2. Academic Validation
  3. A cell-based assay to discover inhibitors of Zika virus RNA-dependent RNA polymerase

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

  • Virology. 2024 Jan:589:109939. doi: 10.1016/j.virol.2023.109939.
Lidan Wang 1,  Rui Zhou 1,  Yitong Liu 1,  Saisai Guo 1,  Dongrong Yi 1,  Jianyuan Zhao 1,  Quanjie Li 1,  Yongxin Zhang 1,  Chen Liang 2,  Jing Wang 3,  Guangzhi Shan 4,  Shan Cen 5
Affiliations

Affiliations

  • 1 CAMS Key Laboratory of Antiviral Drug Research, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, 1 Tiantanxili, Beijing, 100050, China.
  • 2 Lady Davis Institute for Medical Research, Jewish General Hospital, McGill University, Montreal, H3T 1E2, Canada.
  • 3 CAMS Key Laboratory of Antiviral Drug Research, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, 1 Tiantanxili, Beijing, 100050, China. Electronic address: [email protected].
  • 4 CAMS Key Laboratory of Antiviral Drug Research, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, 1 Tiantanxili, Beijing, 100050, China. Electronic address: [email protected].
  • 5 CAMS Key Laboratory of Antiviral Drug Research, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, 1 Tiantanxili, Beijing, 100050, China. Electronic address: [email protected].
PMID: 37979208 DOI: 10.1016/j.virol.2023.109939
Abstract

Zika virus (ZIKV) belongs to Flaviviridae, the Flavivirus genus. Its Infection causes congenital brain abnormalities and Guillain-Barré 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 μM. 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.

Keywords

5-Azacytidine; Antiviral; NS5; Nucleotide analog inhibitor; ZIKV.

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