ABSTRACT
Feline infectious peritonitis virus (FIPV: virulent feline coronavirus) causes a fatal disease called feline infectious peritonitis (FIP) in wild and domestic cat species. Recent studies identified several antiviral drugs that are effective against FIPV. Drug combination is one of the important strategies in the development of novel treatments for viral infections. GS-441524, a nucleoside analog, and itraconazole, a triazole antifungal drug, have been reported that have antiviral effect against FIPV. This study aims to investigate whether the combination of GS-441524 and itraconazole has synergic antiviral effect against FIPV. The antiviral effect was measured by plaque reduction assay using felis catus whole fatus-4 cell. The plaque reduction of GS-441524 against type I FIPVs increased as the concentration of itraconazole increased. The similar result was obtained for type II FIPV. In addition, the calculated combination index (CI) demonstrated that there was a strong synergy between GS-441524 and itraconazole. It is concluded that the combination of GS-441524 and itraconazole may enhance the individual effect of each drug against replication of type I FIPVs and may contribute to development more effective treatment strategy for FIP.
Subject(s)
Cat Diseases , Coronavirus, Feline , Feline Infectious Peritonitis , Adenosine/analogs & derivatives , Animals , Antiviral Agents/pharmacology , Antiviral Agents/therapeutic use , Cat Diseases/drug therapy , Cats , Feline Infectious Peritonitis/drug therapy , Itraconazole/pharmacology , Itraconazole/therapeutic useABSTRACT
Canine parvovirus 2 (CPV-2) is an important pathogen of domestic dogs and wild canids. In Japan, CPV-2 infection is one of the most common infectious diseases of dogs. We analyzed samples collected between 2014 and 2019 to identify antigenic variants of CPV-2 in dogs in Japan. Our results demonstrated that the CPV-2b variant was predominant. The CPV-2c variant was not found among our samples. Our findings demonstrate that the distribution of CPV-2 antigenic variants in Japan was more similar to that in Australia than to that in neighboring countries in Asia.
Subject(s)
Dog Diseases/epidemiology , Parvoviridae Infections/veterinary , Parvovirus, Canine/immunology , Animals , Antigenic Variation , Dog Diseases/virology , Dogs , Female , Japan , Male , Parvoviridae Infections/epidemiology , Parvoviridae Infections/virology , Parvovirus, Canine/isolation & purification , PhylogenyABSTRACT
Feline infectious peritonitis (FIP) is a fatal disease in wild and domestic cat species. Although several drugs are expected to be useful as treatments for FIP, no drugs are available in clinical practice. In this study, we evaluated the therapeutic effect of combined use of adalimumab (an anti-human-TNF-alpha monoclonal antibody, ADA) and itraconazole (ICZ), which are presently available to veterinarians. The neutralizing activity of ADA against fTNF-alpha-induced cytotoxicity was measured in WEHI-164 cells. Ten specific pathogen-free (SPF) cats were inoculated intraperitoneally with type I FIPV KU-2. To the cats that developed FIP, ADA (10 mg/animal) was administered twice between day 0 and day 4 after the start of treatment. ICZ (50 mg/head, SID) was orally administered daily from day 0 after the start of treatment. ADA demonstrated dose-dependent neutralizing activity against rfTNF-alpha. In an animal experiment, 2 of 3 cats showed improvements in FIP clinical symptoms and blood chemistry test results, an increase in the peripheral blood lymphocyte count, and a decrease in the plasma alpha 1-AGP level were observed after the beginning of treatment. One of the cats failed to respond to treatment and was euthanized, although the viral gene level in ascites temporarily decreased after the start of treatment. ADA was found to have neutralizing activity against rfTNF-alpha. The combined use of ADA and ICZ showed a therapeutic effect for experimentally induced FIP. We consider these drugs to be a treatment option until effective anti-FIPV drugs become available.
