Inhibition of herpes simplex virus-induced DNA polymerase activity and viral DNA replication by 9-(2-hydroxyethoxymethyl)guanine and its triphosphate.
The effect of the nucleoside analog 9-(2-hydroxyethoxymethyl)guanine (acycloguanosine) on herpes simplex virus type 1 DNA synthesis was examined. Acycloguanosine inhibited herpesvirus DNA synthesis in virus-infected cells. The synthesis of host cell DNA was only partially inhibited in actively growing cells at acycloguanosine concentrations several hundred-fold greater than the 50% effective dose for herpes simplex virus type 1. Studies using partially purified enzymes revealed that the triphosphate of this compound inhibited the virus-induced DNA polymerases (DNA nucleotidyltransferases) to a greater degree than the DNA polymerase of the host cell, that the inhibition was dependent upon the base composition of the template, and that the triphosphate was a better substrate for the virus-induced polymerases than for the alpha cellular DNA polymerases.
D000818:Animals; D002460:Cell Line; D004247:DNA / Q000096:biosynthesis; D004261:DNA Replication / Q000187:drug effects*; D004279:DNA, Viral / Q000096:biosynthesis*; D004259:DNA-Directed DNA Polymerase / Q000378:metabolism; D006150:Guanine Nucleotides / Q000494:pharmacology*; D006151:Guanosine / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D000882:Haplorhini; D007668:Kidney; D019384:Nucleic Acid Synthesis Inhibitors; D018139:Simplexvirus / Q000187:drug effects* / Q000378:metabolism; D013698:Templates, Genetic
D004279:DNA, Viral; D006150:Guanine Nucleotides; D019384:Nucleic Acid Synthesis Inhibitors; D006151:Guanosine; D004247:DNA; D004259:DNA-Directed DNA Polymerase