CN107970253B - 台勾霉素衍生物在制备治疗寨卡病毒感染引起的相关疾病和/或症状的药物中的应用 - Google Patents
台勾霉素衍生物在制备治疗寨卡病毒感染引起的相关疾病和/或症状的药物中的应用 Download PDFInfo
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- 208000001455 Zika Virus Infection Diseases 0.000 title abstract description 7
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Abstract
本发明公开了台勾霉素衍生物在制备治疗寨卡病毒感染引起的相关疾病和/或症状的药物中的应用，台勾霉素作为已经被临床批准使用的抗艰难梭菌感染药物，安全性高，本发明台勾霉素衍生物能够显著抑制寨卡病毒，且活性高，有望成为新的有效的抗寨卡病毒感染药物。
Description
技术领域
本发明属于医药领域，更具体地，涉及台勾霉素衍生物在制备治疗寨卡病毒感染引起的相关疾病和/或症状的药物中的应用。
背景技术
台勾霉素是（Tiacumicins）是一系列18元大环内酯抗生素的总成，是一类重要的治疗用抗生素。
寨卡病毒属于黄病毒科黄病毒属，是RNA正链病毒，通过蚊虫传播，可通过性传播。感染者可出现全身性发热、出疹、关节炎和脑炎等症状。令人关注的，寨卡病毒会引起格林-巴利综合征、新生儿小头症。
目前针对寨卡病毒，缺少临床批准的有效药物。
发明内容
本发明的目的在于根据现有技术中的不足，提供了台勾霉素衍生物在制备治疗寨卡病毒感染引起的相关疾病和/或症状的药物中的应用。
本发明通过以下技术方案实现上述技术目的：
台勾霉素衍生物在制备抑制寨卡病毒药物中的应用，所述台勾霉素衍生物为如下结构式中的一种：
本发明提供了台勾霉素衍生物在制备治疗寨卡病毒感染引起的相关疾病和/或症状的药物中的应用。
所述药物还包括药学上可接受的盐或载体。
与现有技术相比，本发明具有如下优点和有益效果：
本发明提供了台勾霉素衍生物作为抑制寨卡病毒上的新应用，台勾霉素作为已经被临床批准使用的抗艰难梭菌感染药物，安全性高，且台勾霉素衍生物抑制寨卡病毒活性高，有望成为新的有效的抗寨卡病毒感染药物。
附图说明
图1为台勾霉素衍生物在A549细胞中抑制ZIKV-NS3蛋白。
具体实施方式
以下结合具体实施例和附图来进一步说明本发明，但实施例并不对本发明做任何形式的限定。除非特别说明，本发明采用的试剂、方法和设备为本技术领域常规试剂、方法和设备。
除非特别说明，本发明所用试剂和材料均为市购。
以下简称
为化合物1。
实施例1：台勾霉素衍生物在细胞水平上的抑制ZIKV的活性
病毒株：寨卡病毒ZIKV（Z16019）
细胞系：A549
检测方法：
台勾霉素衍生物抗病毒半数有效剂量（50% Effective Concentration，EC50）：DMSO，梯度浓度台勾霉素衍生物提前1h饱和细胞，病毒感染2h后，换含对应浓度药物的无病毒培养基维持48h；收集细胞上清，提取上清中病毒RNA，用qRT-PCR方法检测上清中ZIKV病毒RNA拷贝数。抑制率（%） = （1-给药组病毒RNA拷贝数/溶剂对照组病毒RNA拷贝数）100%，用EXCEL 2013的Forcast公式计算，当抑制率等于50%时，对应台勾霉素衍生物的浓度，作为EC50。三次重复实验取平均值。
台勾霉素衍生物细胞毒半数细胞活性抑制剂量（50% CytotoxcitiveConcentration，CC50）：MTT法，台勾霉素衍生物梯度剂量加入到A549细胞上清中，维持48h后加入MTT孵育4h，吸出培养基，加入DMSO检测490nm出吸光度值与DMSO溶剂对照组进行比较，计算抑制剂率（%）=（1-给药组490nm吸光度值/溶剂对照组490nm吸光度值）100%，用EXCEL2013的Forcast公式计算，当抑制率等于50%时，对应台勾霉素衍生物的浓度，作为CC50。三次重复实验取平均值。
得出结果表1：
表1：台勾霉素衍生物在A549细胞中抑制ZIKV EC50及CC50
| antiviral EC<sub>50</sub>（μM） | CC<sub>50</sub>（μM） | |
| ZIKV（Z16019） | A549 | |
| 化合物1 | 3.11±0.76 | 15.29±0.86 |
| 化合物2 | 2.58±1.15 | 40.23±2.40 |
实施例2台勾霉素衍生物在A549细胞系中对ZIKV-NS3蛋白的抑制活性
病毒株：寨卡病毒ZIKV（Z16019）
细胞系：A549
检测方法：
DMSO，1、5、10μM台勾霉素衍生物提前1h饱和细胞，病毒感染2h后，换含对应浓度药物的无病毒培养基维持48h；收集细胞沉淀，用蛋白质免疫印迹电泳检测不同处理下细胞内ZIKV-NS3蛋白的相对表达量，以GAPDH作为内参蛋白。如图1。由图1得出化合物 1与化合物2在细胞培养ZIKV体系里，1~5μM浓度下即可有效抑制ZIKV的NS3蛋白表达，进而阻止ZIKV的繁殖。
Claims (2)
1.台勾霉素衍生物在制备抑制寨卡病毒药物中的应用，其特征在于，台勾霉素衍生物为如下结构式中的一种：
2.根据权利要求1所述的应用，其特征在于，所述药物包括药学上可接受的盐或载体。
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| CN110974936A (zh) * | 2019-12-26 | 2020-04-10 | 中山大学 | Vx-765在制备治疗寨卡病毒感染引起的相关疾病和/或症状的药物中的应用 |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101340919A (zh) * | 2005-10-21 | 2009-01-07 | 奥普蒂姆药物公司 | 治疗艰难梭菌相关的腹泻的方法 |
| WO2013040206A1 (en) * | 2011-09-14 | 2013-03-21 | Lewis Thomas J | Novel formulations comprising macrolide and tetracycline and their uses |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101340919A (zh) * | 2005-10-21 | 2009-01-07 | 奥普蒂姆药物公司 | 治疗艰难梭菌相关的腹泻的方法 |
| WO2013040206A1 (en) * | 2011-09-14 | 2013-03-21 | Lewis Thomas J | Novel formulations comprising macrolide and tetracycline and their uses |
Non-Patent Citations (2)
| Title |
|---|
| Siwen Niu等.Characterization of a Sugar-O-methyltransferase TiaS5 Affords New Tiacumicin Analogues with Improved Antibacterial Properties and Reveals Substrate Promiscuity.《ChemBioChem》.2011,第12卷第1740-1748页. * |
| 张硕 等.寨卡病毒和寨卡病毒病.《病毒学报》.2016,第32卷(第1期),第121-127页. * |
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