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THE presence of a guanidine moiety in a number of antiviral drugs1–5 prompted us to investigate whether some simple guanidine derivatives may reduce the infectivity of viruses for cultured mammalian cells. The following compounds were examined: guanidine hydrochloride, aminoguanidine bicarbonate, creatine hydrate, arginine, uridine, urea, thiourea, decyl- and dodecyl-bis-guanidine, N,N′-bis(beta-hydroxyethyl)biguanide. The chemicals dissolved in water were boiled for about 15 min. and then added to the culture media.

PREVIOUSLY1,2 we have shown that guanidine possesses a strong and highly specific inhibitory action against enteroviruses. This antivirus activity of guanidine seemed to us of interest due to: (1) its specificity; (2) the simplicity of guanidine molecule; (3) the ability of guanidine to stop the cytotoxic effect of poliovirus even when added to cell cultures which were infected several hours previously.

Simple methylated and ethylated compounds (trimethylamine, tetramethylammonium iodide, methylformate, methylacetate, methanol, triethylamine, tetraethylammonium iodide, choline, hemicholinium HC-3, methionine, ethionine, etc.) are able to inhibit the influence of guanidine on in vitro poliovirus replication either when guanidine acts as a growth inhibitor, or when it acts as a growth-promoting factor. The mechanism by which these compounds antagonize guanidine is not clear. The lack of activity of betaine, with the antiguanidine activity of ethionine, seems to exclude the involvement of known biological methylating systems.

Il virus poliomielitico puo essere reso,in vitro, guanidino-resistente se propagato serialmente in culture cellulari contenenti dosi crescenti di guanidina. Proseguendo nei passaggi seriali in presenza delle dosi massime di guanidina tollerate dalle cellule, si ottiene un ceppo di polio virus che si sviluppa assai meglio in terreni contenenti la sostanza che non in terreni che ne siano privi.

Guanidine-dependent polioviruses are obtained in vitro by subculturing Brunenders, Mahoney, and Sabin strains in the presence of increasing concentrations of guanidine. Mahoney viruses dependent on guanidine lose virulence (as indicated by paralysis) for monkeys inoculated intramuscularly or intracerebrally. Protection against virulent Mahoney viruses is induced by treatment with guanidine-dependent strains, and serum antibodies against the virulent strains are present in the treated animals