National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)
U24 GM129539
米国
National Institutes of Health/National Institute Of Allergy and Infectious Diseases (NIH/NIAID)
UM1 AI100645
米国
National Institutes of Health/National Institute Of Allergy and Infectious Diseases (NIH/NIAID)
UM1 AI44371
米国
National Institutes of Health/National Institute of Environmental Health Sciences (NIH/NIEHS)
ZIC ES103326
米国
引用
ジャーナル: bioRxiv / 年: 2020 タイトル: Controlling the SARS-CoV-2 Spike Glycoprotein Conformation. 著者: Rory Henderson / Robert J Edwards / Katayoun Mansouri / Katarzyna Janowska / Victoria Stalls / Sophie Gobeil / Megan Kopp / Allen Hsu / Mario Borgnia / Rob Parks / Barton F Haynes / Priyamvada Acharya / 要旨: 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- ...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.