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A thermostable, closed SARS-CoV-2 spike protein trimer

2020; Nature Portfolio; Volume: 27; Issue: 10 Linguagem: Inglês

10.1038/s41594-020-0478-5

1545-9993

Xiaoli Xiong, Kun Qu, Katarzyna A. Ciazynska, Myra Hosmillo, Andrew P. Carter, Soraya Ebrahimi, Zunlong Ke, Sjors H. W. Scheres, Laura Bergamaschi, Guinevere L. Grice, Ying Zhang, John R. Bradley, Paul Lyons, Kenneth G. C. Smith, Mark Toshner, Anne Elmer, Carla M. S. Ribeiro, Jenny Kourampa, Sherly Jose, Jane Kennet, Jane Rowlands, Anne Meadows, Criona O’Brien, Rebecca Rastall, Cherry Crucusio, Sarah Hewitt, Jane Price, Jo Calder, Laura Canna, Ashlea Bucke, Hugo Tordesillas, Julie R. Harris, Valentina Ruffolo, Jason Domingo, Barbara Graves, Helen Butcher, Daniela Caputo, Emma Le Gresley, Benjamin J. Dunmore, Jennifer Martin, Ekaterina Legchenko, Carmen Treacy, Christopher Huang, Jennifer Wood, Rachel Sutcliffe, Josh Hodgson, Joy Shih, Stefan Ting Graf, Zhen Tong, Federica Mescia, Tobias Tilly, Ciara O’Donnell, Kelvin Hunter, Linda Pointon, Nicole Pond, Marta Wylot, Emma Jones, Stuart Fawke, Ben Bullman, Laura Bergamaschi, Lori Turner, Isobel Jarvis, Ommar Omarjee, Aloka De, Joe Marsden, Ariana Betancourt, Marianne Perera, Maddie Epping, Nathan Richoz, Georgie Bower, Rahul Sharma, Francesca Nice, Oisín Huhn, Hannah Stark, Neil Walker, Kathy Stirrups, Nigel Ovington, Eleanor Dewhust, Emily Li, Sofia Papadia, James A. Nathan, Stephen Baker, Leo C. James, Helen Baxendale, Ian Goodfellow, Rainer Döffinger, John A. G. Briggs,

SARS-CoV-2 detection and testing

The spike (S) protein of SARS-CoV-2 mediates receptor binding and cell entry and is the dominant target of the immune system. It exhibits substantial conformational flexibility. It transitions from closed to open conformations to expose its receptor-binding site and, subsequently, from prefusion to postfusion conformations to mediate fusion of viral and cellular membranes. S-protein derivatives are components of vaccine candidates and diagnostic assays, as well as tools for research into the biology and immunology of SARS-CoV-2. Here we have designed mutations in S that allow the production of thermostable, disulfide-bonded S-protein trimers that are trapped in the closed, prefusion state. Structures of the disulfide-stabilized and non-disulfide-stabilized proteins reveal distinct closed and locked conformations of the S trimer. We demonstrate that the designed, thermostable, closed S trimer can be used in serological assays. This protein has potential applications as a reagent for serology, virology and as an immunogen. The SARS-CoV-2 spike glycoprotein is flexible, and its receptor-binding domain (RBD) fluctuates between open and closed conformations. Disulfide bonds are engineered into the spike ectodomain to lock the RBD in the closed state, leading to a construct with high thermostability.