Close relatives of MERS-CoV in bats use ACE2 as their functional receptors.
Nature
; 612(7941): 748-757, 2022 12.
Artigo
em Inglês
| MEDLINE | ID: covidwho-2151056
ABSTRACT
Middle East respiratory syndrome coronavirus (MERS-CoV) and several bat coronaviruses use dipeptidyl peptidase-4 (DPP4) as an entry receptor1-4. However, the receptor for NeoCoV-the closest known MERS-CoV relative found in bats-remains unclear5. 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.
Texto completo:
Disponível
Coleções:
Bases de dados internacionais
Base de dados:
MEDLINE
Assunto principal:
Receptores Virais
/
Quirópteros
/
Internalização do Vírus
/
Coronavírus da Síndrome Respiratória do Oriente Médio
/
Enzima de Conversão de Angiotensina 2
Tipo de estudo:
Ensaios controlados aleatorizados
Limite:
Animais
/
Humanos
Idioma:
Inglês
Revista:
Nature
Ano de publicação:
2022
Tipo de documento:
Artigo
País de afiliação:
S41586-022-05513-3
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