RT Journal Article
SR Electronic
T1 The circulating SARS-CoV-2 spike variant N439K maintains fitness while evading antibody-mediated immunity
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2020.11.04.355842
DO 10.1101/2020.11.04.355842
A1 Thomson, Emma C.
A1 Rosen, Laura E.
A1 Shepherd, James G.
A1 Spreafico, Roberto
A1 da Silva Filipe, Ana
A1 Wojcechowskyj, Jason A.
A1 Davis, Chris
A1 Piccoli, Luca
A1 Pascall, David J.
A1 Dillen, Josh
A1 Lytras, Spyros
A1 Czudnochowski, Nadine
A1 Shah, Rajiv
A1 Meury, Marcel
A1 Jesudason, Natasha
A1 De Marco, Anna
A1 Li, Kathy
A1 Bassi, Jessica
A1 O’Toole, Aine
A1 Pinto, Dora
A1 Colquhoun, Rachel M.
A1 Culap, Katja
A1 Jackson, Ben
A1 Zatta, Fabrizia
A1 Rambaut, Andrew
A1 Jaconi, Stefano
A1 Sreenu, Vattipally B.
A1 Nix, Jay
A1 Jarrett, Ruth F.
A1 Beltramello, Martina
A1 Nomikou, Kyriaki
A1 Pizzuto, Matteo
A1 Tong, Lily
A1 Cameroni, Elisabetta
A1 Johnson, Natasha
A1 Wickenhagen, Arthur
A1 Ceschi, Alessandro
A1 Mair, Daniel
A1 Ferrari, Paolo
A1 Smollett, Katherine
A1 Sallusto, Federica
A1 Carmichael, Stephen
A1 Garzoni, Christian
A1 Nichols, Jenna
A1 Galli, Massimo
A1 Hughes, Joseph
A1 Riva, Agostino
A1 Ho, Antonia
A1 Semple, Malcolm G.
A1 Openshaw, Peter J.M.
A1 Baillie, J. Kenneth
A1 ,
A1 ,
A1 Rihn, Suzannah J.
A1 Lycett, Samantha J.
A1 Virgin, Herbert W.
A1 Telenti, Amalio
A1 Corti, Davide
A1 Robertson, David L.
A1 Snell, Gyorgy
YR 2020
UL http://biorxiv.org/content/early/2020/11/05/2020.11.04.355842.abstract
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.