Inhibition of RNA-Dependent DNA Polymerase of Rous Sarcoma Virus by Thiosemicarbazones and Several Cations

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Abstract
The RNA-dependent DNA polymerase of Rous sarcoma virus is inhibited by N -methyl isatin β-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 β-thiosemicarbazone and Cu ++ occurs, since treatment of the virus with a low dose of either N -methyl isatin β-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.

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