Authors
Emma C Thomson, Laura E Rosen, James G Shepherd, Roberto Spreafico, Ana da Silva Filipe, Jason A Wojcechowskyj, Chris Davis, Luca Piccoli, David J Pascall, Josh Dillen, Spyros Lytras, Nadine Czudnochowski, Rajiv Shah, Marcel Meury, Natasha Jesudason, Anna De Marco, Kathy Li, Jessica Bassi, Aine O’Toole, Dora Pinto, Rachel M Colquhoun, Katja Culap, Ben Jackson, Fabrizia Zatta, Andrew Rambaut, Stefano Jaconi, Vattipally B Sreenu, Jay Nix, Ivy Zhang, Ruth F Jarrett, William G Glass, Martina Beltramello, Kyriaki Nomikou, Matteo Pizzuto, Lily Tong, Elisabetta Cameroni, Tristan I Croll, Natasha Johnson, Julia Di Iulio, Arthur Wickenhagen, Alessandro Ceschi, Aoife M Harbison, Daniel Mair, Paolo Ferrari, Katherine Smollett, Federica Sallusto, Stephen Carmichael, Christian Garzoni, Jenna Nichols, Massimo Galli, Joseph Hughes, Agostino Riva, Antonia Ho, Marco Schiuma, Malcolm G Semple, Peter JM Openshaw, Elisa Fadda, J Kenneth Baillie, John D Chodera, Suzannah J Rihn, Samantha J Lycett, Herbert W Virgin, Amalio Telenti, Davide Corti, David L Robertson, Gyorgy Snell
Publication date
2021/3/4
Journal
Cell
Volume
184
Issue
5
Pages
1171-1187. e20
Publisher
Elsevier
Description
SARS-CoV-2 can mutate and evade immunity, with consequences for efficacy of emerging vaccines and antibody therapeutics. Here, we demonstrate that the immunodominant SARS-CoV-2 spike (S) receptor binding motif (RBM) is a highly variable region of S and provide epidemiological, clinical, and molecular characterization of a prevalent, sentinel RBM mutation, N439K. We demonstrate N439K S protein has enhanced binding affinity to the hACE2 receptor, and N439K viruses have similar in vitro replication fitness and cause infections with similar clinical outcomes as compared to wild type. We show the N439K mutation confers resistance against several neutralizing monoclonal antibodies, including one authorized for emergency use by the US Food and Drug Administration (FDA), and reduces the activity of some polyclonal sera from persons recovered from infection. Immune evasion mutations that maintain …
Total citations
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