Anti-bovine viral diarrhoea virus and hepatitis C virus activity of the cyclooxygenase inhibitor SC-560.
Anti-bovine viral diarrhoea virus and hepatitis C virus activity of the cyclooxygenase inhibitor SC-560.
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DOI：
10.3851/imp1372
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发表时间：
2009-09-25
影响因子：
--
通讯作者：
Baba, Masanori
中科院分区：
文献类型：
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作者：
Okamoto, Mika;Sakai, Masashi;Baba, Masanori
背景技术：本文研究了几种化合物对牛病毒性腹泻病毒（BVDV）在细胞培养中的抑制作用，发现某些环氧化酶（考克斯）抑制剂具有抗BVDV的活性。方法：以抑制BVDV在Mardin-Darby牛肾（MDBK）细胞中的致细胞病变作用为基础，测定化合物的抗BVDV活性。通过抑制亚基因组HCV RNA复制子细胞中病毒RNA合成来评估抗丙型肝炎病毒（HCV）活性。在测试化合物中，5-（4-氯苯基）-1-（4-甲氧基苯基）-3-（三氟甲基）-1H-吡唑（SC-560）对BVDV的活性最强，在病毒和模拟感染的MDBK细胞中，其50%有效浓度和细胞毒性浓度分别为10.9 +/-2.8和93.9 +/-24.5 μ M。该化合物还以剂量依赖性方式抑制BVDV RNA合成。对作用机制的研究表明，SC-560不干扰病毒进入宿主细胞。此外，推测SC-560的抗病毒活性与其对考克斯的抑制作用无关。SC-560和干扰素-α联合使用在抑制BVDV复制方面具有相加至协同作用。结论：SC-560及其衍生物有可能成为新型抗HCV药物。
BACKGROUND: A number of compounds were examined for their inhibitory effect on bovine viral diarrhoea virus (BVDV) replication in cell cultures and found that some cyclooxygenase (COX) inhibitors had antiviral activity against the virus.METHODS: Determination of compounds for their anti-BVDV activity was on the basis of the inhibition of virus-induced cytopathogenicity in Mardin-Darby bovine kidney (MDBK) cells. Anti-hepatitis C virus (HCV) activity was assessed by the inhibition of viral RNA synthesis in the subgenomic HCV RNA replicon cells.RESULTS: Among the test compounds, 5-(4-chlorophenyl)-1-(4-methoxyphenyl)-3-(trifluoromethyl)-1H-pyrazole (SC-560) was the most active against BVDV, and its 50% effective and cytotoxic concentrations were 10.9 +/-2.8 and 93.9 +/-24.5 microM in virus and mock-infected MDBK cells, respectively. The compound also suppressed BVDV RNA synthesis in a dose-dependent fashion. Studies on the mechanism of action revealed that SC-560 did not interfere with viral entry to the host cells. Furthermore, it was assumed that the antiviral activity of SC-560 was not associated with its inhibitory effect on COX. The combination of SC-560 and interferon-alpha was additive to synergistic in inhibiting BVDV replication. More importantly, the compound proved to be a selective inhibitor of HCV replication.CONCLUSIONS: SC-560 and its derivative might have potential as novel antiviral agents against HCV.