| Literature DB >> 33621484 |
Emma C Thomson1, Laura E Rosen2, James G Shepherd3, Roberto Spreafico2, Ana da Silva Filipe3, Jason A Wojcechowskyj2, Chris Davis3, Luca Piccoli4, David J Pascall5, Josh Dillen2, Spyros Lytras3, Nadine Czudnochowski2, Rajiv Shah3, Marcel Meury2, Natasha Jesudason3, Anna De Marco4, Kathy Li3, Jessica Bassi4, Aine O'Toole6, Dora Pinto4, Rachel M Colquhoun6, Katja Culap4, Ben Jackson6, Fabrizia Zatta4, Andrew Rambaut6, Stefano Jaconi4, Vattipally B Sreenu3, Jay Nix7, Ivy Zhang8, Ruth F Jarrett3, William G Glass9, Martina Beltramello4, Kyriaki Nomikou3, Matteo Pizzuto4, Lily Tong3, Elisabetta Cameroni4, Tristan I Croll10, Natasha Johnson3, Julia Di Iulio2, Arthur Wickenhagen3, Alessandro Ceschi11, Aoife M Harbison12, Daniel Mair3, Paolo Ferrari13, Katherine Smollett3, Federica Sallusto14, Stephen Carmichael3, Christian Garzoni15, Jenna Nichols3, Massimo Galli16, Joseph Hughes3, Agostino Riva16, Antonia Ho3, Marco Schiuma16, Malcolm G Semple17, Peter J M Openshaw18, Elisa Fadda12, J Kenneth Baillie19, John D Chodera9, Suzannah J Rihn3, Samantha J Lycett20, Herbert W Virgin21, Amalio Telenti2, Davide Corti4, David L Robertson22, Gyorgy Snell23.
Abstract
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.Entities:
Keywords: COVID-19; N439K; SARS-CoV-2; Spike; monoclonal antibody escape; mutation; protein structure; receptor binding motif; variant
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Year: 2021 PMID： 33621484 PMCID： PMC7843029 DOI： 10.1016/j.cell.2021.01.037
Source DB: PubMed Journal: Cell ISSN： 0092-8674 Impact factor: 66.850