The addition of 5 mM
dithiothreitol to a cell-free assay system for
influenza ribonucleic acid (
RNA) polymerase activity reverses the inhibitory activity otherwise possessed by three established
antiviral compounds:
selenocystine, 4-(2-propinyloxy)-beta-nitrostyrene, and
acetylaranotin. Although 50% or greater
enzyme inhibitory activity is repeatedly achieved for these compounds at a concentration of approximately 50 mug/ml (0.1 to 0.25 mM) in the absence of
dithiothreitol, no inhibition is seen in its presence at inhibitor concentrations as high as 200 mug/ml. Against the
deoxyribonucleic acid-directed
RNA polymerases of Escherichia coli and chicken embryo cells,
acetylaranotin and 4-(2-propinyloxy)-beta-nitrostyrene caused very little inhibition. Only
selenocystine significantly inhibited these two
enzymes in the absence of
reducing agent, but to an extent substantially less than that obtained against the viral
enzyme. These results appear to suggest that
influenza RNA polymerase is uniquely sensitive to a variety of structurally diverse
antiviral compounds as a consequence of their sulfhydryl reactivity-a fact which might aid in the search for and development of more potent chemotherapeutic agents.