Antiviral effect of mefloquine on feline calicivirus in vitro

Abstract

Feline calicivirus (FCV) is an important viral pathogen of domestic cats causing clinical signs ranging from mild to severe oral ulceration or upper respiratory tract disease through to a severe fatal systemic disease. Current therapeutic options are limited, with no direct acting antivirals available for treatment. This study screened a panel of 19 compounds for potential antiviral activity against FCV strain F9 and recent field isolates in vitro. Using a resazurin-based cytopathic effect (CPE) inhibition assay, mefloquine demonstrated a marked inhibitory effect on FCV induced CPE, albeit with a relatively low selectivity index. Orthogonal assays confirmed inhibition of CPE was associated with a significant reduction in viral replication. Mefloquine exhibited a strong inhibitory effect against a panel of seven recent FCV isolates from Australia, with calculated IC50 values for the field isolates approximately 50% lower than against the reference strain FCV F9. In vitro combination therapy with recombinant feline interferon-ω, a biological response modifier currently registered for the treatment of FCV, demonstrated additive effects with a concurrent reduction in the IC50 of mefloquine. These results are the first report of antiviral effects of mefloquine against a calicivirus and support further in vitro and in vivo evaluation of this compound as an antiviral therapeutic for FCV.

Interferon-omega: Current status in clinical applications

“…Combination antiviral therapy has become a common practice. Recently, researchers revealed that a combination treatment of rFeIFN-ω and mefloquine resulted in additive effects with a reduction in the half maximal inhibitory concentration [79]. Another study conducted by Lee et al [80] showed that the relative expression of IFN-ω, Mx, and ZAPS mRNA in Crandell-Reese Feline Kidney cells was upregulated significantly in FCV-infected cats.…”

Antiviral effect of lithium chloride on feline calicivirus in vitro

“…Confluent CRFK cell monolayers in 96-well plates (10 4 cells) were incubated overnight at 37°C and 5 % CO 2 in complete medium. The cell supernatant was removed, and the monolayers were overlaid with 100 lL of LiCl at a series of concentrations (20,40,60, 80 and 100 mM) in serum-free DMEM for 24 h and 72 h; the monolayers were then washed with PBS. Mock-treated CRFK cells served as a control.…”

“…Feline-calicivirus-specific antiviral phosphorodiamidate morpholino oligomers (PMO) were tested in naturally occurring outbreaks of FCV, and the results demonstrated that PMO can work as a high-efficiency drug to treat FCV disease [30]. Mefloquine was employed as monotherapy or combination treatment with rFeIFN-x [20], but deficiencies in a number of drug metabolism pathways have been recognized in humans [20]. For more than fifty years, lithium chloride (LiCl) has been used as a major treatment for bipolar disorder [18], and the mechanisms of LiCl have been explored, particularly for treating Alzheimer's disease [10], diabetes [16], and serous ovarian cancer [21], and also as an antimicrobial agent.…”

Identification of Inonotus obliquus polysaccharide with broad-spectrum antiviral activity against multi-feline viruses

“…To further evaluate the anti-FCV activity, the resazurin-based CPE inhibition assay as described previously [5] was used. Titration of IOP showed a concentration-response relationship, showing nearly 80% inhibition of the cytopathic effect (CPE) at a concentration of 100 g/mL and 30% inhibition at a concentration of 10 g/mL when the cells were infected at an MOI of 0.005 (Fig.…”