2--c-methylcytidine and Cat-Diseases

Feline calicivirus (FCV) causes upper respiratory tract disease (URTD) and sporadic outbreaks of virulent systemic disease (FCV-VSD). The basis for the increased pathogenicity of FCV-VSD viruses is incompletely understood, and antivirals for FCV-VSD have yet to be developed. We investigated the clinicoepidemiology and viral features of three FCV-VSD outbreaks in Australia and evaluated the in vitro efficacy of nitazoxanide (NTZ), 2'-C-methylcytidine (2CMC) and NITD-008 against FCV-VSD viruses. Overall mortality among 23 cases of FCV-VSD was 39%. Metagenomic sequencing identified five genetically distinct FCV lineages within the three outbreaks, all seemingly evolving in situ in Australia. Notably, no mutations that clearly distinguished FCV-URTD from FCV-VSD phenotypes were identified. One FCV-URTD strain likely originated from a recombination event. Analysis of seven amino-acid residues from the hypervariable E region of the capsid in the cultured viruses did not support the contention that properties of these residues can reliably differentiate between the two pathotypes. On plaque reduction assays, dose-response inhibition of FCV-VSD was obtained with all antivirals at low micromolar concentrations; NTZ EC

Topics: Animals; Antiviral Agents; Australia; Caliciviridae Infections; Calicivirus, Feline; Capsid; Cat Diseases; Cats; Cytidine; Disease Outbreaks; Female; Male; Metagenome; Nitro Compounds; Phylogeny; Thiazoles

Feline calicivirus (FCV) is a major cause of upper respiratory tract disease in cats, with widespread distribution in the feline population. Recently, virulent systemic diseases caused by FCV infection has been associated with mortality rates up to 50%. Currently, there are no direct-acting antivirals approved for the treatment of FCV infection. Here, we tested 15 compounds from different antiviral classes against FCV using in vitro protein and cell culture assays. After the expression of FCV protease-polymerase protein, we established two in vitro assays to assess the inhibitory activity of compounds directly against the FCV protease or polymerase. Using this recombinant enzyme, we identified quercetagetin and PPNDS as inhibitors of FCV polymerase activity (IC

Topics: Animals; Antiviral Agents; Caliciviridae Infections; Calicivirus, Feline; Cat Diseases; Cats; Cell Line; Cytidine; DNA-Directed RNA Polymerases; Epithelial Cells; Flavones; Gene Expression; High-Throughput Screening Assays; Inhibitory Concentration 50; Nitro Compounds; Peptide Hydrolases; Polyproteins; Pyridoxal Phosphate; Recombinant Proteins; Respiratory Tract Infections; Sulfonic Acids; Thiazoles