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

Yanhong Wei,Kaimei Wang,Xiaofeng Cai,Liqiao Shi,Qingyu Yang,Zhongyi Wan,Ziwen Yang,Wei Fang

doi:10.1186/s12985-014-0195-y

Yanhong Wei, Kaimei Wang + Show 6 more

Open Access

https://doi.org/10.1186/s12985-014-0195-y

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Abstract

BackgroundThe 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.MethodsThe 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.ResultsPimprinethine, 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.ConclusionThe 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.

Highlights

The pimprinine family of compounds represent very important and promising microbial metabolites for drug discovery
The antiviral activity of pimprinine, pimprinethine, WS-30581 A and WS-30581 B against Enterovirus 71 (EV71) The antiviral activity of pimprinine and its analogues pimprinethine, WS-30581 A and WS-30581 B (Figure 1), against EV71 based on inhibition of virus-induced cytopathic effects (CPE) in human rhabdomyosarcoma (RD) cells was examined
Treatments of RD cells with pimprinine, pimprinethine, WS-30581 A and WS-30581 B produced a slight protection against EV71-induced CPE at the lower concentrations, while a nearly complete inhibition of EV71-induced CPE was observed at the higher concentrations, which was used for the subsequent experiments in this study

Summary

Introduction

The pimprinine family of compounds represent very important and promising microbial metabolites for drug discovery Their ability in inhibiting viral infections has not yet been tested. Enterovirus 71 (EV71) is a single positive-stranded RNA virus that belongs to the Enterovirus genus of the Picornaviridae family. It was first isolated and characterized from cases of neurological disease in the United States in 1969 [1], subsequent outbreaks of EV71 infections have been reported around the world especially in the Asia-Pacific region [2,3,4,5,6,7], which mainly affected young children. These emerging problems highlight the need for new, effective and well-tolerated antiviral drugs

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