ArticleCell host & microbe2021
Potent SARS-CoV-2 neutralizing antibodies directed against spike N-terminal domain target a single supersite.
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Article in Cell host & microbe, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 374 papers.
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374 citing papers in PubMed, 580 citations in OpenAlex.
- Cell-Mediated Immunity of mRNA-1283 Vaccine Encoding SARS-CoV-2 Spike Receptor-Binding and N-Terminal Domains in Preclinical and Clinical Studies.The Journal of infectious diseases · 2026Trial
- Structural serology of polyclonal antibody responses to mRNA-1273 and NVX-CoV2373 COVID-19 vaccines.Cell reports · 2025Trial
- Functional and structural basis of Omicron BA.3.2.1 spike.Cell reports · 2026Article
- NTD Remodeling in the SARS-CoV-2 BA.3.2 Variant May Influence Spike Stability and Immune Escape.Pathogens (Basel, Switzerland) · 2026Article
- Broad Neutralizing Antibodies Against SARS-CoV-2: Current Progress and Engineering Strategies.Viruses · 2026Review
- Cetacean coronavirus spikes highlight S glycoprotein structural plasticity.PLoS pathogens · 2026Article
- Determinants of natural killer cell-mediated antibody dependent cellular cytotoxicity in SARS-CoV-2 antibodies.PLoS pathogens · 2026Article
- Transition from infectivity and immune escape to pure escape as an evolutionary strategy during the COVID-19 pandemic.bioRxiv : the preprint server for biology · 2026Article
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- From single-sequences to evolutionary trajectories: protein language models capture the evolutionary potential of SARS-CoV-2.Nature communications · 2026Article
- A SARS-CoV-2 variant-induced NTD-targeting antibody enhances viral infection via a distinctive binding mode.PLoS pathogens · 2026Article
- Article
- The Enigmatic Conserved Q134-F135-N137 Triad in SARS-CoV-2 Spike Protein: A Conformational Transducer?Biomolecules · 2026Review
- Antigenic remodeling of the SARS-CoV-2 Spike N-terminal domain links sequence variability to structural reorganization of a neutralizing antibody supersite.Frontiers in cellular and infection microbiology · 2026Article
- Insertion outside the supersite in the N-terminal domain of the SARS-CoV-2 spike glycoprotein may contribute to evasion of neutralizing antibodies.Frontiers in microbiology · 2026Article
- Conservation of Bacterial Lipopolysaccharide Binding by SARS-CoV-2 Spike across Major Viral Variants.Computational and structural biotechnology journal · 2026Article
- Systematic characterization of SARS-CoV-2 spike protein subunit trafficking and secretion reveals enhanced strategies for vaccine design and quantification.Frontiers in microbiology · 2026Article
- EMoMiS: A pipeline for epitope-based molecular mimicry search in protein structures with potential applications to SARS-CoV-2.Computational and structural biotechnology journal · 2026Article
- Contrasting effects of SARS-CoV-2 vaccination vs. infection on antibody and TCR repertoires.PloS one · 2026Article
- Cleaved versus Uncleaved: How furin cleavage reshapes the conformational landscape of SARS-CoV-2 spike.Protein science : a publication of the Protein Society · 2025Article
314 more citing papers are in PubMed but not listed here.
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Authors and funding
23 authors at 3 institutions in 1 country.
Gabriele CeruttiDepartment of Biochemistry and Molecular Biophysics, Columbia University, New York, NY 10032, USA; Zuckerman Mind Brain Behavior Institute, Columbia University, New York, NY 10027, USA.
Yicheng GuoZuckerman Mind Brain Behavior Institute, Columbia University, New York, NY 10027, USA.
Tongqing ZhouVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Jason GormanVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Myungjin LeeVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Micah RappDepartment of Biochemistry and Molecular Biophysics, Columbia University, New York, NY 10032, USA; Zuckerman Mind Brain Behavior Institute, Columbia University, New York, NY 10027, USA.
Eswar R ReddemDepartment of Biochemistry and Molecular Biophysics, Columbia University, New York, NY 10032, USA; Zuckerman Mind Brain Behavior Institute, Columbia University, New York, NY 10027, USA.
Jian YuAaron Diamond AIDS Research Center, Columbia University Vagelos College of Physicians and Surgeons, New York, NY 10032, USA.
Fabiana BahnaDepartment of Biochemistry and Molecular Biophysics, Columbia University, New York, NY 10032, USA; Zuckerman Mind Brain Behavior Institute, Columbia University, New York, NY 10027, USA.
Jude BimelaDepartment of Biochemistry and Molecular Biophysics, Columbia University, New York, NY 10032, USA; Zuckerman Mind Brain Behavior Institute, Columbia University, New York, NY 10027, USA.
Yaoxing HuangAaron Diamond AIDS Research Center, Columbia University Vagelos College of Physicians and Surgeons, New York, NY 10032, USA.
Phinikoula S KatsambaDepartment of Biochemistry and Molecular Biophysics, Columbia University, New York, NY 10032, USA; Zuckerman Mind Brain Behavior Institute, Columbia University, New York, NY 10027, USA.
Lihong LiuAaron Diamond AIDS Research Center, Columbia University Vagelos College of Physicians and Surgeons, New York, NY 10032, USA.
Manoj S NairAaron Diamond AIDS Research Center, Columbia University Vagelos College of Physicians and Surgeons, New York, NY 10032, USA.
Reda RawiVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Adam S OliaVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Pengfei WangAaron Diamond AIDS Research Center, Columbia University Vagelos College of Physicians and Surgeons, New York, NY 10032, USA.
Baoshan ZhangVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Gwo-Yu ChuangVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
David D HoAaron Diamond AIDS Research Center, Columbia University Vagelos College of Physicians and Surgeons, New York, NY 10032, USA.
Zizhang ShengZuckerman Mind Brain Behavior Institute, Columbia University, New York, NY 10027, USA; Aaron Diamond AIDS Research Center, Columbia University Vagelos College of Physicians and Surgeons, New York, NY 10032, USA.
Peter D KwongDepartment of Biochemistry and Molecular Biophysics, Columbia University, New York, NY 10032, USA; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA. Electronic address: pdkwong@nih.gov.
Lawrence ShapiroDepartment of Biochemistry and Molecular Biophysics, Columbia University, New York, NY 10032, USA; Zuckerman Mind Brain Behavior Institute, Columbia University, New York, NY 10027, USA; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA; Aaron Diamond AIDS Research Center, Columbia University Vagelos College of Physicians and Surgeons, New York, NY 10032, USA. Electronic address: lss8@columbia.edu.
National Institutes of Health · USAaron Diamond AIDS Research Center · USColumbia University · US
Funding
NCCAT: National Center for CryoEM Access and Training- Supplement for Windows 10 and FFIU24GM129539 · NIGMS · NEW YORK STRUCTURAL BIOLOGY CENTER · PI DE MARCO, ALEX, KIEFT, JEFFREY S · 2018 to 2023
$53.9MUser Training and OutreachP30GM124165 · NIGMS · CORNELL UNIVERSITY · PI STEVEN E EALICK · 2018 to 2026
$34.2MNeutralization Mechanisms Of Anti-HIV-1 Monoclonal AntibodiesZIAAI005022 · NIAID · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · PI ZHOU, TONGQING · 2009 to 2025
$24.6MTRD #3: An automated and streamlined pipeline for in-situ molecular microscopyP41GM103310 · NIGMS · SCRIPPS RESEARCH INSTITUTE, THE · PI DE MARCO, ALEX, KIEFT, JEFFREY S · 2012 to 2021
$14.7MComputational Tools for Structural AnalysisZICAI005112 · NIAID · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · PI RAWI, REDA · 2010 to 2025
$4.1MIdentification, structures and ontogenies of SARS-CoV-2 antibodiesZIAAI005147 · NIAID · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · PI ZHOU, TONGQING · 2020 to 2025
$2.9MComprehensive analysis of human adaptive immune receptors to elucidate correlates of Epstein-Barr virus disease suppressionDP5OD023118 · OD · UNIVERSITY OF KANSAS LAWRENCE · PI DEKOSKY, BRANDON JAMES · 2016 to 2022
$2.2MComprehensive molecular and functional analyses of anti-HIV-1 broadly neutralizing antibody repertoiresR21AI143407 · NIAID · UNIVERSITY OF KANSAS LAWRENCE · PI DEKOSKY, BRANDON JAMES, FORREST, MARCUS LAIRD · 2019 to 2020
$435kProbing antigen specificity and response of autoimmune B cells in Neuromyelitis OpticaR21AI144408 · NIAID · UNIVERSITY OF KANSAS LAWRENCE · PI DEKOSKY, BRANDON JAMES · 2019 to 2020
$417kIntramural NIH HHS ZIA AI005022NIAID NIH HHS R21 AI143407NIAID NIH HHS R21 AI144408NIGMS NIH HHS P30 GM124165NIGMS NIH HHS P41 GM103310NIGMS NIH HHS U24 GM129539NIH HHS DP5 OD023118
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.
Indexed as
Antibodies, NeutralizingAntibodies, ViralHumansMutationProtein ConformationProtein DomainsSARS-CoV-2Spike Glycoprotein, CoronavirusAntibodies, NeutralizingAntibodies, ViralSpike Glycoprotein, Coronavirusspike protein, SARS-CoV-2antibody classantigenic supersiteCOVID-19multi-donor antibodyneutralizing antibodyN-terminal domainSARS-CoV-2
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