Martín-Acebes Miguel A, Jiménez de Oya Nereida, Saiz Juan-Carlos
Department of Biotechnology, Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria (INIA), 28040 Madrid, Spain.
Pharmaceuticals (Basel). 2019 Jun 21;12(2):97. doi: 10.3390/ph12020097.
The Zika virus (ZIKV) is a mosquito-borne flavivirus that can lead to birth defects (microcephaly), ocular lesions and neurological disorders (Guillain-Barré syndrome). There is no licensed vaccine or antiviral treatment against ZIKV infection. The effort to understand the complex interactions of ZIKV with cellular networks contributes to the identification of novel host-directed antiviral (HDA) candidates. Among the cellular pathways involved in infection, lipid metabolism gains attention. In ZIKV-infected cells lipid metabolism attributed to intracellular membrane remodeling, virion morphogenesis, autophagy modulation, innate immunity and inflammation. The key roles played by the cellular structures associated with lipid metabolism, such as peroxisomes and lipid droplets, are starting to be deciphered. Consequently, there is a wide variety of lipid-related antiviral strategies that are currently under consideration, which include an inhibition of sterol regulatory element-binding proteins (SREBP), the activation of adenosine-monophosphate activated kinase (AMPK), an inhibition of acetyl-Coenzyme A carboxylase (ACC), interference with sphingolipid metabolism, blockage of intracellular cholesterol trafficking, or a treatment with cholesterol derivatives. Remarkably, most of the HDAs identified in these studies are also effective against flaviviruses other than ZIKV (West Nile virus and dengue virus), supporting their broad-spectrum effect. Considering that lipid metabolism is one of the main cellular pathways suitable for pharmacological intervention, the idea of repositioning drugs targeting lipid metabolism as antiviral candidates is gaining force.
寨卡病毒（ZIKV）是一种通过蚊子传播的黄病毒，可导致出生缺陷（小头畸形）、眼部病变和神经紊乱（吉兰 - 巴雷综合征）。目前尚无针对ZIKV感染的许可疫苗或抗病毒治疗方法。了解ZIKV与细胞网络复杂相互作用的研究有助于识别新型宿主导向抗病毒（HDA）候选物。在参与感染的细胞途径中，脂质代谢受到关注。在ZIKV感染的细胞中，脂质代谢与细胞内膜重塑、病毒粒子形态发生、自噬调节、先天免疫和炎症有关。与脂质代谢相关的细胞结构（如过氧化物酶体和脂滴）所起的关键作用正开始被破解。因此，目前正在考虑各种各样与脂质相关的抗病毒策略，包括抑制固醇调节元件结合蛋白（SREBP）、激活单磷酸腺苷激活激酶（AMPK）、抑制乙酰辅酶A羧化酶（ACC）、干扰鞘脂代谢、阻断细胞内胆固醇运输或用胆固醇衍生物进行治疗。值得注意的是，这些研究中确定的大多数HDA对ZIKV以外的黄病毒（西尼罗河病毒和登革热病毒）也有效，这支持了它们的广谱效应。鉴于脂质代谢是适合进行药物干预的主要细胞途径之一，将靶向脂质代谢的药物重新定位为抗病毒候选物的想法正越来越受到关注。
