The circulating SARS-CoV-2 spike variant N439K maintains fitness while evading antibody-mediated immunity
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Laura E Rosen;
James G Shepherd;
Roberto Spreafico;
Ana da Silva Filipe;
Jason A Wojcechowskyj;
Chris Davis;
Luca Piccoli;
David J Pascall;
Josh Dillen;
+48 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;
Ruth F Jarrett;
Martina Beltramello;
Kyriaki Nomikou;
Matteo Pizzuto;
Lily Tong;
Elisabetta Cameroni;
Natasha Johnson;
Arthur Wickenhagen;
Alessandro Ceschi;
Daniel Mair;
Paolo Ferrari;
Katherine Smollett;
Federica Sallusto;
Stephen Carmichael;
Christian Garzoni;
Jenna Nichols;
Massimo Galli;
Joseph Hughes;
Agostino Riva;
Antonia Ho;
Malcolm G Semple;
Peter JM Openshaw;
J Kenneth Baillie;
Suzannah J Rihn;
Samantha J Lycett;
Herbert W Virgin;
Amalio Telenti;
Davide Corti;
David L Robertson;
Gyorgy Snell;
(2020)
The circulating SARS-CoV-2 spike variant N439K maintains fitness while evading antibody-mediated immunity.
bioRXiv preprints.
DOI: 10.1101/2020.11.04.355842
<jats:p>SARS-CoV-2 can mutate to evade immunity, with consequences for the efficacy of emerging vaccines and antibody therapeutics. Herein we demonstrate that the immunodominant SARS-CoV-2 spike (S) receptor binding motif (RBM) is the most divergent region of S, and provide epidemiological, clinical, and molecular characterization of a prevalent RBM variant, N439K. We demonstrate that N439K S protein has enhanced binding affinity to the hACE2 receptor, and that N439K virus has similar clinical outcomes and <jats:italic>in vitro</jats:italic> replication fitness as compared to wild- type. We observed that the N439K mutation resulted in immune escape from a panel of neutralizing monoclonal antibodies, including one in clinical trials, as well as from polyclonal sera from a sizeable fraction of 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.</jats:p>
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picture_as_pdf - 2020.11.04.355842v1.full.pdf
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subject - Published Version
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- Available under Creative Commons: 3.0