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In Vitro Evaluation of Novel Inhibitors against the NS2B-NS3 Protease of Dengue Fever Virus Type 4
Department of Biotechnology and Bioengineering, Chonnam National University, 77 Yongbong-ro, Buk-gu, Gwangju 500-757, Korea
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
Research Center for Information Technology Innovation, Academia Sinica, 128, Sec.2, Academia Rd., Nankang, Taipei 11529, Taiwan
Genomics Research Center, Academia Sinica, 128, Sec.2, Academia Rd., Nankang, Taipei 11529, Taiwan
Department of Physics, Gangneung-Wonju National University, Gangneung 210-702, Korea
* Author to whom correspondence should be addressed.
Received: 28 October 2013; in revised form: 2 December 2013 / Accepted: 11 December 2013 / Published: 13 December 2013
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
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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.
Nguyen TTH, Lee S, Wang H-K, Chen H-Y, Wu Y-T, Lin SC, 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(12):15600-15612.
Nguyen, Thi T.H.; Lee, Sun; Wang, Hsi-Kai; Chen, Hsin-Yen; Wu, Ying-Ta; Lin, Simon C.; Kim, Do-Won; Kim, Doman. 2013. "In Vitro Evaluation of Novel Inhibitors against the NS2B-NS3 Protease of Dengue Fever Virus Type 4." Molecules 18, no. 12: 15600-15612.