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刘镭, 宋大伟, 刘广路, 单立鹏, 裘天休, 陈炯. 2020: 羟基香豆素在体和离体抗鲤春病毒血症病毒研究. 动物学研究, 41(4): 395-409. DOI: 10.24272/j.issn.2095-8137.2020.037
引用本文: 刘镭, 宋大伟, 刘广路, 单立鹏, 裘天休, 陈炯. 2020: 羟基香豆素在体和离体抗鲤春病毒血症病毒研究. 动物学研究, 41(4): 395-409. DOI: 10.24272/j.issn.2095-8137.2020.037
Lei Liu, Da-Wei Song, Guang-Lu Liu, Li-Peng Shan, Tian-Xiu Qiu, Jiong Chen. 2020: Hydroxycoumarin efficiently inhibits spring viraemia of carp virus infection in vitro and in vivo. Zoological Research, 41(4): 395-409. DOI: 10.24272/j.issn.2095-8137.2020.037
Citation: Lei Liu, Da-Wei Song, Guang-Lu Liu, Li-Peng Shan, Tian-Xiu Qiu, Jiong Chen. 2020: Hydroxycoumarin efficiently inhibits spring viraemia of carp virus infection in vitro and in vivo. Zoological Research, 41(4): 395-409. DOI: 10.24272/j.issn.2095-8137.2020.037

羟基香豆素在体和离体抗鲤春病毒血症病毒研究

Hydroxycoumarin efficiently inhibits spring viraemia of carp virus infection in vitro and in vivo

  • 摘要: 鲤春病毒血症病毒(SVCV)作为一种鱼类弹状病毒病病原,在水产养殖业中已造成严重的经济损失。香豆素因化学结构优势被用来充当新型特异性抗病毒药物的先导化合物。本研究探索了一种羟基香豆素7-6-苯并咪唑-己氧基香豆素(C10)在体内和体外的抗SVCV活性。实验结果显示:12.5 mg/L的香豆素C10显著抑制SVCV在鲤上皮瘤细胞(EPC细胞)中增殖,其最大抑制率达到97%;此外,香豆素C10不仅降低线粒体膜电位以保护细胞线粒体,且减少病毒感染诱发的细胞凋亡率,维持细胞生长活力,有效保护细胞免受病毒损伤;通过注射方式研究香豆素C10对斑马鱼死亡率和鱼体内病毒含量的影响,发现C10处理组斑马鱼的累积死亡率相对病毒组明显降低,揭示了香豆素C10在体抗病毒作用。与此同时,香豆素C10提高了EPC细胞和斑马鱼的抗氧化酶活性,平衡抗氧化-氧化系统,并在SVCV复制前期通过激活鱼体干扰素表达对病毒增殖产生一定的抑制作用,最终抑制SVCV感染斑马鱼,维持病毒在鱼体内的低载量,持续激活宿主先天免疫系统发挥作用。综上所述,在水产养殖业中,香豆素 C10对防控SVC具有潜在的应用前景。

     

    Abstract: Spring viremia of carp virus (SVCV) causes devastating losses in aquaculture. Coumarin has an advantageous structure for the design of novel antiviral agents with high affinity and specificity. In this study, we evaluated a hydroxycoumarin medicine, i.e., 7-(6-benzimidazole) coumarin (C10), regarding its anti-SVCV effects in vitro and in vivo. Results showed that up to 12.5 mg/L C10 significantly inhibited SVCV replication in the epithelioma papulosum cyprini (EPC) cell line, with a maximum inhibitory rate of >97%. Furthermore, C10 significantly reduced cell death and relieved cellular morphological damage in SVCV-infected cells. Decreased mitochondrial membrane potential (ΔΨm) also suggested that C10 not only protected mitochondria, but also reduced apoptosis in SVCV-infected cells. For in vivo studies, intraperitoneal injection of C10 resulted in an anti-SVCV effect and substantially enhanced the survival rate of virus-infected zebrafish. Furthermore, C10 significantly enhanced antioxidant enzyme activities and decreased reactive oxygen species (ROS) to maintain antioxidant-oxidant balance within the host, thereby contributing to inhibition of SVCV replication. The up-regulation of six interferon (IFN)-related genes also demonstrated that C10 indirectly activated IFNs for the clearance of SVCV in zebrafish. This was beneficial for the continuous maintenance of antiviral effects because of the low viral loads in fish. Thus, C10 is suggested as a therapeutic agent with great potential against SVCV infection in aquaculture.

     

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