7L0N

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

7L0N の概要

• エントリーDOI: 10.2210/pdb7l0n/pdb
• 分子名称: Monoclonal antibody S309 Fab light chain, SULFATE ION, SODIUM ION, ... (17 entities in total)
• 機能のキーワード: covid-19, sars-cov-2, variant rbd, viral protein-receptor complex, viral protein, viral protein-hydrolase complex, viral protein/hydrolase
• 由来する生物種: Homo sapiens; 詳細
• タンパク質・核酸の鎖数: 12
• 化学式量合計: 380023.63

構造登録者

Snell, G.,Czudnochowski, N.,Dillen, J.,Nix, J.C.,Croll, T.I.,Corti, D. (登録日: 2020-12-11, 公開日: 2021-02-17, 最終更新日: 2024-10-23)

主引用文献

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

実験手法

X-RAY DIFFRACTION (2.78 Å)