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. 2009 Jun;82(3):169-71.
doi: 10.1016/j.antiviral.2009.02.201. Epub 2009 Mar 10.

Effect of T-705 treatment on western equine encephalitis in a mouse model

Justin G Julander  1 , Donald F Smee, John D Morrey, Yousuke Furuta
Affiliations

Effect of T-705 treatment on western equine encephalitis in a mouse model

Justin G Julander et al. Antiviral Res. 2009 Jun.

Abstract

A mouse model of western equine encephalitis (WEE) was characterized for use in antiviral studies. Virus was detected in several tissues, most notably an average titer of 9. 5+/-1. 1 log(10) 50% cell culture infectious doses (CCID(50))/g tissue in the brains of infected animals. Signs of WEE included limb weakness, paralysis, involuntary spasms or extension of limbs, clenching of paws, hunching, ruffling of fur, and eye exudates, many of which are indicative of neurological disease. The pyrazinecarboxamide derivative, T-705, was found to be active in Vero cells against WEE virus (WEEV) with an 90% effective concentration (EC(90)) of 49microg/ml (selective index [SI]>20). Treatment with T-705 in this WEE mouse model resulted in significant improvement in survival and mean day to death after oral treatment administered twice a day for 7 days at a dose of 400mg/(kgd). Virus titer in the brain was not significantly reduced, despite a 1-log reduction in average brain titer in treated animals on 4dpi. Signs of disease were relatively mild in treated animals, but were not eliminated. Treatment with T-705 improved morbidity and mortality of WEEV-infected mice, further illustrating the broad-spectrum activity of T-705 in the treatment of RNA viruses VSports手机版. .

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Figure 1
Figure 1
A) Titer, measured as log10 50% cell culture infectious doses (CCID50)/g tissue or ml serum, of WEEV in various tissues taken from mice on 2, 3, 4, 5, and 6 days post-virus infection (dpi) with 103.9 pfu/ml WEEV. B) Time-course weight change (g) of mice infected with WEEV.
Figure 2
Figure 2
Survival of C57BL/6 mice infected with WEEV and treated twice a day for 8 days with T-705 given p.o [n=15], or −4 h and 2 dpi with ampligen given i.p. [n=10] (***P<0.001, **P<0.01, as compared with placebo-treated controls [n=20], as determined by Wilcoxon log-rank survival analysis).
Figure 3
Figure 3
Brain titers of C57BL/6 mice infected with WEEV and treated twice a day for 7 days with T-705 administered orally at a dose of 400 mg/kg/d. Lines represent mean titers for each group (P = 0.3287 as determined by one-way Student’s t-test).
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