Close relatives of MERS-CoV in bats use ACE2 as their functional receptors

Article

关键词: RESPIRATORY SYNDROME CORONAVIRUS;    DIPEPTIDYL PEPTIDASE 4;    CELL ENTRY;    BAYESIAN-APPROACH;    BINDING DOMAIN;    VIRUS;    REFINEMENT;    USAGE;    RECOGNITION;    MICROSCOPY;   

DOI  :  10.1038/s41586-022-05513-3

来源: SCIE

【 摘 要 】

Middle East respiratory syndrome coronavirus (MERS-CoV) and several bat coronaviruses use dipeptidyl peptidase-4 (DPP4) as an entry receptor(1-4). However, the receptor for NeoCoV-the closest known MERS-CoV relative found in bats-remains unclear(5). Here, using a pseudotype virus entry assay, we found that NeoCoV and its close relative, PDF-2180, can efficiently bind to and use specific bat angiotensin-converting enzyme 2 (ACE2) orthologues and, less favourably, human ACE2 as entry receptors through their receptor-binding domains (RBDs) on the spike (S) proteins. Cryo-electron microscopy analysis revealed an RBD-ACE2 binding interface involving protein-glycan interactions, distinct from those of other known ACE2-using coronaviruses. We identified residues 337-342 of human ACE2 as a molecular determinant restricting NeoCoV entry, whereas a NeoCoV S pseudotyped virus containing a T510F RBD mutation efficiently entered cells expressing human ACE2. Although polyclonal SARS-CoV-2 antibodies or MERS-CoV RBD-specific nanobodies did not cross-neutralize NeoCoV or PDF-2180, an ACE2-specific antibody and two broadly neutralizing betacoronavirus antibodies efficiently inhibited these two pseudotyped viruses. We describe MERS-CoV-related viruses that use ACE2 as an entry receptor, underscoring a promiscuity of receptor use and a potential zoonotic threat.

【 授权许可】

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