Antiviral Activity of Ecklonia cava Extracts and Dieckol Against Zika Virus

<i>Ecklonia cava</i> and its major compound dieckol, both natural marine products, possess antioxidant, anti-inflammatory, and metabolic-regulating effects. Zika virus (ZIKV), an arbovirus from the <i>Flaviviridae</i> family, is transmitted by mosquitoes and causes serious illnesses in humans. This study aimed to evaluate the anti-ZIKV potential of <i>Ecklonia cava</i> and dieckol. The antiviral activity of <i>Ecklonia cava</i> extract (ECE), prepared with 80% ethanol, was assessed in ZIKV-infected Vero E6 cells through MTT assay, plaque assay, and quantitative polymerase chain reaction (qPCR), demonstrating no cytotoxicity and a significant reduction in viral titers and ZIKV mRNA levels. In addition, ECE decreased the expression of tumor necrosis factor-α and interferon-induced protein with tetratricopeptide repeats in the ZIKV-infected cells. Dieckol, the primary active compound in ECE, exhibited potent anti-ZIKV activity, with a half maximal inhibitory concentration (IC₅₀), value of 4.8 µM. In silico molecular docking analysis revealed that dieckol forms stable complexes with key ZIKV proteins, including the envelope, NS2B/NS3, and RNA-dependent RNA polymerase (RdRp) protein, exhibiting high binding energies of -438.09 kcal/mol, -1040.51 kcal/mol, and -1043.40 kcal/mol, respectively. Overall, our findings suggest that ECE and dieckol are promising candidates for the development of anti-ZIKV agents.