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A proof of concept for the reduction of classical swine fever infection in pigs by a novel viral polymerase inhibitor

¹ VAR;
² Rega Institute for Medical Research, KULeuven;
³ Institute of Pharmacy, University of Innsbruck;
⁴ Gilead Sciences;
⁵ AFSSA, Ploufragan

⁶ E-mail: rovra{at}var.fgov.be

BPIP [5-[(4-bromophenyl)methyl]-2-phenyl-5H-imidazo[4,5-c]pyridine] is a representative of a class of imidazopyridines with potent in vitro antiviral activity against pestiviruses including classical swine fever virus (CSFV). We studied whether the lead compound BPIP is able to reduce viral replication in infected piglets. The compound, administered in feed, was readily bioavailable and well tolerated. Eight specific pathogen free pigs received a daily dose of 75 mg/kg (mixed in feed) for a period of 15 consecutive days, starting one day before infection with the CSFV field-isolate Wingene. BPIP-treated pigs developed a short, transient viraemia (one animal remained negative) and leucopenia (3 animals did not develop leucopenia). Virus titres at peak viraemia (7 days post infection) were markedly lower (~1000 fold) than in untreated animals (p=0.00005) and also the viral genome load in blood was significantly lower (p0.001) in drug-treated animals than in untreated animals over the entire experiment. At the end of the experiment (day 33) no infectious virus was detectable in the tonsils of BPIP-treated animals, although low levels of viral RNA were measured. The inability to isolate infectious virus from the tonsils indicates that the risk for a persistent CSF-infection is negligible. Further optimization of the antiviral potency and bioavailability of this lead compounds may result in molecules completely suppressing viral replication. A potent antiviral could potentially be used as a primary control measure against virus spread in case of an outbreak in addition to present countermeasures. This study provides the first proof of concept for the prophylaxis/treatment of CSFV-infections in pigs.

Received 14 November 2008; accepted 24 February 2009.