Department of Biophysics, College of Basic Medical Sciences, Second Military Medical University, Shanghai, 200433, China.
Team SMMU-China of the International Genetically Engineered Machine (iGEM) competition, Department of Biophysics, Second Military Medical University, Shanghai, 200433, China.
Nat Commun. 2020 Apr 24;11(1):2070. doi: 10.1038/s41467-020-16048-4.
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.
严重急性呼吸综合征冠状病毒 2（SARS-CoV-2）于 2019 年底在中国武汉出现，目前尚无特定的抗病毒治疗方法或疫苗。SARS-CoV-2 已被证明使用与 SARS-CoV 相同的细胞进入受体，即血管紧张素转换酶 2（ACE2）。在本报告中，我们通过将人 ACE2 的细胞外结构域连接到人免疫球蛋白 IgG1 的 Fc 区来生成重组蛋白。本研究还使用了一种含有低催化活性 ACE2 突变体的融合蛋白。然后对融合蛋白进行了表征。两种融合蛋白对 SARS-CoV 和 SARS-CoV-2 的受体结合域均具有高结合亲和力，并在小鼠体内表现出理想的药理学特性。此外，融合蛋白在体外中和了带有 SARS-CoV 或 SARS-CoV-2 刺突蛋白的病毒假型。由于这些融合蛋白对冠状病毒具有交叉反应性，因此它们有可能应用于 SARS-CoV-2 的诊断、预防和治疗。
