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Screening and activity analysis of ZIKV RdRp inhibitors
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Hong-juan ZHANG, Ying CHEN, Yan-xing HAN, Yuan LIN*, Jian-dong JIANG*
Acta Pharmaceutica Sinica | 2022, 57(10) : 2995 - 3001
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Acta Pharmaceutica Sinica | 2022, 57(10): 2995-3001
• Special Reports Ⅰ: New Targets, New Strategies for Drug Discovery and Advances in Antiviral Drug Research •
Screening and activity analysis of ZIKV RdRp inhibitors
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Hong-juan ZHANG, Ying CHEN, Yan-xing HAN, Yuan LIN*, Jian-dong JIANG*
Affiliations
  • State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China
Published: 2022-10-12 doi: 10.16438/j.0513-4870.2022-0701
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The epidemic of Zika virus (ZIKV) raises critical public health and safety problems. However, there are currently no vaccines or drugs that are clinically approved for ZIKV infections. Since RNA-dependent RNA polymerase (RdRp) plays an important role in replication and transcription of ZIKV and is absent in human beings, it is a potential drug screening target of anti-ZIKV agents. According to the fluorescence-based alkaline phosphatase-coupled polymerase assay method, we established the NS5 RdRp inhibitor screening model. Through screening from an anti-infection compound library, we found a compound octenidine dihydrochloride (OCT) that could inhibit ZIKV RdRp activity with a half maximal inhibitory concentration (IC50) of 5.43 μmol·L-1. Biolayer interferometry (BLI) assay showed that OCT could bind to ZIKV RdRp and had a strong affinity. Moreover, OCT exhibited an inhibitory effect on ZIKV replication with a half maximal effective concentration (EC50) of 29.94 μmol·L-1. All these results indicated that OCT had the anti-ZIKV activity by targeting ZIKV RdRp, and it is likely to be a promising lead compound against ZIKV.

Zika virus  /  RNA-dependent RNA polymerase  /  screening model  /  inhibitor  /  octenidine dihydrochloride
Hong-juan ZHANG, Ying CHEN, Yan-xing HAN, Yuan LIN, Jian-dong JIANG. Screening and activity analysis of ZIKV RdRp inhibitors[J]. Acta Pharmaceutica Sinica, 2022 , 57 (10) : 2995 -3001 . DOI: 10.16438/j.0513-4870.2022-0701
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Year 2022 volume 57 Issue 10
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Article Info
doi: 10.16438/j.0513-4870.2022-0701
  • Receive Date：2022-06-06
  • Online Date：2025-12-24
  • Published：2022-10-12
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  • Received：2022-06-06
  • Revised：2022-06-22
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    State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China
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