THE compound 1-β-D-ribofuranosyl-2,2,4-triazole-3-carboxamide (Ribavirin) has been reported to inhibit the replication of both RNA and DNA viruses in vitro, and to inhibit influenza virus infection of tissue cultures and mice1-3. The compound acts by interfering with guanidine monophosphate formation and subsequent nucleic acid synthesis; at a concentration which completely inhibited influenza viral polypeptide production in tissue culture, however, there was no demonstrable effect on cellular protein synthesis4. To test the activity of Ribavirin further, we examined the effect of this compound on influenza virus infection of ferrets. Four adult ferrets were inoculated intraperitoneally with 100 mg kg-1 d -1 of Ribavirin each for 7 d; this dose although it did not cause deaths or other signs of toxicity, was probably close to the toxic level as judged by standard tests in mice. Two hours after the second inoculation of drug, these animals and four untreated ferrets were lightly anaesthetised and inoculated intranasally with 103.0 ferret-infective doses of egg-grown influenza virus A/Port Chalmers/73 (H3N2). Following virus infection, the drug-treated ferrets were given 5 further doses of Ribavirin. The response of the animals to virus infection was measured, as described previously 5,6. The results are shown in Table 1. Ribavirin had a marked effect on the response of ferrets to influenza virus infection; compared with control ferrets, influenza virus-infected animals treated with Ribavirin did not exhibit a febrile reaction to infection, did not develop a significant increase in nasal wash protein and did not develop either local or serum antibody. In addition, the titre of virus in nasal washings collected 3 d after virus infection from drug-treated animals was 100-fold less than that found in control ferrets.
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