Abstract

Various nucleoside analogues were examined for their inhibitory effects on plaque formation ofthe laboratory strain AD-169 and 11 clinical isolates of human cytomegalovirus (CMV) in human embryonic fibroblast (MRC-5) cells. The most selective inhibitors of CMV replication were 9-(1,3-dihydroxy-2-propoxymethy1)guanine (DHPG), (S)-1-(3-hydroxy-2-phosphonylmethoxypropyl) cytosine (HPMPC), and (S)-9-(3-hydroxy-2-phosphonylmethoxypropyl)adenine (HPMPA). The 50% effective concentrations (EC50) for CMV plaque formation were 0.65, 0.25, and 0.28 µg/ml, respectively. Selectivity indexes were 462,300, and 107, respectively. At a concentration fourfold higher than the EC50, HPMPC completely inhibited CMV growth, whereas DHPG still allowed it. Carbocyclic 3-deazaadenosine, recognized as an S-adenosylhomocysteine (SAD) hydrolase inhibitor, had an EC52 of 13.7 µg/ml and a selectivity index of 29. These results suggest that HPMPC should be further pursued for its usefulness in the treatment of CMV infections and SAH hydrolase inhibitors represent potentially important anti-CMV agents.

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