Z1, a novel DENV2 NS5 RdRp small molecular inhibitor, inhibits DENV2 replication and infection
10.3969/j.issn.1001-1978.2018.06.011
- VernacularTitle:新型登革病毒RNA聚合酶小分子抑制剂Z1降低登革病毒复制和感染的研究
- Author:
Song-Xin GUO
1
;
Shi-Jun HE
;
Cui-Hong HUANG
;
Xin-Gang YAO
;
Shu-Wen LIU
Author Information
1. 南方医科大学药学院
- Keywords:
NS5 RdRp inhibitors;
DENV RNA poly-merase;
DENV2 infection;
antiviral drugs;
SPR;
virus replication
- From:
Chinese Pharmacological Bulletin
2018;34(6):790-796
- CountryChina
- Language:Chinese
-
Abstract:
Aim To screen novel NS5 inhibitors a-gainst dengue virus ( DENV) replication. Methods His-tagged DENV2 NS5 RNA-dependent polymerase ( NS5 RdRp ) was expressed and purified in BL21 cells. The binding ability of the small molecules to NS5 polymerase was determined by SPR assay. The activity of dengue inhibition by Z1 was determined by CPE, LDH and plaque assay. RNA synthesis was as-sessed by Real-time PCR. The dsRNA synthesis and viral proteins were detected by immunofluorescence as-say. The level of viral proteins was examined by West-ern blot. The stage of DENV life cycle was evaluated by time of drug-addition assay. Results A small mo-lecular Z1 was discovered, which could bind to NS5 RdRp. Z1 inhibited DENV2 RNA replication, synthe-sis of dsRNA and protein synthesis in post-entry stage of dengue life-cycle. Cell based assay confirmed that Z1 inhibited DENV-induced cell death with EC50 val-ues of 4. 75μmol·L-1 . Conclusions The novel NS5 inhibitor Z1, inhibits DENV2 RNA replication, protein synthesis and release of progeny virus, which may be severed as an anti-DENV2 antiviral drug for further de-velopment.
