Antiviral Activity of Ecklonia cava Extracts and Dieckol Against Zika Virus

Int J Mol Sci. 2024 Dec 21;25(24):13694. doi: 10.3390/ijms252413694.

Abstract

Ecklonia cava and its major compound dieckol, both natural marine products, possess antioxidant, anti-inflammatory, and metabolic-regulating effects. Zika virus (ZIKV), an arbovirus from the Flaviviridae family, is transmitted by mosquitoes and causes serious illnesses in humans. This study aimed to evaluate the anti-ZIKV potential of Ecklonia cava and dieckol. The antiviral activity of Ecklonia cava 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.

Keywords: Ecklonia cava; Vero E6 cells; Zika virus; dieckol; in silico assays.

MeSH terms

  • Animals
  • Antiviral Agents* / chemistry
  • Antiviral Agents* / pharmacology
  • Benzofurans* / chemistry
  • Benzofurans* / pharmacology
  • Chlorocebus aethiops
  • DEAD-box RNA Helicases
  • Humans
  • Molecular Docking Simulation*
  • Nucleoside-Triphosphatase
  • Phaeophyceae* / chemistry
  • Plant Extracts / chemistry
  • Plant Extracts / pharmacology
  • RNA-Dependent RNA Polymerase / metabolism
  • Serine Endopeptidases
  • Vero Cells
  • Viral Nonstructural Proteins / metabolism
  • Viral Proteases
  • Virus Replication / drug effects
  • Zika Virus Infection / drug therapy
  • Zika Virus Infection / virology
  • Zika Virus* / drug effects

Substances

  • Antiviral Agents
  • dieckol
  • Benzofurans
  • Plant Extracts
  • Viral Nonstructural Proteins
  • RNA-Dependent RNA Polymerase
  • NS2B protein, flavivirus
  • NS3 protein, Zika virus
  • Viral Proteases
  • Serine Endopeptidases
  • Nucleoside-Triphosphatase
  • DEAD-box RNA Helicases