8ZWE

Cryo-EM structure of MRCoV RBD in complex with mink ACE2

Summary for 8ZWE

• Entry DOI: 10.2210/pdb8zwe/pdb
• EMDB information: 60524
• Descriptor: Spike glycoprotein, Angiotensin-converting enzyme, 2-acetamido-2-deoxy-beta-D-glucopyranose (3 entities in total)
• Functional Keywords: neogale vison hku5-related coronavirus, mink ace2, complex, viral protein/hydrolase, viral protein-hydrolase complex
• Biological source: Bat coronavirus HKU5 (BtCoV, BtCoV/HKU5/2004); More
• Total number of polymer chains: 2
• Total formula weight: 96055.61

Authors

Ji, W.,Zhang, S. (deposition date: 2024-06-12, release date: 2025-03-12, Last modification date: 2025-07-23)

Primary citation

Wang, N.,Ji, W.,Jiao, H.,Veit, M.,Sun, J.,Wang, Y.,Ma, X.,Wang, Y.,Wang, Y.,Li, X.X.,Zhang, X.,Chen, J.,Wei, J.,Xu, Y.,Guo, D.,Zhai, X.,Merits, A.,Li, C.,Rey, F.A.,Dobrikov, G.M.,Gao, G.F.,Zhang, S.,Bi, Y.,Su, S.
A MERS-CoV-like mink coronavirus uses ACE2 as an entry receptor.
Nature, 642:739-746, 2025

PubMed Abstract: Despite accumulating evidence that bat-derived coronaviruses often require intermediate hosts to facilitate transmission to humans, the potential role of fur animals in zoonotic coronavirus spillovers has largely been overlooked. 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.

PubMed: 40306315
DOI: 10.1038/s41586-025-09007-w

Experimental method

ELECTRON MICROSCOPY (3 Å)