COMPOSITIONS AND METHODS FOR THE TREATMENT OF VIRAL INFECTIONS
Compositions and methods for the treatment of viral infections include conjugates containing inhibitors of viral neuraminidase (e.g., zanamivir, peramivir, or analogs thereof) linked to an Fc monomer, an Fc domain, and Fc-binding peptide, an albumin protein, or albumin-binding peptide. In particular, conjugates can be used in the treatment of viral infections (e.g., influenza viral infections).
1 . A conjugate described by formula (D-I):
wherein each of A 1 and A 2 is zanamivir;
E comprises an Fc domain monomer;
L is a linker covalently attached to each of A 1 , A 2 , and E, wherein L is covalently attached to each of A 1 and A 2 at position C7 or position C9 of zanamivir;
n is 1 or 2; and
T is an integer from 1 to 20;
or a pharmaceutically acceptable salt thereof.
2 . The conjugate of claim 1 , wherein each L is covalently attached to the nitrogen atom of a surface exposed lysine of E.
3 . The conjugate of claim 1 , wherein each L is covalently attached to the sulfur atom of a surface exposed cysteine of E.
4 . The conjugate of claim 1 , wherein n is 2, and each E dimerizes to form an Fc domain.
5 . The conjugate of claim 1 , wherein each E comprises a serine substitution at C220, numbered according to the Kabat Index.
6 . The conjugate of claim 1 , wherein T is 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10.
7 . A population of conjugates of claim 1 , wherein the average value of T is 1 to 5.
8 . A method for the treatment of a subject having a viral infection or presumed to have a viral infection, the method comprising administering to the subject an effective amount of a conjugate of claim 1 .
9 . A method for the prophylactic treatment of a viral infection in a subject in need thereof, the method comprising administering to the subject an effective amount of a conjugate of claim 1 .