Fexaramine as an entry blocker for feline caliciviruses

Kim, Yun-Jeong; Chang, Kyeong‐Ok

doi:10.1016/j.antiviral.2018.02.009

Cited by 6 publications

(7 citation statements)

References 39 publications

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“…Then, we demonstrated the inhibitory effect of copper chloride on the viral titre and RNA levels of FCV at different times. FCV was significantly inhibited when copper chloride was added 8 h before FCV was used to infect the cells, but copper chloride did not significantly inhibit FCV after 16 h. Because our findings differed from those of previous studies using fexaramine, LiCl, ginger extracts,or CSX [13,14,27,28], we speculated that copper chloride can inhibit the replication of FCV in cells and does not affect the adsorption or entry of the virus into the cells, but its mechanism of inhibiting replication needs further verification. We found that cupric chloride also inhibited other strains of FCV replication in the F81 cells, which is further evidence of the antiviral activity of copper chloride against FCV.…”

Section: Discussioncontrasting

confidence: 98%

Antiviral effect of copper chloride on feline calicivirus and Synergy with Ribavirin in vitro

Cui

et al. 2020

Preprint

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Background: Feline calicivirus (FCV) is a common pathogen causing widely prevalent upper respiratory disease for kitten and felines in recent years. Due to the substantial genetic variability of the viral genes, existing vaccines cannot provide complete protection. Therefore, researches on FCV antiviral drugs have received much attention. Results: In this study, we found that copper chloride had dose-dependent antiviral effects against FCV in F81 cells. We also found that the combination of copper chloride and ribavirin had a synergistic effect against FCV in the F81 cells. In contrast, the combination of and horse anti-FCV immunoglobulin F(ab’)2 showed an antagonistic effect, likely because the copper chloride has an effect on the F(ab’)2 immunoglobulin; however, further research is needed to clarify this supposition.Conclusions: In summary, we found that copper chloride had low cytotoxicity and significant antiviral effects against FCV in F81 cells, providing a new drug candidate for the prevention and treatment of FCV infection.

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Section: Discussioncontrasting

confidence: 98%

Antiviral effect of copper chloride on feline calicivirus and Synergy with Ribavirin in vitro

Cui

et al. 2020

Preprint

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“…The viral titer for FCV F9 strain was determined by immunofluorescence assays as described previously [ 12 , 13 ]. Briefly, confluent CRFK cells grown on 96-well plates were inoculated with 200 μl of each diluted sample and then incubated at 37°C in a 5% CO 2 incubator.…”

Section: Methodsmentioning

confidence: 99%

“…FCV vaccines are available for cats [ 20 ]; however, there is a limit on its efficacy because of low or no preventive effect against FCVs with different antigenicity and short-lived immunity [ 13 , 20 ]. A lack of a robust and reproducible in vitro cultivation system for human noroviruses (HNoVs) has not been developed until recently, thereby hindering the development of effective interventions [ 21 ].…”

Section: Introductionmentioning

confidence: 99%

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Feline calicivirus- and murine norovirus-induced COX-2/PGE2 signaling pathway has proviral effects

et al. 2018

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Cyclooxygenases (COXs)/prostaglandin E2 (PGE2) signaling pathways are known to modulate a variety of homeostatic processes and are involved in various pathophysiological conditions. COXs/PGE2 signaling pathways have also been demonstrated to have proviral or antiviral effects, which appeared different even in the same virus family. A porcine sapovirus Cowden strain, a member of genus Sapovirus within the Caliciviridae family, induces strong COX-2/PGE2 but transient COX-1/PGE2 signaling to enhance virus replication. However, whether infections of other viruses in the different genera activate COXs/PGE2 signaling, and thus affect the replication of viruses, remains unknown. In the present study, infections of cells with the feline calicivirus (FCV) F9 strain in the genus Vesivirus and murine norovirus (MNV) CW-1 strain in the genus Norovirus only activated the COX-2/PGE2 signaling in a time-dependent manner. Treatment with pharmacological inhibitors or transfection of small interfering RNAs (siRNAs) against COX-2 enzyme significantly reduced the production of PGE2 as well as FCV and MNV replications. The inhibitory effects of these pharmacological inhibitors against COX-2 enzyme on the replication of both viruses were restored by the addition of PGE2. Silencing of COX-1 via siRNAs and inhibition of COX-1 via an inhibitor also decrease the production of PGE2 and replication of both viruses, which can be attributed to the inhibition COX-1/PGE2 signaling pathway. These data indicate that the COX-2/PGE2 signaling pathway has proviral effects for the replication of FCV and MNV, and pharmacological inhibitors against these enzymes serve as potential therapeutic candidates for treating FCV and MNV infections.

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“…Several studies have reported different antiviral strategies against FCV [ 25 , 26 , 27 , 28 , 29 ]. One of the earliest attempts used phosphorodiamidate morpholino oligomers (PMO) to treat cats during three FCV outbreaks (two caused by the FCV-VSD and one linked with a non-lethal FCV pathotype), showing promising results (79.6% vs. 9.7% of cats survived with or without PMO treatment, respectively) [ 27 ].…”

Section: Introductionmentioning

confidence: 99%

Potential Therapeutic Agents for Feline Calicivirus Infection

Fumian

Tuipulotu

Netzler

et al. 2018

Viruses

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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 (IC50 values of 2.8 μM and 2.7 μM, respectively). We also demonstrate the inhibition of FCV protease activity by GC376 (IC50 of 18 µM). Using cell culture assays, PPNDS, quercetagetin and GC376 did not display antivirals effects, however, we identified nitazoxanide and 2′-C-methylcytidine (2CMC) as potent inhibitors of FCV replication, with EC50 values in the low micromolar range (0.6 μM and 2.5 μM, respectively). In conclusion, we established two in vitro assays that will accelerate the research for FCV antivirals and can be used for the high-throughput screening of direct-acting antivirals.

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Fexaramine as an entry blocker for feline caliciviruses

Cited by 6 publications

References 39 publications

Antiviral effect of copper chloride on feline calicivirus and Synergy with Ribavirin in vitro

Antiviral effect of copper chloride on feline calicivirus and Synergy with Ribavirin in vitro

Feline calicivirus- and murine norovirus-induced COX-2/PGE2 signaling pathway has proviral effects

Potential Therapeutic Agents for Feline Calicivirus Infection

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