EXPERIMENTAL CHEMOTHERAPY OF INFLUENZA VIRUS WITH PARTICULAR REFERENCE TO THIOSEMICARBAZONES AND DIPHENYL COMPOUNDS

¹ Department of Pharmacology, The George Washington University School of Medicine, Washington 5, D. C.

Of 568 compounds tested, six diphenyl and related compounds, four thiosemicarbazones, an aliphatic compound and a pyrimidine analog were found to inhibit the PR8 strain of influenza A virus in chorioallantoic membrane tissue culture. They also exhibited activity against the Lee strain of influenza B virus. None of these drugs inhibited hemagglutination in the presence of the virus. The effectiveness of the compounds was found to be related directly to. the inoculating dose of virus. None of the inhibitors were found to exert their action by a direct effect on the virus, by an inhibition of tissue respiration, by an effect on the adsorption of the virus to the host cell, or by interfering with the release of the virus from the cell.

Most of the inhibitors were effective in tissue culture when given at intervals from 3 to 36 hours after infection, suggesting action at an intracellular level.

In studies of the effect on the virus multiplication rate inhibitor compounds prolonged the latent period from 4 to 36 hours and peak titers achieved were 4 or more log units less than the normal.

The inhibition of the action of p-hydroxybenzaldehyde-3-thiosemicarbazone by pantothenic acid seemed to be competitive with a ratio of approximately 1:120,000. There was no quantitative relationship between the other classes of inhibitors and antagonists tested.

In preliminary experiments some compounds prolonged the survival of mice infected with a 100 per cent lethal dose of virus.