Abstract
Since common cold viruses are responsive to interferon, we developed two animal models to test the efficacy of the interferon inducer 7-thia-8-oxoguanosine: (i) an intranasal coronavirus infection in suckling rats; and (ii) an intranasal encephalomyocarditis (EMC) virus infection in adult mice. Concentrations of 0.3 and 1% 7-thia-8-oxoguanosine delivered intranasally to rats 24 and 18 hours before virus inoculation were highly protective against the otherwise lethal coronavirus infection. A 1% concentration of drug administered 4 and 8 hours after virus challenge increased mean survival times of rats but did not increase numbers of survivors. Intranasal treatment of an EMC infection produced moderate improvements in mean survival times and survival. Titrations of EMC virus indicated >300-fold reductions in nasal titres in drug-treated relative to placebo control animals on days 2–4 following virus challenge. The distribution of [14C]-7-thia-8-oxoguanosine was determined shortly after intranasal delivery to mice and rats. Approximately 50% of total doses were deposited in the inner noses and mouths of both species. Most of the rest was found on/in the outer noses, stomachs, tracheas, oesophagi, and lungs. By analogy, the infecting viruses were deposited on/in the same organs and tissues of each species. The results suggest that containment of the viruses primarily occurred in the nasopharyngeal area prior to their spread to the lungs (rat coronavirus) or the brain (EMC), where fatal pathologies were manifest. Intranasal application of an interferon-inducing nucleoside analogue represents a new approach for the study of treatment of the common cold.