Antiviral activity of Gas6 inhibitor
Compositions and methods are provided for treating viral infection in a mammal by administering a therapeutic dose of a pharmaceutical composition that inhibits AXL, MER or Tyro3 protein activity, for example by inhibition of the binding interaction between AXL, MER or Tyro3 and its ligand GAS6.
1. A method of inhibiting entry of an enveloped virus that expresses or incorporates phosphatidylserine in its outer membrane, into a cell, the method comprising:
administering a soluble AXL variant polypeptide in a dose effective to inhibit the interaction between phosphatidylserine present at the outer membrane of the virus and of GAS6, wherein the virus is a filovirus, a lentivirus, a poxvirus, or a herpesvirus; and wherein said soluble AXL variant polypeptide lacks the AXL transmembrane domain and comprises amino acid modifications selected from the group consisting of:
(i) Gly32Ser, Asp87Gly, Val92Ala, and Gly127Arg; and
(ii) Gly32Ser, Ala72Val, Asp87Gly, Val92Ala, and Gly127Arg.
2. A method of inhibiting entry of an enveloped Flavivirus that expresses or incorporates phosphatidylserine in its outer membrane, into an AXL-expressing cell, the method comprising:
administering a soluble AXL variant polypeptide in a dose effective to inhibit infection of AXL-expressing cells by the flavivirus, wherein said soluble AXL variant polypeptide lacks the AXL transmembrane domain and comprises amino acid modifications selected from the group consisting of:
(i) Gly32Ser, Asp87Gly, Val92Ala, and Gly127Arg; and
(ii) Gly32Ser, Ala72Val, Asp87Gly, Val92Ala, and Gly127Arg.