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Antiviral Res. 2014 May;105:59-63. doi: 10.1016/j.antiviral.2014.02.009. Epub 2014 Feb 25.

In vitro surrogate models to aid in the development of antivirals for the containment of foot-and-mouth disease outbreaks.

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Okapi Sciences NV, Ambachtenlaan 1, 3001 Heverlee, Belgium.
Unit of Vesicular and Exotic Diseases, Virology Department, CODA-CERVA, Veterinary and Agrochemical Research Centre, Groeselenberg 99, 1180 Brussel, Belgium.
Okapi Sciences NV, Ambachtenlaan 1, 3001 Heverlee, Belgium; Department of Microbiology and Immunology, Rega Institute for Medical Research, University of Leuven (KU Leuven), 3000 Leuven, Belgium.
Okapi Sciences NV, Ambachtenlaan 1, 3001 Heverlee, Belgium. Electronic address:


Foot-and-mouth disease virus (FMDV) is a highly pathogenic member of the genus Aphthovirus (family Picornaviridae) that is only to be manipulated in high-containment facilities, thus complicating research on and discovery of antiviral strategies against the virus. Bovine rhinitis B virus (BRBV) and equine rhinitis A virus (ERAV), phylogenetically most closely related to FMDV, were explored as surrogates for FMDV in antiviral studies. Although no efficient cell culture system has been reported so far for BRBV, we demonstrate that infection of primary bovine kidney cells resulted in an extensive but rather poorly-reproducible induction of cytopathic effect (CPE). Madin-Darby bovine kidney cells on the other hand supported viral replication in the absence of CPE. Antiviral tests were developed for ERAV in Vero A cells employing a viral RNA-reduction assay and CPE-reduction assay; the latter having a Z' factor of 0.83±0.07. The BRBV and ERAV models were next used to assess the anti-aphthovirus activity of two broad-spectrum antiviral agents 2'-C-methylcytidine (2CMC) and ribavirin, as well as of the enterovirus-specific inhibitor enviroxime. The effects of the three compounds in the CPE-reduction (ERAV) and viral RNA-reduction assays (BRBV and ERAV) were comparable. Akin to 2CMC, compound A, a recently-discovered non-nucleoside pan-serotype FMDV inhibitor, also inhibited the replication of both BRBV and ERAV, whereas enviroxime was devoid of activity. The BRBV and ERAV surrogate models reported here can be manipulated in BSL-2 laboratories and may facilitate studies to unravel the mechanism of action of novel FMDV inhibitors.


Antivirals; Aphthovirus; FMDV; Surrogate model

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