NUCLEOTIDE ANALOGS RELATED TO ACYCLOVIR AND GANCICLOVIR ARE EFFECTIVEAGAINST MURINE CYTOMEGALOVIRUS INFECTIONS IN BALB C AND SEVERE COMBINED IMMUNODEFICIENT MICE/

Acyclovir phosphonate [9-(3-phosphono-propyloxymethyl)guanine; SR3722] and the S enantiomer (SR3772), R enantiomer (SR3773), and R,S enantio meric mixture (SR3745A) of ganciclovir phosphonate hydroxymethyl-3-pho sphono)propyloxymethyl]guanine} were evaluated for their antiviral act ivities against murine cytomegalovirus. In severe combined immunodefic ient mice infected with murine cytomegalovirus, SR3773 and SR3745A (12 .5, 25, and 50 mg/kg of body weight per day) were superior to ganciclo vir in extending the mean time to death, whereas SR3722 and SR3772 was less potent than ganciclovir. In normal BALB/c mice, SR3773 and ganci clovir were approximately equally active in preventing death. SR3773 c aused renal tubular damage when administered at 50 mg/kg/day for 15 da ys. These results suggest that SR3773 may have potential for use in th e treatment of human cytomegalovirus infections, but it may also exhib it renal toxicity.