Submitted to: American Association of Veterinary Laboratory Diagnosticians
Publication Type: Abstract Only
Publication Acceptance Date: 7/28/2010
Publication Date: 11/11/2010
Citation: Newcomer, B., Marley, M., Ridpath, J.F., Neill, J.D., Givens, D. 2010. Characterization of an Antiviral Compound Effective Against Several Pestiviruses [abstract]. American Association of Veterinary Laboratory Diagnosticians. p. 103. Interpretive Summary:
Technical Abstract: The Pestivirus genus of the Flaviviridae family consists of four separate species: bovine viral diarrhea virus (BVDV) type 1 and type 2, classical swine fever virus, and border disease virus (BDV). Classification of several other viral isolates as pestiviruses has been proposed due to their genetic and structural relatedness to the current member viruses, including HoBi virus and pronghorn virus (PhV). An aromatic cationic compound, 2-(2-benzimidazolyl)-5-[4-(2-imidazolino)phenyl]furan dihydrochloride (DB772), has previously been shown to inhibit both BVDV 1 and BVDV 2 in vitro at concentrations lacking cytotoxic side effects. The compound also inhibits BVDV replication in vivo. The aim of this study was to determine the scope of antiviral activity of DB772 among the pestiviruses. Isolates of BDV, HoBi, or PhV were tested for in vitro susceptibility to DB772. A 24-well plate was seeded with ovine fetal turbinate cells (BDV and PhV) or MDBK cells (HoBi). After incubating for 24 hours, DB772 was added to the wells to achieve a concentration of 25, 12.5, 6.25, 3.13, 1.56, 0.78, 0.39, 0.20, 0.10, 0.05, 0.02, 0.01, or 0.006 uM DB772 except for the positive control well containing no DB772. The plates were then infected with the appropriate virus at a multiplicity of infection of 0.5 and incubated for four days. The plates were then frozen and wells assayed for the presence of virus by virus isolation and titration (BDV) or PCR (HoBi, and PhV). Each virus was tested in triplicate. Complete inhibition of BDV was seen when DB772 was included in the culture media at concentrations of 0.05 uM and higher. A concentration of 0.02 uM DB772 was sufficient to decrease viral titers of BDV by 3 log scores. Pronghorn virus was completely inhibited at concentrations of 0.20 uM. Partial inhibition at lesser concentrations was not detected. A concentration of 0.05 uM DB772 was sufficient to completely inhibit HoBi virus replication. DB772 effectively inhibits all pestiviruses studied at concentrations of 0.20 uM or less. As cytotoxicity is not seen until concentrations of DB772 exceed 60 uM, a wide therapeutic window exists. This antiviral compound represents a potential new therapeutic and/or preventative for use in pestivirus infections.