扎那米韦长链酯衍生物1c体内外抗流感病毒活性研究

The anti-influenza virus activities of a long chain ester derivative-1c of zanamivir in vitro and in vivo

目的研究扎那米韦长链酯衍生物1c的体内外抗流感病毒活性。方法体外实验以流感病毒感染的MDCK细胞为模型,以细胞病变为指标,研究了化合物1c的细胞毒性以及对4种流感病毒A型和3种流感病毒B型的抑制活性。体内实验应用感染了流感病毒甲1(H1N1)亚型FM1株的小鼠动物模型,观察不同给药方案、不同剂量、不同给药途径的多项指标。结果在细胞培养内,化合物1c抑制流感病毒A型的IC50在0.23～26.86μmol/L之间;抑制流感病毒B型的IC50在21.79～246.80μmol/L之间。体内实验中,应用不同给药方案1c治疗可以明显改善FM1感染小鼠的存活率,平均生活日及肺指数。结论化合物1c有潜能开发为抗流感病毒药物。

Objective To test the anti-influenza virus activities of a zanamlvir derivative lc. Methods The cytotoxicities and antiviral activities of lc in vitro on four influenza virus A strains and three influenza virus B strains were tested in MDCK cells. The antiviral activities of lc in vivo were tested in the mice infected with influenza A virus subtype FM1. Results In cell culture, the IC50s of lc for influenza virus A strains were 0.23 to 26.86 μmol/L, and for influenza virus B strains were 21.79 to 246.80 μmol/L. In vivo, lc displayed significant therapeutical effects on mice infected with influenza virus A subtype FM1 on survival rates, survival days and lung indexes with different medications. Conclusion The new compound lc may be a potential candidate for new antiviral drugs.