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A synthetic derivative of houttuynoid B prevents cell entry of Zika virus.
Antiviral Research ( IF 7.6 ) Pub Date : 2019-11-04 , DOI: 10.1016/j.antiviral.2019.104644
Michael Basic 1 , Fabian Elgner 1 , Daniela Bender 1 , Catarina Sabino 1 , Marie-Luise Herrlein 1 , Hanna Roth 1 , Mirco Glitscher 1 , Alicia Fath 1 , Thomas Kerl 2 , Hans-Günther Schmalz 2 , Eberhard Hildt 3
Affiliation  

Zika virus (ZIKV) is a re-emerging virus belonging to the family of Flaviviridae, which contains several human pathogens. A great deal of attention came through the association of ZIKV infection with an increasing number of microcephaly cases in newborns during the 2016 outbreak in Brazil. Currently, no anti-viral drug or vaccine is available. Houttuynoids are a group of structurally related flavonoid glycosides that can be isolated from Houttuynia cordata belonging to the family of Sauraceae. Moreover, H. cordata was described to have an antiviral effect on herpes simplex virus type 1 (HSV-1), human immunodeficiency virus type 1 (HIV-1) and influenza A virus (Hayashi et al., 1995). In light of this, this study aimed to investigate a potential antiviral effect of the synthetic houttuynoids TK1023 and TK1024 (i.e. houttuynoid B) on two ZIKV isolates (Uganda and French Polynesia). A significant decrease in the amount of intra- and extracellular viral genomes as well as infectious viral particles was observed after treatment with the tetra-O-acetylated houttuynoid TK1023 independent from the analyzed virus isolate. In contrast, TK1024 (houttuynoid B) had no effect on ZIKV. Treatment with TK1023 significantly decreases the number of infected cells 24 h and 48 h after infection, as compared to the control. Analysis of the mode of action revealed that TK1023 neither affects the viral genome replication nor the production of viral proteins nor morphogenesis or release. Binding and entry assays showed that TK1023 interferes with the entry of the virus in the cell. Thereby, the spread of ZIKV infection is impaired as the infection of the individual cell is inhibited. These data indicate that for both analyzed virus isolates the spread of ZIKV infection can be impaired by the synthetic houttuynoid TK1023 due to an inhibition of the viral entry.

中文翻译:

Houttuynoidoid B的合成衍生物可防止Zika病毒进入细胞。

寨卡病毒(ZIKV)是属于黄病毒科的一种新出现的病毒,其中包含几种人类病原体。在2016年巴西爆发的新生儿中,ZIKV感染与新生儿小头畸形病例数量增加相关,引起了极大的关注。当前,没有抗病毒药物或疫苗。鱼腥草素是一组结构相关的类黄酮糖苷,可从茄科的鱼腥草中分离出来。此外,据描述,H。cordata对单纯疱疹病毒1型(HSV-1),人类免疫缺陷病毒1型(HIV-1)和A型流感病毒具有抗病毒作用(Hayashi et al。,1995)。有鉴于此,本研究旨在研究合成鱼腥草素TK1023和TK1024的潜在抗病毒作用(即 huttuynoid B)在两个ZIKV分离株(乌干达和法属玻里尼西亚)上。在用四-O-乙酰化的类胡桃突肌TK1023进行治疗后,观察到细胞内和细胞外病毒基因组以及感染性病毒颗粒的数量显着减少,而与所分析的病毒分离物无关。相反,TK1024(类胡桃木B)对ZIKV没有影响。与对照相比,用TK1023处理可显着减少感染后24小时和48小时的感染细胞数量。对作用方式的分析表明,TK1023既不影响病毒基因组复制,也不影响病毒蛋白的产生,也不影响形态发生或释放。结合和进入试验表明,TK1023干扰病毒进入细胞。从而,ZIKV感染的传播受到阻碍,因为单个细胞的感染被抑制。这些数据表明,对于两种分析的病毒分离物,由于抑制了病毒的进入,合成的类胡芦巴素TK1023可能会损害ZIKV感染的传播。
更新日期:2019-11-04
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