Abstract
Zika virus (ZIKV) remains a significant global public health concern, and growing resistance to existing antiviral drugs underscores the necessity of developing alternative therapeutic options. In this study, we investigated the inhibitory effects of ethyl gallate against ZIKV using antiviral activity evaluation, molecular docking, and molecular dynamic simulations. Treatment of ZIKV-infected Vero E6 cells with ethyl gallate resulted in dose-dependent suppression of viral infection without inducing cytotoxicity. In addition, ethyl gallate inhibited the increase in the expression of interferon-stimulated genes in ZIKV-infected cells. It also exhibited binding energies of -5.9868, -247.271, and -200.43 kcal/mol for ZIKV envelope, NS3, and RdRp proteins, respectively. Furthermore, the molecular dynamic simulation results showed that the ethyl gallate-NS3 and ethyl gallate-RdRp complexes were more stable than the ethyl gallate-envelope protein complex, suggesting that ethyl gallate has the potential to inhibit ZIKV replication. These findings position ethyl gallate as an antiviral agent with potential against Zika infection.