HKU25 clade MERS-related coronaviruses use ACE2 as a functional receptor.

ABSTRACT: Dipeptidyl peptidase-4 (DPP4) is an established receptor for Middle East respiratory syndrome-related coronaviruses (MERSr-CoVs), while recent studies have identified angiotensin-converting enzyme 2 (ACE2) usage in multiple merbecovirus clades. Yet, receptor usage of many genetically diverse bat MERSr-CoVs remains unclear. Here we show that broadly distributed HKU25 clade merbecoviruses use ACE2, rather than DPP4, as their receptor. Cryo-electron microscopy revealed that HsItaly2011 and VsCoV-a7 strains engage ACE2 similarly to HKU5 but with remodelled interfaces and distinct orthologue selectivity, suggesting a shared evolutionary origin of ACE2 recognition. EjCoV-3, a close relative of the DPP4-using BtCoV422, showed broad multi-species ACE2 tropism and preadaptation to human ACE2. Sever

SUBMITTER: Liu C 

PROVIDER: S-EPMC12578636 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature