METHODS: Theaflavins TF1 and TF2 were selected by evaluating the anti-Zika virus activity of four kinds of theaflavins in vitro. Subsequently, in vivo, we investigated the effects of TF1 and TF2 on weight, survival, tissue viral load, and cytokines in ZIKV-infected mice.
RESULTS: We compared the anti-ZIKV activity of four theaflavins (TFs) in cells and found that TF1 and TF2b significantly inhibited the replication of ZIKV/Z16006 toxic strain in BHK and Vero cells by inhibiting the replication and release of ZIKV, while no similar effects were observed for TF2a and TF3. In vivo assay, we only found that TF2b improved the survival rate of infected mice. In tissues of ZIKV-infected mice, the viral load was higher in spleen and blood, followed by liver, epididymis, and testis, the lowest in muscle. Additionally, TF2b treatment significantly reduced the expression of cytokines (IL-6, IL-1β, TNF-α) and chemokines (CCL2, CCL5, CXCL10) induced by ZIKV infection.
CONCLUSIONS: These findings suggest that TF2b has a potent antiviral effect and can be used as a potential candidate for the treatment of ZIKV infection.
方法:通过评价四种茶黄素的体外抗寨卡病毒活性,选择茶黄素TF1和TF2。随后,在体内,我们研究了TF1和TF2对体重的影响,生存,组织病毒载量,和ZIKV感染小鼠的细胞因子。
结果:我们比较了四种茶黄素(TF)在细胞中的抗ZIKV活性,发现TF1和TF2b通过抑制ZIKV的复制和释放,显著抑制了ZIKV/Z16006毒株在BHK和Vero细胞中的复制,而对于TF2a和TF3没有观察到类似的效果。体内试验,我们只发现TF2b提高了感染小鼠的存活率。在ZIKV感染小鼠的组织中,脾脏和血液中的病毒载量较高,其次是肝脏,附睾,和睾丸,肌肉最低。此外,TF2b处理显著降低细胞因子的表达(IL-6,IL-1β,ZIKV感染诱导的TNF-α)和趋化因子(CCL2,CCL5,CXCL10)。
结论:这些发现表明TF2b具有有效的抗病毒作用,可用作治疗ZIKV感染的潜在候选药物。