Inhibition of RNA-dependent DNA polymerase of Rous sarcoma virus by thiosemicarbazones and several cations.
The RNA-dependent DNA polymerase of Rous sarcoma virus is inhibited by N-methyl isatin beta-thiosemicarbazone and by thiosemicarbazide, but not by semicarbazide. These inhibitors also inactivate, upon contact with the virion, the transforming ability of Rous sarcoma virus. Sulfhydryl donors, such as 2-mercapto-ethanol, can prevent these effects. The RNA-directed activity of the purified polymerase is inhibited to a greater degree than is the DNA-directed activity. Two cations, Cu(++) and Hg(++), can inhibit RNA-dependent DNA polymerase and inactivate the transforming ability of the virus. Synergism between N-methyl isatin beta-thiosemicarbazone and Cu(++) occurs, since treatment of the virus with a low dose of either N-methyl isatin beta-thiosemicarbazone or Cu(++) has little effect; however, when the two compounds are mixed together, significant inactivation occurs. This observation supports the hypothesis that the antiviral action of thiosemicarbazones is a function of their ability to act as a ligand for metallic ions. Several cations (Ag(+), Co(++), Zn(++), Cd(++), and Ni(++)) significantly inactivate the RNA-dependent DNA polymerase, but have little effect on the transforming ability. In view of this result, the conclusion that the enzyme activity is required for transformation remains open to question.
D000818:Animals; D001358:Avian Sarcoma Viruses / Q000201:enzymology* / Q000254:growth & development; D002104:Cadmium / Q000494:pharmacology; D002478:Cells, Cultured; D002614:Chelating Agents / Q000494:pharmacology; D002642:Chick Embryo; D003035:Cobalt / Q000494:pharmacology; D003300:Copper / Q000494:pharmacology; D004247:DNA / Q000378:metabolism; D004357:Drug Synergism; D004492:Edetic Acid / Q000494:pharmacology; D007211:Indoles / Q000494:pharmacology; D008623:Mercaptoethanol / Q000494:pharmacology; D008628:Mercury / Q000494:pharmacology; D009532:Nickel / Q000494:pharmacology; D012367:RNA, Viral / Q000378:metabolism; D012194:RNA-Directed DNA Polymerase / Q000378:metabolism; D018894:Reverse Transcriptase Inhibitors; D012834:Silver / Q000494:pharmacology; D013698:Templates, Genetic; D013882:Thiosemicarbazones / Q000494:pharmacology*; D013890:Thiourea / Q000494:pharmacology; D015032:Zinc / Q000494:pharmacology
D002614:Chelating Agents; D007211:Indoles; D012367:RNA, Viral; D018894:Reverse Transcriptase Inhibitors; D013882:Thiosemicarbazones; D002104:Cadmium; D003035:Cobalt; D012834:Silver; D008623:Mercaptoethanol; D003300:Copper; D009532:Nickel; D004247:DNA; D004492:Edetic Acid; D012194:RNA-Directed DNA Polymerase; D008628:Mercury; D013890:Thiourea; D015032:Zinc