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  • Title: Antiviral effects of natural small molecules on aquatic rhabdovirus by interfering with early viral replication.
    Author: Zhou Y, Qiu TX, Hu Y, Liu L, Chen J.
    Journal: Zool Res; 2022 Nov 18; 43(6):966-976. PubMed ID: 36257828.
    Abstract:
    Spring viremia of carp virus (SVCV) is globally widespread and poses a serious threat to aquatic ecology and aquaculture due to its broad host range. To develop effective agents to control SVCV infection, we selected 16 naturally active small molecules to assess their anti-SVCV activity. Notably, dihydroartemisinin (DHA) (100 µmol/L) and (S, S)-(+)-tetrandrine (TET) (16 µmol/L) exhibited high antiviral effects in epithelioma papulosum cyprinid (EPC) cells, with inhibitory rates of 70.11% and 73.54%, respectively. The possible antiviral mechanisms were determined as follows: 1. Pre-incubation with DHA and TET decreased viral particle infectivity in fish cells, suggesting that horizontal transmission of SVCV in the aquatic environment was disrupted; 2. Although neither had an effect on viral adhesion, TET (but not DHA) interfered with SVCV entry into host cells (>80%), suggesting that TET may have an antiviral function in early viral replication. For in vivo study, both agents enhanced the survival rate of SVCV-infected zebrafish by 53.3%, significantly decreased viral load, and modulated the expression of antiviral-related genes, indicating that DHA and TET may stimulate the host innate immune response to prevent viral infection. Overall, our findings indicated that DHA and TET had positive effects on suppressing SVCV infection by affecting early-stage viral replication, thus holding great potential as immunostimulants to reduce the risk of aquatic rhabdovirus disease outbreaks. 因缺乏有效的防控措施，鲤春病毒血症病毒（Spring viremia of carp virus，SVCV）在世界各地的广泛传播与爆发对水域生态安全和水产养殖业都构成了严重威胁。该研究从16种天然活性小分子中发现双氢青蒿素（dihydroartemisinin，DHA）和粉防己碱（(S, S)-(+)-Tetrandrine，TET）具有较高的抗SVCV活性。实验结果显示：100 µmol/L的DHA和16 µmol/L的TET显著抑制SVCV在鲤上皮瘤细胞（EPC细胞）中增殖，其最大抑制率分别达到70.11%和73.54%。通过比较两种药物的抗病毒机制，我们发现：1） DHA和TET预孵育细胞明显降低病毒感染性，表明采用浸泡方式可有效阻断SVCV水平传播；2） DHA和TET均不影响病毒识别宿主表面受体，但TET干扰病毒的内化过程，揭示了TET在病毒复制早期阶段发挥抗病毒作用。与此同时，在体实验结果表明，DHA和TET提高患病斑马鱼的存活率超过50%，并持续激活鱼类先天免疫系统抑制体内病毒复制，维持病毒在鱼体内的低载量，使鱼类有效抵御SVCV感染。综上所述，DHA和TET作为免疫调节剂对防控SVC爆发风险具有一定的应用潜力。.
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