Thomson, Emma 
ORCID: 0000-0003-1482-0889, Rosen, Laura, Shepherd, James ORCID: 0000-0003-3915-048X, Spreafico, Roberto, da Silva Filipe, Ana, Wojcechowskyj, Jason, Davis, Chris ORCID: 0000-0002-7317-3266, Piccoli, Luca, Pascall, David, Dillen, Josh et al (show 50 more authors)
(2020)
The circulating SARS-CoV-2 spike variant N439K maintains fitness while evading antibody-mediated immunity.
bioRxiv.
Abstract
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.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | The ISARIC4C Investigators, the COVID-19 Genomics UK (COG-UK) consortium |
| Depositing User: | Symplectic Admin |
| Date Deposited: | 11 Jan 2021 11:20 |
| Last Modified: | 18 Jan 2023 23:04 |
| DOI: | 10.1101/2020.11.04.355842 |
| Open Access URL: | https://doi.org/10.1101/2020.11.04.355842 |
| Related URLs: | |
| URI: | https://livrepository.liverpool.ac.uk/id/eprint/3112390 |
Dimensions
Dimensions
