9LAE

Locally refined region of SARS-CoV-2 spike in complex with antibodies 9G11 and 3E2.

9LAE の概要

• エントリーDOI: 10.2210/pdb9lae/pdb
• EMDBエントリー: 62925
• 分子名称: Spike protein S1, Light chain of 3E2, Heavy chain of 3E2, ... (6 entities in total)
• 機能のキーワード: sars-cov-2, rbd, fab, viral protein/immune system, viral protein-immune system complex
• 由来する生物種: Severe acute respiratory syndrome coronavirus 2 (2019-nCoV, SARS-CoV-2); 詳細
• タンパク質・核酸の鎖数: 5
• 化学式量合計: 74542.08

構造登録者

Jiang, Y.,Sun, H.,Zheng, Q.,Li, S. (登録日: 2025-01-02, 公開日: 2025-02-12, 最終更新日: 2025-07-16)

主引用文献

Jiang, W.,Jiang, Y.,Sun, H.,Deng, T.,Yu, K.,Fang, Q.,Ge, H.,Lan, M.,Lin, Y.,Fang, Z.,Zhang, Y.,Zhou, L.,Li, T.,Yu, H.,Zheng, Q.,Li, S.,Xia, N.,Gu, Y.
Structural insight into broadening SARS-CoV-2 neutralization by an antibody cocktail harbouring both NTD and RBD potent antibodies.
Emerg Microbes Infect, 13:2406300-, 2024

PubMed Abstract: The continual emergence of highly pathogenic novel coronaviruses and their variants has underscored the importance of neutralizing monoclonal antibodies (mAbs) as a pivotal therapeutic approach. In the present study, we report the specific neutralizing antibodies 13H7 and 9G11, which target the N-terminal domain (NTD) and receptor-binding domain (RBD) of the SARS-CoV-2, respectively. The comparative analysis observed that 13H7 not only neutralizes early variants of concern (VOCs) but also exhibits neutralizing activity against the Omicron sublineage, including BA.4, BA.5, BQ.1, and BQ.1.1. 9G11, as an RBD antibody, also demonstrated remarkable neutralizing efficacy. A cocktail antibody combining 13H7 and 9G11 with the previously reported 3E2 broaden the neutralization spectrum against new variants of the SARS-CoV-2. We elucidated the cryo-EM structure of the complex, clarifying the mechanism of action of the cocktail antibody combination. Additionally, we also emphasized the molecular mechanism between 13H7 and SARS-CoV-2 NTD, revealing the impact of Y144 and H146 residue deletions and mutations on the neutralizing efficacy of 13H7. Taken together, our findings not only offer novel insights into the combination therapy of NTD and RBD neutralizing mAbs but also lay a theoretical foundation for the development of vaccines targeting NTD antibodies, thus providing valuable understanding of alleviating the emergence of SARS-CoV-2 variants.

PubMed: 39470577
DOI: 10.1038/s41467-023-39265-z

実験手法

ELECTRON MICROSCOPY (3.46 Å)