Kinase inhibitors for preventing or treating pathogen infection and method of use thereof

Abstract

The present invention provides compositions and methods of use thereof to prevent and/or treat pathogenic infection. In particular, the present invention provides the use of kinase inhibitors to inhibit kinases that involve in pathogen-host cell interactions that are associated with or cause pathogenic infections, therefore, to effectively prevent and/or treat pathogenic infections with far less likely to engender resistance as compared to conventional antibiotics and anti-viral drugs. The present invention further provides the use of kinase inhibitors for the treatment of acute pathogenic infections for a short period of time to avoid toxicities that may caused by long term use of these kinase inhibitors.

1 . A method of preventing or treating pathogenic infection comprising administering a therapeutically effective amount of compositions comprising one or more kinase inhibitors as set forth in Table A to a patient in need thereof for preventing or treating infection caused by a broad array of pathogens. 
     
     
         2 . The method of  claim 1 , wherein said kinase inhibitors are tyrosine kinase inhibitors. 
     
     
         3 . The method of  claim 2 , wherein said tyrosine kinase inhibitors are Abl- or Src-family tyrosine kinase inhibitors. 
     
     
         4 . The method of  claim 1 , wherein said pathogenic infection is caused by bacterial pathogens. 
     
     
         5 . The method of  claim 4 , wherein said bacterial pathogens are selected from the group consisting of  Escherichia coli  (enteropathogenic  Escherichia coli  (EPEC), enterohemmorhagic  Escherichia coli  (EHEC), uropathogenic  Escherichia coli  (UPEC), and enteroinvasive  Escherichia coli  (EIEC)),  Mycobacterium tuberculosis  (mTB),  Pseudomonas aerginosa, Chlamydia trachomatis , Pox viruses (including Vaccinia and variola viruses), polyoma viruses (including JC and BK viruses), human immunodeficiency viruses (for example, HIV-1), Herpes viruses (including Herpes Simplex virus, Epstein Barr virus, and Gamma Herpes virus), influenza virus,  Shigella flexneri , Coxsakie virus,  Helicobacter pylori , West Nile virus,  Listeria monocytogeres, Salmonella typhimurium , cytomegalovirus (CMV), and other pathogens. 
     
     
         6 . The method of  claim 1 , wherein said pathogenic infection is caused by viral pathogens. 
     
     
         7 . The method of  claim 6 , wherein said viral pathogens are selected from the group consisting of Adenoviridae, Arenaviridae, Astroviridae, Bacteriophages, Baculoviridae, Bunyaviridae, Calciviridae; Coronaviridae, Deltavirus, Filoviridae, Flaviviridae, Geminiviridae, Hepadnaviridae, Herpesviridae, Nodaviridae, Orthomyxoviridae, Papovaviridae, Paramyxoviridae, Parvoviridae, Phycodnaviridae, Picornaviridae, Poxyiridae, Reoviridae, Retroviridae, Rhabdoviridae, Tobainoviridae, and Togaviridae, Poxviruses including Vaccinia and variola viruses, polyoma viruses including JC and BK viruses, Herpes viruses including Herpes Simplex virus, Epstein Barr virus, and Gamma Herpes virus, cytomegalovirus (CMV), and human immunodeficiency viruses (HIV-1). 
     
     
         8 . The method of  claim 6 , wherein said pathogenic infection is caused by poxvirus. 
     
     
         9 . The method of  claim 8 , wherein said pathogenic infection is caused by vaccinia viruses. 
     
     
         10 . The method of  claim 6 , wherein pathogenic infection is caused by Herpes viruses including Herpes Simplex virus, Epstein Barr virus, and Gamma Herpes virus. 
     
     
         11 . The method of  claim 1 , wherein said kinase inhibitor is StiAF3-iAR or LG2-71. 
     
     
         12 . The method of  claim 1 , wherein said kinase inhibitor is WBZ-6, CGP51148WBZ-4, Eph2_wbz, Apck103, Apck21, APck25, APcK36, APCK50, APCK51, APCK53, LG2-55, LG2-77, or LG2-81. 
     
     
         13 . The method of  claim 1 , wherein said pathogenic infection is an acute infection. 
     
     
         14 . The method of  claim 13 , wherein said acute infection is treated for short periods of time. 
     
     
         15 . The method of  claim 14 , wherein said short periods of time is less than three weeks. 
     
     
         16 . The method of  claim 1 , wherein said kinase inhibitors are set forth in Summary Table B.