title: Mutations induced in the NS5B gene of bovine viral diarrhea virus by antiviral treatment convey resistance to the compound.
abstract: Bovine viral diarrhea virus (BVDV) is a widespread bovine pathogen for which there is no specific therapeutic agent. A previous study using 2-(2-benzimidazolyl)-5-[4-(2-imidazolino)phenyl]furan dihydrochloride (DB772) to treat calves persistently infected with BVDV resulted in a decrease in the viral load of infected calves but treatment resulted in the rapid selection of drug-resistant mutant isolates. In this article we describe three mutations found in the mutant isolates associated with in vivo and in vitro resistance to DB772. All three mutations are found in the NS5B which functions as the RNA-dependent-RNA-polymerase during viral replication. Growth curves for the mutant isolates were not largely different from those of wild-type isolates when cultured in the absence of DB772. Thus, DB772 appears to act by binding to the specified domain but binding is disrupted or inhibited by the described mutation.
authors.affiliation: Department of Clinical Sciences, College of Veterinary Medicine, Auburn University, 1500 Wire Road, AL 36849-5522, USA. bwn0001@auburn.edu
authors.forename: Benjamin W
authors.initials: BW
authors.lastname: Newcomer
authors.forename: John D
authors.initials: JD
authors.lastname: Neill
authors.forename: M Shonda
authors.initials: MS
authors.lastname: Marley
authors.forename: Julia F
authors.initials: JF
authors.lastname: Ridpath
authors.forename: M Daniel
authors.initials: MD
authors.lastname: Givens
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001562:Benzimidazoles / Q000494:pharmacology / Q000627:therapeutic use*; D002417:Cattle; D002418:Cattle Diseases / Q000188:drug therapy / Q000821:virology*; D004252:DNA Mutational Analysis; D030241:Diarrhea Virus 1, Bovine Viral / Q000187:drug effects / Q000235:genetics* / Q000302:isolation & purification; D024882:Drug Resistance, Viral; D005663:Furans / Q000494:pharmacology / Q000627:therapeutic use*; D008969:Molecular Sequence Data; D020125:Mutation, Missense; D018182:Pestivirus Infections / Q000188:drug therapy / Q000821:virology*; D012367:RNA, Viral / Q000235:genetics; D012641:Selection, Genetic; D017422:Sequence Analysis, DNA; D017361:Viral Nonstructural Proteins / Q000235:genetics*
chemical_list: C571880:2-(2-benzimidazolyl)-5-(4-(2-imidazolino)phenyl)furan; D000998:Antiviral Agents; D001562:Benzimidazoles; D005663:Furans; D012367:RNA, Viral; D017361:Viral Nonstructural Proteins