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

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.