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TitleA highly potent nanobody-based bispecific therapeutic provides broad-spectrum protection against ebolavirus.
Journal, issue, pagesNat Commun, Vol. 17, Year 2026
Publish dateJul 11, 2025
AuthorsMeihua Wang / Xinghai Zhang / Wujian Li / Yanfeng Yao / Entao Li / Baoyue Zhang / Jinge Zhou / Shunli Liu / Yongxiang Gao / Zhongliang Zhu / Lixia Zhu / Mengyao Liu / Jing Hu / Cheng Peng / Fangxu Li / Miaoyu Chen / Hang Liu / Chengbing Yao / Yuhua Shang / Feihu Yan / Peng Gong / Tengchuan Jin / Sandra Chiu /
PubMed AbstractThe 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 ...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.
External linksNat Commun / PubMed:41839884 / PubMed Central
MethodsEM (single particle)
Resolution2.56 - 2.96 Å
Structure data

65314
EMDB Unreleased entry

9vt4

EMDB-65314, PDB-9vt4:
EBOV GP/BA2-VHH complex
Method: EM (single particle) / Resolution: 2.96 Å

65343
EMDB Unreleased entry

9vts

EMDB-65343, PDB-9vts:
EBOV GP/1A10-VHH complex
Method: EM (single particle) / Resolution: 2.56 Å

Source
  • zaire ebolavirus
  • ebola virus - gabon (1994-1997)
  • vicugna pacos (alpaca)
KeywordsMEMBRANE PROTEIN / ebolavirus / glycoprotein / Nanobody / Complex

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