2021/01/28 by Emma C. Thomson, Laura E. Rosen, James G. Shepherd +63 · 1 citation
Medicine · Biochemistry, Genetics and Molecular Biology · #SARS-CoV-2 and COVID-19 Research #vaccines and immunoinformatics approaches #Monoclonal and Polyclonal Antibodies Research
paper · pdf · doi:10.1016/j.cell.2021.01.037
openalex publication_date 2021/01/28 · openalex created_date 2021/02/15 · openalex updated_date 2026/08/04
SARS-CoV-2 can mutate and evade immunity, with consequences for efficacy of emerging vaccines and antibody therapeutics. Here, we demonstrate that the immunodominant SARS-CoV-2 spike (S) receptor binding motif (RBM) is a highly variable region of S and provide epidemiological, clinical, and molecular characterization of a prevalent, sentinel RBM mutation, N439K. We demonstrate N439K S protein has enhanced binding affinity to the hACE2 receptor, and N439K viruses have similar in vitro replication fitness and cause infections with similar clinical outcomes as compared to wild type. We show the N439K mutation confers resistance against several neutralizing monoclonal antibodies, including one authorized for emergency use by the US Food and Drug Administration (FDA), and reduces the activity of some polyclonal sera from 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.