A MERS-CoV-like mink coronavirus uses ACE2 as an entry receptor

• 成果类型: Article
• 署名作者: Wang, Ningning; Ji, Weiwei; Jiao, Houqi; Veit, Michael; Sun, Ju; Wang, Yanjun; Ma, Xing; Wang, Yu; Wang, Yutong; Li, Xin-xin; Zhang, Xiaoguang; Chen, Jie; Wei, Jiayu; Xu, Ying; Guo, Dawei; Zhai, Xiaofeng; Merits, Andres; Li, Chang; Rey, Felix A.; Dobrikov, Georgi M.; Gao, George F.; Zhang, Shuijun; Bi, Yuhai; Su, Shuo
• 署名单位: Nanjing Agricultural University; Nanjing Agricultural University; Nanjing Agricultural University; Free University of Berlin; Chinese Academy of Sciences; University of Tartu; Chinese Academy of Medical Sciences - Peking Union Medical College; Centre National de la Recherche Scientifique (CNRS); CNRS - National Institute for Biology (INSB); Pasteur Network; Universite Paris Cite; Institut Pasteur Paris; Bulgarian Academy of Sciences; Chinese Academy of Sciences; University of Chinese Academy of Sciences, CAS; Zhejiang University; Jinzhou Medical University; Fudan University
• 刊物名称: Nature
• ISSN/ISSBN: 0028-2158
• DOI: 10.1038/s41586-025-09007-w
• 发表日期: 2025-06-19
• 关键词: respiratory syndrome coronavirus; bat coronavirus; cryo-em; sars-cov-2; binding; protein; domain; hku5

摘要

Despite accumulating evidence that bat-derived coronaviruses often require intermediate hosts to facilitate transmission to humans1, the potential role of fur animals in zoonotic coronavirus spillovers has largely been overlooked2. Here we report the isolation and characterization of a previously undescribed mink respiratory coronavirus (MRCoV) from farmed minks with pneumonia. Notably, MRCoV uses angiotensin-converting enzyme 2 (ACE2) as an entry receptor and can infect mink, bat, monkey and human cells. Cryo-electron microscopy analyses revealed that the MRCoV receptor-binding domain (RBD) binds to the same interface on ACE2 receptors as the RBD of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) despite structural differences. We identify the key determinants on the RBD of MRCoV and ACE2 that confer efficient binding. HKU5-33S, a bat coronavirus closely related to MRCoV, uses ACE2 of the bat Pipistrellus abramus for cell entry and requires only two amino acid substitutions to adapt to mink ACE2. SARS-CoV-2 protease and polymerase inhibitors potently block MRCoV infection, thereby indicating a potential therapeutic strategy. Collectively, these findings enhance our understanding of coronavirus receptor dynamics and highlight their zoonotic potential. Given the risks posed by fur farms as reservoirs for emerging pathogens, our study underscores the need for enhanced surveillance to mitigate future coronavirus outbreaks.