A novel biparatopic hybrid antibody-ACE2 fusion that blocks SARS-CoV-2 infection: implications for therapy.

• 影响指数: 6.44
• 发表时间: Jan-Dec 2020
• 来源期刊: MAbs
• DOI: 10.1080/19420862.2020.1804241
• PMID: 32804015
• 文章类型: Journal Article
• 中科院分区: Q2
• 方向: 医学
• 作者列表: Miao X,Luo Y,Huang X,Lee SMY,Yuan Z,Tang Y,Chen L,Wang C,Wu F,Xu Y,Jiang W,Gao W,Song X,Yan Y,Pang T,Chen C,Zou Y,Fu W,Wan L,Gilbert-Jaramillo J,Knight M,Tan TK,Rijal P,Townsend A,Sun J,Liu X,James W,Tsun A,Xu Y

关键词: Biparatopic; COVID-19; SARS-CoV-2; antibody-ACE2 fusion; neutralizing antibody

Mesh: Angiotensin-Converting Enzyme 2; Antibodies, Monoclonal / pharmacology; Antibodies, Neutralizing / pharmacology; Antibodies, Viral / pharmacology; Betacoronavirus / drug effects; COVID-19; Coronavirus Infections; Drug Design; Drug Discovery; Humans; Pandemics; Peptidyl-Dipeptidase A / drug effects; Pneumonia, Viral; Recombinant Proteins; SARS-CoV-2; Spike Glycoprotein, Coronavirus / drug effects

Abstract

In the absence of a proven effective vaccine preventing infection by SARS-CoV-2, or a proven drug to treat COVID-19, the positive results of passive immune therapy using convalescent serum provide a strong lead. We have developed a new class of tetravalent, biparatopic therapy, 89C8-ACE2. It combines the specificity of a monoclonal antibody (89C8) that recognizes the relatively conserved N-terminal domain of the viral Spike (S) glycoprotein, and the ectodomain of ACE2, which binds to the receptor-binding domain of S. This molecule shows exceptional performance in vitro, inhibiting the interaction of recombinant S1 to ACE2 and transduction of ACE2-overexpressing cells by S-pseudotyped lentivirus with IC50s substantially below 100 pM, and with potency approximately 100-fold greater than ACE2-Fc itself. Moreover, 89C8-ACE2 was able to neutralize authentic viral infection in a standard 96-h co-incubation assay at low nanomolar concentrations, making this class of molecule a promising lead for therapeutic applications.