2-Acetylpyridine 5-[(dimethylamino)thiocarbonyl]-thiocarbonohydrazone (1110U81) potently inhibits human cytomegalovirus replication and potentiates the antiviral effects of ganciclovir.
We studied the effects of 2-acetylpyridine 5-[(dimethylamino)thiocarbonyl]-thiocarbonohydrazone (1110U81 or A1110U), a potent inhibitor of the ribonucleotide reductases encoded by herpes simplex virus types 1 and 2 and by varicella-zoster virus, against human cytomegalovirus (HCMV) replication in infected MRC-5 cells. We show that 1110U81 is a potent inhibitor of HCMV DNA replication (50% inhibitory concentration [IC50], 3.6 microM; IC90, 5.6 microM) and also potentiates the effects of ganciclovir (GCV) against HCMV. The IC90 of GCV is reduced from 65 microM when GCV alone is given to 2.8 microM when GCV is combined with 1110U81 at a molar ratio of 1:1.
Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205.
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Hamzeh
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Lietman
D000998:Antiviral Agents / Q000494:pharmacology*; D002478:Cells, Cultured; D003587:Cytomegalovirus / Q000187:drug effects* / Q000502:physiology; D004261:DNA Replication / Q000187:drug effects; D004279:DNA, Viral / Q000096:biosynthesis; D004357:Drug Synergism; D015774:Ganciclovir / Q000494:pharmacology*; D006801:Humans; D006835:Hydrazones / Q000494:pharmacology*; D009693:Nucleic Acid Hybridization; D011725:Pyridines / Q000494:pharmacology*; D014779:Virus Replication / Q000187:drug effects*
D000998:Antiviral Agents; D004279:DNA, Viral; D006835:Hydrazones; D011725:Pyridines; D015774:Ganciclovir