Anti-tumor virus activity of copper-binding drugs

Several, structurally different, copper-binding ligands can inhibit the RNA-dependent DNA polymerase of Rous sarcoma virus (RSV) and can inactivate the ability of the virus to malignantly transform chick embryo cells. These ligands include the anti-microbial agents, thiosemicarbazones, 8-hydroxyquinolines, isonicotinic acid hydrazide, and others. Many of these compounds bind to DNA and RNA in the presence of copper, which may play a role in their anti-viral activity. However, not all agents active against RSV bind to nucleic acids and not all ligands that bind to nucleic acids are active against RSV. Some copper-binding ligands are neither active against RSV, nor bind nucleic acids. It appears that there is no simple relationship between the anti-viral activity of copper-binding ligands and their nucleic acid-binding ability. The biological importance of thiosemicarbazone-copper complex binding to nucleic acids is supported by the observation that treatment of intact RSV virions with the complex causes the genome 70S RNA to sediment abnormally in velocity sucrose gradient analysis.