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Nature Microbiology· 2026Q1

Convergent use of aminopeptidase N receptor by hedgehog merbecoviruses

Peng Liu, Qianhui Zhu, Jingyi Liu, Zhixing Ma et al.

Short summary

Hedgehog aminopeptidase N (APN) is identified as the functional receptor for European and Asian hedgehog merbecoviruses (EriCoVs), with a distinct binding mode compared to other coronavirus families.

AI-generated from the title and abstract; the full text is not read.

Key points

  • Hedgehog aminopeptidase N (APN) is the functional receptor for European and Asian hedgehog merbecoviruses (EriCoVs).
  • EriCoVs exhibit restricted tropism, mainly using APN from hedgehogs and, to a lesser extent, felids.
  • The EriCoV-APN complex displays a distinct binding mode compared to alpha- and deltacoronaviruses.
  • Proteolytic activation of EriCoV spikes is context- and strain-dependent, facilitated by multiple proteases.
  • Antibodies targeting the EriCoV receptor-binding domain and hedgehog APN effectively inhibit viral entry.

AI-generated from the title and abstract; the full text is not read.

Abstract

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.

The authors' abstract, as published at the source. Nature Microbiology, 2026 · DOI ↗

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Field: Animal Science and Zoology

Animal Science and ZoologyAgricultural and Biological Sciences