Identification of natural compounds extracted from crude drugs as novel inhibitors of hepatitis C virus
Identification of natural compounds extracted from crude drugs as novel inhibitors of hepatitis C virus
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从药材中提取的天然化合物作为新型丙型肝炎病毒抑制剂的鉴定
DOI：
10.1016/j.bbrc.2021.06.022
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发表时间：
2021
影响因子：
3.1
通讯作者：
Masamichi Muramats
中科院分区：
文献类型：
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作者：
Xin Zheng;Rui Guo;Qingbo Liu;Kousho Wakae;Noriyuki Watanabe;Kento Fukano;Lusheng Que;Yingfang Li;Hussein H. Aly;Koichi Watashi;Ryosuke Suzuki;Asako Murayama;Takanobu Kato;Hideki Aizaki;Takaji Wakita;Xiaoxiao Huang;Yi Yan;Shao-Jiang Song;Masamichi Muramats
天然产物衍生的原料药有望产生大量治疗传染病的新药。丙型肝炎病毒是一种致癌病毒，严重影响公众健康。在这项研究中，我们试图从天然产物的提取物中鉴定抗丙型肝炎病毒的化合物。从几种草药植物中提取的110种天然化合物被检测了抗丙型肝炎病毒的活性。使用Huh7-mCherry-NLS-IPS报告系统检测丙型肝炎病毒感染，我们首先对从生药中提取的抗丙型肝炎病毒化合物进行了快速筛选。Compoundsthreo-2，3-bis(4-hydroxy-3-methoxyphenyl)-3-butoxypropan-1-ol(#106)和Mediresinol(#110)从山楂中提取，具有抗丙型肝炎病毒的活性，并以剂量依赖的方式显著抑制丙型肝炎病毒的产生。使用丙型肝炎病毒伪粒子和亚基因组复制子系统的分析表明，化合物#106和#110特异性地抑制丙型肝炎病毒的RNA复制，但不能抑制病毒的进入或翻译。有趣的是，化合物#106还抑制甲型肝炎病毒的复制和生产。我们的发现表明，C.C.是新型抗肝炎病毒药物开发的新来源。
Natural product–derived crude drugs are expected to yield an abundance of new drugs to treat infectious diseases. Hepatitis C virus (HCV) is an oncogenic virus that significantly impacts public health. In this study, we sought to identify anti-HCV compounds in extracts of natural products. A total of 110 natural compounds extracted from several herbal medicine plants were examined for antiviral activity against HCV. Using a Huh7-mCherry-NLS-IPS reporter system for HCV infection, we first performed a rapid screening for anti-HCV compounds extracted from crude drugs. The compoundsthreo-2,3-bis(4-hydroxy-3-methoxyphenyl)-3-butoxypropan-1-ol (#106) and medioresinol (#110), which were extracted fromCrataeguscuneate, exhibited anti-HCV activity and significantly inhibited HCV production in a dose-dependent manner. Analyses using HCV pseudoparticle and subgenomic replicon systems indicated that compounds#106and#110specifically inhibit HCV RNA replication but not viral entry or translation. Interestingly, compound#106also inhibited the replication and production of hepatitis A virus. Our findings suggest thatC. cuneateis a new source for novel anti-hepatitis virus drug development.