化学
类黄酮
甲型肝炎病毒
亚基因组mRNA
复制子
病毒学
体外
病毒
微生物学
核糖核酸
生物化学
生物
质粒
DNA
抗氧化剂
基因
作者
Shao-Chun Shi,Xin Zheng,Ryosuke Suzuki,Ziyue Li,Tomoyuki Shiota,Jiayin Wang,Asuka Hirai-Yuki,Qingbo Liu,Masamichi Muramatsu,Shao‐Jiang Song
标识
DOI:10.1016/j.ejmech.2022.114452
摘要
Two series of flavonoid hybrids, totaling 42 compounds, were designed, synthesized and evaluated to develop antiviral compounds effective against hepatitis A virus (HAV). A recombinant viral screening system revealed that most of the synthesized derivatives exhibited significant anti-HAV activity, and compounds B2, B3, B5 and B27 were identified as potential inhibitors of HAV. Post-treatment of cells with B2, B3, B5 and B27 after HAV infection strongly suppressed HAV infection, whereas pretreatment or simultaneous treatment were ineffective. Furthermore, these four compounds significantly inhibited HAV (HM175/18f strain) production in a dose-dependent manner. Analyses using HAV subgenomic replicon systems indicated that these compounds specifically inhibit HAV RNA replication. More importantly, the most potent compounds B2 and B27 also showed clear inhibitory effects on two other HAV strains, KRM031 and TKM005, which also isolated from clinical patients. Our study is the first to report these newly designed flavonoid hybrids as lead compounds for the development of novel anti-HAV drugs.
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