The circulating SARS-CoV-2 spike variant N439K maintains fitness while evading antibody-mediated immunity
Emma C. Thomson,
Laura E. Rosen,
James G Shepherd,
Ana da Silva Filipe,
Jason A. Wojcechowskyj,
David J Pascall,
Anna De Marco,
Rachel M Colquhoun,
Vattipally B. Sreenu,
Ruth F Jarrett,
Malcolm G Semple,
Peter JM Openshaw,
The ISARIC4C Investigators,
COVID-19 Genomics UK (COG-UK) consortium,
Suzannah J. Rihn,
Samantha J Lycett,
Herbert W Virgin,
David L Robertson,
Posted 05 Nov 2020
bioRxiv DOI: 10.1101/2020.11.04.355842
Posted 05 Nov 2020
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 Statement L.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.
- Downloaded 14,295 times
- Download rankings, all-time:
- Site-wide: 560
- In microbiology: 62
- Year to date:
- Site-wide: 550
- Since beginning of last month:
- Site-wide: 3,611
Downloads over time
Distribution of downloads per paper, site-wide
- 27 Nov 2020: The website and API now include results pulled from medRxiv as well as bioRxiv.
- 18 Dec 2019: We're pleased to announce PanLingua, a new tool that enables you to search for machine-translated bioRxiv preprints using more than 100 different languages.
- 21 May 2019: PLOS Biology has published a community page about Rxivist.org and its design.
- 10 May 2019: The paper analyzing the Rxivist dataset has been published at eLife.
- 1 Mar 2019: We now have summary statistics about bioRxiv downloads and submissions.
- 8 Feb 2019: Data from Altmetric is now available on the Rxivist details page for every preprint. Look for the "donut" under the download metrics.
- 30 Jan 2019: preLights has featured the Rxivist preprint and written about our findings.
- 22 Jan 2019: Nature just published an article about Rxivist and our data.
- 13 Jan 2019: The Rxivist preprint is live!