Antiviral effect of compound 2′-nor-cGMP against cytomegalovirus infection in the guinea pig model : Z.H. YANG, R.L. TOLMAN, R.J. COLONNO and G.D. HSIUNG. Yale University School of Medicine, New Haven, CT. 06510, Merck, Sharp & Dohme Research Laboratory, West Point, PA. 19486 and VA Medical Center, West Haven, CT. 06516 U.S.A.

Abstract

The anti-cytomegalovirus activities of four phosphate derivatives of 9-(1,3-dihydroxy-2-propoxymethyl)guanine (DHPG) were evaluated against human, monkey and murine viruses. The 5′-mono-, 3′,5′-bis(mono-), and 3′,5′-cyclic monophosphate and 5′-homophosphonate forms of DHPG inhibited virus plaque formation at 1–15 μM. The cyclic phosphate and homophosphonate were more active than the other compounds against murine cytomegalovirus (MCMV) in vitro. In an in vivo MCMV infection model, DHPG homophosphonate and DHPG were equally effective at reducing mortality at ⩾10 mg/kg. The cyclic phosphate was active at 10–20 mg/kg but toxic at ⩾40 mg/kg. The phosphorylation of DHPG phosphate and DHPG phosphonate, as well as the inhibition of human cytomegalovirus DNA polymerase by their respective triphosphates, were also examined.