Inhibition of RNA-Dependent DNA Polym by Thiosemicarbazones and Several Catior

The RNA-dependent DNA polymerase of Rous sarcoma virus is inhibited by N-methyl isatin /3- 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 f-thio- semicarbazone and Cu++ occurs, since treatment of the virus with a low dose of either N-methyl isatin fj-thio- semicarbazone or Cu++ has little effect; however, when the two compounds are mixed together, significant inactiva- tion occurs. This observation supports the hypothesis that the antiviral action of thiosemicarbazones is a func- tion of their ability to act as a ligand for metallic ions. Several cations (Ag+, Co++, Zn++, Cd++, and Ni++) sig- nificantly 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 re- quired for transformation remains open to question.