title: Antiviral treatment of calves persistently infected with bovine viral diarrhoea virus.
abstract: BACKGROUND
  Animals persistently infected (PI) with bovine viral diarrhoea virus (BVDV) are a key source of viral propagation within and among herds. Currently, no specific therapy exists to treat PI animals. The purpose of this research was to initiate evaluation of the pharmacokinetic and safety data of a novel antiviral agent in BVDV-free calves and to assess the antiviral efficacy of the same agent in PI calves.
  
  
  METHODS
  One BVDV-free calf was treated with 2-(2-benzimidazolyl)-5-[4-(2-imidazolino)phenyl]furan dihydrochloride (DB772) once at a dose of 1.6 mg/kg intravenously and one BVDV-free calf was treated three times a day for 6 days at 9.5 mg/kg intravenously. Subsequently, four PI calves were treated intravenously with 12 mg/kg DB772 three times a day for 6 days and two PI control calves were treated with an equivalent volume of diluent only.
  
  
  RESULTS
  Prior to antiviral treatment, the virus isolated from each calf was susceptible to DB772 in vitro. The antiviral treatment effectively inhibited virus for 14 days in one calf and at least 3 days in three calves. Subsequent virus isolated from the three calves was resistant to DB772 in vitro. No adverse effects of DB772 administration were detected.
  
  
  CONCLUSIONS
  Results demonstrate that DB772 administration is safe and exhibits antiviral properties in PI calves while facilitating the rapid development of viral resistance to this novel therapeutic agent.
authors.affiliation: Department of Clinical Sciences, College of Veterinary Medicine, Auburn University, Auburn, AL, USA. bwn0001@auburn.edu
authors.forename: Benjamin W
authors.initials: BW
authors.lastname: Newcomer
authors.forename: M Shonda
authors.initials: MS
authors.lastname: Marley
authors.forename: Patricia K
authors.initials: PK
authors.lastname: Galik
authors.forename: Paul H
authors.initials: PH
authors.lastname: Walz
authors.forename: Yijing
authors.initials: Y
authors.lastname: Zhang
authors.forename: Kay P
authors.initials: KP
authors.lastname: Riddell
authors.forename: Christine C
authors.initials: CC
authors.lastname: Dykstra
authors.forename: David W
authors.initials: DW
authors.lastname: Boykin
authors.forename: Arvind
authors.initials: A
authors.lastname: Kumar
authors.forename: Crisanta
authors.initials: C
authors.lastname: Cruz-Espindola
authors.forename: Dawn M
authors.initials: DM
authors.lastname: Boothe
authors.forename: Kellye S
authors.initials: KS
authors.lastname: Joiner
authors.forename: M Daniel
authors.initials: MD
authors.lastname: Givens
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D001562:Benzimidazoles / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D001912:Bovine Virus Diarrhea-Mucosal Disease / Q000188:drug therapy*; D002417:Cattle; D001908:Diarrhea Viruses, Bovine Viral / Q000187:drug effects* / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D024882:Drug Resistance, Viral / Q000187:drug effects / Q000502:physiology; D005663:Furans / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D008826:Microbial Sensitivity Tests; D009994:Osmolar Concentration; D013997:Time Factors
chemical_list: C571880:2-(2-benzimidazolyl)-5-(4-(2-imidazolino)phenyl)furan; D000998:Antiviral Agents; D001562:Benzimidazoles; D005663:Furans