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甲氟喹对猫杯状病毒的体外抗病毒作用。

Antiviral effect of mefloquine on feline calicivirus in vitro.

作者信息

McDonagh Phillip, Sheehy Paul A, Fawcett Anne, Norris Jacqueline M

机构信息

Faculty of Veterinary Science, Building B14, The University of Sydney, Sydney, NSW 2006, Australia.

Faculty of Veterinary Science, Building B19, The University of Sydney, Sydney, NSW 2006, Australia.

出版信息

Vet Microbiol. 2015 Apr 17;176(3-4):370-7. doi: 10.1016/j.vetmic.2015.02.007. Epub 2015 Feb 16.

Abstract

Feline calicivirus (FCV) is an important viral pathogen of domestic cats causing clinical signs ranging from mild to severe oral ulceration or upper respiratory tract disease through to a severe fatal systemic disease. Current therapeutic options are limited, with no direct acting antivirals available for treatment. This study screened a panel of 19 compounds for potential antiviral activity against FCV strain F9 and recent field isolates in vitro. Using a resazurin-based cytopathic effect (CPE) inhibition assay, mefloquine demonstrated a marked inhibitory effect on FCV induced CPE, albeit with a relatively low selectivity index. Orthogonal assays confirmed inhibition of CPE was associated with a significant reduction in viral replication. Mefloquine exhibited a strong inhibitory effect against a panel of seven recent FCV isolates from Australia, with calculated IC50 values for the field isolates approximately 50% lower than against the reference strain FCV F9. In vitro combination therapy with recombinant feline interferon-ω, a biological response modifier currently registered for the treatment of FCV, demonstrated additive effects with a concurrent reduction in the IC50 of mefloquine. These results are the first report of antiviral effects of mefloquine against a calicivirus and support further in vitro and in vivo evaluation of this compound as an antiviral therapeutic for FCV.

摘要

猫杯状病毒(FCV)是家猫的一种重要病毒病原体,可引发从轻度至重度口腔溃疡或上呼吸道疾病,直至严重致命的全身性疾病等一系列临床症状。目前的治疗选择有限,尚无直接作用的抗病毒药物可用于治疗。本研究筛选了19种化合物,以检测其对FCV毒株F9和近期野外分离株的潜在体外抗病毒活性。使用基于刃天青的细胞病变效应(CPE)抑制试验,甲氟喹对FCV诱导的CPE表现出显著抑制作用,尽管其选择性指数相对较低。正交试验证实,CPE的抑制与病毒复制的显著减少相关。甲氟喹对一组来自澳大利亚的7株近期FCV分离株表现出强烈抑制作用,计算得出的野外分离株IC50值比对参考毒株FCV F9的低约50%。与重组猫干扰素-ω(一种目前已注册用于治疗FCV的生物反应调节剂)进行体外联合治疗,显示出相加效应,同时甲氟喹的IC50降低。这些结果是关于甲氟喹对杯状病毒抗病毒作用的首次报道,并支持进一步对该化合物进行体外和体内评估,以作为FCV的抗病毒治疗药物。

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