9CFF

Cryo-EM Refinement of Antibody 19-77 in complex with SARS-CoV-2 HK.3 RBD

9CFF の概要

• エントリーDOI: 10.2210/pdb9cff/pdb
• EMDBエントリー: 45544
• 分子名称: heavy chain, light chain, Spike protein S1 (3 entities in total)
• 機能のキーワード: neutralizing antibody, viral fusion protein, sars-cov-2, viral protein-immune system complex, viral protein, viral protein/immune system
• 由来する生物種: Homo sapiens; 詳細
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 49182.30

構造登録者

Casner, R.G.,Shapiro, L. (登録日: 2024-06-27, 公開日: 2025-07-02, 最終更新日: 2025-10-01)

主引用文献

Wang, Q.,Guo, Y.,Casner, R.G.,Yu, J.,Nair, M.S.,Ho, J.,Reddem, E.R.,Mellis, I.A.,Wu, M.,Tzang, C.C.,Hong, H.,Huang, Y.,Shapiro, L.,Liu, L.,Ho, D.D.
Optimizing a human monoclonal antibody for better neutralization of SARS-CoV-2.
Nat Commun, 16:6195-6195, 2025

PubMed Abstract: SARS-CoV-2 has largely evolved to resist antibody pressure, with each successive viral variant becoming more and more resistant to serum antibodies in the population. This evolution renders all previously authorized anti-spike therapeutic monoclonal antibodies inactive, and it threatens the remaining pipelines against COVID-19. We report herein the isolation of a human monoclonal antibody with a broad but incomplete SARS-CoV-2 neutralization profile, but structural analyses and mutational scanning lead to the engineering of variants that result in greater antibody flexibility while binding to the viral spike. Three such optimized monoclonal antibodies neutralize all SARS-CoV-2 strains tested with much improved potency and breadth, including against subvariants XEC and LP.8.1. The findings of this study not only present antibody candidates for clinical development against COVID-19, but also introduce an engineering approach to improve antibody activity via increasing conformational flexibility.

PubMed: 40615407
DOI: 10.1038/s41467-025-61472-z

実験手法

ELECTRON MICROSCOPY (3 Å)