Next Article in Journal
Total Synthesis of Six 3,4-Unsubstituted Coumarins
Next Article in Special Issue
Theoretical Study on the Allosteric Regulation of an Oligomeric Protease from Pyrococcus horikoshii by Cl Ion
Previous Article in Journal
Antimicrobial and Antioxidant Activities and Effect of 1-Hexadecene Addition on Palmarumycin C2 and C3 Yields in Liquid Culture of Endophytic Fungus Berkleasmium sp. Dzf12
Previous Article in Special Issue
The Effect of Conformational Variability of Phosphotriesterase upon N-acyl-L-homoserine Lactone and Paraoxon Binding: Insights from Molecular Dynamics Studies
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

1,2
, 1
, 3
, 3
, 4
, 3
, 5
 and 1,2,*
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)
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.

Share & Cite This Article

Export to BibTeX |
EndNote


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.

View more citation formats

Supplement

Related Articles

Article Metrics

Comments

Citing Articles

[Return to top]
Molecules EISSN 1420-3049 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert