PT  - JOURNAL ARTICLE
AU  - Thomson, Emma C.
AU  - Rosen, Laura E.
AU  - Shepherd, James G.
AU  - Spreafico, Roberto
AU  - da Silva Filipe, Ana
AU  - Wojcechowskyj, Jason A.
AU  - Davis, Chris
AU  - Piccoli, Luca
AU  - Pascall, David J.
AU  - Dillen, Josh
AU  - Lytras, Spyros
AU  - Czudnochowski, Nadine
AU  - Shah, Rajiv
AU  - Meury, Marcel
AU  - Jesudason, Natasha
AU  - De Marco, Anna
AU  - Li, Kathy
AU  - Bassi, Jessica
AU  - O’Toole, Aine
AU  - Pinto, Dora
AU  - Colquhoun, Rachel M.
AU  - Culap, Katja
AU  - Jackson, Ben
AU  - Zatta, Fabrizia
AU  - Rambaut, Andrew
AU  - Jaconi, Stefano
AU  - Sreenu, Vattipally B.
AU  - Nix, Jay
AU  - Jarrett, Ruth F.
AU  - Beltramello, Martina
AU  - Nomikou, Kyriaki
AU  - Pizzuto, Matteo
AU  - Tong, Lily
AU  - Cameroni, Elisabetta
AU  - Johnson, Natasha
AU  - Wickenhagen, Arthur
AU  - Ceschi, Alessandro
AU  - Mair, Daniel
AU  - Ferrari, Paolo
AU  - Smollett, Katherine
AU  - Sallusto, Federica
AU  - Carmichael, Stephen
AU  - Garzoni, Christian
AU  - Nichols, Jenna
AU  - Galli, Massimo
AU  - Hughes, Joseph
AU  - Riva, Agostino
AU  - Ho, Antonia
AU  - Semple, Malcolm G.
AU  - Openshaw, Peter J.M.
AU  - Baillie, J. Kenneth
AU  - , 
AU  - , 
AU  - Rihn, Suzannah J.
AU  - Lycett, Samantha J.
AU  - Virgin, Herbert W.
AU  - Telenti, Amalio
AU  - Corti, Davide
AU  - Robertson, David L.
AU  - Snell, Gyorgy
TI  - The circulating SARS-CoV-2 spike variant N439K maintains fitness while evading antibody-mediated immunity
AID  - 10.1101/2020.11.04.355842
DP  - 2020 Jan 01
TA  - bioRxiv
PG  - 2020.11.04.355842
4099  - http://biorxiv.org/content/early/2020/11/05/2020.11.04.355842.short
4100  - http://biorxiv.org/content/early/2020/11/05/2020.11.04.355842.full
AB  - 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 in vitro 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.Competing Interest StatementL.E.R., R. Sp., J.A.W., L.P., J.D., N.C., M.M., A.D.M., J.B., D.P., K.C., F.Z., S.J., M.B., M.P., E.C., H.W.V., A.T., D.C., and G.S. are or were employees of Vir Biotechnology Inc. and may hold shares in Vir Biotechnology Inc. C.G. is a consultant to Humabs BioMed SA. J.Nix is a consultant with Vir Biotechnology Inc. The other authors declare no competing interests.