ACE2-Fc Trap

Abstract

An ACE2-Fc hybrid construct is used as a therapeutic and/or analytic entity to treat an individual infected with a coronavirus or to detect a coronavirus in an analyte. In selected embodiments, the Fc portion of the hybrid construct is an IgA Fc portion, and in still further embodiments the ACE2 portion has a mutation that reduces or abolishes ACE2 catalytic activity.

1 . A soluble ACE2-Fc hybrid construct, having an amino acid sequence at least 85% identical to SEQ ID NO:7 or SEQ ID NO:8. 
     
     
         2 . The soluble hybrid construct of  claim 1 , wherein a C-terminus of the ACE2 portion is coupled to an N-terminus of the immunoglobulin IgA Fc portion, and wherein:
 a) the ACE2 portion has at least 85% sequence identity to SEQ ID NO:9; and/or   b) the immunoglobulin IgA Fc portion has at least 85% sequence identity to SEQ ID NO:10 or 11.   
     
     
         3 . The soluble hybrid construct of  claim 1 , wherein the ACE2 portion is catalytically inactive. 
     
     
         4 . The soluble hybrid construct of  claim 1 , further comprising a J-chain portion. 
     
     
         5 . The soluble hybrid construct of  claim 1 , having an amino acid sequence at least 95% identity to SEQ ID NO:7 or SEQ ID NO:8. 
     
     
         6 . The soluble hybrid construct of  claim 1 , further comprising a detectable label coupled to the hybrid construct. 
     
     
         7 . The soluble hybrid construct of  claim 1 , formulated in a pharmaceutically acceptable carrier. 
     
     
         8 . The soluble hybrid construct of  claim 7 , wherein the pharmaceutically acceptable carrier is formulated for inhalation, nasal administration, or injection. 
     
     
         9 . A recombinant nucleic acid encoding the ACE2-Fc hybrid construct of  claim 1 . 
     
     
         10 . The recombinant nucleic acid of  claim 9 , wherein the nucleic acid is an RNA. 
     
     
         11 . The recombinant nucleic acid of  claim 9 , wherein the nucleic acid is a DNA. 
     
     
         12 . The recombinant nucleic acid of  claim 11 , wherein the recombinant nucleic acid is an expression vector. 
     
     
         13 . The recombinant4 nucleic acid of  claim 12 , having a nucleic acid sequence of SEQ ID NO:3 or SEQ ID NO:4. 
     
     
         14 . A method of treating a coronavirus infection in an individual in need thereof, the method comprising:
 administering to the individual a therapeutically effective amount of an ACE2-Fc hybrid construct of  claim 1 .   
     
     
         15 . The method of  claim 14 , wherein the coronavirus is SARS-CoV-2. 
     
     
         16 . The method of  claim 14 , wherein the administering comprises nasal or pulmonary administration or intravenous injection. 
     
     
         17 . A method of detecting a coronavirus, the method comprising:
 adding a test sample to a surface to which an ACE2-Fc hybrid construct is coupled, to thereby bind coronaviral Spike protein to the ACE2-Fc hybrid construct;   contacting the Spike protein that is bound to the ACE2-Fc hybrid construct with a detectable binder; and   detecting the detectable binder.   
     
     
         18 . The method of  claim 17 , wherein the ACE2-Fc hybrid construct is coupled to the test surface via a biotin group that is coupled to the ACE2-Fc hybrid construct. 
     
     
         19 . The method of  claim 17  or  claim 18 , wherein the detectable binder is an ACE2-Fc hybrid construct that is coupled to a detectable label. 
     
     
         20 . The method of any one of  claims 17 - 19 , wherein the detectable binder includes an electrochemiluminescent moiety.