Use of cotton rats to evaluate the efficacy of antivirals in treatment of measles virus infections

No practical animal models for the testing of chemotherapeutic or biologic agents identified in cell culture assays as being active against measles vi rus (MV) are currently available. Cotton rats may serve this purpose. To ev aluate this possibility, 5-ethynyl-1-beta-D-ribofuranosylimidazole-4 (EICAR ) and poly(acryl-amidomethyl propanesulfonate) (PAMPS), two compounds that have been reported to inhibit MV in vitro, and ribavirin, an established an tiviral drug with MV-inhibitory activity, were evaluated for their antivira l activities against MV and respiratory syncytial virus (RSV) in tissue cul ture and in hispid cotton rats. A single administration of PAMPS markedly i nhibited pulmonary RSV or MV replication (>3 log(10) reduction in pulmonary titer compared to that for controls), but only if this compound was admini stered intranasally at about the time of virus inoculation. Both EICAR and ribavirin exhibited therapeutic activity against RSV and MV in cotton rats when they were administered parenterally. However, both of these compounds were less effective against MV. On the basis of the pulmonary virus titers on day 4 after virus inoculation, the minimal efficacious dose of EICAR aga inst MV (120 mg/kg of body weight/day when delivered intraperitoneally twic e daily) appeared to be three times lower against this virus than that of r ibavirin delivered at a similar dose (i.e., 360 mg/kg/day). These findings correlated with those obtained in vitro. The data obtained suggest that cot ton rats may indeed be useful for the initial evaluation of the activities of antiviral agents against MV.