Antiviral evaluation of an Hsp90 inhibitor, gedunin, against dengue virus
Résumé
Purpose: To evaluate the antiviral potential of a tetranortriterpenoid, gedunin, against dengue virus (DENV) replication by targeting the host chaperone, Hsp90.Methods: The compound, gedunin, was tested against the replication of DENV in vitro using BHK-15 cells transfected with DENV-2 subgenomic replicon. Molecular docking of gedunin with Hsp90 protein was performed for evaluation of mode of action, using the program, Autodock vina.Results: In vitro antiviral data showed that gedunin significantly (p < 0.05) reduced DENV replication with EC50 of 10 μM. Further, in silico molecular docking data revealed strong interaction of gedunin with the ATP/ADP binding site of the host protein, Hsp90, with an estimated average free binding energy of -8.9 kcal/mol.Conclusion: The results validate gedunin as a potential antiviral candidate. Further in vitro assays and in vivo viral challenge studies are required to confirm the exact mode of action and pharmacological profile of gedunin in DENV infections.Keywords: Dengue virus replication, Hsp90, Gedunin, Antiviral, Molecular docking
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