9N7E

Eptesicus fuscus ACE2 peptidase domain bound to VsCoV-a7 RBD complex

Summary for 9N7E

• Entry DOI: 10.2210/pdb9n7e/pdb
• EMDB information: 49093
• Descriptor: Angiotensin-converting enzyme 2, VsCoV-a7-S RBD, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (6 entities in total)
• Functional Keywords: virus, hku25 clade mers-related coronaviruses, ace2, glycoprotein, receptor, structural genomics, seattle structural genomics center for infectious disease, ssgcid, hydrolase-viral protein complex, hydrolase/viral protein
• Biological source: Eptesicus fuscus; More
• Total number of polymer chains: 2
• Total formula weight: 122257.71

Authors

Park, Y.J.,Veesler, D.,Seattle Structural Genomics Center for Infectious Disease (SSGCID) (deposition date: 2025-02-05, release date: 2025-08-27)

Primary citation

Liu, C.,Park, Y.J.,Ma, C.B.,Stuart, C.,Gen, R.,Sun, Y.C.,Yang, X.,Lin, M.Y.,Xiong, Q.,Si, J.Y.,Liu, P.,Veesler, D.,Yan, H.
ACE2 utilization of HKU25 clade MERS-related coronaviruses with broad geographic distribution.
Biorxiv, 2025

PubMed Abstract: Dipeptidyl peptidase-4 (DPP4) is a well-established receptor for several MERS-related coronaviruses (MERSr-CoVs) isolated from humans, camels, pangolins, and bats (1-6). However, the receptor usage of many genetically diverse bat MERSr-CoVs with broad geographical distributions remains poorly understood. Recent studies have identified angiotensin-converting enzyme 2 (ACE2) as an entry receptor for multiple merbecovirus clades. Here, using viral antigen and pseudovirus-based functional assays, we demonstrate that several bat merbecoviruses from the HKU25 clade previously thought to utilize DPP4 (7), employ ACE2 as their functional receptor. Cryo-electron microscopy analysis revealed that HsItaly2011 and VsCoV-a7 recognize ACE2 with a binding mode sharing similarity with that of HKU5 but involving remodeled interfaces and distinct ortholog selectivity, suggesting a common evolutionary origin of ACE2 utilization for these two clades of viruses. EjCoV-3, a strain closely related to the DPP4-using MERSr-CoV BtCoV-422, exhibited relatively broad ACE2 ortholog tropism and could utilize human ACE2 albeit suboptimally. Despite differences in entry mechanisms and spike proteolytic activation compared to MERS-CoV, these viruses remain sensitive to several broadly neutralizing antibodies and entry inhibitors. These findings redefine our understanding of the evolution of receptor usage among MERSr-CoVs and highlight the versatility of ACE2 as a functional receptor for diverse coronaviruses.

PubMed: 40027745
DOI: 10.1101/2025.02.19.639017

Experimental method

ELECTRON MICROSCOPY (2.5 Å)