title: Comparative inhibitory effects of nucleoside analogues on different clinical isolates of human cytomegalovirus in vitro.
abstract: 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.
authors.affiliation: Department of Bacteriology, Fukushima Medical College, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Shigeta
authors.forename: K
authors.initials: K
authors.lastname: Konno
authors.forename: M
authors.initials: M
authors.lastname: Baba
authors.forename: T
authors.initials: T
authors.lastname: Yokota
authors.forename: E
authors.initials: E
authors.lastname: De Clercq
mesh_terms: D000225:Adenine / Q000031:analogs & derivatives / Q000494:pharmacology; D000241:Adenosine / Q000031:analogs & derivatives; D000998:Antiviral Agents / Q000494:pharmacology*; D002460:Cell Line; D000077404:Cidofovir; D003562:Cytidine / Q000031:analogs & derivatives; D003587:Cytomegalovirus / Q000187:drug effects*; D003596:Cytosine / Q000031:analogs & derivatives / Q000494:pharmacology; D015774:Ganciclovir / Q000031:analogs & derivatives / Q000494:pharmacology; D006151:Guanosine / Q000031:analogs & derivatives; D006801:Humans; D009705:Nucleosides / Q000494:pharmacology*; D063065:Organophosphonates; D009943:Organophosphorus Compounds / Q000494:pharmacology; D013936:Thymidine / Q000031:analogs & derivatives
chemical_list: D000998:Antiviral Agents; D009705:Nucleosides; D063065:Organophosphonates; D009943:Organophosphorus Compounds; D006151:Guanosine; D003562:Cytidine; D003596:Cytosine; C045895:9-((2,3-dihydroxy-1-propoxy)methyl)guanine; C050127:9-(S)-(3-hydroxy-2-(phosphonomethoxy)propyl)adenine; D000225:Adenine; D000077404:Cidofovir; D000241:Adenosine; D015774:Ganciclovir; D013936:Thymidine