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

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

1
Department of Biotechnology and Bioengineering, Chonnam National University, 77 Yongbong-ro, Buk-gu, Gwangju 500-757, Korea
2
Research Institute of Bio Food Industry, The Green Bio Research Complex, Seoul National University, San 967-2 Shin-ri, Pyeongchang-gun, Gangwon-do 232-916, Korea
3
Research Center for Information Technology Innovation, Academia Sinica, 128, Sec.2, Academia Rd., Nankang, Taipei 11529, Taiwan
4
Genomics Research Center, Academia Sinica, 128, Sec.2, Academia Rd., Nankang, Taipei 11529, Taiwan
5
Department of Physics, Gangneung-Wonju National University, Gangneung 210-702, Korea
*
Author to whom correspondence should be addressed.
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)
View Full-Text   |   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. View Full-Text
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 (CC BY 3.0).

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MDPI and ACS Style

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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