Tropical Journal of Pharmaceutical Research

Original Research Article | OPEN ACCESS

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

Deeba Amraiz, Najam-us-Sahar Sadaf Zaidi , Munazza Fatima

Atta-ur-Rahman School of Applied Biosciences, National University of Sciences and Technology, Sector H-12, Islamabad, Pakistan 44000;

For correspondence:- Najam-us-Sahar Zaidi Email: zaidi.sahar@gmail.com Tel:+925190856132

Received: 17 November 2016 Accepted: 7 April 2017 Published: 30 May 2017

Citation: Amraiz D, Zaidi NS, Fatima M. Antiviral evaluation of an Hsp90 inhibitor, gedunin, against dengue virus. Trop J Pharm Res 2017; 16(5):997-1004 doi: 10.4314/tjpr.v16i5.5

© 2017 The authors.
This is an Open Access article that uses a funding model which does not charge readers or their institutions for access and distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0) and the Budapest Open Access Initiative (http://www.budapestopenaccessinitiative.org/read), which permit unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited..

Abstract

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