Inhibition of human immunodeficiency virus type 1 RNase H by sulfated polyanions.
The reverse transcriptase (RT) activity of human immunodeficiency virus type 1 and other retroviruses is closely associated with a hybrid-degrading RNase H activity which is essential for retroviral replication. We have analyzed the effect of sulfated polysaccharides on human immunodeficiency virus type 1 recombinant RT and RNase H activities in vitro. Heparin, dextran sulfates, and xylan polysulfate were found to be much more potent inhibitors of RNase H than of RT and exhibit 50% infective doses of 0.04 to 0.1 micrograms/ml (corresponding to 0.1 to 25 nM) which is up to 5,000-fold more efficient than that for RT. Inhibitors of RNase H activity are attractive as antiviral drugs.
Moelling
K
K
Max-Planck-Institut für Molekulare Genetik, Berlin, Federal Republic of Germany.
Schulze
T
T
Diringer
H
H
D000838:Anions; D016264:Dextran Sulfate; D003911:Dextrans / Q000494:pharmacology*; D004722:Endoribonucleases / Q000037:antagonists & inhibitors*; D015497:HIV-1 / Q000201:enzymology*; D007700:Kinetics; D008970:Molecular Weight; D009838:Oligodeoxyribonucleotides / Q000494:pharmacology*; D010426:Pentosan Sulfuric Polyester / Q000494:pharmacology*; D011089:Polydeoxyribonucleotides / Q000494:pharmacology*; D011134:Polysaccharides / Q000494:pharmacology*; D018894:Reverse Transcriptase Inhibitors; D016914:Ribonuclease H; D013498:Suramin / Q000494:pharmacology
D000838:Anions; D003911:Dextrans; D009838:Oligodeoxyribonucleotides; D011089:Polydeoxyribonucleotides; D011134:Polysaccharides; D018894:Reverse Transcriptase Inhibitors; C061805:poly(dC).oligo(dG)12; D010426:Pentosan Sulfuric Polyester; D013498:Suramin; D016264:Dextran Sulfate; D004722:Endoribonucleases; D016914:Ribonuclease H