TY - JOUR T1 - A thiazepino[4,5-a]benzimidazole derivative hampers the RNA replication of Eurasian serotypes of foot-and-mouth disease virus. JF - Biochem Biophys Res Commun Y1 - 2014 A1 - David Lefebvre A1 - Annebel De Vleeschauwer A1 - Goris, Nesya A1 - Steven Van Borm A1 - Chimirri, Alba A1 - Monforte, Anna Maria A1 - Valdazo-Gonzalez, Begona A1 - King, Donald P A1 - Neyts, Johan A1 - Kris De Clercq KW - Animals KW - Antiviral Agents KW - Benzimidazoles KW - Cell Line KW - Cell Survival KW - Foot-and-Mouth Disease KW - Foot-and-Mouth Disease Virus KW - Mutation KW - Sequence Analysis, DNA KW - Serogroup KW - Swine KW - Thiazepines KW - Virus Replication AB -

The stamping-out policy for the control of foot-and-mouth disease virus (FMDV) in countries that are free from FMD without vaccination has a dramatic socio-economic impact, huge animal welfare issues and may result in the loss of farm animal genetic resources. As an alternative to pre-emptive culling or emergency vaccination we further explore the possibility to use antiviral drugs in the event of an FMD outbreak. In the present study, we tested the in vitro cytotoxicity and anti-FMDV activity of 1,2,4,5-tetrahydro-[1,4]thiazepino[4,5-a]benzimidazole. The molecule was shown to inhibit the replication of reference strains of the Eurasian FMDV serotypes O, A, C and Asia but not the FMDV serotypes from the South African Territories (SAT) neither a related picornavirus, i.e. swine vesicular disease virus. The molecule can be added until 2h post inoculation in a 'single replication cycle experiment' without losing its antiviral activity. The genetic characterization of progressively selected resistant FMD viruses shows that the molecule presumably interacts with the non-structural 2C protein of FMDV. Further studies are required on the use of this molecule in vivo.

VL - 455 CP - 3-4 U1 - https://www.ncbi.nlm.nih.gov/pubmed/25446115?dopt=Abstract M3 - 10.1016/j.bbrc.2014.11.023 ER -