability in SARS-CoV-2 spike N-terminal domain2211-124710.1016/j.celrep.2021.109928https://doaj.org/article/119804b01c4646e6825cbbdee4f5658b2021-11-01T00:00:00Zhttp://www.sciencedirect.com/science/article/pii/S2211124721014017https://doaj.org/toc/2211-1247Summary: Antibodies that potently neutralize SARS-CoV-2 target mainly the receptor-binding domain or the N-terminal domain (NTD). Over a dozen potently neutralizing NTD-directed antibodies have been studied structurally, and all target a single antigenic supersite in NTD (site 1). Here, we report the cryo-EM structure of a potent NTD-directed neutralizing antibody 5-7, which recognizes a site distinct from other potently neutralizing antibodies, inserting a binding loop into an exposed hydrophobic pocket between the two sheets of the NTD β sandwich. Interestingly, this pocket was previously identified as the binding site for hydrophobic molecules, including heme metabolites, but we observe that their presence does not substantially impede 5-7 recognition. Mirroring its distinctive binding, antibody 5-7 retains neutralization potency with many variants of concern (VOCs). Overall, we reveal that a hydrophobic pocket in NTD proposed for immune evasion can be used by the immune system for recognition.Gabriele CeruttiYicheng GuoPengfei WangManoj S. NairMaple WangYaoxing HuangJian YuLihong LiuPhinikoula S. KatsambaFabiana BahnaEswar R. ReddemPeter D. KwongDavid D. HoZizhang ShengLawrence ShapiroElsevierarticleCOVID-19cryo-EMneutralizing antibodyN-terminal domainNTDantigenic supersiteBiology (General)QH301-705.5ENCell Reports, Vol 37, Iss 5, Pp 109928- (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	COVID-19 cryo-EM neutralizing antibody N-terminal domain NTD antigenic supersite Biology (General) QH301-705.5
spellingShingle	COVID-19 cryo-EM neutralizing antibody N-terminal domain NTD antigenic supersite Biology (General) QH301-705.5 Gabriele Cerutti Yicheng Guo Pengfei Wang Manoj S. Nair Maple Wang Yaoxing Huang Jian Yu Lihong Liu Phinikoula S. Katsamba Fabiana Bahna Eswar R. Reddem Peter D. Kwong David D. Ho Zizhang Sheng Lawrence Shapiro Neutralizing antibody 5-7 defines a distinct site of vulnerability in SARS-CoV-2 spike N-terminal domain
description	Summary: Antibodies that potently neutralize SARS-CoV-2 target mainly the receptor-binding domain or the N-terminal domain (NTD). Over a dozen potently neutralizing NTD-directed antibodies have been studied structurally, and all target a single antigenic supersite in NTD (site 1). Here, we report the cryo-EM structure of a potent NTD-directed neutralizing antibody 5-7, which recognizes a site distinct from other potently neutralizing antibodies, inserting a binding loop into an exposed hydrophobic pocket between the two sheets of the NTD β sandwich. Interestingly, this pocket was previously identified as the binding site for hydrophobic molecules, including heme metabolites, but we observe that their presence does not substantially impede 5-7 recognition. Mirroring its distinctive binding, antibody 5-7 retains neutralization potency with many variants of concern (VOCs). Overall, we reveal that a hydrophobic pocket in NTD proposed for immune evasion can be used by the immune system for recognition.
format	article
author	Gabriele Cerutti Yicheng Guo Pengfei Wang Manoj S. Nair Maple Wang Yaoxing Huang Jian Yu Lihong Liu Phinikoula S. Katsamba Fabiana Bahna Eswar R. Reddem Peter D. Kwong David D. Ho Zizhang Sheng Lawrence Shapiro
author_facet	Gabriele Cerutti Yicheng Guo Pengfei Wang Manoj S. Nair Maple Wang Yaoxing Huang Jian Yu Lihong Liu Phinikoula S. Katsamba Fabiana Bahna Eswar R. Reddem Peter D. Kwong David D. Ho Zizhang Sheng Lawrence Shapiro
author_sort	Gabriele Cerutti
title	Neutralizing antibody 5-7 defines a distinct site of vulnerability in SARS-CoV-2 spike N-terminal domain
title_short	Neutralizing antibody 5-7 defines a distinct site of vulnerability in SARS-CoV-2 spike N-terminal domain
title_full	Neutralizing antibody 5-7 defines a distinct site of vulnerability in SARS-CoV-2 spike N-terminal domain
title_fullStr	Neutralizing antibody 5-7 defines a distinct site of vulnerability in SARS-CoV-2 spike N-terminal domain
title_full_unstemmed	Neutralizing antibody 5-7 defines a distinct site of vulnerability in SARS-CoV-2 spike N-terminal domain
title_sort	neutralizing antibody 5-7 defines a distinct site of vulnerability in sars-cov-2 spike n-terminal domain
publisher	Elsevier
publishDate	2021
url	https://doaj.org/article/119804b01c4646e6825cbbdee4f5658b
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Neutralizing antibody 5-7 defines a distinct site of vulnerability in SARS-CoV-2 spike N-terminal domain

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