A cell-based assay to discover inhibitors of Zika virus RNA-dependent RNA polymerase

被引：1
|
作者：
Wang, Lidan [1 ]
Zhou, Rui [1 ]
Liu, Yitong [1 ]
Guo, Saisai [1 ]
Yi, Dongrong [1 ]
Zhao, Jianyuan [1 ]
Li, Quanjie [1 ]
Zhang, Yongxin [1 ]
Liang, Chen [2 ]
Wang, Jing [1 ]
Shan, Guangzhi [1 ]
Cen, Shan [1 ]
机构：
[1] Chinese Acad Med Sci & Peking Union Med Coll, Inst Med Biotechnol, CAMS Key Lab Antiviral Drug Res, 1 Tiantanxili, Beijing 100050, Peoples R China
[2] McGill Univ, Jewish Gen Hosp, Lady Davis Inst Med Res, Montreal, PQ H3T 1E2, Canada
来源：
VIROLOGY | 2024年 / 589卷
基金：
中国国家自然科学基金;
关键词：
ZIKV; NS5; Antiviral; Nucleotide analog inhibitor; 5-Azacytidine; 5-AZACYTIDINE;
D O I：
10.1016/j.virol.2023.109939
中图分类号：
Q93 [微生物学];
学科分类号：
071005 ; 100705 ;
摘要：
Zika virus (ZIKV) belongs to Flaviviridae, the Flavivirus genus. Its infection causes congenital brain abnormalities and Guillain-Barre ' syndrome. However, there are no effective vaccines, no FDA-approved drugs to manage ZIKV infection. The non-structural protein NS5 of ZIKV has been recognized as a valuable target of antivirals because of its RNA-dependent RNA polymerase (RdRp) and methyltransferase (MTase) activities essential for viral RNA synthesis. Here, we report a cell-based assay for discovering inhibitors of ZIKV NS5 and found that 5-Azacytidine potently inhibits ZIKV NS5, with EC50 of 4.9 mu M. Furthermore, 5-Azacytidine suppresses ZIKV replication by inhibiting NS5-mediated viral RNA transcription. Therefore, we have developed a cell-based ZIKV NS5 assay which can be deployed to discover ZIKV NS5 inhibitors and demonstrated the potential of 5-Azacytidine for further development as a ZIKV NS5 inhibitor.
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页数：8
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