Fully human single-domain antibody targeting a highly conserved cryptic epitope on the Nipah virus G protein
Nipah virus infection, one of the top priority diseases recognized by the World Health Organization, underscores the urgent need to develop effective countermeasures against potential epidemics and pandemics. Here, we identify a fully human single-domain antibody that targets a highly conserved cryptic epitope situated at the dimeric interface of the Nipah virus G protein (receptor binding protein, RBP), as elucidated through structures by high-resolution cryo-electron microscopy (cryo-EM). This unique binding mode disrupts the tetramerization of the G protein, consequently obstructing the activation of the F protein and inhibiting viral membrane fusion. Furthermore, our investigations reveal that this compact antibody displays enhanced permeability across the blood-brain barrier (BBB) and demonstrates superior efficacy in eliminating pseudovirus within the brain in a murine model of Nipah virus infection, particularly compared to the well-characterized antibody m102.4 in an IgG1 format. Consequently, this single-domain antibody holds promise as a therapeutic candidate to prevent Nipah virus infections and has potential implications for vaccine development.
Authors
- Yifang Sun
- Qiyu Mao (ORCID: https://orcid.org/0000-0003-4924-2820)
- Lei Sun (ORCID: https://orcid.org/0000-0001-8741-0202)
- Changyou Zhan (ORCID: https://orcid.org/0000-0002-5215-2829)
- Jun Qian (ORCID: https://orcid.org/0009-0001-8131-9704)
- Wenping Song (ORCID: https://orcid.org/0000-0002-1171-4266)
- Zhenlin Yang (ORCID: https://orcid.org/0000-0001-9735-4742)
- Shibo Jiang (ORCID: https://orcid.org/0000-0001-8283-7135)
- Tianlei Ying (ORCID: https://orcid.org/0000-0002-9597-2843)
- Dimiter S. Dimitrov (ORCID: https://orcid.org/0000-0002-2258-1024)
- Lu Lu (ORCID: https://orcid.org/0000-0002-2255-0391)
- Cong Wang (ORCID: https://orcid.org/0000-0002-2724-9274)
- Yajie Wang (ORCID: https://orcid.org/0000-0001-7259-3886)
- Yulu Wang (ORCID: https://orcid.org/0000-0002-8320-3529)
- Yu Kong
- Zhenguo Chen
- Fan Wu (ORCID: https://orcid.org/0000-0002-5953-4168)
- Yanling Wu (ORCID: https://orcid.org/0000-0001-8780-8640)
- Zhaoling Shen (ORCID: https://orcid.org/0009-0005-7163-8428)
Institutions
- Shanghai Medical College of Fudan University (CN)
- University of Pittsburgh (US)
- Fudan University (CN)
- Zhongshan Hospital (CN)
- Pudong Medical Center (CN)
Publication Details
- Journal
- Nature Communications
- Published
- 2024-08-12
- DOI
- https://doi.org/10.1038/s41467-024-51066-6
- Citations
- 16
- Primary Topic
- Virology and Viral Diseases
- Type
- article
- Field-Weighted Citation Impact
- 6.19
Funders
- Shanghai Municipal Health Commission
- National Natural Science Foundation of China
- Chinese Academy of Sciences
- Fudan University
- Science and Technology Commission of Shanghai Municipality
- Shanghai Municipal Health Bureau
- Department of Science and Technology for Social Development
- Shanghai Medical College, Fudan University
- Wuhan National Biosafety Laboratory