@entity25443 ( @entity25443 ), a @entity25444 (FCoV) induced disease, is almost invariably fatal with median life expectancy measured in days. Current treatment options are, at best, palliative. The objectives of this study were to evaluate a panel of nineteen candidate compounds for antiviral activity against FCoV in vitro to determine viable candidates for therapy. A resazurin-based cytopathic effect inhibition assay, which detects viable cells through their reduction of the substrate @entity30367 to fluorescent resorufin, was developed for screening compounds for antiviral efficacy against FCoV. Plaque reduction and virus yield reduction assays were performed to confirm antiviral effects of candidate compounds identified during screening, and the possible antiviral mechanisms of action of these compounds were investigated using virucidal suspension assays and CPE inhibition and IFA-based time of addition assays. Three compounds, @entity503 , @entity8775 , and @entity68593 demonstrated marked inhibition of virus induced CPE at low micromolar concentrations. Orthogonal assays confirmed inhibition of CPE was associated with significant reductions in viral replication. Selectivity indices calculated based on in vitro @entity137 screening and reductions in extracellular viral titre were 217, 24, and 20 for @entity503 , @entity8775 , and @entity68593 respectively. Preliminary experiments performed to inform the antiviral mechanism of the compounds demonstrated all three acted at an early stage of viral replication. These results suggest that these direct acting antiviral compounds, or their derivatives, warrant further investigation for clinical use in @entity468 with @entity25443 .

Identification and characterisation of small molecule inhibitors of XXXX replication.

@entity25443 :: ('MESH:D016766', 'Disease') :: ['FIP', 'Feline infectious peritonitis'] @entity137 :: ('MESH:D064420', 'Disease') :: ['cytotoxicity'] @entity30367 :: ('MESH:C005843', 'Chemical') :: ['resazurin'] @entity468 :: ('9685', 'Species') :: ['cats'] @entity25444 :: ('12663', 'Species') :: ['feline coronavirus'] @entity8775 :: ('MESH:D015767', 'Chemical') :: ['mefloquine'] @entity68593 :: ('MESH:C057360', 'Chemical') :: ['hexamethylene amiloride'] @entity503 :: ('MESH:D002738', 'Chemical') :: ['chloroquine']
@entity25444 :: (12663,Species) :: ['feline coronavirus']
