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Nat Struct Mol Biol . Controlling the SARS-CoV-2 spike glycoprotein conformation

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  • Nat Struct Mol Biol . Controlling the SARS-CoV-2 spike glycoprotein conformation

    Nat Struct Mol Biol

    . 2020 Jul 22.
    doi: 10.1038/s41594-020-0479-4. Online ahead of print.
    Controlling the SARS-CoV-2 spike glycoprotein conformation

    Rory Henderson 1 2 , Robert J Edwards 3 4 , Katayoun Mansouri 3 , Katarzyna Janowska 3 , Victoria Stalls 3 , Sophie M C Gobeil 3 , Megan Kopp 3 , Dapeng Li 3 , Rob Parks 3 , Allen L Hsu 5 , Mario J Borgnia 5 , Barton F Haynes 3 4 6 , Priyamvada Acharya 7 8



    The coronavirus (CoV) spike (S) protein, involved in viral-host cell fusion, 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. Despite an overall similarity in domain organization, we found that S-proteins from different β-CoVs display distinct configurations. Based on this analysis, we developed two soluble ectodomain constructs for the SARS-CoV-2 S-protein, in which the highly immunogenic and mobile receptor binding domain (RBD) is either locked in the all-RBDs 'down' position or adopts 'up' state conformations more readily than the wild-type S-protein. These results demonstrate that the conformation of the S-protein can be controlled via rational design and can provide a framework for the development of engineered CoV S-proteins for vaccine applications.