Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in Wuhan, China, at the end of 2019, and there are currently no specific antiviral treatments or vaccines available. SARS-CoV-2 has been shown to use the same cell entry receptor as SARS-CoV, angiotensin-converting enzyme 2 (ACE2). In this report, we generate a recombinant protein by connecting the extracellular domain of human ACE2 to the Fc region of the human immunoglobulin IgG1. A fusion protein containing an ACE2 mutant with low catalytic activity is also used in this study. The fusion proteins are then characterized. Both fusion proteins have a high binding affinity for the receptor-binding domains of SARS-CoV and SARS-CoV-2 and exhibit desirable pharmacological properties in mice. Moreover, the fusion proteins neutralize virus pseudotyped with SARS-CoV or SARS-CoV-2 spike proteins in vitro. As these fusion proteins exhibit cross-reactivity against coronaviruses, they have potential applications in the diagnosis, prophylaxis, and treatment of SARS-CoV-2. SARS-CoV-2 uses ACE2 as the entry receptor. Here, the authors show that an ACE2-Ig fusion protein inhibits entry of virus pseudotyped with the SARS-CoV-2 spike protein, show differential binding kinetics of SARS-CoV and SARSCoV-2 spike proteins to ACE2, and determine pharmakocinetic parameters of ACE2-Ig in mice.
【저자키워드】 SARS-CoV-2, viral infection, Recombinant protein therapy, 【초록키워드】 Treatment, ACE2, Coronaviruses, Vaccine, coronavirus, SARS-CoV, Diagnosis, Antiviral treatment, in vitro, virus, binding affinity, Spike protein, Prophylaxis, cross-reactivity, human ACE2, Protein, mice, SARS-CoV-2 spike protein, mutant, receptor, fusion protein, IgG1, binding kinetics, SARSCoV-2, acute respiratory syndrome, enzyme, domain, Fc region, parameter, catalytic activity, human immunoglobulin, pseudotyped, pharmacological, neutralize, Extracellular, Wuhan, China, cell entry receptor, shown, inhibit, generate, characterized, determine, the receptor-binding domain, 【제목키워드】 Pseudotyped virus, SARS-CoV-2 spike,