Effect of 1-β- d -Ribofuranosyl-1,2,4-Triazole-3-Carboxamide (Virazole, ICN 1229) on Herpes and Vaccinia Keratitis and Encephalitis in Laboratory Animals

Abstract

Topical application of 1-β- d -ribofuranosyl-1,2,4-triazole-3-carboxamide (Virazole) significantly inhibited the development of herpetic keratitis in the eyes of rabbits, as determined by both infectivity and Draize scoring parameters. Significant inhibition of the infection was demonstrated with 10% concentrations of Virazole; a 1% solution had a moderate effect, whereas doses of 0.1 and 0.01% had little activity in this system. A 5% concentration of Virazole similarly inhibited vaccinia keratitis in rabbits. Encephalitis-induced mortality in hamsters initially infected intraocularly with herpesvirus was significantly prevented or inhibited by topical application of 5, 10, and 20% concentrations of Virazole. Surviving, treated hamsters had no signs of herpes keratitis. The 20% concentration was the approximate LD 50 in hamsters. Virazole administered subcutaneously or intraperitoneally to mice did not appreciably alter the course of herpes virus- or vaccinia virus-induced encephalitis in these animals, although in a herpesvirus experiment direct injection of the drug into the brains 3 hr prior to virus inoculation resulted in a significant survivor increase.