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.

We claim:  
     
         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 ddl, 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 1     6 , 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 ddl, 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.