中国药理学通报2025，Vol.41Issue(8)：1436-1444,9.DOI:10.12360/CPB202412122
泽漆二萜化合物体外抗寨卡病毒机制
Antiviral mechanism of Euphorbia helioscopia diterpenoids against Zika virus in vitro
摘要
Abstract
Aim To investigate the anti-Zika virus(ZIKV)mechanism of diterpenoid compound 9 from Euphorbia helioscopia in vitro.Methods The cytotox-icity of compound 9 was evaluated using the CCK-8 as-say.A ZIKV-infected Vero cell model was established,and the antiviral activity was assessed through RT-qPCR,plaque assay,Western blot,and immunofluores-cence.Furthermore,the mechanism of action was elu-cidated using multi-cell line validation,nanoparticle tracking analysis,cellular thermal shift assay,and mo-lecular docking.Results In Vero cells,compound 9 exhibited an EC50 of(3.95±0.15)μmol·L-1 and a CC50 of(272.12±8.56)μmol·L-1,demonstrating significantly higher antiviral efficacy than the positive control drug ribavirin(RBV).Its virus inactivation effect was time-dependent and could significantly re-duce viral load and plaque formation.Studies revealed that compound 9 altered the physicochemical properties of ZIKV particles,including reducing surface charge and increasing particle size distribution.Additionally,it significantly enhanced the thermal stability of the prM protein.Molecular docking analysis indicated that compound 9 formed a high-affinity interaction with the prM protein(binding energy:-38.52 kJ·mol-1)and stabilized its structure through hydrophobic interac-tions.Conclusion Compound 9 exerts in vitro anti-ZIKV activity by directly inactivating the virus,disrup-ting viral particle integrity,and targeting the prM pro-tein.关键词
寨卡病毒/泽漆二萜类化合物/病毒进入抑制/prM蛋白/分子对接/天然产物抗病毒药物Key words
Zika virus/Euphorbia helioscopia diterpe-noid compound/viral entry inhibition/prM protein/molecular docking/natural product antivirals分类
医药卫生引用本文复制引用
庞攀攀,邱雄,江英杰,刘欣月,马维喆,尹健秋蓉,肖伟烈,郑昌博..泽漆二萜化合物体外抗寨卡病毒机制[J].中国药理学通报,2025,41(8):1436-1444,9.基金项目
国家自然科学基金资助项目(No 82460105) （No 82460105）
科技部"四大慢病重大专项"(No 2023ZD0502800) （No 2023ZD0502800）
云南省科技厅昆明医科大学基础研究联合专项-杰青培育项目(No 202401AY070001-303) （No 202401AY070001-303）
