Use of active ingredients for the prophylaxis and/or therapy of viral diseases

Abstract

The invention relates to the use preferably of at least one active ingredient for the prophylaxis and/or therapy of a viral disease, wherein this active ingredient inhibits at least one component of the cellular signal transduction pathway for the activation of the transcription factor NF-kB such that the virus multiplication is inhibited. The present invention relates furthermore to the local, preferably aerogenic administration of the active ingredient according to the invention for inhibiting a virus multiplication. The active ingredient according to the invention may be combined with at least one further antivirally effective substance for the prophylaxis and/or therapy of a viral disease.

1 . A method for the prophylaxis or treatment of at least one viral disease comprising administering a physiologically effective dose of a pharmaceutical composition comprising at least one active ingredient inhibiting a component of the NF-kB signal transduction pathway such that a virus multiplication is inhibited.  
   
   
       2 . The method of  claim 1 , wherein the component of the NF-kB signal transduction pathway is selected from the group consisting of tumor necrosis factor receptor associated factor (TRAF), NF-kB inducing kinase (NIK), mitogen-activated protein kinase kinase kinase 1 (MEKKK1), mitogen-activated protein kinase kinase kinase 3 (MEKKK3), AKR mouse thymoma kinase (AKT), TGFβ activated kinase (TAK1), inhibitor of NF-kB kinase alpha (IKKalpha), inhibitor of NF-kB kinase beta (IKKbeta), NEMO, inhibitor of kB (IkB), RELA (p65), C-REL, RELB, NF-kB1 (p105), NF-kB2 (p100), P50, and P52.  
   
   
       3 . The method of  claim 1 , wherein the active ingredients are selected from the group consisting of inhibitors of a kinase of the NF-kB signal transduction pathway, e.g. nonsteroidal anti-inflammatory substances inhibiting the NF-kB activation, comprising phenylalkyl acid derivatives, sulindac, or derivatives of sulindac comprising sulindac sulphoxide, sulindac sulphone, sulindac sulphide or benzylamide sulindac analogues, salicylic acid derivatives comprising salicylic acid or acetylsalicylic acid, salcylamide, salacetamide, ethenzamide, diflunisal, olsalazine or salazosulfapyridine, curcumin, antioxidants comprising pyrrolidine dithiocarbamate (PDTC), oxicams comprising piroxicam, vitamin E and derivatives thereof comprising pentamethyl hydroxychroman (PMC), 17 beta oestradiol and derivatives thereof, polyphenoles of tea comprising (−)-epigallo-catechin-3-gallate (EGCG), Bay11-7182, peptides inhibiting the interaction of at least two components of the NF-kB signal transduction pathway, comprising peptides binding to NEMO, inhibitors of a proteosome comprising PS-341 and lactacystin, antisense oligonucleotides specifically adding to the DNA sequence or m-RNA sequence coding for a component of the NF-kB signal transduction pathway and inhibiting the transcription or translation thereof, comprising antisense nucleotide sequences specific for p65 or p50, dominant-negative mutants of a component of the NF-kB signal transduction pathway, ds-oligonucleotides, suitable for the specific degradation of the mRNAs of a component of the NF-kB signal transduction pathway by the RNAi technology, antibodies or antibody fragments specific for a component of the NF-kB signal transduction pathway, or fusion proteins, containing at least one antibody fragment comprising a Fv fragment which inhibits at least one component of the NF-kB signal transduction pathway.  
   
   
       4 . The method of  claim 1 , wherein the viral disease is caused by an infection by RNA or DNA viruses comprising influenza viruses.  
   
   
       5 . A combination preparation for the prophylaxis or therapy of at least one viral disease comprising at least two different active ingredients, wherein at least one active ingredient is selected from the group according to  claim 3 , wherein the combination preparation is in the form of a mixture or as individual components for simultaneous or non-simultaneous application at identical or different administration sites.  
   
   
       6 . A combination preparation according to  claim 5 , wherein at least one antivirally acting substance is 1-adamantanamine, rimantadine, a neuraminidase inhibitor or a nucleoside analogue such as ribavirin.  
   
   
       7 . A method for the prophylaxis or therapy of an infection by negative-strand RNA viruses comprising influenza viruses or Borna viruses, comprising administering a physiologically effective dose of the combination preparation of  claim 5 .  
   
   
       8 . The method of  claim 7 , wherein the preparation is administered nasally, bronchially, or aerogenically, and wherein the active ingredient is present in a concentration from 0.1 to 4 mM in the preparation, wherein the total amount of the active ingredient per administration unit is in the range of 0.1 to 70 mg, wherein the pharmaceutical composition is prepared for a daily dose of less than or equal to 70 mg.  
   
   
       9 . A test system for identifying active ingradients which act on at least one component of the NF-kB signal transduction pathway such that a virus multiplication is substantially inhibited comprising a) at least one cell infectible by at least one virus, said cell containing the NF-kB signal transduction pathway and at least one virus infecting the cells, or b) at least one cell infected by at least one virus, said cell overexpressing the NF-kB signal transduction pathway.  
   
   
       10 . A test system according to  claim 9 , wherein the virus is an RNA or DNA virus comprising an influenza virus.  
   
   
       11 . A test system according to  claim 9 , wherein the cell contains at least one overexpressed component of the NF-kB signal transduction pathway in a constitutively active mutated form.  
   
   
       12 . A test system according to  claim 9 , wherein at least one gene coding for at least one dominant-negative mutant of at least one component of the NF-kB signal transduction pathway is overexpressed by the cell.  
   
   
       13 . A test system according to  claim 9 , wherein the expression for at least one component of the NF-kB signal transduction pathway is overexpressed in the cell.  
   
   
       14 . A method for identifying at least one active ingredient for the prophylaxis or therapy of viral diseases, said active ingredients substantially inhibiting the multiplication of viruses in viral diseases, comprising the following steps: a) bringing at least one potential active ingredient into contact with at least one test system according to  claim 9 , b) determining the effect on the virus multiplication, and c) selecting a potential active ingredient if the virus multiplication is reduced compared to an execution of step a) without a potential active ingredient or with an active reference ingredient or with a control substance.  
   
   
       15 . A method for preparing a drug for the prophylaxis or therapy of at least one viral disease, said drug inhibiting the multiplication of viruses in the case of viral diseases, comprising the following steps: a) executing a test system according to  claim 9 , b) reacting the identified active ingredient(s) in a physiologically effective dosage with at least one auxiliary or additional substance and a defined galenic preparation.