title: The activity of (S)-1-[(3-hydroxy-2-phosphonyl methoxy) propyl] cytosine (HPMPC) against equine herpesvirus-1 (EHV-1) in cell cultures, mice and horses.
abstract: The activity of the nucleotide analogue, (S)-1-[(3-hydroxy-2-phosphonyl methoxy) propyl] cytosine (HPMPC), against equine herpesvirus-1 (EHV-1) was tested in cell culture, mice and foals. The ED50 for plaque reduction was found to be 0.07 and 0.03 microgram/ml in RK-13 and EEL cells respectively. In mice, a single administration of HPMPC (20 mg/kg, s.c.) was very effective at reducing clinical signs and virus replication if given on the day before intranasal inoculation with EHV-1. Treatment on the day of infection or day 1 p.i. was less effective, but still significantly reduced clinical signs and virus titres in the target organs (lungs and nasal tissue). Furthermore, HPMPC was found to protect mice partially from an intracerebral inoculation with EHV-1. Experiments in the horse suggested that HPMPC was also very active against EHV-1 in the natural host. Thus a single administration of HPMPC at 20 mg/kg, s.c., on the day of infection, markedly reduced clinical signs and nasal excretion of virus following intranasal inoculation with EHV-1. HPMPC given as a divided dose of 1 mg/kg on day 0 and day 3 p.i. had no effect on clinical signs but did reduce nasal excretion of virus. The significance of these results is discussed.
authors.affiliation: Department of Clinical Veterinary Medicine, Cambridge, UK.
authors.forename: J S
authors.initials: JS
authors.lastname: Gibson
authors.forename: J D
authors.initials: JD
authors.lastname: Slater
authors.forename: H J
authors.initials: HJ
authors.lastname: Field
mesh_terms: D000281:Administration, Intranasal; D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001927:Brain Diseases / Q000188:drug therapy / Q000662:veterinary; D000077404:Cidofovir; D003596:Cytosine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D004334:Drug Administration Schedule; D005260:Female; D006566:Herpesviridae Infections / Q000188:drug therapy* / Q000662:veterinary*; D004861:Herpesvirus 1, Equid / Q000187:drug effects* / Q000302:isolation & purification; D006734:Horse Diseases / Q000188:drug therapy*; D006736:Horses; D051379:Mice; D008807:Mice, Inbred BALB C; D063065:Organophosphonates; D009943:Organophosphorus Compounds / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D000998:Antiviral Agents; D063065:Organophosphonates; D009943:Organophosphorus Compounds; D003596:Cytosine; D000077404:Cidofovir