Convergent use of aminopeptidase N receptor by hedgehog merbecoviruses
8 affiliations
- 1State Key Laboratory of Virology and Biosafety, Hubei Provincial Research Center for Basic Biological Sciences, College of Life Sciences, TaiKang Center for Life and Medical Sciences, Wuhan University, Wuhan, China
- 2Key Laboratory of Biomacromolecules (CAS), National Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China
- 3University of Chinese Academy of Sciences, Beijing, China
- 4Biomedical Pioneering Innovation Center (BIOPIC), Peking University, Beijing, China
- 5Changping Laboratory, Beijing, China
- 6College of Future Technology, Peking University, Beijing, China
- 7Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences (CAMS) & Peking Union Medical College (PUMC), Beijing, China
- 8Peking-Tsinghua Center for Life Sciences, Tsinghua University, Beijing, China
Abstract
Coronaviruses circulating in wildlife, such as European and Asian hedgehog merbecoviruses (EriCoVs), pose a potential transmission risk. Knowledge of viral receptors can inform risk assessment and development of countermeasures; however, the functional receptor for EriCoVs is unknown. Here we identify hedgehog aminopeptidase N (APN) as a functional receptor for various EriCoVs. Analysis of APN orthologues from 93 species reveals a restricted APN tropism for EriCoVs, primarily utilizing APN from hedgehogs and to a lesser extent felid APN. Cryogenic electron microscopy analysis of the EriCoV–APN complex reveals an APN-binding mode that is distinct from those used by alpha- and deltacoronaviruses. Functional assays suggest that proteolytic activation of EriCoV spikes can be facilitated by multiple proteases in a context- and strain-dependent manner. Neutralizing antibodies targeting the EriCoV receptor-binding domain and hedgehog APN effectively blocked EriCoV pseudovirus entry or amplification. Receptor-binding-domain-targeting antibodies were further elucidated by cryogenic electron microscopy analysis. Together, these findings can inform assessment of merbecovirus spillover and pathogenesis.
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BibTeX
@article{liu2026convergent,
title = {{Convergent use of aminopeptidase N receptor by hedgehog merbecoviruses}},
author = {Peng Liu and Qianhui Zhu and Jingyi Liu and Zhixing Ma and Guocui Mou and Yuanling Yu and Chen Liu and Chengbao Ma and Junyu Si and Xiao Yang and Meiling Huang and Yanchu Liu and Yehui Sun and Xiao Yu and Yucheng Sun and Tianci Liu and Lingling Yu and Qianran Wang and Honghao Ma and Qi Lv and Jing Li and Linlin Bao and Yunlong Cao and Xiangxi Wang and Huan Yan},
journal = {Nature Microbiology},
year = {2026},
month = sep,
doi = {10.1038/s41564-026-02478-1},
url = {https://doi.org/10.1038/s41564-026-02478-1},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Convergent use of aminopeptidase N receptor by hedgehog merbecoviruses
AU - Peng Liu
AU - Qianhui Zhu
AU - Jingyi Liu
AU - Zhixing Ma
AU - Guocui Mou
AU - Yuanling Yu
AU - Chen Liu
AU - Chengbao Ma
AU - Junyu Si
AU - Xiao Yang
AU - Meiling Huang
AU - Yanchu Liu
AU - Yehui Sun
AU - Xiao Yu
AU - Yucheng Sun
AU - Tianci Liu
AU - Lingling Yu
AU - Qianran Wang
AU - Honghao Ma
AU - Qi Lv
AU - Jing Li
AU - Linlin Bao
AU - Yunlong Cao
AU - Xiangxi Wang
AU - Huan Yan
PY - 2026
DA - 2026/09/16
JO - Nature Microbiology
DO - 10.1038/s41564-026-02478-1
UR - https://doi.org/10.1038/s41564-026-02478-1
AB - Coronaviruses circulating in wildlife, such as European and Asian hedgehog merbecoviruses (EriCoVs), pose a potential transmission risk. Knowledge of viral receptors can inform risk assessment and development of countermeasures; however, the functional receptor for EriCoVs is unknown. Here we identify hedgehog aminopeptidase N (APN) as a functional receptor for various EriCoVs. Analysis of APN orthologues from 93 species reveals a restricted APN tropism for EriCoVs, primarily utilizing APN from hedgehogs and to a lesser extent felid APN. Cryogenic electron microscopy analysis of the EriCoV–APN complex reveals an APN-binding mode that is distinct from those used by alpha- and deltacoronaviruses. Functional assays suggest that proteolytic activation of EriCoV spikes can be facilitated by multiple proteases in a context- and strain-dependent manner. Neutralizing antibodies targeting the EriCoV receptor-binding domain and hedgehog APN effectively blocked EriCoV pseudovirus entry or amplification. Receptor-binding-domain-targeting antibodies were further elucidated by cryogenic electron microscopy analysis. Together, these findings can inform assessment of merbecovirus spillover and pathogenesis.
SN - 2058-5276
ER -