7L0N

Circulating SARS-CoV-2 spike N439K variants maintain fitness while evading antibody-mediated immunity

Summary for 7L0N

• Entry DOI: 10.2210/pdb7l0n/pdb
• Descriptor: Monoclonal antibody S309 Fab light chain, SULFATE ION, SODIUM ION, ... (17 entities in total)
• Functional Keywords: covid-19, sars-cov-2, variant rbd, viral protein-receptor complex, viral protein, viral protein-hydrolase complex, viral protein/hydrolase
• Biological source: Homo sapiens; More
• Total number of polymer chains: 12
• Total formula weight: 380023.63

Authors

Snell, G.,Czudnochowski, N.,Dillen, J.,Nix, J.C.,Croll, T.I.,Corti, D. (deposition date: 2020-12-11, release date: 2021-02-17, Last modification date: 2024-10-23)

Primary citation

Thomson, E.C.,Rosen, L.E.,Shepherd, J.G.,Spreafico, R.,da Silva Filipe, A.,Wojcechowskyj, J.A.,Davis, C.,Piccoli, L.,Pascall, D.J.,Dillen, J.,Lytras, S.,Czudnochowski, N.,Shah, R.,Meury, M.,Jesudason, N.,De Marco, A.,Li, K.,Bassi, J.,O'Toole, A.,Pinto, D.,Colquhoun, R.M.,Culap, K.,Jackson, B.,Zatta, F.,Rambaut, A.,Jaconi, S.,Sreenu, V.B.,Nix, J.,Zhang, I.,Jarrett, R.F.,Glass, W.G.,Beltramello, M.,Nomikou, K.,Pizzuto, M.,Tong, L.,Cameroni, E.,Croll, T.I.,Johnson, N.,Di Iulio, J.,Wickenhagen, A.,Ceschi, A.,Harbison, A.M.,Mair, D.,Ferrari, P.,Smollett, K.,Sallusto, F.,Carmichael, S.,Garzoni, C.,Nichols, J.,Galli, M.,Hughes, J.,Riva, A.,Ho, A.,Schiuma, M.,Semple, M.G.,Openshaw, P.J.M.,Fadda, E.,Baillie, J.K.,Chodera, J.D.,Rihn, S.J.,Lycett, S.J.,Virgin, H.W.,Telenti, A.,Corti, D.,Robertson, D.L.,Snell, G.
Circulating SARS-CoV-2 spike N439K variants maintain fitness while evading antibody-mediated immunity.
Cell, 184:1171-1187.e20, 2021

PubMed 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.

PubMed: 33621484
DOI: 10.1016/j.cell.2021.01.037

Experimental method

X-RAY DIFFRACTION (2.78 Å)