9VT4

EBOV GP/BA2-VHH complex

9VT4 の概要

• エントリーDOI: 10.2210/pdb9vt4/pdb
• EMDBエントリー: 65314
• 分子名称: Envelope glycoprotein,GP1, Envelope glycoprotein, nanobody BA2, ... (4 entities in total)
• 機能のキーワード: ebolavirus, glycoprotein, nanobody, complex, membrane protein
• 由来する生物種: Zaire ebolavirus; 詳細
• タンパク質・核酸の鎖数: 9
• 化学式量合計: 200624.55

構造登録者

Wang, M.,Gao, Y.,Jin, T. (登録日: 2025-07-09, 公開日: 2026-07-08)

主引用文献

Wang, M.,Zhang, X.,Li, W.,Yao, Y.,Li, E.,Zhang, B.,Zhou, J.,Liu, S.,Gao, Y.,Zhu, Z.,Zhu, L.,Liu, M.,Hu, J.,Peng, C.,Li, F.,Chen, M.,Liu, H.,Yao, C.,Shang, Y.,Yan, F.,Gong, P.,Jin, T.,Chiu, S.
A highly potent nanobody-based bispecific therapeutic provides broad-spectrum protection against ebolavirus.
Nat Commun, 17:-, 2026

PubMed Abstract: The highly lethal Ebola virus species-Zaire (EBOV), Sudan (SUDV), and Bundibugyo (BDBV)-pose persistent threats to global health. Current antibody therapies target EBOV but lack broad neutralization across ebolaviruses. Recent pan-ebolavirus strategies rely on antibody cocktails. Here, we identified two camelid-derived nanobodies (1A10 and BA2) that neutralize EBOV, SUDV, and BDBV in vitro and protect female rodents against these pathogens. High-resolution cryo-EM structures of their GP complexes showed that 1A10 and BA2 bind conserved but non-overlapping epitopes near the GP1 base and GP2's internal fusion loop (IFL), and biochemical analyses revealed their distinct neutralization mechanisms. To further improve efficacy, we engineered a bispecific antibody (BA2-1A10) via GS linker-mediated IgG-Fc fusion, which provided highly potent protection against all three viruses in female rodents model and positions it as a strong broad-spectrum anti-ebolavirus candidate. Our work demonstrates a structure-guided bispecific nanobody strategy for pan-ebolavirus therapy and highlights compact antibodies for next-generation antivirals.

PubMed: 41839884
DOI: 10.1038/s41467-026-70464-6

実験手法

ELECTRON MICROSCOPY (2.96 Å)