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

Résumé fourni par la source

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. Several ACE2 glycans and residues within or near the binding interface were identified as determinants of orthologue selectivity. These viruses remain sensitive to several broadly neutralizing antibodies and entry inhibitors, indicating potential countermeasures for future outbreaks. These findings highlight the versatility of ACE2 as a functional receptor for diverse coronaviruses. The HKU25 clade MERS-related coronaviruses with broad distribution are shown to use ACE2 as a functional receptor, revealing unexpected receptor plasticity and offering new insights into coronavirus evolution, host range and potential zoonotic risk.

Ce résumé expose les affirmations des auteurs. BNTIC ne l’interprète pas comme une validation indépendante des résultats.