Comparative Inhibitory Effects of Nucleoside Analogues on Different Clinical Isolates of Human Cytomegalovirus In Vitro

Various nucleoside analogues were examined for their inhibitory effects on plaque formation of the 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-propoxymethyl)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 microgram/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 (SAH) hydrolase inhibitor, had an EC50 of 13.7 micrograms/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.