title: Inhibition of herpes simplex virus DNA polymerase by purine ribonucleoside monophosphates.
abstract: Purine ribonucleoside monophosphates were found to inhibit chain elongation catalyzed by herpes simplex virus (HSV) DNA polymerase when DNA template-primer concentrations were rate-limiting. Inhibition was fully competitive with DNA template-primer during chain elongation; however, DNA polymerase-associated exonuclease activity was inhibited noncompetitively with respect to DNA. Combinations of 5'-GMP and phosphonoformate were kinetically mutually exclusive in dual inhibitor studies. Pyrimidine nucleoside monophosphates and deoxynucleoside monophosphates were less inhibitory than purine riboside monophosphates. The monophosphates of 9-beta-D-arabinofuranosyladenine, Virazole (1-beta-D-ribofuranosyl-1,2,4-triazole-3-carboxamide), 9-(2-hydroxyethoxymethyl)guanine, and 9-(1,3-dihydroxy-2-propoxymethyl)guanine exerted little or no inhibition. In contrast to HSV DNA polymerase, human DNA polymerase alpha was not inhibited by purine ribonucleoside monophosphates. These studies suggest the possibility of a physiological role of purine ribonucleoside monophosphates as regulators of herpesvirus DNA synthesis and a new approach to developing selective anti-herpesvirus compounds.
mesh_terms: D000998:Antiviral Agents / Q000494:pharmacology; D004259:DNA-Directed DNA Polymerase / Q000378:metabolism; D003854:Deoxyribonucleotides / Q000494:pharmacology; D017245:Foscarnet; D006157:Guanosine Monophosphate / Q000494:pharmacology; D007700:Kinetics; D019384:Nucleic Acid Synthesis Inhibitors; D010746:Phosphonoacetic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D012265:Ribonucleotides / Q000494:pharmacology*; D018139:Simplexvirus / Q000201:enzymology*; D014764:Viral Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D000998:Antiviral Agents; D003854:Deoxyribonucleotides; D019384:Nucleic Acid Synthesis Inhibitors; D012265:Ribonucleotides; D014764:Viral Proteins; D017245:Foscarnet; D006157:Guanosine Monophosphate; D004259:DNA-Directed DNA Polymerase; D010746:Phosphonoacetic Acid