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Structural diversity of the SARS-CoV-2 Omicron spike

View ORCID ProfileSophie M-C. Gobeil, View ORCID ProfileRory Henderson, Victoria Stalls, Katarzyna Janowska, Xiao Huang, Aaron May, Micah Speakman, Esther Beaudoin, Kartik Manne, Dapeng Li, Rob Parks, Maggie Barr, Margaret Deyton, Mitchell Martin, Katayoun Mansouri, Robert J. Edwards, Gregory D. Sempowski, Kevin O. Saunders, Kevin Wiehe, Wilton Williams, Bette Korber, Barton F. Haynes, Priyamvada Acharya
doi: https://doi.org/10.1101/2022.01.25.477784
Sophie M-C. Gobeil
1Duke Human Vaccine Institute, Durham NC 27710, USA
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  • ORCID record for Sophie M-C. Gobeil
Rory Henderson
1Duke Human Vaccine Institute, Durham NC 27710, USA
2Duke University, Department of Medicine, Durham NC 27710, USA
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Victoria Stalls
1Duke Human Vaccine Institute, Durham NC 27710, USA
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Katarzyna Janowska
1Duke Human Vaccine Institute, Durham NC 27710, USA
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Xiao Huang
1Duke Human Vaccine Institute, Durham NC 27710, USA
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Aaron May
1Duke Human Vaccine Institute, Durham NC 27710, USA
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Micah Speakman
1Duke Human Vaccine Institute, Durham NC 27710, USA
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Esther Beaudoin
1Duke Human Vaccine Institute, Durham NC 27710, USA
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Kartik Manne
1Duke Human Vaccine Institute, Durham NC 27710, USA
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Dapeng Li
1Duke Human Vaccine Institute, Durham NC 27710, USA
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Rob Parks
1Duke Human Vaccine Institute, Durham NC 27710, USA
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Maggie Barr
1Duke Human Vaccine Institute, Durham NC 27710, USA
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Margaret Deyton
1Duke Human Vaccine Institute, Durham NC 27710, USA
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Mitchell Martin
1Duke Human Vaccine Institute, Durham NC 27710, USA
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Katayoun Mansouri
1Duke Human Vaccine Institute, Durham NC 27710, USA
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Robert J. Edwards
1Duke Human Vaccine Institute, Durham NC 27710, USA
2Duke University, Department of Medicine, Durham NC 27710, USA
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Gregory D. Sempowski
1Duke Human Vaccine Institute, Durham NC 27710, USA
2Duke University, Department of Medicine, Durham NC 27710, USA
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Kevin O. Saunders
1Duke Human Vaccine Institute, Durham NC 27710, USA
3Duke University, Department of Surgery, Durham NC 27710, USA
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Kevin Wiehe
1Duke Human Vaccine Institute, Durham NC 27710, USA
2Duke University, Department of Medicine, Durham NC 27710, USA
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Wilton Williams
1Duke Human Vaccine Institute, Durham NC 27710, USA
3Duke University, Department of Surgery, Durham NC 27710, USA
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Bette Korber
4Theoretical Biology and Biophysics, Los Alamos National Laboratory, Los Alamos, NM 87545, USA
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Barton F. Haynes
1Duke Human Vaccine Institute, Durham NC 27710, USA
2Duke University, Department of Medicine, Durham NC 27710, USA
5Duke University, Department of Immunology, Durham NC 27710, USA
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  • For correspondence: barton.haynes@duke.edu priyamvada.acharya@duke.edu
Priyamvada Acharya
1Duke Human Vaccine Institute, Durham NC 27710, USA
3Duke University, Department of Surgery, Durham NC 27710, USA
6Duke University, Department of Biochemistry, Durham NC 27710, USA
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  • For correspondence: barton.haynes@duke.edu priyamvada.acharya@duke.edu
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Abstract

Aided by extensive spike protein mutation, the SARS-CoV-2 Omicron variant overtook the previously dominant Delta variant. Spike conformation plays an essential role in SARS-CoV-2 evolution via changes in receptor binding domain (RBD) and neutralizing antibody epitope presentation affecting virus transmissibility and immune evasion. Here, we determine cryo-EM structures of the Omicron and Delta spikes to understand the conformational impacts of mutations in each. The Omicron spike structure revealed an unusually tightly packed RBD organization with long range impacts that were not observed in the Delta spike. Binding and crystallography revealed increased flexibility at the functionally critical fusion peptide site in the Omicron spike. These results reveal a highly evolved Omicron spike architecture with possible impacts on its high levels of immune evasion and transmissibility.

Competing Interest Statement

B.F.H., G.D.S., and K.O.S., have patents submitted on the SARS-CoV-2 monoclonal antibodies studied in this paper. Other authors declare no competing interests.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
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Posted January 26, 2022.
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Structural diversity of the SARS-CoV-2 Omicron spike
Sophie M-C. Gobeil, Rory Henderson, Victoria Stalls, Katarzyna Janowska, Xiao Huang, Aaron May, Micah Speakman, Esther Beaudoin, Kartik Manne, Dapeng Li, Rob Parks, Maggie Barr, Margaret Deyton, Mitchell Martin, Katayoun Mansouri, Robert J. Edwards, Gregory D. Sempowski, Kevin O. Saunders, Kevin Wiehe, Wilton Williams, Bette Korber, Barton F. Haynes, Priyamvada Acharya
bioRxiv 2022.01.25.477784; doi: https://doi.org/10.1101/2022.01.25.477784
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Structural diversity of the SARS-CoV-2 Omicron spike
Sophie M-C. Gobeil, Rory Henderson, Victoria Stalls, Katarzyna Janowska, Xiao Huang, Aaron May, Micah Speakman, Esther Beaudoin, Kartik Manne, Dapeng Li, Rob Parks, Maggie Barr, Margaret Deyton, Mitchell Martin, Katayoun Mansouri, Robert J. Edwards, Gregory D. Sempowski, Kevin O. Saunders, Kevin Wiehe, Wilton Williams, Bette Korber, Barton F. Haynes, Priyamvada Acharya
bioRxiv 2022.01.25.477784; doi: https://doi.org/10.1101/2022.01.25.477784

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