8C89

SARS-CoV-2 spike in complex with the 17T2 neutralizing antibody Fab fragment (local refinement of RBD and Fab)

8C89 の概要

• エントリーDOI: 10.2210/pdb8c89/pdb
• EMDBエントリー: 16473
• 分子名称: Spike protein S2', 17T2 Fab heavy chain, 17T2 Fab light chain, ... (4 entities in total)
• 機能のキーワード: complex sars-cov-2 spike s 17t2, viral protein
• 由来する生物種: Severe acute respiratory syndrome coronavirus; 詳細
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 72664.48

構造登録者

Modrego, A.,Carlero, D.,Bueno-Carrasco, M.T.,Santiago, C.,Carolis, C.,Arranz, R.,Blanco, J.,Magri, G. (登録日: 2023-01-19, 公開日: 2024-01-10, 最終更新日: 2024-11-13)

主引用文献

de Campos-Mata, L.,Trinite, B.,Modrego, A.,Tejedor Vaquero, S.,Pradenas, E.,Pons-Grifols, A.,Rodrigo Melero, N.,Carlero, D.,Marfil, S.,Santiago, C.,Raich-Regue, D.,Bueno-Carrasco, M.T.,Tarres-Freixas, F.,Abanco, F.,Urrea, V.,Izquierdo-Useros, N.,Riveira-Munoz, E.,Ballana, E.,Perez, M.,Vergara-Alert, J.,Segales, J.,Carolis, C.,Arranz, R.,Blanco, J.,Magri, G.
A monoclonal antibody targeting a large surface of the receptor binding motif shows pan-neutralizing SARS-CoV-2 activity.
Nat Commun, 15:1051-1051, 2024

PubMed Abstract: Here we report the characterization of 17T2, a SARS-CoV-2 pan-neutralizing human monoclonal antibody isolated from a COVID-19 convalescent individual infected during the first pandemic wave. 17T2 is a class 1 VH1-58/κ3-20 antibody, derived from a receptor binding domain (RBD)-specific IgA memory B cell, with a broad neutralizing activity against former and new SARS-CoV-2 variants, including XBB.1.16 and BA.2.86 Omicron subvariants. Consistently, 17T2 demonstrates in vivo prophylactic and therapeutic activity against Omicron BA.1.1 infection in K18-hACE2 mice. Cryo-electron microscopy reconstruction shows that 17T2 binds the BA.1 spike with the RBD in "up" position and blocks the receptor binding motif, as other structurally similar antibodies do, including S2E12. Yet, unlike S2E12, 17T2 retains its neutralizing activity against all variants tested, probably due to a larger RBD contact area. These results highlight the impact of small structural antibody changes on neutralizing performance and identify 17T2 as a potential candidate for future clinical interventions.

PubMed: 38316751
DOI: 10.1038/s41467-024-45171-9

実験手法

ELECTRON MICROSCOPY (4.41 Å)