دورية أكاديمية
A Refined Guinea Pig Model of Foot-and-Mouth Disease Virus Infection for Assessing the Efficacy of Antiviral Compounds.
| العنوان: | A Refined Guinea Pig Model of Foot-and-Mouth Disease Virus Infection for Assessing the Efficacy of Antiviral Compounds. |
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| المؤلفون: | De Vleeschauwer AR; Unit of Vesicular and Exotic Diseases, OD Viral Diseases, CODA-CERVA, Veterinary and Agrochemical Research Centre, Brussel, Belgium., Lefebvre DJ; Unit of Vesicular and Exotic Diseases, OD Viral Diseases, CODA-CERVA, Veterinary and Agrochemical Research Centre, Brussel, Belgium., Willems T; Unit of Vesicular and Exotic Diseases, OD Viral Diseases, CODA-CERVA, Veterinary and Agrochemical Research Centre, Brussel, Belgium., Paul G; MSD Animal Health, Intervet International GmbH, Köln, Germany., Billiet A; Aratana Therapeutics NV, Leuven, Belgium., Murao LE; Aratana Therapeutics NV, Leuven, Belgium., Neyts J; Aratana Therapeutics NV, Leuven, Belgium.; Department of Microbiology and Immunology, Rega Institute for Medical Research, Katholieke Universiteit Leuven, Leuven, Belgium., Goris N; Aratana Therapeutics NV, Leuven, Belgium., De Clercq K; Unit of Vesicular and Exotic Diseases, OD Viral Diseases, CODA-CERVA, Veterinary and Agrochemical Research Centre, Brussel, Belgium. |
| المصدر: | Transboundary and emerging diseases [Transbound Emerg Dis] 2016 Apr; Vol. 63 (2), pp. e205-12. Date of Electronic Publication: 2014 Aug 28. |
| نوع المنشور: | Comparative Study; Journal Article; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: Blackwell Verlag Country of Publication: Germany NLM ID: 101319538 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1865-1682 (Electronic) Linking ISSN: 18651674 NLM ISO Abbreviation: Transbound Emerg Dis Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: Berlin : Blackwell Verlag |
| مواضيع طبية MeSH: | Antiviral Agents/*therapeutic use , Foot-and-Mouth Disease/*drug therapy , Pyrazines/*therapeutic use, Animals ; Antibodies, Viral/blood ; Disease Models, Animal ; Europe ; Foot-and-Mouth Disease/prevention & control ; Foot-and-Mouth Disease Virus/isolation & purification ; Guinea Pigs ; RNA, Viral/blood ; Vaccination/veterinary ; Viral Vaccines/administration & dosage |
| مستخلص: | An antiviral containment strategy for foot-and-mouth disease (FMD) outbreaks could support or replace current contingency plans in case of an outbreak in Europe and could spare many healthy animals from being pre-emptively culled. Recently, substantial progress has been made towards the development of small molecule drugs that inhibit FMD virus (FMDV) replication in vitro. For the initial in vivo evaluation of antiviral lead molecules, a refined FMDV-infection model in guinea pigs (GP) is herewith described. This GP model was validated by demonstrating the antiviral effect of T-1105 (an influenza virus inhibitor with reported activity against FMDV). Sixteen animals were orally administered with T-1105 twice daily (400 mg/kg/day) for five consecutive days and inoculated intraplantarly with 100 GPID50 of the GP-adapted FMDV strain O1 Manisa 1 h after the first administration. The efficacy of T-1105 was compared with that of prophylactic vaccination with a highly potent double-oil emulsion-inactivated O1 Manisa vaccine. Ten animals received a single, full (2 ml) cattle vaccine dose and were inoculated 3 weeks later. Fourteen T-1105-treated and all vaccinated GP were completely protected from generalization of vesicular lesions. At 2 dpi, viral RNA was detected in serum of 9/16 T-1105-treated and of 6/10 vaccinated animals. At 4 dpi, viral RNA was detected in serum, organs and oral swabs of half of the T-1105-treated animals and only in the serum of 1/10 of the vaccinated animals. Mean viral RNA levels in serum and organs of T-1105-treated and vaccinated animals were reduced compared to untreated controls (P < 0.01). T-1105 conferred a substantial clinical and virological protection against infection with O1 Manisa, similar to the protection afforded by vaccination. These results validate the suitability of the enhanced GP model for the purpose of initial evaluation of inhibitors of FMDV replication and illustrate the potential of selective inhibitors of viral replication to control FMD outbreaks. (© 2014 Blackwell Verlag GmbH.) |
| فهرسة مساهمة: | Keywords: 3-oxo-3,4-dihydro-2-pyrazinecarboxamide derivative T-1105; animal welfare; antiviral drug; biosecurity; foot-and-mouth disease virus; guinea pig; proof-of-concept |
| المشرفين على المادة: | 0 (Antibodies, Viral) 0 (Antiviral Agents) 0 (Pyrazines) 0 (RNA, Viral) 0 (T 1105) 0 (Viral Vaccines) |
| تواريخ الأحداث: | Date Created: 20140829 Date Completed: 20161108 Latest Revision: 20181202 |
| رمز التحديث: | 20240628 |
| DOI: | 10.1111/tbed.12255 |
| PMID: | 25164494 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 1865-1682 |
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| DOI: | 10.1111/tbed.12255 |