J Gen Virol Email Content Delivery
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

Originally published as JGV in Press, 10.1099/vir.0.008839-0 on March 4, 2009 J Gen Virol 90 (2009), 1335-1342; DOI 10.1099/vir.0.008839-0

This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
vir.0.008839-0v1
90/6/1335    most recent
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via CrossRef
Google Scholar
Right arrow Articles by Vrancken, R.
Right arrow Articles by Koenen, F.
PubMed
Right arrow PubMed Citation
Right arrow Articles by Vrancken, R.
Right arrow Articles by Koenen, F.
Agricola
Right arrow Articles by Vrancken, R.
Right arrow Articles by Koenen, F.

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

Robert Vrancken1, Andy Haegeman1, Jan Paeshuyse2, Gerhard Puerstinger3, Jef Rozenski2, Matthew Wright4, Marylène Tignon1, Marie-Frédérique Le Potier5, Johan Neyts2 and Frank Koenen1

1 Veterinary and Agrochemical Research Centre, Groeselenberg 99, B-1180 Ukkel, Belgium
2 Rega Institute for Medical Research, Katholieke Universiteit Leuven, Minderbroederstraat 10, B-3000 Leuven, Belgium
3 Department of Pharmaceutical Chemistry, Institute of Pharmacy, University of Innsbruck, Innrain 52a, A-6020 Innsbruck, Austria
4 Gilead Sciences, Drug Metabolism and Pharmacokinetics, 333 Lakeside Drive, Foster City, CA, USA
5 Agence Française de Sécurité Sanitaire des Aliments, Unité de Virologie Immunologie Porcines, BP53, F-22440 Ploufragan, France

Correspondence
Robert Vrancken
rovra{at}var.fgov.be

5-[(4-Bromophenyl)methyl]-2-phenyl-5H-imidazo[4,5-c]pyridine (BPIP) is a representative of a class of imidazopyridines with potent in vitro antiviral activity against pestiviruses including classical swine fever virus (CSFV). This study analysed whether the lead compound, BPIP, was able to reduce virus replication in infected piglets. The compound, administered in feed, was readily bioavailable and was well tolerated. Eight specific-pathogen-free pigs received a daily dose of 75 mg kg–1 (mixed in feed) for a period of 15 consecutive days, starting 1 day before infection with the CSFV field isolate Wingene. BPIP-treated pigs developed a short, transient viraemia (one animal remained negative) and leukopenia (three animals did not develop leukopenia). Virus titres at peak viraemia (7 days post-infection) were markedly lower (~1000-fold) than in untreated animals (P=0.00005) and the viral genome load in blood was also significantly lower (P≤0.001) 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 detected. The inability to isolate infectious virus from the tonsils indicates that the risk of a persistent CSFV infection is negligible. Further optimization of the antiviral potency and bioavailability of this lead compound may result in molecules completely suppressing virus 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 infection in pigs.






HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
INT J SYST EVOL MICROBIOL MICROBIOLOGY J GEN VIROL
J MED MICROBIOL ALL SGM JOURNALS
Copyright © 2009 by the Society for General Microbiology.