title: A thiazepino[4,5-a]benzimidazole derivative hampers the RNA replication of Eurasian serotypes of foot-and-mouth disease virus.
abstract: 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.
authors.affiliation: Department of Virology, CODA-CERVA, Groeselenberg 99, 1180 Brussels, Belgium. Electronic address: david.lefebvre@coda-cerva.be.
authors.forename: David J
authors.initials: DJ
authors.lastname: Lefebvre
authors.affiliation: Department of Virology, CODA-CERVA, Groeselenberg 99, 1180 Brussels, Belgium. Electronic address: annebel.devleeschauwer@coda-cerva.be.
authors.forename: Annebel R
authors.initials: AR
authors.lastname: De Vleeschauwer
authors.affiliation: Department of Virology, CODA-CERVA, Groeselenberg 99, 1180 Brussels, Belgium. Electronic address: ngoris@aratana.com.
authors.forename: Nesya
authors.initials: N
authors.lastname: Goris
authors.affiliation: Department of Virology, CODA-CERVA, Groeselenberg 99, 1180 Brussels, Belgium. Electronic address: steven.vanborm@coda-cerva.be.
authors.forename: Steven
authors.initials: S
authors.lastname: Van Borm
authors.affiliation: Department of Pharmaco-Chemistry, University of Messina, C. da Annunziata, 98168 Messina, Italy. Electronic address: achimirri@unime.it.
authors.forename: Alba
authors.initials: A
authors.lastname: Chimirri
authors.affiliation: Department of Pharmaco-Chemistry, University of Messina, C. da Annunziata, 98168 Messina, Italy. Electronic address: ammonforte@unime.it.
authors.forename: Anna Maria
authors.initials: AM
authors.lastname: Monforte
authors.affiliation: The Pirbright Institute, Ash Road, Pirbright, Woking, Surrey GU24 0NF, United Kingdom. Electronic address: begona.valdazo-gonzalez@pirbright.ac.uk.
authors.forename: Begona
authors.initials: B
authors.lastname: Valdazo-Gonzalez
authors.affiliation: The Pirbright Institute, Ash Road, Pirbright, Woking, Surrey GU24 0NF, United Kingdom. Electronic address: donald.king@pirbright.ac.uk.
authors.forename: Donald P
authors.initials: DP
authors.lastname: King
authors.affiliation: Department of Microbiology and Immunology, Rega Institute, KULeuven, Minderbroedersstraat 10, 3000 Leuven, Belgium. Electronic address: johan.neyts@rega.kuleuven.be.
authors.forename: Johan
authors.initials: J
authors.lastname: Neyts
authors.affiliation: Department of Virology, CODA-CERVA, Groeselenberg 99, 1180 Brussels, Belgium. Electronic address: kris.declercq@coda-cerva.be.
authors.forename: Kris
authors.initials: K
authors.lastname: De Clercq
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000737:chemistry; D001562:Benzimidazoles / Q000737:chemistry*; D002460:Cell Line; D002470:Cell Survival; D005536:Foot-and-Mouth Disease / Q000821:virology; D029544:Foot-and-Mouth Disease Virus / Q000235:genetics / Q000502:physiology*; D009154:Mutation; D017422:Sequence Analysis, DNA; D065288:Serogroup; D013552:Swine; D013841:Thiazepines / Q000737:chemistry*; D014779:Virus Replication
chemical_list: D000998:Antiviral Agents; D001562:Benzimidazoles; D013841:Thiazepines
keywords: Antiviral drug; Control policy; Foot-and-mouth disease virus; RNA replication