%0 Journal Article
%T A novel biparatopic hybrid antibody-ACE2 fusion that blocks SARS-CoV-2 infection: implications for therapy.
%A Miao X
%A Luo Y
%A Huang X
%A Lee SMY
%A Yuan Z
%A Tang Y
%A Chen L
%A Wang C
%A Wu F
%A Xu Y
%A Jiang W
%A Gao W
%A Song X
%A Yan Y
%A Pang T
%A Chen C
%A Zou Y
%A Fu W
%A Wan L
%A Gilbert-Jaramillo J
%A Knight M
%A Tan TK
%A Rijal P
%A Townsend A
%A Sun J
%A Liu X
%A James W
%A Tsun A
%A Xu Y
%J MAbs
%V 12
%N 1
%D Jan-Dec 2020
%M 32804015
%F 6.44
%R 10.1080/19420862.2020.1804241
%X 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.