Compositions and methods for the treatment of viral infections

Abstract

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-II-6): 
       
         
           
           
               
               
           
         
         wherein each E comprises an Fc domain monomer; 
         n is 1 or 2; 
         T is an integer from 1 to 20; 
         L is a linker; 
         R 7  is selected from C 1 -C 20  alkyl; and 
         the squiggly line indicates that L is covalently attached to E; 
       
       or a pharmaceutically acceptable salt thereof. 
     
     
         2 . The conjugate of  claim 1 , wherein the squiggly line indicates that L is covalently attached to a nitrogen atom of a solvent-exposed lysine of E. 
     
     
         3 . The conjugate of  claim 1 , wherein the squiggly line indicates that L is covalently attached to a sulfur atom of a solvent-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 T is 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10. 
     
     
         6 . A population of conjugates of  claim 1 , wherein the average value of T is 1 to 10, 5 to 10, 1 to 5, 3 to 7, or 3.5 to 5.5. 
     
     
         7 . The conjugate of  claim 1 , wherein R 7  is methyl, ethyl, propyl, or butyl. 
     
     
         8 . The conjugate of  claim 7 , wherein the conjugate is described by formula (D-II-7): 
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt thereof. 
       
     
     
         9 . The conjugate of  claim 8 , wherein the conjugate is described by formula (D-II-8): 
       
         
           
           
               
               
           
         
         wherein L′ is the remainder of L, and 
         y 1  and y 2  are each independently an integer from 1-20, 
         or a pharmaceutically acceptable salt thereof. 
       
     
     
         10 . The conjugate of  claim 9 , wherein the conjugate has the structure of: 
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt thereof. 
       
     
     
         11 . The conjugate of  claim 10 , wherein the conjugate has the structure of: 
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt thereof. 
       
     
     
         12 . The conjugate of  claim 11 , wherein n is 2, and each E dimerizes to form an Fc domain. 
     
     
         13 . The conjugate of  claim 11 , wherein T is 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10. 
     
     
         14 . A population of conjugates of  claim 11 , wherein the average value of T is 1 to 10, 5 to 10, 1 to 5, 3 to 7, or 3.5 to 5.5. 
     
     
         15 . A method for the treatment of a subject having a viral infection, the method comprising administering to the subject an effective amount of a conjugate of  claim 1 . 
     
     
         16 . 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 . 
     
     
         17 . A method of preventing a secondary infection in a subject diagnosed with an influenza infection, the method comprising administering to the subject an effective amount of a conjugate of  claim 1 .