Synthesis of arctigenin derivatives against infectious hematopoietic necrosis virus
Synthesis of arctigenin derivatives against infectious hematopoietic necrosis virus
复制标题
抗传染性造血坏死病毒牛蒡甙元衍生物的合成
DOI：
10.1016/j.ejmech.2018.11.064
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发表时间：
2019-02-01
影响因子：
6.7
通讯作者：
Zhu, Bin
中科院分区：
文献类型：
--
作者：
Hu, Yang;Liu, Lei;Zhu, Bin
传染性造血细胞坏死病毒（Infectious hematopoieticnecrosis virus，IHNV）是鲑科鱼类养殖中常见的一种病原病毒，可引起鲑科鱼类的严重病害，造成巨大的经济损失。本文合成了一系列牛蒡子苷元衍生物，以评价其抗IHNV的活性。结果表明，连接基和咪唑取代基的长度在降低IHNV复制中起重要作用。在该研究中，具有8个碳原子长度的接头的牛蒡子苷元咪唑杂合衍生物15以13 μ M的IC 50值减少IHNV复制。此外，衍生物15显著抑制IHNV诱导的细胞凋亡和细胞形态学损伤。在机理上，衍生物15不能直接损伤病毒颗粒。而添加时间和病毒结合试验表明，衍生物15主要影响IHNV的早期复制，但不干扰IHNV的吸附。总之，衍生物15可以被认为是开发为治疗IHNV感染的有希望的药剂。(C)2018 Elsevier Masson SAS。All rights reserved.
Infectious hematopoietic necrosis virus (IHNV) is a common pathogen that causes severe disease and huge economic losses in the salmonid aquaculture industry. Herein, a series of arctigenin derivatives are synthesized to evaluate their antiviral activity against IHNV. The results indicate that the length of linker and imidazole substituent groups play an important role in decreasing IHNV replication. In this study, the arctigenin imidazole hybrid derivative 15 with an eight carbon atoms length of the linker reduces IHNV replication with an IC50 value of 13 mu M. In addition, derivative 15 significantly inhibits apoptosis and cellular morphological damage induced by IHNV. Mechanistically, derivative 15 can not damage the viral particle directly. While time-of-addition and viral binding assays reveal that derivative 15 mainly affect the early replication of IHNV but do not interfere with IHNV adsorption. Overall, derivative 15 could be considered to develop as a promising agent to treat IHNV infection. (C) 2018 Elsevier Masson SAS. All rights reserved.