tetano
Editor, Senior Moderator
Nature
. 2025 Apr 30.
doi: 10.1038/s41586-025-09007-w. Online ahead of print. A MERS-CoV-like mink coronavirus uses ACE2 as entry receptor
Ningning Wang[SUP] #[/SUP][SUP] 1 [/SUP], Weiwei Ji[SUP] #[/SUP][SUP] 2 [/SUP], Houqi Jiao[SUP] #[/SUP][SUP] 1 3 [/SUP], Michael Veit[SUP] #[/SUP][SUP] 4 [/SUP], Ju Sun[SUP] #[/SUP][SUP] 5 [/SUP], Yanjun Wang[SUP] 5 [/SUP], Xing Ma[SUP] 1 [/SUP], Yu Wang[SUP] 1 [/SUP], Yutong Wang[SUP] 1 [/SUP], Xin-Xin Li[SUP] 1 [/SUP], Xiaoguang Zhang[SUP] 1 [/SUP], Jie Chen[SUP] 1 [/SUP], Jiayu Wei[SUP] 2 [/SUP], Ying Xu[SUP] 2 [/SUP], Dawei Guo[SUP] 1 [/SUP], Xiaofeng Zhai[SUP] 1 [/SUP], Andres Merits[SUP] 6 [/SUP], Chang Li[SUP] 7 [/SUP], Félix A Rey[SUP] 8 [/SUP], Georgi M Dobrikov[SUP] 9 [/SUP], George F Gao[SUP] 5 10 11 [/SUP], Shuijun Zhang[SUP] 12 [/SUP], Yuhai Bi[SUP] 13 14 15 16 [/SUP], Shuo Su[SUP] 17 18 19 [/SUP]
Affiliations
Despite accumulating evidence that bat-derived coronaviruses often require intermediate hosts to facilitate transmission to humans[SUP]1[/SUP], the potential role of fur animals in zoonotic coronavirus spillovers has largely been overlooked[SUP]2[/SUP]. Here we report the isolation and characterization of a novel mink respiratory coronavirus (MRCoV) from farmed minks with pneumonia. Notably, MRCoV uses angiotensin-converting enzyme 2 (ACE2) as a receptor and can infect mink, bat, monkey, and human cells. Cryo-electron microscopy analysis revealed that the MRCoV receptor-binding domain (RBD) binds to the same interface on ACE2 receptors as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RBD, despite exhibiting notable structural differences. We identify the key determinants on ACE2 and MRCoV RBD that confer efficient binding. HKU5-33S, a bat coronavirus closely related to MRCoV, utilizes ACE2 of bat Pipistrellus abramus and requires only two amino acid substitutions to adapt to mink ACE2. Furthermore, SARS-CoV-2 protease and polymerase inhibitors potently block MRCoV infection, indicating a potential therapeutic strategy. Collectively, these findings enhance the 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 urgent need for enhanced surveillance to mitigate future coronavirus outbreaks.
. 2025 Apr 30.
doi: 10.1038/s41586-025-09007-w. Online ahead of print. A MERS-CoV-like mink coronavirus uses ACE2 as entry receptor
Ningning Wang[SUP] #[/SUP][SUP] 1 [/SUP], Weiwei Ji[SUP] #[/SUP][SUP] 2 [/SUP], Houqi Jiao[SUP] #[/SUP][SUP] 1 3 [/SUP], Michael Veit[SUP] #[/SUP][SUP] 4 [/SUP], Ju Sun[SUP] #[/SUP][SUP] 5 [/SUP], Yanjun Wang[SUP] 5 [/SUP], Xing Ma[SUP] 1 [/SUP], Yu Wang[SUP] 1 [/SUP], Yutong Wang[SUP] 1 [/SUP], Xin-Xin Li[SUP] 1 [/SUP], Xiaoguang Zhang[SUP] 1 [/SUP], Jie Chen[SUP] 1 [/SUP], Jiayu Wei[SUP] 2 [/SUP], Ying Xu[SUP] 2 [/SUP], Dawei Guo[SUP] 1 [/SUP], Xiaofeng Zhai[SUP] 1 [/SUP], Andres Merits[SUP] 6 [/SUP], Chang Li[SUP] 7 [/SUP], Félix A Rey[SUP] 8 [/SUP], Georgi M Dobrikov[SUP] 9 [/SUP], George F Gao[SUP] 5 10 11 [/SUP], Shuijun Zhang[SUP] 12 [/SUP], Yuhai Bi[SUP] 13 14 15 16 [/SUP], Shuo Su[SUP] 17 18 19 [/SUP]
Affiliations
- PMID: 40306315
- DOI: 10.1038/s41586-025-09007-w
Despite accumulating evidence that bat-derived coronaviruses often require intermediate hosts to facilitate transmission to humans[SUP]1[/SUP], the potential role of fur animals in zoonotic coronavirus spillovers has largely been overlooked[SUP]2[/SUP]. Here we report the isolation and characterization of a novel mink respiratory coronavirus (MRCoV) from farmed minks with pneumonia. Notably, MRCoV uses angiotensin-converting enzyme 2 (ACE2) as a receptor and can infect mink, bat, monkey, and human cells. Cryo-electron microscopy analysis revealed that the MRCoV receptor-binding domain (RBD) binds to the same interface on ACE2 receptors as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RBD, despite exhibiting notable structural differences. We identify the key determinants on ACE2 and MRCoV RBD that confer efficient binding. HKU5-33S, a bat coronavirus closely related to MRCoV, utilizes ACE2 of bat Pipistrellus abramus and requires only two amino acid substitutions to adapt to mink ACE2. Furthermore, SARS-CoV-2 protease and polymerase inhibitors potently block MRCoV infection, indicating a potential therapeutic strategy. Collectively, these findings enhance the 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 urgent need for enhanced surveillance to mitigate future coronavirus outbreaks.