A cell-based assay to discover inhibitors of Zika virus RNA-dependent RNA polymerase
Copyright © 2023 Elsevier Inc. All rights reserved..
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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 2023 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:589 |
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| Enthalten in: |
Virology - 589(2023) vom: 18. Jan., Seite 109939 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Wang, Lidan [VerfasserIn] |
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| Links: |
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| Themen: |
5-Azacytidine |
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| Anmerkungen: |
Date Completed 16.12.2023 Date Revised 16.12.2023 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.virol.2023.109939 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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NLM364707410 |
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| 520 | |a Copyright © 2023 Elsevier Inc. All rights reserved. | ||
| 520 | |a 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 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a 5-Azacytidine | |
| 650 | 4 | |a Antiviral | |
| 650 | 4 | |a NS5 | |
| 650 | 4 | |a Nucleotide analog inhibitor | |
| 650 | 4 | |a ZIKV | |
| 650 | 7 | |a Antiviral Agents |2 NLM | |
| 650 | 7 | |a RNA-Dependent RNA Polymerase |2 NLM | |
| 650 | 7 | |a EC 2.7.7.48 |2 NLM | |
| 650 | 7 | |a Viral Nonstructural Proteins |2 NLM | |
| 650 | 7 | |a RNA, Viral |2 NLM | |
| 650 | 7 | |a Azacitidine |2 NLM | |
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| 700 | 1 | |a Zhou, Rui |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, Yitong |e verfasserin |4 aut | |
| 700 | 1 | |a Guo, Saisai |e verfasserin |4 aut | |
| 700 | 1 | |a Yi, Dongrong |e verfasserin |4 aut | |
| 700 | 1 | |a Zhao, Jianyuan |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Quanjie |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Yongxin |e verfasserin |4 aut | |
| 700 | 1 | |a Liang, Chen |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Jing |e verfasserin |4 aut | |
| 700 | 1 | |a Shan, Guangzhi |e verfasserin |4 aut | |
| 700 | 1 | |a Cen, Shan |e verfasserin |4 aut | |
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