Antiviral activity of theaflavins against Zika virus in vivo and in vitro.

INTRODUCTION: The prevalence and infection of the Zika virus (ZIKV) have recently posed a major threat to global public health security. However, there is currently a lack of specific vaccines and effective antiviral drugs for ZIKV infection. 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-1ß, 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.

Anti-inflammatory effects of theaflavin-3'-gallate during influenza virus infection through regulating the TLR4/MAPK/p38 pathway.

Severe pathological damage caused by the influenza virus is one of the leading causes of death. However, the prevention and control strategies for influenza virus infection have certain limitations, and the exploration for new influenza antiviral drugs has become the major research direction. This study evaluated the antiviral activities of four theaflavin derivatives (TFs). Cytopathic effect (CPE) reduction assay revealed that theaflavin-3'-gallate (TF2b) and theaflavin (TF1) could effectively inhibit the replication of influenza viruses H1N1-UI182, H1N1-PR8, H3N2, and H5N1, and TF2b exhibited the most significant antiviral activity in vivo. Intraperitoneal injection of TF2b at 40 mg/kg/d effectively alleviated viral pneumonia, maintained body weight, and improved the survival rate of mice infected with a lethal dose of H1N1-UI182 to 55.56%. Hematological analysis of peripheral blood further showed that TF2b increased the number of lymphocytes and decreased the number of neutrophils, monocytes, and platelets in the blood of infected mice. RT-qPCR results showed that TF2b reduced the mRNA expression levels of inflammatory cytokines (IL-6, TNF-α, and IL-1ß), chemokines (CXCL-2 and CCL-3), and interferons (IFN-α and IFN-γ) after influenza virus infection. In addition, TF2b significantly down-regulated the expression levels of TLR4, p-p38, p-ERK, and cytokines IL-6, TNF-α, IL-1ß, and IL-10. These results suggest that TF2b not only significantly inhibits viral replication and proliferation in vitro, but also alleviates pneumonia injury in vivo. Its antiviral effect might be attributed to the down-regulation of influenza virus-induced inflammatory cytokines by regulating the TLR4/MAPK/p38 signaling pathway.