Treatment of experimental herpes simplex virus type 1 encephalitis in mice with (E)-5-(2-bromovinyl)- and 5-vinyl-1-beta-D-arabinofuranosyluracil: comparison with bromovinyl-deoxyuridine and acyclovir.
The efficiency of (E)-5-(2-bromovinyl)- and 5-vinyl-1-beta-D-arabinofuranosyluracil (BrVaraU, VaraU) as inhibitors of three herpes simplex virus type 1 (HSV-1) strains was assessed in comparison to (E)-5-(2-bromovinyl)-2'-deoxyuridine (BrVUdR), 9-(2-hydroxyethoxymethyl)guanine (ACV), and trisodium phosphonoformate (Na3PFA) using a plaque assay in human embryonic lung fibroblast (HELF) cell cultures. The following order of decreasing activity was found: BrVaraU greater than VaraU greater than BrVU-dR greater than ACV much greater than Na3PFA. In HELF cell cultures, the selectivity indexes of VaraU and BrVaraU were 10 times higher than those of BrVUdR and ACV. Protection of mice from encephalitis and death due to intracerebral (i.c.) infection with a clinical HSV-1 isolate was nearly complete if mice were treated intraperitoneally (i.p.) with two daily doses of VaraU and BrVaraU (100 or 200 mg/kg per day) over a period of 5 or 10 days. The efficacy was similar to ACV, but, using a treatment schedule of three daily i.p. doses over 10 days, with equimolar amounts of the nucleoside analogs, VaraU and BrVaraU (140 and 180 mg/kg per day) were superior to ACV (130 mg/kg per day) (P less than 0.05).
D000212:Acyclovir / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D001086:Arabinofuranosyluracil / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D001973:Bromodeoxyuridine / Q000031:analogs & derivatives / Q000494:pharmacology / Q000627:therapeutic use; D002478:Cells, Cultured; D004660:Encephalitis / Q000188:drug therapy* / Q000382:microbiology; D005260:Female; D017245:Foscarnet; D006561:Herpes Simplex / Q000188:drug therapy*; D006801:Humans; D051379:Mice; D010746:Phosphonoacetic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D018139:Simplexvirus / Q000187:drug effects*; D014529:Uridine / Q000031:analogs & derivatives*; D010948:Viral Plaque Assay
C020235:brivudine; D001086:Arabinofuranosyluracil; D017245:Foscarnet; C048730:5-vinyl-1-arabinofuranosyluracil; C031368:sorivudine; D001973:Bromodeoxyuridine; D010746:Phosphonoacetic Acid; D014529:Uridine; D000212:Acyclovir