2. Academic Validation
  3. Controlling the SARS-CoV-2 Spike Glycoprotein Conformation

Controlling the SARS-CoV-2 Spike Glycoprotein Conformation

  • bioRxiv. 2020 May 18;2020.05.18.102087. doi: 10.1101/2020.05.18.102087.
Rory Henderson 1 2,  Robert J Edwards 1 2,  Katayoun Mansouri 1,  Katarzyna Janowska 1,  Victoria Stalls 1,  Sophie Gobeil 1,  Megan Kopp 1,  Allen Hsu 3,  Mario Borgnia 3,  Rob Parks 1,  Barton F Haynes 1 2 4,  Priyamvada Acharya 1 5
Affiliations

Affiliations

  • 1 Duke Human Vaccine Institute, Durham NC 27710, USA.
  • 2 Duke University, Department of Medicine, Durham NC 27710, USA.
  • 3 Genome Integrity and Structural Biology Laboratory, NIEHS, NIH, Department of Health and Human Services, Research Triangle Park, NC 27709, USA.
  • 4 Duke University, Department of Immunology, Durham NC 27710, USA.
  • 5 Duke University, Department of Surgery, Durham NC 27710, USA.
PMID: 32511343 DOI: 10.1101/2020.05.18.102087
Abstract

The coronavirus (CoV) viral host cell fusion spike (S) protein is the primary immunogenic target for virus neutralization and the current focus of many vaccine design efforts. The highly flexible S-protein, with its mobile domains, presents a moving target to the immune system. Here, to better understand S-protein mobility, we implemented a structure-based vector analysis of available β-CoV S-protein structures. We found that despite overall similarity in domain organization, different β-CoV strains display distinct S-protein configurations. Based on this analysis, we developed two soluble ectodomain constructs in which the highly immunogenic and mobile receptor binding domain (RBD) is locked in either the all-RBDs 'down' position or is induced to display a previously unobserved in SARS-CoV-2 2-RBDs 'up' configuration. These results demonstrate that the conformation of the S-protein can be controlled via rational design and provide a framework for the development of engineered coronavirus spike proteins for vaccine applications.

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