SELECTIVE-INHIBITION OF CYTOMEGALOVIRUSES BY PHONO-1'-HYDROXYMETHYL-1'-PROPYLOXY-METHYL)GUANINE

phono-1'-hydroxymethyl-1'-propyloxy-methyl)guanine (SR 3727A) was sign ificantly inhibitory to strain AD169 of human cytomegalovirus (HCMV) u tilizing plaque reduction and inhibition of intra- and extracellular v irus yield in MRC-5 cells. The 50% effective concentrations (EC50) ran ged from 6-17 muM for three laboratory strains of HCMV, whereas the 50 % cytotoxic doses were > 4200 muM as determined by viable cell assay a nd inhibition of radiolabeled precursors into DNA, RNA and protein. EC 50 values against ganciclovir-sensitive clinical isolates ranged from 8-47 muM. Against two ganciclovir-resistant strains of HCMV, EC50 Valu es of SR 3727A were 84 and 320 muM; against murine CMV (MCMV); 17 muM and against guinea pig CMV, 56 muM. SR 3727A was most effective when i nfected cells were treated 24 h or less after virus adsorption. BALB/c mice infected intraperitoneally (i.p.) with a lethal dose of MCMV wer e treated i.p. with 31.3, 62.5, 125, or 250 mg/kg/day of SR 3727 twice daily for 5 days beginning 4 h pre-virus inoculation. All doses were well tolerated; the 125 and 250 mg/kg/day doses significantly prevente d death. In a second experiment, SR 3727 at 125 mg/kg/day markedly red uced titers of recoverable virus from spleens, kidneys, and salivary g lands harvested at varying times after virus inoculation.