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Biochem Biophys Res Commun. 2014 Dec 12;455(3-4):378-81. doi: 10.1016/j.bbrc.2014.11.023. Epub 2014 Nov 15.

A thiazepino[4,5-a]benzimidazole derivative hampers the RNA replication of Eurasian serotypes of foot-and-mouth disease virus.

Author information

1
Department of Virology, CODA-CERVA, Groeselenberg 99, 1180 Brussels, Belgium. Electronic address: david.lefebvre@coda-cerva.be.
2
Department of Virology, CODA-CERVA, Groeselenberg 99, 1180 Brussels, Belgium. Electronic address: annebel.devleeschauwer@coda-cerva.be.
3
Department of Virology, CODA-CERVA, Groeselenberg 99, 1180 Brussels, Belgium. Electronic address: ngoris@aratana.com.
4
Department of Virology, CODA-CERVA, Groeselenberg 99, 1180 Brussels, Belgium. Electronic address: steven.vanborm@coda-cerva.be.
5
Department of Pharmaco-Chemistry, University of Messina, C. da Annunziata, 98168 Messina, Italy. Electronic address: achimirri@unime.it.
6
Department of Pharmaco-Chemistry, University of Messina, C. da Annunziata, 98168 Messina, Italy. Electronic address: ammonforte@unime.it.
7
The Pirbright Institute, Ash Road, Pirbright, Woking, Surrey GU24 0NF, United Kingdom. Electronic address: begona.valdazo-gonzalez@pirbright.ac.uk.
8
The Pirbright Institute, Ash Road, Pirbright, Woking, Surrey GU24 0NF, United Kingdom. Electronic address: donald.king@pirbright.ac.uk.
9
Department of Microbiology and Immunology, Rega Institute, KULeuven, Minderbroedersstraat 10, 3000 Leuven, Belgium. Electronic address: johan.neyts@rega.kuleuven.be.
10
Department of Virology, CODA-CERVA, Groeselenberg 99, 1180 Brussels, Belgium. Electronic address: kris.declercq@coda-cerva.be.

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.

KEYWORDS:

Antiviral drug; Control policy; Foot-and-mouth disease virus; RNA replication

PMID:
25446115
DOI:
10.1016/j.bbrc.2014.11.023
[Indexed for MEDLINE]

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