Comparative efficacy of three 2'-fluoropyrimidine nucleosides and 9-(1,3-dihydroxy-2-propoxymethyl)guanine (BW B759U) against pseudorabies and equine rhinopneumonitis virus infection in vitro and in laboratory animals.
The three 2'-fluoropyrimidine nucleosides 1-(2-deoxy-2-fluoro-beta-D-arabinofuranosyl)-5-iodocytosine (FIAC), 1-(2-deoxy-2-fluoro-beta-D-arabinofuranosyl)-5-iodouracil (FIAU), and 1-(2-deoxy-2-fluoro-beta-D-arabinofuranosyl)-5-methyluracil (FMAU), showed high activity in RK13 monolayers against equine rhinopneumonitis virus, (EHV-1, IC50 range 0.02-0.18 microM), Aujeszky's disease virus (SHV-1, pseudorabies, IC50 range 0.25-7 microM) and infectious bovine rhinotracheitis virus (1BR, BHV-1, IC50 range 0.1-3 microM). The activity of these compounds was compared with 9-(1,3-dihydroxy-2-propoxymethyl)guanine (BW B759U, DHPG) in two laboratory animal disease models: EHV-1-induced hepatitis in hamsters and SHV-1-induced encephalitis in mice. All the compounds, provided from 3 to 5 h pre-infection for 5 days, were effective in preventing EHV-1 mortality (at 3-5 mg/kg per day) and in significantly reducing SHV-1 mortality (at 60 mg/kg per day). While FIAU had the greatest activity in vitro, FMAU tended to be more potent in vivo. The reasons for these differences between relative in vitro and in vivo activities are briefly discussed.
D000212:Acyclovir / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D000998:Antiviral Agents / Q000627:therapeutic use*; D001086:Arabinofuranosyluracil / Q000031:analogs & derivatives / Q000494:pharmacology / Q000627:therapeutic use; D006224:Cricetinae; D003561:Cytarabine / Q000031:analogs & derivatives / Q000494:pharmacology / Q000627:therapeutic use; D015774:Ganciclovir; D006566:Herpesviridae Infections / Q000188:drug therapy*; D004861:Herpesvirus 1, Equid / Q000187:drug effects; D011558:Herpesvirus 1, Suid / Q000187:drug effects; D008297:Male; D051379:Mice; D011557:Pseudorabies / Q000188:drug therapy*; D011741:Pyrimidine Nucleosides / Q000494:pharmacology / Q000627:therapeutic use*
D000998:Antiviral Agents; D011741:Pyrimidine Nucleosides; D003561:Cytarabine; D001086:Arabinofuranosyluracil; C026023:fiacitabine; C043457:fialuridine; C034935:clevudine; D015774:Ganciclovir; D000212:Acyclovir