Treatment of viral infections

Abstract

The present invention concerns polypeptides derived from a tandem repeat of apoE 141-149 and their uses as medicaments. The peptides may comprise the tandem repeat, and truncations thereof, for which at least one Leucine (L) is replaced by an amino acid with a side chain comprising at least 4 carbon atoms and at least one Nitrogen atom. Such peptides are useful for preventing or treating viral infections.

1 . A polypeptide, derivative or analogue thereof comprising a tandem repeat of apoE141-149 of SEQ ID No 2 or a truncation thereof, characterised in that at least one Leucine (L) residue of SEQ ID No. 2 is replaced by an amino acid with a side chain comprising at least 4 carbon atoms and at least one Nitrogen atom. 
     
     
         2 . The polypeptide, derivative or analogue thereof according to  claim 1  wherein the amino acid used to replace the Leucine is selected from the group consisting of: Tryptophan (W), Arginine (R), Lysine (K) and derivatives thereof. 
     
     
         3 . The polypeptide, derivative or analogue thereof according to  claim 2  wherein the amino acid used to replace the Leucine is Tryptophan (W) or a derivative thereof. 
     
     
         4 . The polypeptide, derivative or analogue thereof according to  claim 1  wherein at least two W, R or K substitutions are made. 
     
     
         5 . The polypeptide, derivative or analogue thereof according to  claim 1  wherein at least one further amino acid is replaced with Asparagine (N), Tyrosine (Y), Cysteine (C), Methionine (M), Phenylalanine (F), Isoleucine (I), Glutamine (Q), or Histidine (H) or is deleted. 
     
     
         6 . The polypeptide, derivative or analogue thereof according to  claim 1  with the amino acid sequence: 
       
         
           
                 
                 
                 
               
                     
                   WRKWRKRWWWRKWRKRWW; 
                   (SEQ ID No. 3) 
                 
                     
                     
                 
                     
                   WRKWRKRWRKWRKR; 
                   (SEQ ID No. 4) 
                 
                     
                     
                 
                     
                   WRKWRKRWWLRKLRKRLL; 
                   (SEQ ID No. 5) 
                 
                     
                     
                 
                     
                   YRKYRKRYYYRKYRKRYY; 
                   (SEQ ID No. 6) 
                 
                     
                     
                 
                     
                   WRKWRKRWWRKWRKRWW; 
                   (SEQ ID No. 52) 
                 
                     
                     
                 
                     
                   WRKWRKRWRKWRKRW; 
                   (SEQ ID No. 53) 
                 
                     
                     
                 
                     
                   WRKWRKRWWFRKWRKRWW; 
                   (SEQ ID No. 54) 
                 
                     
                     
                 
                     
                   WRKWRKRWFFRKWRKRFF; 
                   (SEQ ID No. 55) 
                 
                     
                     
                 
                     
                   WRKCRKRCWWRKCRKRCW; 
                   (SEQ ID No. 56) 
                 
                     
                     
                 
                     
                   LRKLRKRLLWRKWRKRWW; 
                   (SEQ ID No. 57) 
                 
                     
                     
                 
                     
                   LRKLRKRLLLRKLRKRWW; 
                   (SEQ ID No. 58) 
                 
                     
                     
                 
                     
                   LRKLRKRLLWRKWRKRLL; 
                   (SEQ ID No. 59) 
                 
                     
                     
                 
                     
                   WRKWRKRLLLRKLRKRLL; 
                   (SEQ ID No. 60) 
                 
                     
                     
                 
                     
                   WRKLRKRLLLRKLRKRLL; 
                   (SEQ ID No. 61) 
                 
                     
                     
                 
                     
                   WRKWRKFFFRKWRKRWW; 
                   (SEQ ID No. 62) 
                 
                     
                     
                 
                     
                   WRKWRKRWWFRKFRKRFF; 
                   (SEQ ID No. 63) 
                 
                     
                     
                 
                     
                   RRKRRKRRRRRKRRKRRR; 
                   (SEQ ID No. 64) 
                 
                     
                   or 
                 
                     
                     
                 
                     
                   KRKKRKRKKKRKKRKRKK 
                   (SEQ ID No. 65) 
                 
             
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
               
            
           
         
       
     
     
         7 . The polypeptide, derivative or analogue according to  claim 1  wherein an amino acid is added to the peptide. 
     
     
         8 . The polypeptide, derivative or analogue according to  claim 7  wherein the amino acid is added to the N terminal, C terminal and/or between the ninth and tenth amino acids of SEQ ID No.2. 
     
     
         9 . The polypeptide, derivative, or analogue according to  claim 8  comprising WRKWRKRWWRWRKWRKRWWR (SEQ ID No. 66). 
     
     
         10 . The polypeptide, derivative or analogue according to  claim 1  which is a peptide analogue. 
     
     
         11 . The polypeptide, derivative or analogue according to  claim 1  which is a peptide/peptoid hybrid. 
     
     
         12 . A polypeptide, derivative or analogue thereof comprising YRKYRKRYYYRKYRKRYY (SEQ ID No. 6), or LRKLRKRLLLRKLRK (SEQ ID No. 7). 
     
     
         13 . (canceled) 
     
     
         14 . A polypeptide, derivative or analogue thereof comprising LRKLRKRLRKLRKR (SEQ ID No. 8) or LRKLRKLRKLRKLRKLRK (SEQ ID No. 9). 
     
     
         15 . (canceled) 
     
     
         16 . A composition, comprising the polypeptide, derivative or analogue according to  claim 1 . 
     
     
         17 . (canceled) 
     
     
         18 . An agent adapted to increase the biological activity of the polypeptide, derivative or analogue according to  claim 1 . 
     
     
         19 . A method of preventing and/or treating a viral infection, comprising administering to a subject in need of such treatment a therapeutically effective amount of a polypeptide, derivative or analogue according to  claim 1 . 
     
     
         20 . A nucleic acid sequence encoding a polypeptide, derivative or analogue according to  claim 1 . 
     
     
         21 . A composition, comprising the nucleic acid sequence according to  claim 20 . 
     
     
         22 . A method Of preventing and/or treating a viral infection comprising administering to a subject in need of such treatment a therapeutically effective amount of a nucleic acid sequence according to  claim 20 .