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Structural characterization of human monoclonal antibodies targeting uncommon antigenic sites on spike glycoprotein of SARS-CoV
by
Binshtein, Elad
, Bangaru, Sandhya
, Carnahan, Robert H.
, Suryadevara, Naveenchandra
, Scobey, Trevor D.
, Martinez, David R.
, Kose, Nurgun
, Crowe, James E.
, Baric, Ralph S.
, Schäfer, Alexandra
, Munt, Jennifer
, Ward, Andrew B.
, Myers, Luke
in
Allosteric properties
/ Amino acids
/ Animals
/ Antibodies, Monoclonal - chemistry
/ Antibodies, Monoclonal - immunology
/ Antibodies, Monoclonal - pharmacology
/ Antibodies, Neutralizing - chemistry
/ Antibodies, Neutralizing - immunology
/ Antibodies, Viral - chemistry
/ Antibodies, Viral - immunology
/ Antigenic determinants
/ Antigens
/ Antigens, Viral - chemistry
/ Antigens, Viral - immunology
/ B cells
/ Competition
/ Coronaviruses
/ COVID-19 - immunology
/ COVID-19 - prevention & control
/ Dengue fever
/ Disease prevention
/ Epitopes
/ Epitopes - chemistry
/ Epitopes - immunology
/ Fc receptors
/ Female
/ Fusion protein
/ Glycoproteins
/ Humans
/ Immunology
/ Infection
/ Infections
/ Mice
/ Mice, Inbred BALB C
/ Monoclonal antibodies
/ Mutation
/ Physiological aspects
/ Prevention
/ Protein Domains
/ Proteins
/ SARS-CoV-2 - immunology
/ Severe acute respiratory syndrome coronavirus 2
/ Spike glycoprotein
/ Spike Glycoprotein, Coronavirus - chemistry
/ Spike Glycoprotein, Coronavirus - genetics
/ Spike Glycoprotein, Coronavirus - immunology
/ Spike protein
/ Structure
/ Virology
/ Viruses
2025
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Structural characterization of human monoclonal antibodies targeting uncommon antigenic sites on spike glycoprotein of SARS-CoV
by
Binshtein, Elad
, Bangaru, Sandhya
, Carnahan, Robert H.
, Suryadevara, Naveenchandra
, Scobey, Trevor D.
, Martinez, David R.
, Kose, Nurgun
, Crowe, James E.
, Baric, Ralph S.
, Schäfer, Alexandra
, Munt, Jennifer
, Ward, Andrew B.
, Myers, Luke
in
Allosteric properties
/ Amino acids
/ Animals
/ Antibodies, Monoclonal - chemistry
/ Antibodies, Monoclonal - immunology
/ Antibodies, Monoclonal - pharmacology
/ Antibodies, Neutralizing - chemistry
/ Antibodies, Neutralizing - immunology
/ Antibodies, Viral - chemistry
/ Antibodies, Viral - immunology
/ Antigenic determinants
/ Antigens
/ Antigens, Viral - chemistry
/ Antigens, Viral - immunology
/ B cells
/ Competition
/ Coronaviruses
/ COVID-19 - immunology
/ COVID-19 - prevention & control
/ Dengue fever
/ Disease prevention
/ Epitopes
/ Epitopes - chemistry
/ Epitopes - immunology
/ Fc receptors
/ Female
/ Fusion protein
/ Glycoproteins
/ Humans
/ Immunology
/ Infection
/ Infections
/ Mice
/ Mice, Inbred BALB C
/ Monoclonal antibodies
/ Mutation
/ Physiological aspects
/ Prevention
/ Protein Domains
/ Proteins
/ SARS-CoV-2 - immunology
/ Severe acute respiratory syndrome coronavirus 2
/ Spike glycoprotein
/ Spike Glycoprotein, Coronavirus - chemistry
/ Spike Glycoprotein, Coronavirus - genetics
/ Spike Glycoprotein, Coronavirus - immunology
/ Spike protein
/ Structure
/ Virology
/ Viruses
2025
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Structural characterization of human monoclonal antibodies targeting uncommon antigenic sites on spike glycoprotein of SARS-CoV
by
Binshtein, Elad
, Bangaru, Sandhya
, Carnahan, Robert H.
, Suryadevara, Naveenchandra
, Scobey, Trevor D.
, Martinez, David R.
, Kose, Nurgun
, Crowe, James E.
, Baric, Ralph S.
, Schäfer, Alexandra
, Munt, Jennifer
, Ward, Andrew B.
, Myers, Luke
in
Allosteric properties
/ Amino acids
/ Animals
/ Antibodies, Monoclonal - chemistry
/ Antibodies, Monoclonal - immunology
/ Antibodies, Monoclonal - pharmacology
/ Antibodies, Neutralizing - chemistry
/ Antibodies, Neutralizing - immunology
/ Antibodies, Viral - chemistry
/ Antibodies, Viral - immunology
/ Antigenic determinants
/ Antigens
/ Antigens, Viral - chemistry
/ Antigens, Viral - immunology
/ B cells
/ Competition
/ Coronaviruses
/ COVID-19 - immunology
/ COVID-19 - prevention & control
/ Dengue fever
/ Disease prevention
/ Epitopes
/ Epitopes - chemistry
/ Epitopes - immunology
/ Fc receptors
/ Female
/ Fusion protein
/ Glycoproteins
/ Humans
/ Immunology
/ Infection
/ Infections
/ Mice
/ Mice, Inbred BALB C
/ Monoclonal antibodies
/ Mutation
/ Physiological aspects
/ Prevention
/ Protein Domains
/ Proteins
/ SARS-CoV-2 - immunology
/ Severe acute respiratory syndrome coronavirus 2
/ Spike glycoprotein
/ Spike Glycoprotein, Coronavirus - chemistry
/ Spike Glycoprotein, Coronavirus - genetics
/ Spike Glycoprotein, Coronavirus - immunology
/ Spike protein
/ Structure
/ Virology
/ Viruses
2025
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Structural characterization of human monoclonal antibodies targeting uncommon antigenic sites on spike glycoprotein of SARS-CoV
Journal Article
Structural characterization of human monoclonal antibodies targeting uncommon antigenic sites on spike glycoprotein of SARS-CoV
2025
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Overview
The function of the spike protein N terminal domain (NTD) in coronavirus (CoV) infections is poorly understood. However, some rare antibodies that target the SARS-CoV-2 NTD potently neutralize the virus. This finding suggests the NTD may contribute, in part, to protective immunity. Pansarbecovirus antibodies are desirable for broad protection, but the NTD region of SARS-CoV and SARS-CoV-2 exhibit a high level of sequence divergence; therefore, cross-reactive NTD-specific antibodies are unexpected, and there is no structure of a SARS-CoV NTD-specific antibody in complex with NTD. Here, we report a monoclonal antibody COV1-65, encoded by the IGHV1-69 gene, that recognizes the NTD of SARS-CoV S protein. A prophylaxis study showed the mAb COV1-65 prevented disease when administered before SARS-CoV challenge of BALB/c mice, an effect that requires intact fragment crystallizable region (Fc) effector functions for optimal protection in vivo. The footprint on the S protein of COV1-65 is near to functional components of the S2 fusion machinery, and the selection of COV1-65 escape mutant viruses identified critical residues Y886H and Q974H, which likely affect the epitope through allosteric effects. Structural features of the mAb COV1-65-SARS-CoV antigen interaction suggest critical antigenic determinants that should be considered in the rational design of sarbecovirus vaccine candidates.
Publisher
American Society for Clinical Investigation
Subject
/ Animals
/ Antibodies, Monoclonal - chemistry
/ Antibodies, Monoclonal - immunology
/ Antibodies, Monoclonal - pharmacology
/ Antibodies, Neutralizing - chemistry
/ Antibodies, Neutralizing - immunology
/ Antibodies, Viral - chemistry
/ Antibodies, Viral - immunology
/ Antigens
/ Antigens, Viral - immunology
/ B cells
/ COVID-19 - prevention & control
/ Epitopes
/ Female
/ Humans
/ Mice
/ Mutation
/ Proteins
/ Severe acute respiratory syndrome coronavirus 2
/ Spike Glycoprotein, Coronavirus - chemistry
/ Spike Glycoprotein, Coronavirus - genetics
/ Spike Glycoprotein, Coronavirus - immunology
/ Virology
/ Viruses
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