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Absence of Significant Antiviral Effects of --Methylene GTP on Encephalomyocarditis Virus Infection of L cells and Mice

Searle Research Laboratories, Lane End Road, High Wycombe, Bucks, U.K.

The protein synthesis inhibitor --methylene guanosine triphosphate (Gpp-CH₂p) is shown here to be ineffective as a ‘leaky membrane’ antiviral agent against encephalomyocarditis virus infection of L cells and mice. Studies with GppCH₂p in encephalomyocarditis virus-infected L cells indicate that the cells only become permeable to the inhibitor late in infection because the compound significantly inhibits protein synthesis only when added at 4 h p.i. At this time 50 to 70% of the new infectious virus particles have already been synthesized, and this is reflected in maximum inhibition of virus yields of only about 40%. Moreover, comparison of inhibition of protein synthesis by GppCH₂p in vitro and in cell cultures indicates that the intracellular concentration attained is only 0.25% of that in the medium. The lack of antiviral activity of GppCH₂p in encephalomyocarditis virus-infected mice is probably due to leakiness of infected cells occurring too late for sufficient inhibition of virus synthesis to be obtained.

Received 15 March 1979; accepted 1 June 1979.