National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)
R01GM120553
United States
Citation
Journal: Nat Struct Mol Biol / Year: 2021 Title: Structural basis for broad coronavirus neutralization. Authors: Maximilian M Sauer / M Alejandra Tortorici / Young-Jun Park / Alexandra C Walls / Leah Homad / Oliver J Acton / John E Bowen / Chunyan Wang / Xiaoli Xiong / Willem de van der Schueren / Joel ...Authors: Maximilian M Sauer / M Alejandra Tortorici / Young-Jun Park / Alexandra C Walls / Leah Homad / Oliver J Acton / John E Bowen / Chunyan Wang / Xiaoli Xiong / Willem de van der Schueren / Joel Quispe / Benjamin G Hoffstrom / Berend-Jan Bosch / Andrew T McGuire / David Veesler / Abstract: Three highly pathogenic β-coronaviruses have crossed the animal-to-human species barrier in the past two decades: SARS-CoV, MERS-CoV and SARS-CoV-2. To evaluate the possibility of identifying ...Three highly pathogenic β-coronaviruses have crossed the animal-to-human species barrier in the past two decades: SARS-CoV, MERS-CoV and SARS-CoV-2. To evaluate the possibility of identifying antibodies with broad neutralizing activity, we isolated a monoclonal antibody, termed B6, that cross-reacts with eight β-coronavirus spike glycoproteins, including all five human-infecting β-coronaviruses. B6 broadly neutralizes entry of pseudotyped viruses from lineages A and C, but not from lineage B, and the latter includes SARS-CoV and SARS-CoV-2. Cryo-EM, X-ray crystallography and membrane fusion assays reveal that B6 binds to a conserved cryptic epitope located in the fusion machinery. The data indicate that antibody binding sterically interferes with the spike conformational changes leading to membrane fusion. Our data provide a structural framework explaining B6 cross-reactivity with β-coronaviruses from three lineages, along with a proof of concept for antibody-mediated broad coronavirus neutralization elicited through vaccination. This study unveils an unexpected target for next-generation structure-guided design of a pan-β-coronavirus vaccine.
History
Deposition
Mar 23, 2021
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Header (metadata) release
May 26, 2021
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Map release
May 26, 2021
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Update
Jun 23, 2021
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Current status
Jun 23, 2021
Processing site: RCSB / Status: Released
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Structure visualization
Movie
Surface view with section colored by density value
Entire : MERS-CoV S ectodomain trimer bound to the B6 Fab fragment in the ...
Entire
Name: MERS-CoV S ectodomain trimer bound to the B6 Fab fragment in the presence of 100 mM neuraminic acid
Components
Complex: MERS-CoV S ectodomain trimer bound to the B6 Fab fragment in the presence of 100 mM neuraminic acid
Complex: MERS-CoV S ectodomain trimer
Protein or peptide: Spike glycoprotein
Complex: B6 Fab fragment
Ligand: FOLIC ACID
Ligand: 2-acetamido-2-deoxy-beta-D-glucopyranose
Ligand: N-acetyl-alpha-neuraminic acid
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Supramolecule #1: MERS-CoV S ectodomain trimer bound to the B6 Fab fragment in the ...
Supramolecule
Name: MERS-CoV S ectodomain trimer bound to the B6 Fab fragment in the presence of 100 mM neuraminic acid type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1
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