9ECX

Crystal structure of the SARS-CoV-2 NTD-targeted neutralizing antibody WRAIR-2008

9ECX の概要

• エントリーDOI: 10.2210/pdb9ecx/pdb
• 分子名称: WRAIR-2008 Fab heavy chain, WRAIR-2008 Fab light chain, GLYCEROL, ... (5 entities in total)
• 機能のキーワード: antibody, neutralizing antibody, human antibody, sars-cov-2, immune system
• 由来する生物種: Homo sapiens; 詳細
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 98139.32

構造登録者

Jensen, J.L.,Joyce, M.G. (登録日: 2024-11-15, 公開日: 2025-08-20, 最終更新日: 2025-10-22)

主引用文献

Dussupt, V.,Jensen, J.L.,Thomas, P.V.,Mendez-Rivera, L.,Lal, K.G.,Zemil McCrea, M.,Swafford, I.,Hernandez, J.,Sankhala, R.S.,Rao, M.,Arora, J.,Hajduczki, A.,Jian, N.,Rees, P.A.,Showell-De Leon, I.,Smith, G.,Smith, L.,Wasson, D.,Schmid, A.,Teng, I.T.,Zhou, T.,Kwong, P.D.,Currier, J.R.,Reiley, W.W.,Paquin-Proulx, D.,Polonis, V.R.,Collins, N.D.,Michael, N.L.,Joyce, M.G.,Krebs, S.J.
First-generation N-terminal domain supersite public antibodies retain activity against Omicron-derived lineages and protect mice against Omicron BA.5 challenge.
Mbio, 16:e0103625-e0103625, 2025

PubMed Abstract: Monoclonal antibodies to SARS-CoV-2 can offer prophylactic and therapeutic protection against severe disease, with particular utility for immunosuppressed and vulnerable populations. With the constant emergence of new variants, understanding the neutralizing potency of monoclonal antibodies to dynamic spike protein epitopes is crucial. We show that a set of VH1-24-derived N-terminal domain (NTD)-directed antibodies, isolated from a convalescent donor early in the pandemic, displayed remarkable neutralization resilience against many Omicron SARS-CoV-2 variants, including BA.2, BA.5, and BQ.1.1. Neutralization potency to these Omicron variants is associated with slower off-rates to the spike protein. Structural characterization of the most potent NTD antibody, WRAIR-2008, revealed a conserved mode of interaction shared with other antibodies of the same multi-donor class. WRAIR-2008 protected mice from weight loss following BA.5 challenge and reduced infectious viral titers in the lungs. Our study highlights the retention of neutralization activity and protection of first-generation VH1-24-derived NTD-directed antibodies to specific Omicron variants and provides valuable insights into the shifting landscape of SARS-CoV-2 variants that are vulnerable to select monoclonal antibodies.

PubMed: 40882161
DOI: 10.1128/mbio.01036-25

実験手法

X-RAY DIFFRACTION (2.67 Å)