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Molecules 2013, 18(12), 15600-15612; doi:10.3390/molecules181215600
Article

In Vitro Evaluation of Novel Inhibitors against the NS2B-NS3 Protease of Dengue Fever Virus Type 4

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Received: 28 October 2013 / Revised: 2 December 2013 / Accepted: 11 December 2013 / Published: 13 December 2013
(This article belongs to the Special Issue In-Silico Drug Design and In-Silico Screening)
Download PDF [897 KB, 18 June 2014; original version 18 June 2014]

Abstract

The discovery of potent therapeutic compounds against dengue virus is urgently needed. The NS2B-NS3 protease (NS2B-NS3pro) of dengue fever virus carries out all enzymatic activities needed for polyprotein processing and is considered to be amenable to antiviral inhibition by analogy. Virtual screening of 300,000 compounds using Autodock 3 on the GVSS platform was conducted to identify novel inhibitors against the NS2B-NS3pro. Thirty-six compounds were selected for in vitro assay against NS2B-NS3pro expressed in Pichia pastoris. Seven novel compounds were identified as inhibitors with IC50 values of 3.9 ± 0.6–86.7 ± 3.6 μM. Three strong NS2B-NS3pro inhibitors were further confirmed as competitive inhibitors with Ki values of 4.0 ± 0.4, 4.9 ± 0.3, and 3.4 ± 0.1 μM, respectively. Hydrophobic and hydrogen bond interactions between amino acid residues in the NS3pro active site with inhibition compounds were also identified.
Keywords: dengue fever; inhibitors; NS2B-NS3 protease; virtual screening dengue fever; inhibitors; NS2B-NS3 protease; virtual screening
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Nguyen, T.T.H.; Lee, S.; Wang, H.-K.; Chen, H.-Y.; Wu, Y.-T.; Lin, S.C.; Kim, D.-W.; Kim, D. In Vitro Evaluation of Novel Inhibitors against the NS2B-NS3 Protease of Dengue Fever Virus Type 4. Molecules 2013, 18, 15600-15612.

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