Studies on the antiviral activity of chebulinic acid against dengue and chikungunya viruses and in silico investigation of its mechanism of inhibition

Sci Rep. 2022 Jun 21;12(1):10397. doi: 10.1038/s41598-022-13923-6.

Abstract

Chebulinic acid (CA), originally isolated from the flower extract of the plant Terminalia chebula, has been shown to inhibit infection of herpes simplex virus-2 (HSV-2), suggestively by inhibiting the host entry step of viral infection. Like HSV-2, the dengue virus (DENV) and chikungunya virus (CHIKV) also use receptor glycosaminoglycans (GAG) to gain host entry, therefore, the activity of CA was tested against these viruses. Co-treatment of 8 µM CA with DENV-2 caused 2 log decrease in the virus titer (4.0 log10FFU/mL) at 120 h post infection, compared to virus control (5.95 log10FFU/mL). In contrast, no inhibitory effect of CA was observed against CHIKV infection under any condition. The mechanism of action of CA was investigated in silico by employing DENV-2 and CHIKV envelope glycoproteins. During docking, CA demonstrated equivalent binding at multiple sites on DENV-2 envelope protein, including GAG binding site, which have previously been reported to play a crucial role in host attachment and fusion, indicating blocking of these sites. However, CA did not show binding to the GAG binding site on envelope protein-2 of CHIKV. The in vitro and in silico findings suggest that CA possesses the ability to inhibit DENV-2 infection at the entry stage of its infection cycle and may be developed as a potential therapeutic agent against it.

MeSH terms

  • Antiviral Agents / pharmacology
  • Antiviral Agents / therapeutic use
  • Chikungunya Fever* / drug therapy
  • Chikungunya virus* / physiology
  • Dengue* / drug therapy
  • Glycosaminoglycans / metabolism
  • Herpesvirus 2, Human / metabolism
  • Humans
  • Hydrolyzable Tannins

Substances

  • Antiviral Agents
  • Glycosaminoglycans
  • Hydrolyzable Tannins
  • chebulinic acid