tetano
Editor, Senior Moderator
MedComm (2020)
. 2024 Nov 28;5(12):e70008.
doi: 10.1002/mco2.70008. eCollection 2024 Dec. Defining the features and structure of neutralizing antibody targeting the silent face of the SARS-CoV-2 spike N-terminal domain
Zhaoyong Zhang[SUP] 1 [/SUP], Yuanyuan Zhang[SUP] 2 [/SUP], Yuting Zhang[SUP] 1 [/SUP], Linling Cheng[SUP] 1 [/SUP], Lu Zhang[SUP] 3 [/SUP], Qihong Yan[SUP] 1 [/SUP], Xuesong Liu[SUP] 1 [/SUP], Jiantao Chen[SUP] 1 [/SUP], Jun Dai[SUP] 3 [/SUP], Yingying Guo[SUP] 4 [/SUP], Peilan Wei[SUP] 1 5 [/SUP], Xinyi Xiong[SUP] 6 [/SUP], Juxue Xiao[SUP] 1 [/SUP], Airu Zhu[SUP] 1 [/SUP], Jianfen Zhuo[SUP] 1 [/SUP], Ruoxi Cai[SUP] 1 [/SUP], Jingjun Zhang[SUP] 1 [/SUP], Haiyue Rao[SUP] 1 [/SUP], Bin Qu[SUP] 6 [/SUP], Shengnan Zhang[SUP] 1 [/SUP], Jiaxin Feng[SUP] 1 [/SUP], Jinling Cheng[SUP] 1 [/SUP], Jingyi Su[SUP] 1 [/SUP], Canjie Chen[SUP] 1 [/SUP], Shu Li[SUP] 1 [/SUP], Yuanyuan Zhang[SUP] 1 [/SUP], Lei Chen[SUP] 1 [/SUP], Yingkang Jin[SUP] 7 [/SUP], Yonghao Xu[SUP] 1 [/SUP], Xiaoqing Liu[SUP] 1 [/SUP], Yimin Li[SUP] 1 [/SUP], Jingxian Zhao[SUP] 1 5 [/SUP], Yanqun Wang[SUP] 1 8 9 [/SUP], Qiang Zhou[SUP] 2 [/SUP], Jincun Zhao[SUP] 1 5 6 10 [/SUP]
Affiliations
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.
Keywords: N‐terminal domain; SARS‐CoV‐2; glycan shield; neutralizing antibody; silent face.
. 2024 Nov 28;5(12):e70008.
doi: 10.1002/mco2.70008. eCollection 2024 Dec. Defining the features and structure of neutralizing antibody targeting the silent face of the SARS-CoV-2 spike N-terminal domain
Zhaoyong Zhang[SUP] 1 [/SUP], Yuanyuan Zhang[SUP] 2 [/SUP], Yuting Zhang[SUP] 1 [/SUP], Linling Cheng[SUP] 1 [/SUP], Lu Zhang[SUP] 3 [/SUP], Qihong Yan[SUP] 1 [/SUP], Xuesong Liu[SUP] 1 [/SUP], Jiantao Chen[SUP] 1 [/SUP], Jun Dai[SUP] 3 [/SUP], Yingying Guo[SUP] 4 [/SUP], Peilan Wei[SUP] 1 5 [/SUP], Xinyi Xiong[SUP] 6 [/SUP], Juxue Xiao[SUP] 1 [/SUP], Airu Zhu[SUP] 1 [/SUP], Jianfen Zhuo[SUP] 1 [/SUP], Ruoxi Cai[SUP] 1 [/SUP], Jingjun Zhang[SUP] 1 [/SUP], Haiyue Rao[SUP] 1 [/SUP], Bin Qu[SUP] 6 [/SUP], Shengnan Zhang[SUP] 1 [/SUP], Jiaxin Feng[SUP] 1 [/SUP], Jinling Cheng[SUP] 1 [/SUP], Jingyi Su[SUP] 1 [/SUP], Canjie Chen[SUP] 1 [/SUP], Shu Li[SUP] 1 [/SUP], Yuanyuan Zhang[SUP] 1 [/SUP], Lei Chen[SUP] 1 [/SUP], Yingkang Jin[SUP] 7 [/SUP], Yonghao Xu[SUP] 1 [/SUP], Xiaoqing Liu[SUP] 1 [/SUP], Yimin Li[SUP] 1 [/SUP], Jingxian Zhao[SUP] 1 5 [/SUP], Yanqun Wang[SUP] 1 8 9 [/SUP], Qiang Zhou[SUP] 2 [/SUP], Jincun Zhao[SUP] 1 5 6 10 [/SUP]
Affiliations
- PMID: 39619228
- PMCID: PMC11604724
- DOI: 10.1002/mco2.70008
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.
Keywords: N‐terminal domain; SARS‐CoV‐2; glycan shield; neutralizing antibody; silent face.