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 . A method for inhibiting replication of reverse transcriptase dependent virus in 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.  
   
   
       2 . The method of  claim 1 , wherein said virus is a retrovirus.  
   
   
       3 . The method of  claim 1 , wherein said deoxynucleoside phosphate depleting compound is a deoxynucleotide synthesis inhibitor.  
   
   
       4 . The method of  claim 1 , wherein said deoxynucleoside phosphate depleting compound is an inhibitor of ribonucleotide reductase.  
   
   
       5 . The method of  claim 4 , wherein said compound is hydroxyurea.  
   
   
       6 . The method of  claim 1 , wherein said cells are in vitro.  
   
   
       7 . The method of  claim 1 , wherein said animal cells are mammalian cells.  
   
   
       8 . The method of  claim 1  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 steps of administering to said cells a compound that depletes the intracellular pool of deoxyribonucleoside phosphate, in conjunction with administering to said cells an antiviral nucleoside phosphate analog.  
   
   
       10 . The method of  claim 9 , wherein said deoxynucleotide phosphate depleting compound is an inhibitor of ribonucleotide reductase.  
   
   
       11 . The method of  claim 10 , wherein said compound is hydroxyurea.  
   
   
       12 . A method for inhibiting replication of reverse transcriptase dependent viruses in animal cells, comprising the steps of administering to said cells a first compound that depletes the intracellular pool of deoxyribonucleoside phosphate, in conjunction with a second compound that serves to inhibit replication of said virus by terminating DNA chain elongation.  
   
   
       13 . The method of  claim 12 , wherein said second compound inhibits replication by premature termination of viral DNA synthesis to produce incomplete viral DNA.  
   
   
       14 . The method of  claim 12 , wherein said first compound is an inhibitor of ribonucleotide reductase.  
   
   
       15 . The method of  claim 14 , wherein said first compound is hydroxyurea.  
   
   
       16 . The method of  claim 15 , wherein said second compound is selected from the group consisting of ddI, ddC, 2′-F-dd-ara-A, 2′-F-dd-ara-I and 2′-F-dd-ara-G.  
   
   
       17 . The method of  claim 12 , wherein said second compound is selected from the group consisting of a dideoxynucleoside and AZT.  
   
   
       18 . The method of  claim 16 , wherein said dideoxy nucleoside is a 2′-fluoro purine dideoxynucleoside.  
   
   
       19 . The method of  claim 16 , wherein said dideoxynucleoside is selected from the group consisting of ddI, ddC, 2′-F-dd-ara-A, 2′-F-dd-ara-I and 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 compound that depletes the intracellular pool of deoxyribonucleoside phosphate in an amount effective to inhibit replication of said virus.