Novel-anti-infective strategy against influenza virus and s. aureus coinfections

Abstract

The present invention relates to MEK inhibitor, p38 inhibitor and/or NFκB inhibitor for use in a method for the prophylaxis and/or treatment of a co-infection comprising a bacterial infection and an influenza virus infection or a bacterial infection alone. Also provided are compositions comprising such inhibitors for use in the prophylaxis and/or treatment of a co-infection comprising a bacterial infection and an influenza virus infection or a bacterial infection alone. In addition an in vitro test system, wherein the test system comprises cultured cells infected with an influenza virus and a bacterium or with a bacterium alone is provided.

What is claimed is: 
     
         1 . A method of treating a respiratory co-infection comprising a bacterial infection and an influenza virus infection in a human patient comprising administering to the patient an effective amount of a p38 inhibitor, wherein the bacterial infection is by a Staphylococcaceae bacterium or a Streptococcaceae bacterium. 
     
     
         2 . The method of  claim 1 , wherein the bacterial infection is by a Staphylococcaceae aureus bacterium. 
     
     
         3 . The method of  claim 1 , wherein the influenza virus infection is by an influenza A virus or an influenza B virus. 
     
     
         4 . The method of  claim 3 , wherein the influenza A virus is H1N1, H2N2, H3N2, H6N1, H7N7, H7N9, H9N2 H10N7, H10N8 or H5N1. 
     
     
         5 . The method of  claim 1 , wherein the p38 inhibitor is selected from the group consisting of SB202190, LY2228820, CAY10571, SB 203580, Tie2 Kinase Inhibitor, 2-(4-Chlorophenyl)-4-(fluorophenyl)-5-pyridin-4-yl-1,2-dihydropyrazol-3-one, CGH 2466, SB220025, Antibiotic LL Z1640-2, TAK 715, SB202190 hydrochloride, SKF 86002, AMG548, CMPD-1, EO 1428, JX 401, ML 3403, RWJ 67657, SB 202190, SB 203580, SB 203580 hydrochloride, SB 239063, SCIO 469, SX 011, TAK 715, Pamapimod, Losmapimod (GW856553), Dilmapimod (SB681323), VX 702, VX 745, Doramapimod (BIRB 796), BMS-582949, ARRY-797, PH797804 preferably VX-702, SB202190, Pamapimod, Losmapimod (GW856553), Dilmapimod (SB681323), Doramapimod (BIRB 796), BMS-582949, ARRY-797, PH797804 and SCIO-469. 
     
     
         6 . The method of  claim 1 , wherein the p38 inhibitor is combined with another p38 inhibitor inhibitor, a MEK inhibitor, an NFκB inhibitor, or combinations thereof. 
     
     
         7 . The method of  claim 1 , wherein the p38 inhibitor is combined with one or more inhibitors targeting the influenza virus, the bacterium, or both the virus and the bacterium. 
     
     
         8 . The method of  claim 7 , wherein the p38 inhibitor is administered contemporaneously, previously or subsequently to the one or more inhibitors targeting the influenza virus, the bacterium, or both the virus and the bacterium. 
     
     
         9 . The method of  claim 7 , wherein the one or more inhibitors targeting the influenza virus is a neuraminidase inhibitor. 
     
     
         10 . The method of  claim 9 , wherein the neuraminidase inhibitor is oseltamivir phosphate, zanamivir, oseltamivir, or peramivir 
     
     
         11 . The method of  claim 7 , wherein the one or more inhibitors targeting the influenza virus is a compound targeting an ion channel protein (M2). 
     
     
         12 . The method of  claim 11 , wherein the compound targeting ion channel protein (M2) is amantadine, rimantadine, or both amantadine and rimantadine. 
     
     
         13 . The method of  claim 7 , wherein the one or more inhibitors targeting the influenza virus is a compound targeting polymerase or endonuclease activity via interfering with a component of the viral polymerase complex, PB1, PB2, PA, or NP. 
     
     
         14 . The method of  claim 13 , wherein the compound targeting polymerase or endonuclease activity via interfering with a component of the viral polymerase complex, PB1 PB2, PA, or NP is NP blocker Nucleozin or polymerase inhibitor T-705. 
     
     
         15 . The method of  claim 7 , wherein the one or more inhibitors targeting the bacterium is an antibiotic. 
     
     
         18 . The method of  claim 15 , wherein the antibiotic is Gentamicin, Rifampicin, Lysosthaphin, Erythromycin, Levofloxacin Vancomycin, Teicoplanin, Penicillin, or Oxacillin.