title: Inhibition of enterovirus 71 replication by chrysosplenetin and penduletin.
abstract: In recent years, enterovirus 71 (EV71) infections have caused an increasing epidemic in young children, accompanying with more severe nervous system disease and more deaths. Unfortunately, there is no specific medication for it so far. Here we investigated the anti-EV71 activity of chrysosplenetin and penduletin, two o-methylated flavonols isolated from the leaves of Laggera pterodonta. These two compounds were found to have strong activity in vitro against EV71 with low cytotoxicity. In the cytopathic effect (CPE) inhibition assays, both plaque reduction assay and virus yield inhibition assay, the compounds showed a similar 50% inhibitory concentration (IC(50)) value of about 0.20 μM. The selectivity indices (SI) of chrysosplenetin and penduletin were 107.5 and 655.6 in African green monkey kidney (Vero) cells, and 69.5 and 200.5 in human rhabdomyosarcoma (RD) cells, accordingly. The preliminary mechanism analysis indicates that they function not through blocking virus entry or inactivating virus directly but inhibiting viral RNA replication. In the time-of-addition assay, both compounds inhibited progeny virus production and RNA replication by nearly 100% when introduced within 4h post infection. In addition to EV71, both compounds inhibited several other human enteroviruses with similar efficacy. These findings provide a significant lead for the discovery of anti-EV71 drug.
authors.affiliation: State Key Laboratory of Respiratory Diseases, Guangzhou Institute of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510530, China.
authors.forename: Qin-Chang
authors.initials: QC
authors.lastname: Zhu
authors.forename: Yi
authors.initials: Y
authors.lastname: Wang
authors.forename: Ya-Ping
authors.initials: YP
authors.lastname: Liu
authors.forename: Rui-Qi
authors.initials: RQ
authors.lastname: Zhang
authors.forename: Xiang
authors.initials: X
authors.lastname: Li
authors.forename: Wen-Han
authors.initials: WH
authors.lastname: Su
authors.forename: Fei
authors.initials: F
authors.lastname: Long
authors.forename: Xiao-Dong
authors.initials: XD
authors.lastname: Luo
authors.forename: Tao
authors.initials: T
authors.lastname: Peng
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000302:isolation & purification / Q000494:pharmacology*; D019659:Asteraceae / Q000737:chemistry; D015153:Blotting, Western; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002522:Chlorocebus aethiops; D003588:Cytopathogenic Effect, Viral / Q000187:drug effects; D004591:Electrophoresis, Polyacrylamide Gel; D029821:Enterovirus A, Human / Q000187:drug effects* / Q000502:physiology; D005419:Flavonoids / Q000302:isolation & purification / Q000494:pharmacology*; D006801:Humans; D020128:Inhibitory Concentration 50; D018515:Plant Leaves / Q000737:chemistry; D012367:RNA, Viral / Q000187:drug effects; D014709:Vero Cells; D010948:Viral Plaque Assay; D014779:Virus Replication / Q000187:drug effects*
chemical_list: D000998:Antiviral Agents; D005419:Flavonoids; D012367:RNA, Viral; C570122:penduletin; C570121:chrysosplenetin