Procedure to block the replication of reverse transcriptase dependent viruses by the use of inhibitors of deoxynucleotides synthesis

Abstract

A method for inhibiting replication of reverse transcriptase dependent virus in plant or animal cells, comprising the step of administering to said cells a compound that depletes the intracellular pool of deoxyribonucleoside phosphate in an amount effective to inhibit replication of said virus. Hydroxyurea is one such suitable compound. Also disclosed is a method for producing incomplete reverse- transcriptase dependent viral DNA, by administering a deoxyribonucleoside phosphate-depleting drug to cells infected with such a virus.

1 . (canceled)  
   
   
       2 . The method of  claim 9 , wherein said virus is a retrovirus.  
   
   
       3 - 5 . (canceled)  
   
   
       6 . The method of  claim 9 , wherein said cells are in vitro.  
   
   
       7 . The method of  claim 9 , wherein said animal cells are mammalian cells.  
   
   
       8 . The method of  claim 9  wherein said virus is the human immunodeficiency virus (HIV) and said cells are human cells.  
   
   
       9 . A method for inhibiting replication of reverse transcriptase dependent virus in animal cells, comprising the step of administering to said cells a synergistic combination of hydroxyurea and a nucleoside phosphate analog other than a thymidine or cytidine analog.  
   
   
       10 - 11 . (canceled)  
   
   
       12 . A method for inhibiting replication of reverse transcriptase dependent viruses in animal cells, comprising the step of administering to said cells a synergistic combination of hydroxyurea and a nucleoside phosphate analog other than a thymidine or cytidine analog, wherein the hydroxyurea depletes the intracellular pool of deoxyribonucleoside phosphate and wherein the nucleoside phosphate analog serves to inhibit replication of said virus by terminating DNA chain elongation.  
   
   
       13 - 15 . (canceled)  
   
   
       16 . The method of  claim 12 , wherein said second compound is selected from the group consisting of dideoxyinosine (ddI), 2′-fluoro-2′,3′-dideoxyadenosine (2′-F-dd-ara-A), 2′-fluoro-2′,3′-dideoxyinosine (2′-F-dd-ara-I), and 2′-fluoro-2′,3′-dideoxyguanosine (2′-F-dd-ara-G).  
   
   
       17 . The method of  claim 12 , wherein said nucleoside phosphate analog is a dideoxynucleoside.  
   
   
       18 . The method of  claim 17 , wherein said dideoxy nucleoside is a 2′-fluoro purine dideoxynucleoside.  
   
   
       19 . The method of  claim 17 , wherein said dideoxynucleoside is selected from the group consisting of dideoxyinosine (ddI), 2′-fluoro-2′,3′-dideoxyadenosine (2′-F-dd-ara-A), 2′-fluoro-2′,3′-dideoxyinosine (2′-F-dd-ara-I), and 2′-fluoro-2′,3′-dideoxyguanosine (2′-F-dd-ara-G).  
   
   
       20 . A method of producing incomplete viral DNA from a reverse transcriptase dependent virus in animal cells, comprising the step of administering to said cells a synergistic combination of hydroxyurea and a nucleoside phosphate analog other than a thymidine or cytidine analog, wherein the combination is administered in an amount effective to inhibit replication of said virus.