Anti-heparan sulfate peptides that block herpes simplex virus infection in vivo

Abstract

Provided are anti-heparan sulfate peptides and methods that employ those peptides for the prevention or treatment of viral infections, including herpesviral infections such as α-herpesviral, β-herpesviral, and γ-herpesviral infections, which are exemplified by HSV-1. CMV, and HHV-8 viral infections, respectively. Peptides may comprise at least 10 amino acids of the amino acid sequences X R X R X K XX R X R X (SEQ ID NO: 2), X R X R XX K X R X R X (SEQ ID NO: 8), XX RRRR X RRR X K (SEQ ID NO: 4), and/or K X RRR X RRRR XX (SEQ ID NO: 10), wherein X represents any amino acid. In some embodiments, peptides comprise at least 10 amino acids of the sequence LRSRTKIIRIRH (SEQ ID NO: 1), HRIRIIKTRSRL (SEQ ID NO: 7), MPRRRRIRRRQK (SEQ ID NO: 3), and/or KQRRRIRRRRM (SEQ ID NO: 9). Peptides may be coupled to one or more therapeutic compound(s) to generate peptide-therapeutic compound conjugates, wherein the therapeutic compound may be one or more of a nucleoside analog, an oligosaccharide, and a small molecule.

What is claimed is: 
     
         1 . A peptide comprising at least 10 consecutive amino acids of the sequence X R X R X K XX R X R X (SEQ ID NO: 2) or X R X R XX K X R X R X (SEQ ID NO: 8), wherein X is any amino acid, R is arginine, and K is lysine. 
     
     
         2 . The peptide of  claim 1  wherein said peptide comprises at least 12 consecutive amino acids of the sequence X R X R X K XX R X R X (SEQ ID NO: 2) or X R X R XX K X R X R X (SEQ ID NO: 8). 
     
     
         3 . The peptide of  claim 2  wherein said peptide is 12 amino acids in length. 
     
     
         4 . The peptide of  claim 1  wherein each X is independently selected from the group consisting of leucine, serine, threonine, isoleucine, and histidine. 
     
     
         5 . The peptide of  claim 1  wherein said peptide comprises at least 10 consecutive amino acids of the sequence LRSRTKIIRIRH (SEQ ID NO: 1) or HRIRIIKTRSRL (SEQ ID NO: 7). 
     
     
         6 . The peptide of  claim 5  wherein said peptide comprises at least 12 consecutive amino acids of the sequence LRSRTKIIRIRH (SEQ ID NO: 1) or HRIRIIKTRSRL (SEQ ID NO: 7). 
     
     
         7 . The peptide of  claim 1  wherein said peptide comprises at least one D-amino acid. 
     
     
         8 . The peptide of  claim 6  wherein said peptide is 12 amino acids in length. 
     
     
         9 . The peptide of  claim 1  wherein said peptide comprises at least 10 consecutive amino acids of the sequence RSRTKIIRIR (SEQ ID NO: 5) or RIRIIKTRSR (SEQ ID NO: 11). 
     
     
         10 . The peptide of  claim 7  wherein all the amino acids in said peptide are D-amino acids. 
     
     
         11 . A peptide comprising at least 10 consecutive amino acids of the sequence XX RRRR X RRR X K  (SEQ ID NO: 4) or  K X RRR X RRRR XX (SEQ ID NO: 10) wherein X is any amino acid, R is arginine, and K is lysine. 
     
     
         12 . The peptide of  claim 11  wherein said peptide comprises at least 12 consecutive amino acids of the sequence XX RRRR X RRR X K  (SEQ ID NO: 4) or  K X RRR X RRRR XX (SEQ ID NO: 10). 
     
     
         13 . The peptide of  claim 12  wherein said peptide is 12 amino acids in length. 
     
     
         14 . The peptide of  claim 11  wherein each X is independently selected from the group consisting of methionine, proline, isoleucine, and glutamine. 
     
     
         15 . The peptide of  claim 11  wherein said peptide comprises at least 10 consecutive amino acids of the sequence MPRRRRIRRRQK (SEQ ID NO: 3) or KQRRRIRRRRPM (SEQ ID NO: 9). 
     
     
         16 . The peptide of  claim 15  wherein said peptide comprises at least 12 consecutive amino acids of the sequence MPRRRRIRRRQK (SEQ ID NO: 3) or KQRRRIRRRRPM (SEQ ID NO: 9). 
     
     
         17 . The peptide of  claim 11  wherein said peptide comprises at least one D-amino acid. 
     
     
         18 . The peptide of  claim 11  wherein said peptide is 12 amino acids in length. 
     
     
         19 . The peptide of  claim 11  wherein said peptide comprises at least 10 consecutive amino acids of the sequence RRRRIRRRQK (SEQ ID NO: 6) or KQRRRIRRRR (SEQ ID NO: 12). 
     
     
         20 . The peptide of  claim 17  wherein all the amino acids in said peptide are D-amino acids. 
     
     
         21 . A method for blocking the binding of a virus to a target cell, said method comprising the step of contacting said target cell with a peptide comprising at least 10 consecutive amino acids of a sequence selected from the group consisting of X R X R X K XX R X R X (SEQ ID NO: 2), X R X R XX K X R X R X (SEQ ID NO: 8), XX RRRR X RRR X K  (SEQ ID NO: 4), and  K X RRR X RRRR XX (SEQ ID NO: 10), wherein X is any amino acid, R is arginine, and K is lysine. 
     
     
         22 . A peptide-therapeutic compound conjugate, comprising:
 (a) at least 10 consecutive amino acids of a sequence selected from the group consisting of X R X R X K XX R X R X (SEQ ID NO: 2), X R X R XX K X R X R X (SEQ ID NO: 8), XX RRRR X RRR X K  (SEQ ID NO: 4), and  K X RRR X RRRR XX (SEQ ID NO: 10), wherein X is any amino acid, R is arginine, and K is lysine; and   (b) a therapeutic compound;   wherein said peptide is coupled to said therapeutic compound to generate said conjugate.