PAR-1 Antagonists for Use in the Treatment or Prevention of Influenza Virus Type A Infections

Abstract

The present invention provides methods and compositions (such as pharmaceutical compositions) comprising PAR1 antagonists for treating or preventing influenza virus type A infections, in particular H1N1 infection. PAR1 antagonists may be combined with a PAR2 agonist.

1 .- 8 . (canceled) 
     
     
         9 . A method of treating an influenza virus type A infection which comprises administration of a therapeutically effective amount of at least one Protease-Activated Receptor-1 (PAR-1) antagonist to a subject. 
     
     
         10 . The method according to  claim 9  wherein said influenza virus type A is H1 N1 virus. 
     
     
         11 . The method according to  claim 9  wherein said at least one PAR-1 antagonist is selected from the group consisting of a peptide, a peptide mimetic, a small molecule organic compound, an aptamer, a pepducin, a polynucleotide and an antibody. 
     
     
         12 . The method according to  claim 11  wherein said influenza virus type A is H1 N1 virus. 
     
     
         13 . The method according to  claim 9  wherein said at least one PAR-1 antagonist is N3-cyclopropyl-7-{[4-(1-methylethyl)phenyl]methyl)-7H-pyrrolo[3,2-f]quinazoline-1,3-diamine. 
     
     
         14 . The method according to  claim 13  wherein said influenza virus type A is H1 N1 virus. 
     
     
         15 . The method according to  claim 9  wherein said subject is a mammal. 
     
     
         16 . The method of  claim 9  wherein said subject is a human. 
     
     
         17 . A pharmaceutical composition comprising:
 (i) a therapeutically effective amount of at least one PAR-1 antagonist,   (ii) a therapeutically effective amount of at least one Protease-Activated Receptor-2 (PAR-2) agonist, and   (iii) a pharmaceutically acceptable carrier,   
       wherein said at least one PAR-1 antagonist is N3-cyclopropyl-7-{[4-(1-methylethyl)phenyl]methyl}-7H-pyrrolo[3,2-f]quinazoline-1,3-diamine. 
     
     
         18 . The composition of  claim 17  wherein the at least one PAR-1 antagonist is selected from the group consisting of a peptide, a peptide mimetic, a small molecule organic compound, an aptamer, a pepducin, a polynucleotide and an antibody. 
     
     
         19 . The composition of  claim 17  wherein the at least one PAR-2 agonist is selected from the group consisting of a peptide, a peptide derivative, a small molecule organic compound, an aptamer, and an antibody. 
     
     
         20 . The method of  claim 9  further comprising administration of a therapeutically effective amount of at least one Protease-Activated Receptor-2 (PAR-2) agonist wherein the at least one PAR-1 antagonist and the at least one PAR-2 agonist are administered simultaneously, separately or sequentially to the subject. 
     
     
         22 . The method of  claim 9  wherein the therapeutically effective amount of the PAR-1 antagonist is administered in a pharmaceutical composition comprising:
 a therapeutically effective amount of at least one PAR-1 antagonist, 
 (ii) a therapeutically effective amount of at least one Protease-Activated Receptor-2 (PAR-2) agonist and a pharmaceutically acceptable carrier. 
 
     
     
         23 . A method of treatment of an influenza virus type A infection which comprises administration of a therapeutically effective amount of at least one Protease-Activated Receptor-1 (PAR-1) antagonist to a subject,
 wherein said at least one PAR-1 antagonist is a compound selected from the group consisting of compounds which inhibit or suppress PAR1 biochemical or signalling activity; and   compounds which are capable of suppressing PAR1 expression or down-regulating PAR1 cellular levels.