从研究所得出的结论表明,通过从Dryobalanops aromatica的叶中提取,我们成功地鉴定出一种寡型仙客来素,即Vaticanol B,它对丙型肝炎病毒具有抗病毒活性。
Identification of an Oligostilbene, Vaticanol B, from Dryobalanops aromatica Leaves as an Antiviral Compound against the Hepatitis C Virus.
发表日期:2023
作者:
Chie Aoki-Utsubo, Muhammad Hanafi, Destia Tri Armanti, Hiroyuki Fuchino, Nobuo Kawahara, Sri Hartati, Aty Widyawaruyanti, Pratiwi Sudarmono, Masanori Kameoka, Hak Hotta
来源:
TROPICAL MEDICINE & INTERNATIONAL HEALTH
摘要:
慢性丙型肝炎病毒(HCV)感染可能导致肝硬化和肝细胞癌。尽管目前使用直接作用抗病毒药物(DAAs)治疗慢性HCV患者具有高效和耐受性良好的特点,但高昂的价格和抗DAAs变异株的存在阻碍了治疗。因此需要易于获取且具有不同作用机制的抗病毒药物。在筛选印度尼西亚草药中的抗HCV活性时,我们发现凹叶龙脑香叶的粗提物具有强烈的抗HCV活性。生物检测引导的纯化鉴定出一个寡二倍半萜的活性化合物,即vaticanol B,其对抗HCV活性负责。vaticanol B以剂量依赖方式抑制HCV感染,其50%有效浓度和细胞毒浓度分别为3.6和559.5µg/mL(选择指数:155.4)。添加时间试验显示,在vaticanol B预处理后,HCV病毒的感染能力大大降低。此外,向HCV感染和亚基因HCV复制子细胞中添加vaticanol B稍微但显著抑制了HCV复制和HCV蛋白表达。因此,结果明确表明vaticanol B主要作用于病毒入侵步骤,同时对后期步骤也有微弱作用。此外,将HCV NS5A抑制剂达克拉他韦与vaticanol B联合治疗可增强抗HCV效果。总之,本研究发现一种来自植物的寡二倍半萜物质vaticanol B,作为一种新型抗HCV化合物。
Chronic hepatitis C virus (HCV) infection can lead to liver cirrhosis and hepatocellular carcinoma. Although current medications using direct-acting antivirals (DAAs) are highly effective and well-tolerated for treating patients with chronic HCV, high prices and the existence of DAA-resistant variants hamper treatment. There is thus a need for easily accessible antivirals with different mechanisms of action. During the screening of Indonesian medicinal plants for anti-HCV activity, we found that a crude extract of Dryobalanops aromatica leaves possessed strong antiviral activity against HCV. Bioassay-guided purification identified an oligostilbene, vaticanol B, as an active compound responsible for the anti-HCV activity. Vaticanol B inhibited HCV infection in a dose-dependent manner with 50% effective and cytotoxic concentrations of 3.6 and 559.5 µg/mL, respectively (Selectivity Index: 155.4). A time-of-addition study revealed that the infectivity of HCV virions was largely lost upon vaticanol B pretreatment. Also, the addition of vaticanol B following viral entry slightly but significantly suppressed HCV replication and HCV protein expression in HCV-infected and a subgenomic HCV replicon cells. Thus, the results clearly demonstrated that vaticanol B acted mainly on the viral entry step, while acting weakly on the post-entry step as well. Furthermore, co-treatment of the HCV NS5A inhibitor daclatasvir with vaticanol B increased the anti-HCV effect. Collectively, the present study has identified a plant-derived oligostilbene, vaticanol B, as a novel anti-HCV compound.