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TitleDefining the features and structure of neutralizing antibody targeting the silent face of the SARS-CoV-2 spike N-terminal domain.
Journal, issue, pagesMedComm (2020), Vol. 5, Issue 12, Page e70008, Year 2024
Publish dateNov 28, 2024
AuthorsZhaoyong Zhang / Yuanyuan Zhang / Yuting Zhang / Linling Cheng / Lu Zhang / Qihong Yan / Xuesong Liu / Jiantao Chen / Jun Dai / Yingying Guo / Peilan Wei / Xinyi Xiong / Juxue Xiao / Airu Zhu / Jianfen Zhuo / Ruoxi Cai / Jingjun Zhang / Haiyue Rao / Bin Qu / Shengnan Zhang / Jiaxin Feng / Jinling Cheng / Jingyi Su / Canjie Chen / Shu Li / Yuanyuan Zhang / Lei Chen / Yingkang Jin / Yonghao Xu / Xiaoqing Liu / Yimin Li / Jingxian Zhao / Yanqun Wang / Qiang Zhou / Jincun Zhao /
PubMed AbstractResearch on virus/receptor interactions has uncovered various mechanisms of antibody-mediated neutralization against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, ...Research on virus/receptor interactions has uncovered various mechanisms of antibody-mediated neutralization against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, understanding of neutralization by antibodies targeting the silent face, which recognize epitopes on glycan shields, remains limited, and their potential protective efficacy in vivo is not well understood. This study describes a silent face neutralizing antibody, 3711, which targets a non-supersite on the N-terminal domain (NTD) of the spike protein. Cryo-EM structure determination of the 3711 Fab in the spike complex reveals a novel neutralizing epitope shielded by glycans on the spike's silent face. Antibody 3711 inhibits the interaction between the receptor-binding domain (RBD) and human angiotensin-converting enzyme 2 (hACE2) through steric hindrance and exhibits superior in vivo protective effects compared to other reported NTD-targeted monoclonal antibodies (mAbs). Competition assays and antibody repertoire analysis indicate the rarity of antibodies targeting the 3711-related epitope in SARS-CoV-2 convalescents, suggesting the infrequency of NTD silent face-targeted neutralizing antibodies during SARS-CoV-2 infection. As the first NTD silent face-targeted neutralizing antibody against SARS-CoV-2, the identification of mAb 3711, with its novel neutralizing mechanism, enhances our understanding of neutralizing epitopes on glycan shields and elucidates epitope-guided viral mutations that evade specific antibodies.
External linksMedComm (2020) / PubMed:39619228 / PubMed Central
MethodsEM (single particle)
Resolution2.8 - 2.9 Å
Structure data

34872

8hlc

EMDB-34872, PDB-8hlc:
S protein of SARS-CoV-2 in complex with 3711
Method: EM (single particle) / Resolution: 2.8 Å

EMDB-34873: S protein of SARS-CoV-2 in complex with 3711 focused on NTD_3711 sub-complex
Method: EM (single particle) / Resolution: 2.9 Å

34874

8hld

EMDB-34874, PDB-8hld:
S protein of SARS-CoV-2 in complex with 26434
Method: EM (single particle) / Resolution: 2.8 Å

EMDB-34875: S protein of SARS-CoV-2 in complex with 26434 focused on NTD_26434 sub-complex
Method: EM (single particle) / Resolution: 2.9 Å

Chemicals

ChemComp-NAG:
2-acetamido-2-deoxy-beta-D-glucopyranose

ChemComp-EIC:
LINOLEIC ACID

Source
  • severe acute respiratory syndrome coronavirus 2
  • homo sapiens (human)
KeywordsVIRAL PROTEIN / SARS-CoV-2 / VIRAL PROTEIN/IMMUNE SYSTEM / VIRAL PROTEIN-IMMUNE SYSTEM complex

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