目的 研究茶黄素衍生物的混合物（含茶黄素、茶黄素-3-没食子酸酯、茶黄素-3′-没食子酸酯和茶黄素-3, 3′-双没食子酸酯，简称茶黄素衍生物）抗甲型流感病毒的作用及其机制。方法 采用H5N1假病毒检测体系，观察茶黄素衍生物对A/Thailand/Kan353/2004 H5N1毒株假病毒的抑制作用；采用血凝抑制实验和神经氨酸酶抑制实验进一步分析茶黄素衍生物抗甲型流感病毒的作用机制；采用H1N1 FM_1病毒检测体系，观察茶黄素衍生物对甲型流感病毒FM_1的抑制作用；采用MTT法评价茶黄素衍生物对MDCK细胞的毒性。结果 茶黄素衍生物能明显的抑制H5N1假病毒的感染力，IC₅₀为（151.88±18.95）μg/mL；对血凝素HA1亚基无抑制作用；对神经氨酸酶具有抑制作用，IC₅₀为（129.09±1.33）μg/mL；能明显抑制甲型流感病毒FM_1株。此外，茶黄素衍生物对MDCK细胞的毒性较小，CC₅₀为（879.89±4.54）μg/mL。结论 茶黄素衍生物可能通过与血凝素HA2亚基结合而抑制禽流感病毒的感染，同时能够在一定程度上抑制病毒的神经氨酸酶活性，提示茶黄素衍生物是通过多靶点发挥抗H5N1亚型禽流感病毒的作用。

Objective To study the anti-influenza A virus effect of theaflavin derivatives which contain theaflavin (TF1), theaflavin-3-gallate (TF2A), theaflavin-3′-gallate (TF2B), and theaflavin-3, 3′-digallate (TF3) and to investigate the mechanism. Methods The inhibition of theaflavin derivatives on A/Thailand/Kan353/2004 H5N1 pseudovirus was investigated using pseudotype H5N1 virus system. Hemagglutination inhibition assay and neuraminidase (NA) inhibition assay were used to investigate the mechanism for their anti-influenza activities. The inhibition of theaflavin derivatives on influenza A virus FM_1 was observed by H1N1 FM_1 system. Cytotoxicity of theaflavin derivatives on MDCK cells was determined by MTT assay. Results Theaflavin derivatives could significantly inhibit the infection of pseudovirus H5N1 with IC₅₀ of (151.88 ± 18.95) μg/mL. It had no inhibition on HA1 subunit. Theaflavin derivatives had the inhibition on NA with IC₅₀ of (129.09 ± 1.33) μg/mL. Theaflavin derivatives showed a significant inhibitory activity on FM_1 influenza virus strain in MDCK cells. Theaflavin derivatives showed the low cytotoxicity on MDCK cells with CC₅₀ of (879.89 ± 4.54) μg/mL. Conclusion Theaflavin derivatives could inhibit the infection of avian influenza virus through the combination with hemagglutinin (HA) HA2 subunit and inhibit the activity of viral NA to some extent, which indicates that the anti-H5N1 avian influenza virus of theaflavin derivatives may be through multi-targets.

国家自然科学基金资助项目（81102792）；广东高校国际科技合作创新平台项目（gjhz1105）