Jak/stat inhibitors and mapk/erk inhibitors for rsv infection

Abstract

The present invention concerns a method for treating or reducing the likelihood of developing a respiratory syncytial virus (RSV) infection in a subject by administering an effective amount of an inhibitor of the janus kinase (JAK)/signal transducer and activator of transcription (STAT) signaling pathway or the mitogen-activated kinase (MAPK)/extracellular signal-regulated kinase (ERK1/2) signaling pathway to the subject. Another aspect of the invention concerns a pharmaceutical composition that includes an inhibitor of JAK/STAT or MAPK/ERK signaling to the subject; and a pharmaceutically acceptable carrier. Another aspect of the invention concerns a method for identifying agents useful for treating or reducing the likelihood of developing an RSV infection

What is claimed is: 
     
         1 . A pharmaceutical composition comprising an inhibitor of janus kinase (JAK)/signal transducers and activators of transcription (STAT) signaling pathway or the mitogen-activated kinase (MAPK)/extracellular signal-regulated kinase (ERK) signaling pathway; and a pharmaceutically acceptable carrier. 
     
     
         2 . The pharmaceutical composition of  claim 1 , wherein the inhibitor is a polynucleotide. 
     
     
         3 . The pharmaceutical composition of  claim 1 , wherein the inhibitor is a polypeptide. 
     
     
         4 . The pharmaceutical composition of  claim 1 , wherein the inhibitor is an antibody. 
     
     
         5 . The pharmaceutical composition of  claim 1 , wherein the inhibitor is a small molecule. 
     
     
         6 . The pharmaceutical composition of  claim 1 , wherein the inhibitor is a polynucleotide, and wherein the polynucleotide encodes a polypeptide which, when expressed, inhibits JAK/STAT or MAPK/ERK signaling. 
     
     
         7 . The pharmaceutical composition of  claim 1 , wherein the inhibitor is a polynucleotide, and wherein the polynucleotide is an antisense molecule or a small interfering RNA (siRNA) molecule. 
     
     
         8 . The pharmaceutical composition of  claim 7 , wherein the inhibitor reduces expression of STAT-1 or STAT-3. 
     
     
         9 . The pharmaceutical composition of  claim 7 , wherein the inhibitor reduces expression of ERK1 or ERK2. 
     
     
         10 . The pharmaceutical composition of  claim 1 , wherein the composition is formulated for intranasal administration. 
     
     
         11 . The pharmaceutical composition of  claim 1 , wherein the composition is formulated for inhalation. 
     
     
         12 . The pharmaceutical composition of  claim 1 , wherein the composition further comprises an agent that promotes internalization of the inhibitor by respiratory epithelial cells. 
     
     
         13 . The pharmaceutical composition of  claim 1 , wherein the inhibitor is selected from the group consisting of AG490, PIAS protein, cytokine-inducible Src homology 2-containing (CIS) protein, CIS-related protein, suppressor of cytokine signaling-I protein (SOCS-1), tyrphostin, 4,5-dimethoxy-2-nitrobenzoic acid, 4,5-dimehtoxy-2-nitrobenzamide, 4-(phenyl)-amino-6,7-dimethoxyquinazoline, 4-(4′-hydroxyphenyl)-amino-6,7-dimethoxyquinazoline, 4-(3′-bromo-4′-hydroxylphenyl)-amino-6,7-dimethoxyquinalzoline, forskolin, and 3-isobutyl-1-methylxanthine (IBMX). 
     
     
         14 . The pharmaceutical composition of  claim 1 , wherein the inhibitor is a MAPK/ERK signaling inhibitor selected from the group consisting of GW5074, BAY 43-9006, ISIS 5132, PD98059, PD184352, U0126, Ro 09-2210, L-783,277, purvalanol, and imidazolium trans-imidazoledimethyl sulfoxide-tetrachlororuthenate (NAMI-A).