Screening and activity analysis of ZIKV RdRp inhibitors
10.16438/j.0513-4870.2022-0701
- VernacularTitle:寨卡病毒RdRp抑制剂的筛选及活性研究
- Author:
Hong-juan ZHANG
;
Ying CHEN
;
Yan-xing HAN
;
Yuan LIN
;
Jian-dong JIANG
- Publication Type:Research Article
- Keywords:
Zika virus;
RNA-dependent RNA polymerase;
screening model;
inhibitor;
octenidine dihydrochloride
- From:
Acta Pharmaceutica Sinica
2022;57(10):2995-3001
- CountryChina
- Language:Chinese
-
Abstract:
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.
