title: Antiviral effects against EV71 of pimprinine and its derivatives isolated from Streptomyces sp.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: College of Life Sciences, Wuhan University, Wuhan, 430072, P. R. of China. weiyanhong925@163.com.
authors.forename: Yanhong
authors.initials: Y
authors.lastname: Wei
authors.affiliation: National Biopesticide Engineering Research Center, Hubei Academy of Agricultural Sciences, Wuhan, 430064, P. R. of China. 359088768@qq.com.
authors.forename: Wei
authors.initials: W
authors.lastname: Fang
authors.affiliation: National Biopesticide Engineering Research Center, Hubei Academy of Agricultural Sciences, Wuhan, 430064, P. R. of China. 396253453@qq.com.
authors.forename: Zhongyi
authors.initials: Z
authors.lastname: Wan
authors.affiliation: National Biopesticide Engineering Research Center, Hubei Academy of Agricultural Sciences, Wuhan, 430064, P. R. of China. 1054370156@qq.com.
authors.forename: Kaimei
authors.initials: K
authors.lastname: Wang
authors.affiliation: College of Life Sciences, Wuhan University, Wuhan, 430072, P. R. of China. 774935808@qq.com.
authors.forename: Qingyu
authors.initials: Q
authors.lastname: Yang
authors.affiliation: Kekulé-Institute of Organic Chemistry and Biochemistry, University of Bonn, Bonn, 53121, German. caixiaofeng1234@hotmail.com.
authors.forename: Xiaofeng
authors.initials: X
authors.lastname: Cai
authors.affiliation: National Biopesticide Engineering Research Center, Hubei Academy of Agricultural Sciences, Wuhan, 430064, P. R. of China. shiliqiao_75@163.com.
authors.forename: Liqiao
authors.initials: L
authors.lastname: Shi
authors.affiliation: College of Life Sciences, Wuhan University, Wuhan, 430072, P. R. of China. 18627186188@126.com.|National Biopesticide Engineering Research Center, Hubei Academy of Agricultural Sciences, Wuhan, 430064, P. R. of China. 18627186188@126.com.
authors.forename: Ziwen
authors.initials: Z
authors.lastname: Yang
mesh_terms: D000256:Adenoviridae / Q000187:drug effects / Q000502:physiology; D000998:Antiviral Agents / Q000302:isolation & purification / Q000494:pharmacology*; D003588:Cytopathogenic Effect, Viral / Q000187:drug effects; D029821:Enterovirus A, Human / Q000187:drug effects* / Q000502:physiology*; D018259:Herpesvirus 1, Human; D050296:Microbial Viability / Q000187:drug effects; D010080:Oxazoles / Q000302:isolation & purification / Q000494:pharmacology*; D013302:Streptomyces / Q000737:chemistry; D010948:Viral Plaque Assay; D014779:Virus Replication / Q000187:drug effects
chemical_list: D000998:Antiviral Agents; D010080:Oxazoles; C008912:pimprinine