Synergistic antiviral effect of Galanthus nivalis agglutinin and nelfinavir against feline coronavirus

Abstract

Feline infectious peritonitis (FIP) is a fatal disease in domestic and nondomestic felids caused by feline coronavirus (FCoV). Currently, no effective vaccine is available for the prevention of this disease. In searching for agents that may prove clinically effective against FCoV infection, 16 compounds were screened for their antiviral activity against a local FCoV strain in Felis catus whole fetus-4 cells. The results showed that Galanthus nivalis agglutinin (GNA) and nelfinavir effectively inhibited FCoV replication. When the amount of virus preinoculated into the test cells was increased to mimic the high viral load present in the target cells of FIP cats, GNA and nelfinavir by themselves lost their inhibitory effect. However, when the two agents were added together to FCoV-infected cells, a synergistic antiviral effect defined by complete blockage of viral replication was observed. These results suggest that the combined use of GNA and nelfinavir has therapeutic potential in the prophylaxis and treatment of cats with early-diagnosed FIP.

Potent inhibition of feline coronaviruses with peptidyl compounds targeting coronavirus 3C-like protease

“…Ribavirin was reported to reduce the replication of FIPV with IC 50 of 10 μM and TC 50 of 69 μM, and a later study using specific pathogen free cats infected with FIPV showed that ribavirin treatment at 16.5 mg/kg was not effective at reducing fatality or severity of symptoms (Weiss et al, 1993). In addition, studies on the antiviral agents that directly or indirectly target virus components and/or replication steps are very limited (Barlough and Shacklett, 1994; Hsieh et al, 2010; Regan et al, 2008). …”

Identification and characterisation of small molecule inhibitors of feline coronavirus replication

“…A number of compounds have demonstrated an inhibitory effect on the virus in vitro (Barlough and Shacklett, 1994;Hsieh et al, 2010;Keyaerts et al, 2007), but there is little or no published data regarding their use in treating FIP. The broad spectrum antiviral ribavirin demonstrated in vitro efficacy but provided limited clinical benefit and produced toxicity in cats (Weiss et al, 1993).…”

Effect of chloroquine on feline infectious peritonitis virus infection in vitro and in vivo

“…Combining chloroquine with other ''anti-FIPV agents'' overcomes this problem. Hsieh et al (2010) succeeded in inhibiting FIPV replication in fcwf-4 cells using the low-cytotoxic antiviral agents. It will be necessary to further investigate the possibility of FIP treatment with a combination of chloroquine and other agents.…”

“…Antiviral, immunostimulating, and immunosuppressive drugs have been experimentally used for the treatment of FIP, but none of these have exhibited a sufficient therapeutic effect. Several agents that significantly inhibit FCoV replication in vitro have been identified (Balzarini et al, 2006;Barlough and Shacklett, 1994;Hsieh et al, 2010;Kim et al, 2012;Takano et al, 2008); however, whether or not these agents exhibit a therapeutic effect in cats with FIP has not been investigated.…”