SARS-CoV-2 (the causative agent of COVID-19) is a major public health threat and one of two related coronaviruses that have caused epidemics in modern history. A method of screening potential infectible hosts for preemergent and future emergent coronaviruses would aid in mounting rapid response and intervention strategies during future emergence events. ABSTRACT The angiotensin-converting enzyme 2 (ACE2) receptor is a major severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) host range determinant, and understanding SARS-CoV-2-ACE2 interactions will provide important insights into COVID-19 pathogenesis and animal model development. SARS-CoV-2 cannot infect mice due to incompatibility between its receptor binding domain and the murine ACE2 receptor. Through molecular modeling and empirical in vitro validation, we identified 5 key amino acid differences between murine and human ACE2 that mediate SARS-CoV-2 infection, generating a chimeric humanized murine ACE2. Additionally, we examined the ability of the humanized murine ACE2 receptor to permit infection by an additional preemergent group 2B coronavirus, WIV-1, providing evidence for the potential pan-virus capabilities of this chimeric receptor. Finally, we predicted the ability of these determinants to inform host range identification of preemergent coronaviruses by evaluating hot spot contacts between SARS-CoV-2 and additional potential host receptors. Our results identify residue determinants that mediate coronavirus receptor usage and host range for application in SARS-CoV-2 and emerging coronavirus animal model development.
【저자키워드】 COVID-19, SARS-CoV-2, coronavirus, Virus-host interactions, host range, receptors, 【초록키워드】 ACE2, coronavirus, SARS-COV-2 infection, Infection, Epidemics, ACE2 receptor, Intervention, animal model, in vitro, angiotensin-converting enzyme 2, Receptor binding domain, human ACE2, COVID-19 pathogenesis, mice, receptor, molecular, Amino acid, Evidence, Interaction, Host receptors, Contact, rapid response, chimeric, determinant, acute respiratory syndrome, residue, public health threat, infect, murine, Host, humanized, predicted, identify, examined, caused, events, 【제목키워드】 ACE2, group, determinant,