PT  - JOURNAL ARTICLE
AU  - Rory Henderson
AU  - Robert J Edwards
AU  - Katayoun Mansouri
AU  - Katarzyna Janowska
AU  - Victoria Stalls
AU  - Sophie Gobeil
AU  - Megan Kopp
AU  - Allen Hsu
AU  - Mario Borgnia
AU  - Rob Parks
AU  - Barton F. Haynes
AU  - Priyamvada Acharya
TI  - Controlling the SARS-CoV-2 Spike Glycoprotein Conformation
AID  - 10.1101/2020.05.18.102087
DP  - 2020 Jan 01
TA  - bioRxiv
PG  - 2020.05.18.102087
4099  - http://biorxiv.org/content/early/2020/05/18/2020.05.18.102087.short
4100  - http://biorxiv.org/content/early/2020/05/18/2020.05.18.102087.full
AB  - 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.Competing Interest StatementThe authors have declared no competing interest.