Abstract
Severe acute respiratory syndrome coronavirus (SARS-CoV), SARS-CoV-2, and human coronavirus (hCoV)-NL63 utilize ACE2 as the functional receptor for cell entry, which leads to zoonotic infection. Horses (Equus caballus) attracted our attention because the spike protein receptor-binding domains (RBDs) of SARS-CoV-2 and SARS-CoV-2-related coronaviruses bind equine ACE2 (eACE2) with high affinity. Here we show that eACE2 binds the RBDs of these three coronaviruses and also SARS-CoV-2 variants but with lower affinities compared with human ACE2 (hACE2). Structural analysis and mutation assays indicated that eACE2-H41 accounts for the lower binding affinity of eACE2 to the RBDs of SARS-CoV-2 variants (Alpha, Beta, and Gamma), SARS-CoV, and hCoV-NL63. Pseudovirus infection assays showed that the SARS-CoV-2 Delta strain (B.1.617.2) displayed a significantly increased infection efficiency in eACE2-expressing HeLa cells. Our results reveal the molecular basis of eACE2 binding to the RBDs of SARS-CoV, SARS-CoV-2, and hCoV-NL63, which provides insights into the potential animal transmission of these ACE2-dependent coronaviruses.
Keywords: ACE2; SARS-CoV; SARS-CoV-2; complex structure; hCoV-NL63; horse; pseudovirus infection; receptor binding domain.
【저자키워드】 SARS-CoV-2, ACE2, SARS-CoV, horse, receptor binding domain., HCoV-NL63, pseudovirus infection, complex structure, 【초록키워드】 Coronaviruses, coronavirus, Mutation, SARS-CoV-2 variant, Infection, Delta, B.1.617.2, Transmission, binding affinity, hACE2, Receptor binding domain, human ACE2, Receptor-binding domain, pseudovirus, zoonotic, Gamma, Beta, receptor, affinity, binding, Analysis, RBDs, Efficiency, acute respiratory syndrome, complex, cell entry, high affinity, molecular basis, HeLa cells, equine, bind, significantly increased, indicated, functional, provide, coronavirus, the spike protein, the RBD, Equus, infection assay, the SARS-CoV-2, 【제목키워드】 spike receptor-binding domain, binding,