A dual-glycoprotein-targeting bispecific nanoantibody confers potent neutralization against Nipah virus

Shengdong Wang; Xinghai Zhang; Haiwei Zhang; Guibo Rao; Yanfeng Yao; Guihong Tian; Ge Gao; Yun Peng; Wujian Li; Sheng Cao; Sandra Chiu; Rui Gong; Li Chen

doi:10.1016/j.virs.2026.09.014

October 2026

Citation: Shengdong Wang, Xinghai Zhang, Haiwei Zhang, Guibo Rao, Yanfeng Yao, Guihong Tian, Ge Gao, Yun Peng, Wujian Li, Sheng Cao, Sandra Chiu, Rui Gong, Li Chen. A dual-glycoprotein-targeting bispecific nanoantibody confers potent neutralization against Nipah virus .VIROLOGICA SINICA, 2026, 41(5) : 1213-1226. http://dx.doi.org/10.1016/j.virs.2026.09.014

A dual-glycoprotein-targeting bispecific nanoantibody confers potent neutralization against Nipah virus

Shengdong Wang ^a,b ,
Xinghai Zhang ^a ,
Haiwei Zhang ^a ,
Guibo Rao ^a ,
Yanfeng Yao ^a ,
Guihong Tian ^a,b ,
Ge Gao ^a ,
Yun Peng ^a ,
Wujian Li ^c,d,e ,
Sheng Cao ^{a
,,} ,
Sandra Chiu ^{c,d,e
,,} ,
Rui Gong ^{a,b
,,} ,
Li Chen ^{a
,,}

a. State Key Laboratory of Virology and Biosafety, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan 430071, China;
b. University of Chinese Academy of Sciences, Beijing 100049, China;
c. Department of Infectious Disease, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230027, China;
d. Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230027, China;
e. Key Laboratory of Anhui Province for Emerging and Reemerging Infectious Diseases, Hefei 230027, China

Corresponding author: Sheng Cao, caosheng@wh.iov.cn
Sandra Chiu, qiux@ustc.edu.cn
Rui Gong, gongr@wh.iov.cn
Li Chen, chenli@wh.iov.cn
Received Date: 29 July 2026
Accepted Date: 30 September 2026
Available online: 09 October 2026

Abstract

Nipah virus (NiV) is a biosafety level 4 pathogen that has consistently posed a significant threat to public health. The two envelope proteins on the viral surface, the receptor-binding protein (RBP) and the fusion (F) protein, are the primary targets of neutralizing antibodies. However, the use of antibodies targeting a single viral antigen often leads to the emergence of resistant strains. Here, by panning phage display library, we obtained a C-type nanoantibody (C-Nab), G-3-1, targeting the head domain of RBP. The half-life-extended G-3-1-HLE effectively protected hamsters against authentic NiV challenge. Furthermore, we constructed a fusion protein, 2A1-3-8-(AP)₁₂-G-3-1, by linking G-3-1 to the F-targeting nanobody 2A1-3-8 via a rigid (AP)₁₂ linker. This fusion protein exhibited improved and balanced neutralizing activity. In addition, the in vivo prophylactic efficacy of 2A1-3-8-(AP)₁₂-G-3-1 was validated in a mouse model of NiV pseudovirus infection. Collectively, this study on a dual-envelope-protein-targeting bispecific antibody not only provides a promising antiviral candidate, but also offers an important design strategy for next-generation antibody optimization.
- Nipah virus (NiV)
- , Fusion protein (F)
- , Receptor binding protein (RBP)
- , Rigid linker
- , Dual-glycoproteins target
- , Bispecific nanoantibodies

Electronic Supplementary Material

10.1016j.virs.2026.09.014-ESM.docx
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