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Closing coronavirus spike glycoproteins by structure-guided design

Matthew McCallum, Alexandra C. Walls, Davide Corti, David Veesler
doi: https://doi.org/10.1101/2020.06.03.129817
Matthew McCallum
1Department of Biochemistry, University of Washington, Seattle, Washington 98195, USA
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Alexandra C. Walls
1Department of Biochemistry, University of Washington, Seattle, Washington 98195, USA
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Davide Corti
2Humabs Biomed SA, a subsidiary of Vir Biotechnology, 6500 Bellinzona, Switzerland
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David Veesler
1Department of Biochemistry, University of Washington, Seattle, Washington 98195, USA
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  • For correspondence: dveesler@uw.edu
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Abstract

The recent spillover of SARS-CoV-2 in the human population resulted in the ongoing COVID-19 pandemic which has already caused 4.9 million infections and more than 326,000 fatalities. To initiate infection the SARS-CoV-2 spike (S) glycoprotein promotes attachment to the host cell surface, determining host and tissue tropism, and fusion of the viral and host membranes. Although SARS-CoV- 2 S is the main target of neutralizing antibodies and the focus of vaccine design, its stability and conformational dynamics are limiting factors for developing countermeasures against this virus. We report here the design of a prefusion SARS-CoV-2 S ectodomain trimer construct covalently stabilized in the closed conformation. Structural and antigenicity analysis showed we successfully shut S in the closed state without otherwise altering its architecture. Finally, we show that this engineering strategy is applicable to other β-coronavirus S glycoproteins and might become an important tool for vaccine design, structural biology, serology and immunology studies.

Competing Interest Statement

The authors have declared no competing interest.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC 4.0 International license.
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Posted June 03, 2020.
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Closing coronavirus spike glycoproteins by structure-guided design
Matthew McCallum, Alexandra C. Walls, Davide Corti, David Veesler
bioRxiv 2020.06.03.129817; doi: https://doi.org/10.1101/2020.06.03.129817
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Closing coronavirus spike glycoproteins by structure-guided design
Matthew McCallum, Alexandra C. Walls, Davide Corti, David Veesler
bioRxiv 2020.06.03.129817; doi: https://doi.org/10.1101/2020.06.03.129817

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