药学学报, 2020, 55(12): 2911-2917
引用本文:
姚债文, 汪芳, 陈秀秀, 郑昌博, 杨柳萌, 熊思东, 郑永唐. 环索奈德体外抑制寨卡病毒复制[J]. 药学学报, 2020, 55(12): 2911-2917.
YAO Zhai-wen, WANG Fang, CHEN Xiu-xiu, ZHENG Chang-bo, YANG Liu-meng, XIONG Si-dong, ZHENG Yong-tang. Ciclesonide inhibits Zika virus replication in vitro[J]. Acta Pharmaceutica Sinica, 2020, 55(12): 2911-2917.

环索奈德体外抑制寨卡病毒复制
姚债文1,2, 汪芳2,3, 陈秀秀1,2, 郑昌博4, 杨柳萌2, 熊思东1, 郑永唐2
1. 苏州大学药学院, 江苏 苏州 215021;
2. 中国科学院昆明动物研究所, 云南省活性多肽研究与利用重点实验室/中国科学院动物模型与人类疾病机理重点实验室, 云南 昆明 650223;
3. 昆明理工大学医学院, 云南 昆明 650500;
4. 昆明医科大学药学院暨云南省天然药物药理重点实验室, 云南 昆明 650500
摘要:
寨卡病毒(Zika virus,ZIKV)是一种新发蚊媒传播病毒,与胎儿严重先天性小脑畸形和成人格林-巴利综合征相关,至今尚无批准用于治疗ZIKV感染的药物或预防性疫苗。本文通过噬斑和细胞毒性实验发现环索奈德(ciclesonide)体外具有较好的抗ZIKV活性,其对ZIKV亚洲株SZ01和非洲株MR766的半数有效浓度(50% effective concentration,EC50)分别为(0.40±0.22)和(1.59±1.08)μmol·L-1,对Vero细胞的半数致死浓度(50% cytotoxic concentration,CC50)为(64.70±7.33)μmol·L-1;病毒产量降低实验和蛋白印迹实验显示环索奈德能够抑制ZIKV复制。此外,环索奈德还能够抑制A549细胞中ZIKV的复制;分时给药实验结果表明环索奈德主要作用于ZIKV RNA的合成阶段;进一步研究显示环索奈德还可抑制ZIKV的内化。本研究结果表明环索奈德是一种潜在的抗ZIKV药物。
关键词:    环索奈德      糖皮质激素      寨卡病毒      抑制      活性     
Ciclesonide inhibits Zika virus replication in vitro
YAO Zhai-wen1,2, WANG Fang2,3, CHEN Xiu-xiu1,2, ZHENG Chang-bo4, YANG Liu-meng2, XIONG Si-dong1, ZHENG Yong-tang2
1. College of Pharmacy, Soochow University, Suzhou 215021, China;
2. Key Laboratory of Bioactive Peptides of Yunnan Province/Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, China;
3. College of Medicine, Kunming University of Science and Technology, Kunming 650500, China;
4. School of Pharmaceutical Science and Yunnan Key Laboratory of Pharmacology for Natural Products, Kunming Medical University, Kunming 650500, China
Abstract:
Zika virus (ZIKV) is an emerging mosquito-borne virus that is associated with severe congenital brain malformations in the fetus and Guillain-Barré syndrome in adults. However, there are currently no drugs or preventive vaccines approved for ZIKV infection. Here, ciclesonide has been found significantly against ZIKV activity by plaque and cytotoxicity assays in vitro, and its 50% effective concentration (EC50) to ZIKV SZ01 and MR766 are (0.40±0.22) and (1.59±1.08) μmol·L-1, respectively. Its 50% cytotoxic concentration (CC50) to Vero cells are (64.70±7.33) μmol·L-1; Virus yield reduction and Western blot assays showed that ciclesonide can inhibit replication of ZIKV. In addition, ciclesonide can also inhibit the replication of ZIKV in A549 cells; the results of time of drug addition analysis indicated that ciclesonide mainly acts on the ZIKV RNA synthesis stage. Ciclesonide can also inhibit the internalization of ZIKV. These results indicated that ciclesonide is a potential drug against ZIKV.
Key words:    ciclesonide    glucocorticoid    Zika virus    inhibition    activity   
收稿日期: 2020-05-09
DOI: 10.16438/j.0513-4870.2020-0703
基金项目: 国家自然科学基金资助项目(U1902210);云南省活性多肽研究与利用重点实验室开放课题(AMHD-2017-3).
通讯作者: 熊思东,Tel:86-512-65881255,E-mail:sdxiong@shmu.edu.cn;郑永唐,Tel:86-871-65195684,E-mail:zhengyt@mail.kiz.ac.cn
Email: sdxiong@shmu.edu.cn;zhengyt@mail.kiz.ac.cn
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