A potent protective bispecific nanobody targeting Herpes simplex virus gD reveals vulnerable epitope for neutralizing

Herpes simplex virus (HSV) causes significant health burden worldwide. Currently used antiviral drugs are effective but resistance can occur. Here, we report two high-affinity neutralizing nanobodies, namely Nb14 and Nb32, that target non-overlapping epitopes in HSV gD. Nb14 binds a neutralization epitope located in the N-A' interloop, which prevents the interaction between gD and gH/gL during the second step of conformational changes during membrane fusion after virus attachment. The bispecific nanobody dimer (Nb14-32-Fc) exhibits high potency in vitro and in vivo. Mechanistically, Nb14-32-Fc neutralizes HSVs at both the pre-and post-attachment stages and prevents cell-to-cell spread in vitro. Administration of Nb14-32-Fc at low dosage of 1 mg/kg provides 100% protection in an HSV-1 infection male mouse model and an HSV-2 infection female mouse model. Our results demonstrate that Nb14-32-Fc could serve as a promising drug candidate for treatment of HSV infection, especially in the cases of antiviral drug resistance and severe herpes encephalitis.

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Publication Details

Journal
Nature Communications
Published
2025-05-06
DOI
https://doi.org/10.1038/s41467-025-58669-7
Citations
5
Primary Topic
Herpesvirus Infections and Treatments
Type
article
Field-Weighted Citation Impact
6.77

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article

A potent protective bispecific nanobody targeting Herpes simplex virus gD reveals vulnerable epitope for neutralizing

Dongli Pan, Meng Guo, Shasha Deng, Shu Zhu et al.
5 citations
Nature Communications
Herpesvirus Infections and Treatments
6.77
article

A potent protective bispecific nanobody targeting Herpes simplex virus gD reveals vulnerable epitope for neutralizing

Dongli Pan, Meng Guo, Shasha Deng, Shu Zhu, Peiyi Zheng, Chenmin Yao, Yuhua Shang, Chenghao Huang, Jin Wang, Jiayin Li, Jing Hu, Haoyuan Tan, Mengyao Liu, Meihua Wang, Haifang Qiu, Zhongliang Zhu, Chaolu Hasi, Tengchuan Jin, Anmin Wang, Hongliang He
article en
5 citations

Abstract

Herpes simplex virus (HSV) causes significant health burden worldwide. Currently used antiviral drugs are effective but resistance can occur. Here, we report two high-affinity neutralizing nanobodies, namely Nb14 and Nb32, that target non-overlapping epitopes in HSV gD. Nb14 binds a neutralization epitope located in the N-A' interloop, which prevents the interaction between gD and gH/gL during the second step of conformational changes during membrane fusion after virus attachment. The bispecific nanobody dimer (Nb14-32-Fc) exhibits high potency in vitro and in vivo. Mechanistically, Nb14-32-Fc neutralizes HSVs at both the pre-and post-attachment stages and prevents cell-to-cell spread in vitro. Administration of Nb14-32-Fc at low dosage of 1 mg/kg provides 100% protection in an HSV-1 infection male mouse model and an HSV-2 infection female mouse model. Our results demonstrate that Nb14-32-Fc could serve as a promising drug candidate for treatment of HSV infection, especially in the cases of antiviral drug resistance and severe herpes encephalitis.

Nature CommunicationsVol. 16(1)
University of Science and Technology of China (CN), Xiamen University (CN), Hefei Institutes of Physical Science (CN), Xilinx (United States) (US), National Science Centre (PL), Kai Biotech (South Korea) (KR), Zhejiang University (CN)
Salt Science Research Foundation, National Natural Science Foundation of China, Chinese Academy of Sciences, University of Science and Technology of China, National Key Research and Development Program of China
Openalex Percentile: Top 3%
Herpesvirus Infections and Treatments
6.77
DOIOpen Access PDFOpenAlex
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