Nucleotide analogs related to acyclovir and ganciclovir are effective against murine cytomegalovirus infections in BALB/c and severe combined immunodeficient mice

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Abstract
Acyclovir phosphonate [9-(3-phosphono-propyloxymethyl)guanine; SR3722] and the S enantiomer (SR3772), R enantiomer (SR3773), and R,S enantiomeric mixture (SR3745A) of ganciclovir phosphonate (9-[((+/-)-1-hydroxymethyl-3-phosphono)propyloxymethyl]guanine) were evaluated for their antiviral activities against murine cytomegalovirus. In severe combined immunodeficient mice infected with murine cytomegalovirus, SR3773 and SR3745A (12.5, 25, and 50 mg/kg of body weight per day) were superior to ganciclovir in extending the mean time to death, whereas SR3722 and SR3772 was less potent than ganciclovir. In normal BALB/c mice, SR3773 and ganciclovir were approximately equally active in preventing death. SR3773 caused renal tubular damage when administered at 50 mg/kg/day for 15 days. These results suggest that SR3773 may have potential for use in the treatment of human cytomegalovirus infections, but it may also exhibit renal toxicity.

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