Identification and characterisation of small molecule inhibitors of feline coronavirus replication

McDonagh, Phillip; Sheehy, Paul A.; Norris, Jacqueline M.

doi:10.1016/j.vetmic.2014.10.030

Cited by 24 publications

(45 citation statements)

References 34 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Crandell Rees feline kidney (CRFK) cell line was propagated as outlined previously (McDonagh et al, 2014). The reference feline calicivirus strain F9 was kindly provided by Professor Gilkerson (University of Melbourne).…”

Section: Cell Culture and Virusesmentioning

confidence: 99%

“…Nineteen compounds were selected based on reported in vitro antiviral effects against other RNA viruses (McDonagh et al, 2014). To determine an appropriate screening concentration the cytotoxicity of compounds was investigated using sequential resazurin and sulforhodamine B assays as previously reported (McDonagh et al, 2014). Test compound concentrations selected for subsequent antiviral screening were those resulting in cell viability of 80% or greater and are shown in Table 1.…”

Section: Test Compoundsmentioning

confidence: 99%

“…Test compound concentrations selected for subsequent antiviral screening were those resulting in cell viability of 80% or greater and are shown in Table 1. Stock solutions were prepared as outlined previously (McDonagh et al, 2014). The maximum final in-well DMSO concentration used in these studies was 0.33%, which was demonstrated to have no significant effect on cell viability or viral replication (data not shown).…”

Section: Test Compoundsmentioning

confidence: 99%

“…Antiviral screening was performed using a modification of the optimised resazurin-based CPE inhibition assay outlined previously (McDonagh et al, 2014). After 1 h of compound exposure cells were infected with FCV strain F9 at MOI 0.01 (20 ml well À1 ) for an infection period of 48 h with 50 ml of 1:10 dilution of 4 Â stock resazurin in DMEM (final well concentration of resazurin 44 nM) added for the final 3.5 h. The duration of compound exposure in this assay was from 1 h prior to infection through to the assay endpoint, thereby allowing the identification of agents acting at any stage of the viral lifecycle.…”

Section: Antiviral Screening Using Cpe Inhibition Assaymentioning

confidence: 99%

See 3 more Smart Citations

Antiviral effect of mefloquine on feline calicivirus in vitro

McDonagh

Sheehy

Fawcett

et al. 2015

Veterinary Microbiology

Self Cite

View full text Add to dashboard Cite

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.

show abstract

Section: Cell Culture and Virusesmentioning

confidence: 99%

Section: Test Compoundsmentioning

confidence: 99%

Section: Test Compoundsmentioning

confidence: 99%

Section: Antiviral Screening Using Cpe Inhibition Assaymentioning

confidence: 99%

See 2 more Smart Citations

Antiviral effect of mefloquine on feline calicivirus in vitro

McDonagh

Sheehy

Fawcett

et al. 2015

Veterinary Microbiology

Self Cite

View full text Add to dashboard Cite

show abstract

“…Titration of extracellular virus was performed using the TCID50 method and by plaque assay as previously reported (McDonagh et al, 2011(McDonagh et al, , 2014. Table 1 Sequence of siRNAs targeting FCoV and their position in FCoV FIPV1146 genome (accession number DQ010921).…”

Section: Virus Titrationmentioning

confidence: 99%

Combination siRNA therapy against feline coronavirus can delay the emergence of antiviral resistance in vitro

McDonagh

Sheehy

Norris

2015

Veterinary Microbiology

Self Cite

View full text Add to dashboard Cite

Virulent biotypes of feline coronavirus (FCoV), commonly referred to as feline infectious peritonitis virus (FIPV), can result in the development of feline infectious peritonitis (FIP), a typically fatal immune mediated disease for which there is currently no effective antiviral treatment. We previously reported the successful in vitro inhibition of FIPV replication by synthetic siRNA mediated RNA interference (RNAi) in an immortalised cell line (McDonagh et al., 2011). A major challenge facing the development of any antiviral strategy is that of resistance, a problem which is particularly acute for RNAi based therapeutics due to the exquisite sequence specificity of the targeting mechanism. The development of resistance during treatment can be minimised using combination therapy to raise the genetic barrier or using highly potent compounds which result in a more rapid and pronounced reduction in the viral replication rate, thereby reducing the formation of mutant, and potentially resistant viruses. This study investigated the efficacy of combination siRNA therapy and its ability to delay or prevent viral escape. Virus serially passaged through cells treated with a single or dual siRNAs rapidly acquired resistance, with mutations identified in the siRNA target sites. Combination therapy with three siRNA prevented viral escape over the course of five passages. To identify more potent silencing molecules we also compared the efficacy, in terms of potency and duration of action, of canonical versus Dicer-substrate siRNAs for two previously identified effective viral motifs. Dicer-substrate siRNAs showed equivalent or better potency than canonical siRNAs for the target sites investigated, and may be a more appropriate molecule for in vivo use. Combined, these data inform the potential therapeutic application of antiviral RNAi against FIPV.

show abstract

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

Jin

Liu

et al. 2017

International Journal of Biological Macromolecules

View full text Add to dashboard Cite

Inonotus obliquus polysaccharides (IOPs) are a potential drug for the prevention and treatment of cancer, cardiopathy, diabetes, AIDs, pancreatitis and other diseases. In this study, we found that IOP can act as a broad-spectrum antiviral drug against feline viruses in the in vitro experiment. Using cell models of feline calicivirus (FCV), we demonstrated that IOP treatment was capable of exhibiting anti-FCV strain F9 activity in cell-based assays and also showed low cytotoxicity. Investigation of the mechanism of action of the compound revealed that IOP treatment induces its inhibitory actions directly on virus particles through blocking viral binding/absorpting. The inhibitory activity against other FCV isolates from China was also identified. More importantly, we found that IOP exhibited broad-spectrum antiviral activity against the feline herpesvirus 1, feline influenza virus H3N2 and H5N6, feline panleukopenia virus and feline infectious peritonitis virus that can contribute to respiratory and gastrointestinal diseases in cats. These findings suggest that IOP may be a potential broad-spectrum antiviral drug against feline viruses.

show abstract

Identification and characterisation of small molecule inhibitors of feline coronavirus replication

Cited by 24 publications

References 34 publications

Antiviral effect of mefloquine on feline calicivirus in vitro

Antiviral effect of mefloquine on feline calicivirus in vitro

Combination siRNA therapy against feline coronavirus can delay the emergence of antiviral resistance in vitro

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

Contact Info

Product

Resources

About