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 Emma C. Thomson
A1 Laura E. Rosen
A1 James G. Shepherd
A1 Roberto Spreafico
A1 Ana da Silva Filipe
A1 Jason A. Wojcechowskyj
A1 Chris Davis
A1 Luca Piccoli
A1 David J. Pascall
A1 Josh Dillen
A1 Spyros Lytras
A1 Nadine Czudnochowski
A1 Rajiv Shah
A1 Marcel Meury
A1 Natasha Jesudason
A1 Anna De Marco
A1 Kathy Li
A1 Jessica Bassi
A1 Aine O’Toole
A1 Dora Pinto
A1 Rachel M. Colquhoun
A1 Katja Culap
A1 Ben Jackson
A1 Fabrizia Zatta
A1 Andrew Rambaut
A1 Stefano Jaconi
A1 Vattipally B. Sreenu
A1 Jay Nix
A1 Ruth F. Jarrett
A1 Martina Beltramello
A1 Kyriaki Nomikou
A1 Matteo Pizzuto
A1 Lily Tong
A1 Elisabetta Cameroni
A1 Natasha Johnson
A1 Arthur Wickenhagen
A1 Alessandro Ceschi
A1 Daniel Mair
A1 Paolo Ferrari
A1 Katherine Smollett
A1 Federica Sallusto
A1 Stephen Carmichael
A1 Christian Garzoni
A1 Jenna Nichols
A1 Massimo Galli
A1 Joseph Hughes
A1 Agostino Riva
A1 Antonia Ho
A1 Malcolm G. Semple
A1 Peter J.M. Openshaw
A1 J. Kenneth Baillie
A1 The ISARIC4C Investigators
A1 the COVID-19 Genomics UK (COG-UK) consortium
A1 Suzannah J. Rihn
A1 Samantha J. Lycett
A1 Herbert W. Virgin
A1 Amalio Telenti
A1 Davide Corti
A1 David L. Robertson
A1 Gyorgy Snell
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.