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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\u2013APN 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.<\/jats:p>","DOI":"10.1038\/s41564-026-02478-1","type":"journal-article","created":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T09:02:50Z","timestamp":1789549370000},"page":"2821-2838","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Convergent use of aminopeptidase N receptor by hedgehog merbecoviruses"],"prefix":"10.1038","volume":"11","author":[{"given":"Peng","family":"Liu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qianhui","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingyi","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhixing","family":"Ma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guocui","family":"Mou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuanling","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chen","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chengbao","family":"Ma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junyu","family":"Si","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meiling","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-8411-7470","authenticated-orcid":false,"given":"Yanchu","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yehui","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yucheng","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tianci","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lingling","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qianran","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Honghao","family":"Ma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qi","family":"Lv","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4869-3777","authenticated-orcid":false,"given":"Linlin","family":"Bao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5918-1078","authenticated-orcid":false,"given":"Yunlong","family":"Cao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0635-278X","authenticated-orcid":false,"given":"Xiangxi","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8744-8665","authenticated-orcid":false,"given":"Huan","family":"Yan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,9,16]]},"reference":[{"key":"2478_CR1","doi-asserted-by":"publisher","first-page":"1814","DOI":"10.1056\/NEJMoa1211721","volume":"367","author":"AM Zaki","year":"2012","unstructured":"Zaki, A. 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