Inhibition of herpes simplex virus-induced DNA polymerase activity and viral DNA replication by 9-(2-hydroxyethoxymethyl)guanine and its triphosphate

J Virol. 1979 Oct;32(1):72-7. doi: 10.1128/JVI.32.1.72-77.1979.

Abstract

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.

MeSH terms

  • Animals
  • Cell Line
  • DNA / biosynthesis
  • DNA Replication / drug effects*
  • DNA, Viral / biosynthesis*
  • DNA-Directed DNA Polymerase / metabolism
  • Guanine Nucleotides / pharmacology*
  • Guanosine / analogs & derivatives*
  • Guanosine / metabolism
  • Guanosine / pharmacology
  • Haplorhini
  • Kidney
  • Nucleic Acid Synthesis Inhibitors*
  • Simplexvirus / drug effects*
  • Simplexvirus / metabolism
  • Templates, Genetic

Substances

  • DNA, Viral
  • Guanine Nucleotides
  • Nucleic Acid Synthesis Inhibitors
  • Guanosine
  • DNA
  • DNA-Directed DNA Polymerase