Potent Inhibition of Dengue Virus Infection by Synthetic Compound TXD-174 Through Specific Targeting of IL-24.

Dengue virus (DENV) infection has emerged as a critical global public health challenge, particularly in tropical and subtropical regions, where it continues to cause high morbidity rates and severe disease risks. Given the current lack of specific antiviral therapies in clinical practice, the development of novel anti-DENV agents represents an urgent medical need. In this study, the antiviral activity of a novel compound, TXD-174, was systematically evaluated. It was found that TXD-174 exhibited significant inhibitory effects against DENV2 in vitro. Notably, viral replication was effectively blocked by TXD-174, while cytotoxicity assessments revealed a favorable therapeutic window. Furthermore, the compound demonstrated inhibitory activity against all four DENV serotypes, highlighting its potential as a broad-spectrum anti-dengue agent. Meanwhile, RNA-seq analysis indicated that level of IL-24 was significantly upregulated. Knockdown of IL-24 gene reduced the antiviral effect of TXD-174, while overexpression of IL-24 gene also exhibited good antiviral effects. In virus-infected AG-129 models, TXD-174 was also found to have good in vivo antiviral effects. These findings establish a foundation for further exploration of targeted therapeutic strategies against DENV infections.