Antiviral effects against EV71 of pimprinine and its derivatives isolated from Streptomyces sp

Virology Journal

Ziwen Yang¹  Liqiao Shi¹  Xiaofeng Cai²  Qingyu Yang³  Kaimei Wang¹  Zhongyi Wan¹  Wei Fang¹  Yanhong Wei³ 

[1] National Biopesticide Engineering Research Center, Hubei Academy of Agricultural Sciences, Wuhan 430064, P. R. of China;Kekulé-Institute of Organic Chemistry and Biochemistry, University of Bonn, Bonn 53121, German;College of Life Sciences, Wuhan University, Wuhan 430072, P. R. of China

关键词: Mode of action;    Broad-spectrum antiviral activity;    Enteroviruses 71;    Pimprinine family of compounds;   

Others  :  1148036
DOI  :  10.1186/s12985-014-0195-y

 received in 2014-04-07, accepted in 2014-10-29,  发布年份 2014

【 摘 要 】

Background

The pimprinine family of compounds represent very important and promising microbial metabolites for drug discovery. However, their ability in inhibiting viral infections has not yet been tested.

Methods

The antiviral activity of the pimprinine family of compounds was evaluated by determining the cytopathic effect (CPE), cell viability or plaque-forming unit (PFU), and virus yield. The mechanism of action against EV71 was determined from the virucidal activity, and effective stage and time-of-addition assays. The effects on EV71 replication were evaluated further by determining viral RNA synthesis, protein expression and cells apoptosis using the SYBR Green assays, immunofluorescence assays and flow cytometric assays, respectively.

Results

Pimprinethine, WS-30581 A and WS-30581 B inhibited EV71-induced CPE, reduced progeny EV71 yields, as well as prevented EV71-induced apoptosis in human rhabdomyosarcoma (RD) cells. These compounds were found to target the early stages of the EV71 replication in cells including viral RNA replication and protein synthesis. They also showed antiviral activity against ADV-7, and were slightly active against CVB3, HSV-1 and H1N1 with a few exceptions. Pimprinine was slightly active or inactive against all the viruses tested. The mechanisms by which these compounds act against the viruses tested may be similar to that demonstrated for EV71.

Conclusion

The data described herein demonstrate that the pimprinine family of compounds are inhibitors effective against the replication of EV71 and ADV-7, so they might be feasible therapeutic agents for the treatment of viral infections.

【 授权许可】

   
2014 Wei et al.; licensee BioMed Central Ltd.

【 图 表 】

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