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Controlling the SARS-CoV-2 Spike Glycoprotein Conformation
Rory Henderson; Robert J Edwards; Katayoun Mansouri; Katarzyna Janowska; Victoria Stalls; Sophie Gobeil; Megan Kopp; Allen L Hsu; Mario J. Borgnia; Robert Parks; Barton F Haynes; Priyamvada Acharya.
Afiliación
  • Rory Henderson; Duke University
  • Robert J Edwards; Duke University
  • Katayoun Mansouri; Duke University
  • Katarzyna Janowska; Duke University
  • Victoria Stalls; Duke University
  • Sophie Gobeil; Duke University
  • Megan Kopp; Duke University
  • Allen L Hsu; NIH/NIEHS
  • Mario J. Borgnia; NIH/NIEHS
  • Robert Parks; Duke University
  • Barton F Haynes; Duke University
  • Priyamvada Acharya; Duke University
Preprint en En | PREPRINT-BIORXIV | ID: ppbiorxiv-102087
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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 {beta}-CoV S-protein structures. We found that despite overall similarity in domain organization, different {beta}-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.
Licencia
cc_by_nc_nd
Texto completo: 1 Colección: 09-preprints Base de datos: PREPRINT-BIORXIV Tipo de estudio: Experimental_studies Idioma: En Año: 2020 Tipo del documento: Preprint
Texto completo: 1 Colección: 09-preprints Base de datos: PREPRINT-BIORXIV Tipo de estudio: Experimental_studies Idioma: En Año: 2020 Tipo del documento: Preprint