Antiviral evaluation of an Hsp90 inhibitor, gedunin, against dengue virus
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