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.
© 2022. The Author(s).