Inhibition of viruses

Abstract

Disclosed is a pharmaceutical composition comprising a ribonucleoside analogue in accordance with general formula (I) or (II) as herein defined in admixture with a physiologically acceptable excipient diluent or carrier.

1 . A pharmaceutical composition comprising a ribonucleoside analogue in accordance with general formula I or II  
       
         
           
           
               
               
           
         
       
       where: 
 n=1-4, preferably 2-4,  
 X 1 =N or CH or CR 5    
 X 2 =N or S or CR 5    
 X 3 =NR 6  or O or S, or R 6  when X 2 =N, or X 3 =NR 6  or R 6  when X 2 =S, and X 3  is absent when X 2 =CR 5    
 R 1 =H or alkyl or aryl or alkaryl or acyl  
 R 2 =H or aryl or alkaryl or acyl; when X 2 =S, R 2  is absent;  
 R 3 =H or NR 5 R 6  or NR 5 NR 5 R 6  or NR 5 OR 5    
 R 5 =H or alkyl or alkenyl or alkynyl or aryl or alkaryl or acyl  
 R 6 =H or alkyl or alkenyl or alkynyl or aryl or alkaryl or acyl and  
 R 4 =H or  
                     
 wherein  
 Z=O or S or CH 2  or CHF or CF 2  or NR 5    
 X 4 =OH or F  
 R 7 =H or PO 3   2−  or P 2 O 6   3−  or P 3 O 9   4−  or a masked phosphate derivative,  
 in admixture with a physiologically acceptable excipient, diluent or carrier.  
 
     
     
         2 . A pharmaceutical composition according to  claim 1 , wherein the ribonucleoside analogue is provided as the base analogue or the ribonucleotide analogue.  
     
     
         3 . A pharmaceutical composition according to  claim 1  or  claim 2 , wherein the ribonucleoside analogue comprises a purine analogue.  
     
     
         4 . A pharmaceutical composition according to  claim 1  which, following administration to a human or animal subject, gives rise to a chemical entity which, inside a cell of the subject, is incorporated into a RNA molecule by a cellular, or preferably viral, RNA polymerase present in the cell.  
     
     
         5 . A pharmaceutical composition according to  claim 4 , wherein the cell is infected by an RNA virus, the RNA molecule is an RNA copy of at least part of the viral genomic nucleic acid molecule.  
     
     
         6 . A pharmaceutical composition according to  claim 1 , wherein the ribonucleoside analogue is such that Z is O.  
     
     
         7 . A pharmaceutical composition according to  claim 1 , wherein X 2  is N.  
     
     
         8 . A pharmaceutical composition according to  claim 1 , wherein X 3  is O or comprises N.  
     
     
         9 . A pharmaceutical composition according to  claim 1 , wherein X 4  is OH.  
     
     
         10 . A pharmaceutical composition according to  claim 1 , wherein X 2  is N and X 3  is NH 2 .  
     
     
         11 . A pharmaceutical composition according to  claim 10 , comprising a ribonucleoside analogue having the structure shown in  FIG. 3  or  FIG. 7 .  
     
     
         12 . A pharmaceutical composition according to  claim 1 , wherein X 2  is N, X 3  is O and R 1  is alkyl.  
     
     
         13 . A pharmaceutical composition according to  claim 12 , wherein R 1  is methyl or substituted methyl.  
     
     
         14 . A pharmaceutical composition according to  claim 13 , comprising a ribonucleoside analogue having the structure shown in  FIG. 11 , or the corresponding ribonucleotide analogue.  
     
     
         15 . A method of making a pharmaceutical composition suitable for preventing and/or treating an RNA virus infection in a human or animal subject, the method comprising the step of mixing a ribonucleoside analogue in accordance with general formula I or II of  claim 1  with a physiologically acceptable excipient, diluent or carrier.  
     
     
         16 . (canceled)  
     
     
         17 . A method according to  claim 15 , comprising the step of combining a plurality of different ribonucleoside analogues, each analogue being in accordance with general formula I or II.  
     
     
         18 . A method according to  claim 15 , comprising the step of including in the pharmaceutical composition a further antiviral agent.  
     
     
         19 . A method according to  claim 18 , wherein the further antiviral agent is an inhibitor of reverse transcriptase.  
     
     
         20 . A method according to  claim 18 , wherein the further antiviral agent is active against HIV or other retrovirus.  
     
     
         21 . A method according to  claim 15 , further comprising the step of packaging the composition in unitary dose form.  
     
     
         22 .- 23 . (canceled)  
     
     
         24 . A method of treating an RNA virus infection in a human or animal subject, the method comprising the step of administering to a subject infected with an RNA virus an effective amount of a ribonucleoside analogue in accordance with general formula I or II as defined in  claim 1 .  
     
     
         25 . A method according to  claim 24 , comprising administering to the subject a pharmaceutical composition in accordance with  claim 1 .  
     
     
         26 . (canceled)  
     
     
         27 . A method according to  claim 37 , wherein the ribonucleoside analogue has the structure shown in  FIG. 2  or is the corresponding ribonucleoside analogue.  
     
     
         28 . (canceled)  
     
     
         29 . A pharmaceutical composition according to  claim 1  which, when administered to a human or animal subject infected with an RNA virus, inhibits replication of the virus and/or causes an increase in the mutation frequency of the virus.  
     
     
         30 . A pharmaceutical composition according to  claim 1  which, when administered to a human or animal subject infected with an RNA virus, causes inhibition of LTR-mediated transcription of viral nucleic acid.  
     
     
         31 . (canceled)  
     
     
         32 . A composition suitable for application to a plant, for the purpose of preventing and/or treating an RNA virus infection of the plant, the composition comprising an RNA nucleoside analogue conforming to general formula I or II of  claim 1 .  
     
     
         33 . A composition according to  claim 32 , further comprising a surfactant and/or a plant penetration enhancer.  
     
     
         34 . A method of preventing and/or treating an RNA virus infection in a susceptible plant, the method comprising the step of applying to the plant an efefctive amount of a composition according to  claim 32  or  33 .  
     
     
         35 . and  36 . (canceled)  
     
     
         37 . A method of treating or preventing an RNA virus infection in a human or animal subject which comprises administering thereto an amount of a composition according to  claim 1  sufficient to inhibit LTR-mediated transcription of viral nucleic acid.