| 孙立山,黄亮浩,孙继芹,等.腔肠素抗流感病毒研究[J].中国海洋药物,2023,42(1):42-48. |
| 腔肠素抗流感病毒研究 |
| Study on the anti-influenza virus activity of coelenterazine |
| 投稿时间：2022-02-23 修订日期：2022-04-22 |
| DOI： |
| 中文关键词: 抗流感病毒 腔肠素 血凝素 病毒进入 |
| English Keywords:anti-influenza virus coelenterazine hemagglutinin virus entry |
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| 中文摘要: |
| 目的 对海洋来源的化合物腔肠素进行体外抗流感病毒活性研究。方法 CPE抑制实验评价腔肠素对不同流感病毒株的抗病毒作用。CPE实验检测腔肠素细胞毒性和抗病毒作用方式并结合血凝抑制实验、神经氨酸酶活性实验及微基因组实验初步探究腔肠素的作用靶点。结果 腔肠素体外对不同流感病毒株均有良好抗病毒作用，其中对PR8的抑制作用最强，IC50为5.0 μmol·L?1且细胞毒较小，CC50为144.1 μmol·L?1。通过不同作用方式以及不同作用时间的实验显示，腔肠素在预先处理流感病毒以及在病毒感染后加入均有良好抗病毒作用，并且在病毒吸附后0-3 h的抑制效果较好。用腔肠素预处理病毒后可以呈剂量依赖性地抑制血凝素（HA）的活力。故腔肠素可能是通过与病毒血凝素相互作用来阻断流感病毒的进入。结论 腔肠素具有良好的体外抗甲型流感病毒效果，本研究为海洋来源的小分子化合物的开发与改造提供了借鉴，为寻找新型抗流感病毒药物提供新思路。 |
| English Summary: |
| Objective To study the in vitro anti-influenza virus activity of the marine compound coelenterazine. Methods The inhibitory effect of coelenterazine on various influenza virus strains was determined by CPE inhibition assay. CPE experiments combined with hemagglutination inhibition and neuraminidase activity assay were performed to explore the way that coelenterazine acts on virus invading process and its cytotoxicity, and preliminarily explore the target of coelenterazine. Results Coelenterazine has inhibitory effect on the proliferation of various influenza virus strains in vitro, among which the inhibitory effect on PR8 was the strongest, with IC50 of 5.0 μmol·L?1 and it has low cytotoxicity, with CC50 of 144.1 μmol·L?1. Experiments with different modes of action and different durations of action showed that the addition of coelenterazine after virus infection could well inhibit the proliferation of the virus, and had a good inhibitory effect 0-3 hours after the virus adsorption. Pretreatment of virus with coelenterazine significantly reduced virus proliferation and inhibited the hemagglutinin (HA)induced aggregation of red blood cells in a dose-dependent manner. Therefore, coelenterazine may block the entry process of IAV by binding to viral hemagglutinin and inhibiting its activity. Conclusion Coelenterazine has a good inhibitory effect on influenza A virus in vitro. This study provides ideas and directions for the drug development and rational transformation of marine-derived small molecule compounds. |
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