ACE2-Fc Trap
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.