The activities of the purine acyclic nucleoside 9-(1,3-dihydroxy-2-propoxymethyl)guanine (DHPG) against two human and five animal strains of cytomegalovirus were compared with those of acyclovir. DHPG was significantly more active than acyclovir against all but one (mouse cytomegalovirus) of the strains tested, with 5Oo% effective doses ranging from 5 to 13 ,uM, as determined by plaque reduction assays in human embryonic lung (MRC-5) and human embryonic tonsil cells. Both DHPG and acyclovir inhibited virus replication at concentrations considerably lower than those necessary to inhibit cell proliferation. In mode-of-action studies, the triphosphates of DHPG and acyclovir inhibited human cytomegalovirus DNA polymerase. DHPG phosphorylation to the active triphosphate was enhanced in infected cells; however, this enzymatic activity was unrelated to thymidine kinase. In animal studies, DHPG was slightly more effective than acyclovir in reducing mouse cytomegalovirus-induced mortality.Much effort has been expended within the last few years to find selective inhibitors of cytomegalovirus (CMV) replication. Although acyclovir is the most active compound in this area, its effectiveness against human CMV appears to be less than against other viruses of the herpes group (27). 2'-Fluoroarabinofuranosyl pyrimidines have shown high activity against human CMV in vitro, but they have a very small therapeutic index (9).Recent in vitro tests with a novel acyclic nucleoside, 9-(1,3-dihydroxy-2-propoxymethyl)guafine (DHPG, also known as 2'-NDG, BIOLF-62, and BW759U), showed this agent to be significantly more active than acyclovir against strains of human CMV (7,12,20,27,30,31,33). This report deals with the activity of DHPG against a broader range of animal and human CMVs. The effects of DHPG in vivo against mouse CMV also are presented, as are the results of a limited investigation of the mode of action of DHPG.MATERIALS AND METHODS Compounds. DHPG, acyclovir, and the triphosphates of each acyclic nucleoside were obtained as described previously (22, 27, 29). The nucleosides used in the thymidine kinase (TK) and DNA polymerase assays were BVdU[(E)-5-(2-bromovinyl)-2'-deoxyuridine], provided
