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

Abstract

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 (P50.00005) 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.

Low CD4/CD8 ratio in classical swine fever postnatal persistent infection generated at 3 weeks after birth

“…One of the most common anatomopathological findings associated after CSFV infection is found in the tonsil, a target tissue for CSFV replication and wherein the virus persists for more than 30 days post infection (Koenig et al., ; Vrancken et al., ). The most relevant histopathological finding in the tonsil are congestion of the blood vessels along with focal to diffuse areas of haemorrhage (Malswamkima, Rajkhowa, Chandra, & Dutta, ).…”

“…One of the most common anatomopathological findings associated after CSFV infection is found in the tonsil, a target tissue for CSFV replication and wherein the virus persists for more than 30 days post infection (Koenig et al, 2007;Vrancken et al, 2009).…”

Epidemiology, diagnosis and control of classical swine fever: Recent developments and future challenges

“…According to the EU strategy to control CSF, affected pigs must be slaughtered and the carcasses buried or destroyed in rendering plants. Nevertheless, anti-virals were tested in pilot trials and have been discussed as a possible primary control measure against virus spread in case of an outbreak, in addition to present countermeasures (Vrancken et al, 2009). Anti-viral substances which prevent or diminish the shedding and spread of CSF virus by infected pigs might offer new additional tools for CSF control (Backer, Vrancken, Neyts, & Goris, 2013;Ribbens, Goris, Neyts, & Dewulf, 2012).…”

Meeting report: 32nd International Conference on Antiviral Research

“…Her talk highlighted the potential of antiviral therapy to contain outbreaks of exotic infections, using classical swine fever and the compound BPIP as an example. In experimental studies in piglets, BPIP reduced the viremic period by 74% and the viral load by 1,000-fold, and was highly effective in preventing transmission of infection to untreated sentinels (Vrancken et al, 2009a(Vrancken et al, , 2009b. Modeling studies have shown this to be an economically viable control policy (Backer et al, 2013).…”