Circulating SARS-CoV-2 spike N439K variants maintain fitness while evading antibody-mediated immunity.
;
Laura E Rosen;
James G Shepherd;
Roberto Spreafico;
Ana da Silva Filipe;
Jason A Wojcechowskyj;
Chris Davis;
Luca Piccoli;
David J Pascall;
Josh Dillen;
+58 more...
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;
ISARIC4C Investigators;
COVID-19 Genomics UK (COG-UK) Consortium;
Suzannah J Rihn;
Samantha J Lycett;
Herbert W Virgin;
Amalio Telenti;
Davide Corti;
David L Robertson;
Gyorgy Snell;
ISARIC4C Investigators, COVID-19 Genomics UK (COG-UK) Consortium;
(2021)
Circulating SARS-CoV-2 spike N439K variants maintain fitness while evading antibody-mediated immunity.
Cell, 184 (5).
1171-1187.e20.
ISSN 0092-8674
DOI: 10.1016/j.cell.2021.01.037
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 virulence and fitness such as N439K can emerge within SARS-CoV-2 S, highlighting the need for ongoing molecular surveillance to guide development and usage of vaccines and therapeutics.
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