The circulating SARS-CoV-2 spike variant N439K maintains fitness while evading antibody-mediated immunity
Preprint
- 5 November 2020
- preprint
- research article
- Published by Cold Spring Harbor Laboratory
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.Keywords
Other Versions
- Published version: Version Cell, 184, preprints
This publication has 47 references indexed in Scilit:
- SARS-CoV-2 Neutralizing Antibody LY-CoV555 in Outpatients with Covid-19The New England Journal of Medicine, 2021
- A SARS-CoV-2 vaccine candidate would likely match all currently circulating variantsProceedings of the National Academy of Sciences of the United States of America, 2020
- The coronavirus is mutating — does it matter?Nature, 2020
- Antibody cocktail to SARS-CoV-2 spike protein prevents rapid mutational escape seen with individual antibodiesScience, 2020
- Evolutionary origins of the SARS-CoV-2 sarbecovirus lineage responsible for the COVID-19 pandemicNature Microbiology, 2020
- An integrated national scale SARS-CoV-2 genomic surveillance networkThe Lancet Microbe, 2020
- How single mutations affect viral escape from broad and narrow antibodies to H1 influenza hemagglutininNature Communications, 2018
- Advanced Bayesian Multilevel Modeling with the R Package brmsThe R Journal, 2018
- A Neutralizing Antibody Selected from Plasma Cells That Binds to Group 1 and Group 2 Influenza A HemagglutininsScience, 2011
- Features and development of CootActa crystallographica. Section D, Structural biology, 2010