U18666A

Viral particles are trapped in the Lamp-1 positive late endosome/lysosome compartment when cells are treated with U18666A. In addition, viral replication is also affected by U18666A treatment. An additive anti-viral effect is found when C75, a fatty acid synthase inhibitor, is used in combination with U81666A, suggesting the role of cholesterol and fatty acid in DENV.^[1]

BHK21 cells are seeded with a cell density of 2×10⁴ cells/well into a 96 well plate 1 day before infection. NGC virus is added at a multiplicity of infection (MOI) of 1 in the presence of 2% FBS and is harvested from the cell supernatant 2 days post infection. Viral titer is quantified by plaque assay. For time of addition experiment of U18666A, cells are pretreated for 16 h with the compound, before virus is added to the cells (16 h pretreatment) or cells are pretreated for 16 h and the compound remained throughout the 48 h of infection (throughout). Alternatively, compound is added only during the 1st hour of infection where most of the entry and fusion occurred (1 h entry), or after the 1st hour of infection (after entry) for the remaining of the infection.

When U18666A is administered to cats experimentally infected with type I FIPV, the development of FIP may be suppressed compared with the control group. However, the number of animals with FIP is too low to establish anti-viral effect of U18666A in cats. Two of the five control cats administered PBS alone develops FIP. Four of the five cats administered U18666A develops no signs of FIP. One cat that temporarily developed fever, has no other clinical symptoms, and no gross lesion is noted on an autopsy after the end of the experiment. The FIPV gene is detected intermittently in feces and saliva regardless of the development of FIP or administration of U18666A.^[2]