BROAD-SPECTRUM ACTIVITY OF 8-CHLORO-7-DEAZAGUANOSINE AGAINST RNA VIRUS-INFECTIONS IN MICE AND RATS

A novel nucleoside analog, 8-chloro-7-deazaguanosine (8-Cl-7-dzGuo), w as evaluated for anti-RNA virus activity in rodents in parallel with t he related compound 7-deaza-7-thia-8-oxoguanosine (7-dzTOGuo). Half-da ily intraperitoneal (i.p.) doses of each substance administered 24 and 18 h prior to ip virus challenge protected the majority of mice infec ted with banzi, encephalomyocarditis, San Angelo, and Semliki Forest v iruses at doses of 25, 50 and 100 mg/kg/day. These compounds at 100 mg /kg/day also protected most suckling rats infected intranasally with r at coronavirus. However, no survival benefit was afforded to treated m ice infected intranasally with vesicular stomatitis virus. 8-Cl-7-dzgu o was orally active against Semliki Forest virus in mice at 200 and 40 0 mg/kg/day, whereas 7-dzTOGuo is reported to not be effective orally. In uninfected mice, the two compounds induced similar amounts of inte rferon following i.p, injections. Interferon was induced by oral treat ments with 8-Cl-7-dzGuo but not with 7-dzTOGuo. Fifty percent acute le thal doses to uninfected mice treated i.p. in half-daily doses for one day with 7-deazaguanosine (7-dzGuo), 7-dzTOGuo, and 8-Cl-7-dzGuo were 400, 600 and > 1600 (no mortality at this dose) mg/kg/day, respective ly. Daily, i.p. treatments for 14 days with these substances (100 mg/k g/day) showed 7-dzGuo as 100% lethal and the other two substances as n ot toxic. By virtue of reduced toxicity and oral bioavailability, 8-Cl -7-dzGuo appears to have the greatest clinical potential as an interfe ron-inducing antiviral agent.