Targeting host lipid synthesis and metabolism to inhibit dengue and hepatitis C viruses.
Targeting host lipid synthesis and metabolism to inhibit dengue and hepatitis C viruses.
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DOI：
10.1016/j.antiviral.2015.10.013
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发表时间：
2015-12
影响因子：
7.6
通讯作者：
Yang PL
中科院分区：
文献类型：
--
作者：
Villareal VA;Rodgers MA;Costello DA;Yang PL
脂质对于黄病毒科成员丙型肝炎病毒（HCV）和登革热病毒（DENV）复制周期的每一步都是必需的。近期研究表明，这些病毒复制周期中的各个步骤可被针对介导脂质合成、代谢、运输和信号转导的宿主因子的药物制剂所抑制。尽管如此，由于对宿主的毒性，通过阻断整个通路将宿主脂质代谢和运输作为一种抗病毒策略可能会受到限制。了解脂质在复制中的结构和功能的分子细节以及特定脂质产生并运输到相关位点的机制，可能会实现更具针对性的抗病毒策略，而不会对宿主细胞产生全局影响。在这篇综述中，我们讨论了已被证明对HCV和DENV复制周期至关重要的脂质，并强调了抗病毒研发的潜在领域。这篇综述文章是《抗病毒研究》中关于黄病毒药物发现专题讨论会的一部分。
Lipids are necessary for every step in the replication cycle of hepatitis C virus (HCV) and dengue virus (DENV), members of the family Flaviviridae. Recent studies have demonstrated that discrete steps in the replication cycles of these viruses can be inhibited by pharmacological agents that target host factors mediating lipid synthesis, metabolism, trafficking, and signal transduction. Despite this, targeting host lipid metabolism and trafficking as an antiviral strategy by blockade of entire pathways may be limited due to host toxicity. Knowledge of the molecular details of lipid structure and function in replication and the mechanisms whereby specific lipids are generated and trafficked to the relevant sites may enable more targeted antiviral strategies without global effects on the host cell. In this review, we discuss lipids demonstrated to be critical to the replication cycles of HCV and DENV and highlight potential areas for anti-viral development. This review article forms part of a symposium on flavivirus drug discovery in Antiviral Research.