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Potent SARS-CoV-2 neutralizing antibodies directed against spike N-terminal domain target a single supersite.
<div class='caption-title'>NTD-directed neutralizing antibodies derived from the VH1-24 gene define a multi-donor antibody class</div>
<div class='caption-title'>NTD-directed neutralizing antibodies derived from the closely related VH3-30 and VH3-33 genes show distinct binding modes</div>
Cerutti G, Guo Y, Zhou T, Gorman J, Lee M, Rapp M, Reddem ER, Yu J, Bahna F, Bimela J, Huang Y, Katsamba PS, Liu L, Nair MS, Rawi R, Olia AS, Wang P, Zhang B, Chuang GY, Ho DD, Sheng Z, Kwong PD, Shapiro L
OpenAccess logo Cell Host Microbe 29 819-833.e7 (2021)
Related entries: 7l2c, 7l2d, 7l2e, 7lqw

Cited: 266 times
EuropePMC logo PMID: 33789084

Abstract

Numerous antibodies that neutralize SARS-CoV-2 have been identified, and these generally target either the receptor-binding domain (RBD) or the N-terminal domain (NTD) of the viral spike. While RBD-directed antibodies have been extensively studied, far less is known about NTD-directed antibodies. Here, we report cryo-EM and crystal structures for seven potent NTD-directed neutralizing antibodies in complex with spike or isolated NTD. These structures defined several antibody classes, with at least one observed in multiple convalescent donors. The structures revealed that all seven antibodies target a common surface, bordered by glycans N17, N74, N122, and N149. This site-formed primarily by a mobile β-hairpin and several flexible loops-was highly electropositive, located at the periphery of the spike, and the largest glycan-free surface of NTD facing away from the viral membrane. Thus, in contrast to neutralizing RBD-directed antibodies that recognize multiple non-overlapping epitopes, potent NTD-directed neutralizing antibodies appear to target a single supersite.

Articles - 7l2f mentioned but not cited (5)

  1. Potent SARS-CoV-2 neutralizing antibodies directed against spike N-terminal domain target a single supersite. Cerutti G, Guo Y, Zhou T, Gorman J, Lee M, Rapp M, Reddem ER, Yu J, Bahna F, Bimela J, Huang Y, Katsamba PS, Liu L, Nair MS, Rawi R, Olia AS, Wang P, Zhang B, Chuang GY, Ho DD, Sheng Z, Kwong PD, Shapiro L. Cell Host Microbe 29 819-833.e7 (2021)
  2. A Fc-enhanced NTD-binding non-neutralizing antibody delays virus spread and synergizes with a nAb to protect mice from lethal SARS-CoV-2 infection. Beaudoin-Bussières G, Chen Y, Ullah I, Prévost J, Tolbert WD, Symmes K, Ding S, Benlarbi M, Gong SY, Tauzin A, Gasser R, Chatterjee D, Vézina D, Goyette G, Richard J, Zhou F, Stamatatos L, McGuire AT, Charest H, Roger M, Pozharski E, Kumar P, Mothes W, Uchil PD, Pazgier M, Finzi A. Cell Rep 38 110368 (2022)
  3. Molecular probes of spike ectodomain and its subdomains for SARS-CoV-2 variants, Alpha through Omicron. Teng IT, Nazzari AF, Choe M, Liu T, Oliveira de Souza M, Petrova Y, Tsybovsky Y, Wang S, Zhang B, Artamonov M, Madan B, Huang A, Lopez Acevedo SN, Pan X, Ruckwardt TJ, DeKosky BJ, Mascola JR, Misasi J, Sullivan NJ, Zhou T, Kwong PD. PLoS One 17 e0268767 (2022)
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