Neutralization of SARS-CoV-2 spike pseudotyped virus by recombinant ACE2-Ig

被引:335
作者
Lei, Changhai [1 ,2 ]
Qian, Kewen [1 ,2 ]
Li, Tian [1 ,2 ]
Zhang, Sheng [3 ]
Fu, Wenyan [4 ]
Ding, Min [5 ]
Hu, Shi [1 ,2 ]
机构
[1] Second Mil Med Univ, Coll Basic Med Sci, Dept Biophys, Shanghai 200433, Peoples R China
[2] Second Mil Med Univ, Dept Biophys, Team SMMU China Int Genetically Engn Machine iGEM, Shanghai 200433, Peoples R China
[3] Shanghai Jiao Tong Univ, Ruijin Hosp, Dept Crit Care Med, Sch Med, Shanghai 200011, Peoples R China
[4] Shanghai Jiao Tong Univ, Sch Med, Shanghai Peoples Hosp 9, Dept Assisted Reprod, Shanghai 200011, Peoples R China
[5] Pharchoice Therapeut Inc, Shanghai 201406, Peoples R China
基金
中国国家自然科学基金;
关键词
ANGIOTENSIN-CONVERTING ENZYME; CORONAVIRUS; FIBROSIS; RECEPTOR;
D O I
10.1038/s41467-020-16048-4
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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.
引用
收藏
页数:5
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