Nitazoxanide protects cats from feline calicivirus infection and acts synergistically with mizoribine in vitro

Abstract

Feline calicivirus (FCV) is a highly contagious pathogen that causes acute upper respiratory infections and oral disease in cats, thus seriously endangering feline health. Recently, there have been outbreaks of particularly virulent variant strains of FCV, which can cause both acute symptoms and fatal systemic disease. The discovery of effective antiviral agents to treat FCV infection is, therefore, gradually assuming increased importance. In this study, we showed that both nitazoxanide and mizoribine had antiviral activity in F81 cells infected with different strains of FCV and also demonstrated a synergistic effect between the two drugs. Experiments in cats challenged with FCV showed that nitazoxanide significantly reduced the clinical symptoms of FCV infection, reduced viral load in the trachea and lungs, and reduced viral shedding. Our results showed that nitazoxanide and mizoribine could potentially be used as therapeutic agents to treat FCV infection.

Feline Calicivirus Virulent Systemic Disease: Clinical Epidemiology, Analysis of Viral Isolates and In Vitro Efficacy of Novel Antivirals in Australian Outbreaks

“…NTZ also targets key viral proteins such as the haemagglutinin of influenza A virus and suppresses the secretion of proinflammatory cytokines [40]. It has both in vitro and in vivo efficacy in cats experimentally infected with FCV-URTD strains, and was well tolerated at dose rates from 5 to 20 mg/kg/day orally [41]. Higher dose rates (75 mg/kg/day) in cats cause vomiting and diarrhoea [42].…”

Feline Calicivirus Virulent Systemic Disease: Clinical Epidemiology, Analysis of Viral Isolates and in vitro Efficacy of Novel Antivirals in Australian Outbreaks

“…Similarly, although NITD008 has exhibited in vitro efficacy against human and animal caliciviruses, adverse effects including weight loss, lethargy, nausea and diarrhoea occurred in dogs administered the drug intravenously for 2 weeks [34]. Nitazoxanide (NTZ), a nitrothiazole benzamide compound approved by the US Food and Drug Administration (FDA) for oral treatment of protozoal infections [35], has both in vitro and in vivo efficacy in cats experimentally infected with FCV-URTD strains, and was well tolerated at dose rates from 5 to 20 mg/kg/day orally [36]. Higher dose rates (75 mg/kg/day) in cats cause vomiting and diarrhoea [37].…”

Calicivirus Infection in Cats

“…Nitazoxanide (NTZ), initially identified as an antiparasitic drug which is used in humans, showed dose-dependent antiviral activity in vitro against different strains of FCV and a synergistic effect was observed with mizoribine (MZR), an imidazole nucleoside with antiproliferative activity against some immune cells [ 148 ]. Both substances had low cytotoxicity in vitro.…”

“…Both substances had low cytotoxicity in vitro. Moreover, in experimentally FCV-infected cats, oral NTZ treatment three days post-infection (5–20 mg/kg suspended in 500 µL phosphate buffered saline) significantly reduced viral loads in the trachea and lungs, FCV RNA shedding and clinical signs of FCV infection as well as mortality [ 148 ]. No diarrhoea or vomiting was observed in treated cats despite these having been reported previously as potential side effects [ 148 ].…”

“…Moreover, in experimentally FCV-infected cats, oral NTZ treatment three days post-infection (5–20 mg/kg suspended in 500 µL phosphate buffered saline) significantly reduced viral loads in the trachea and lungs, FCV RNA shedding and clinical signs of FCV infection as well as mortality [ 148 ]. No diarrhoea or vomiting was observed in treated cats despite these having been reported previously as potential side effects [ 148 ]. The authors concluded that NTZ could be used as therapeutic agents to treat FCV infection and that further studies should address potential synergy between NTZ and MZR in vivo, as well as the potential development of drug resistance.…”