Antiviral Activity of Compound L3 against Dengue and Zika Viruses In Vitro and In Vivo.
Fu-Kai ChuangChing-Len LiaoMing-Kuan HuYi-Lin ChiuAn-Rong LeeShih-Ming HuangYu-Lung ChiuPei-Ling TsaiBo-Cyuan SuTsung-Hsien ChangChang-Chi LinChih-Chin ShihLi-Chen YenPublished in: International journal of molecular sciences (2020)
Dengue virus (DENV) and Zika virus (ZIKV) are mosquito-borne flaviviruses that cause severe illness after infection. Currently, there are no specific or effective treatments against DENV and ZIKV. Previous studies have shown that tyrosine kinase activities and signal transduction are involved in flavivirus replication, suggesting a potential therapeutic strategy for DENV and ZIKV. In this study, we found that compound L3 can significantly reduce viral protein expression and viral titers in HEK-293, MCF-7, HepG2, and Huh-7 cells and exhibits superior therapeutic efficacy against flaviviral infection compared to other tyrosine kinase inhibitors. In addition, compound L3 can decrease endogenous HER2 activation and inhibit the phosphorylation of the HER2 downstream signaling molecules Src and ERK1/2, the levels of which have been associated with viral protein expression in MCF-7 cells. Moreover, silencing HER2 diminished DENV-2 and ZIKV expression in MCF-7 cells, which suggests that HER2 activity is involved in flavivirus replication. Furthermore, in DENV-2-infected AG129 mice, treatment with compound L3 increased the survival rates and reduced the viremia levels. Overall, compound L3 demonstrates therapeutic efficacy both in vitro and in vivo and could be developed as a promising antiviral drug against emerging flaviviruses or for concurrent DENV and ZIKV outbreaks.
Keyphrases
- dengue virus
- zika virus
- aedes aegypti
- induced apoptosis
- tyrosine kinase
- cell cycle arrest
- sars cov
- breast cancer cells
- endoplasmic reticulum stress
- type diabetes
- squamous cell carcinoma
- signaling pathway
- oxidative stress
- cell death
- pi k akt
- cell proliferation
- radiation therapy
- adipose tissue
- metabolic syndrome
- long non coding rna
- skeletal muscle
- high fat diet induced
- rectal cancer
- smoking cessation
- infectious diseases