S. Halstead, S. Nimmannitya, C. Yamarat, and P. Russell, Hemorrhagic fever in Thailand, 1967.

R. Zellweger, T. Prestwood, and S. Shresta, Enhanced Infection of Liver Sinusoidal Endothelial Cells in a Mouse Model of Antibody-Induced Severe Dengue Disease, Cell Host & Microbe, vol.7, issue.2, pp.128-139, 2010.
DOI : 10.1016/j.chom.2010.01.004

M. Beatty, A. Stone, D. Fitzsimons, J. Hanna, and S. Lam, Best Practices in Dengue Surveillance: A Report from the Asia-Pacific and Americas Dengue Prevention Boards, PLoS Neglected Tropical Diseases, vol.89, issue.3, p.21103381, 2010.
DOI : 10.1371/journal.pntd.0000890.t002

E. Schwartz, Seasonality, Annual Trends, and Characteristics of Dengue among Ill Returned Travelers, 1997???2006, Emerging Infectious Diseases, vol.14, issue.7, pp.1081-1088, 1997.
DOI : 10.3201/eid1407.071412

C. Caminade, J. Medlock, E. Ducheyne, K. Mcintyre, and S. Leach, Suitability of European climate for the Asian tiger mosquito Aedes albopictus: recent trends and future scenarios, Journal of The Royal Society Interface, vol.22, issue.1, pp.2708-2725, 2012.
DOI : 10.2987/8756-971X(2006)22[149:CAAOOF]2.0.CO;2

D. Gubler, Dengue, Urbanization and Globalization: The Unholy Trinity of the 21st Century, Tropical Medicine and Health, vol.14, issue.1, pp.3-11, 2011.
DOI : 10.1038/nrmicro1690

L. Ruche, G. Souarès, Y. Armengaud, A. Peloux-petiot, F. Delaunay et al., First two autochthonous dengue virus infections in metropolitan France Euro surveillance : bulletin européen sur les maladies transmissibles = European communicable disease bulletin 15, p.20929659, 2010.

C. Franco, N. Hynes, N. Bouri, and D. Henderson, The Dengue Threat to the United States, Biosecurity and Bioterrorism: Biodefense Strategy, Practice, and Science, vol.8, issue.3, pp.273-276, 2010.
DOI : 10.1089/bsp.2010.0032

S. Whitehead, J. Blaney, A. Durbin, and B. Murphy, Prospects for a dengue virus vaccine, Nature Reviews Microbiology, vol.193, issue.7, 2007.
DOI : 10.1038/nrmicro1690

E. Konishi, Issues Related to Recent Dengue Vaccine Development, Tropical Medicine and Health, vol.73, issue.1, pp.63-71, 2011.
DOI : 10.1182/blood-2009-09-242990

H. Steuber and R. Hilgenfeld, Recent Advances in Targeting Viral Proteases for the Discovery of Novel Antivirals, Current Topics in Medicinal Chemistry, vol.10, issue.3, pp.323-345, 2010.
DOI : 10.2174/156802610790725470

I. Umareddy, O. Pluquet, Q. Wang, S. Vasudevan, and E. Chevet, Dengue virus serotype infection specifies the activation of the unfolded protein response, Virology Journal, vol.4, issue.1, pp.10-1186, 2007.
DOI : 10.1186/1743-422X-4-91

B. Falgout, R. Miller, and C. Lai, Deletion analysis of dengue virus type 4 nonstructural protein NS2B: identification of a domain required for NS2B-NS3 protease activity, J Virol, vol.67, pp.2034-2042, 1993.

S. Clum, K. Ebner, and R. Padmanabhan, Cotranslational Membrane Insertion of the Serine Proteinase Precursor NS2B-NS3(Pro) of Dengue Virus Type 2 Is Required for Efficient in Vitro Processing and Is Mediated through the Hydrophobic Regions of NS2B, Journal of Biological Chemistry, vol.272, issue.49, pp.30715-30723, 1997.
DOI : 10.1074/jbc.272.49.30715

S. Natarajan, NS3 protease from flavivirus as a target for designing antiviral inhibitors against dengue virus, Genetics and Molecular Biology, vol.33, issue.2, pp.214-21910, 2010.
DOI : 10.1590/S1415-47572010000200002

J. Lescar, D. Luo, T. Xu, A. Sampath, and S. Lim, Towards the design of antiviral inhibitors against flaviviruses: The case for the multifunctional NS3 protein from Dengue virus as a target, Antiviral Research, vol.80, issue.2, pp.94-101, 2008.
DOI : 10.1016/j.antiviral.2008.07.001

C. Nitsche, M. Behnam, M. Steuer, C. Klein, and C. , Retro peptide-hybrids as selective inhibitors of the Dengue virus NS2B-NS3 protease, Antiviral Research, vol.94, issue.1, pp.72-79, 2012.
DOI : 10.1016/j.antiviral.2012.02.008

K. Tiew, D. Dou, T. Teramoto, H. Lai, and K. Alliston, Inhibition of Dengue virus and West Nile virus proteases by click chemistryderived benz[d]isothiazol-3(2H)-one derivatives, Bioorg Med Chem, vol.20, p.22249124, 2012.

S. Tomlinson and S. Watowich, Use of parallel validation high-throughput screens to reduce false positives and identify novel dengue NS2B-NS3 protease inhibitors, Antiviral Research, vol.93, issue.2, pp.245-252, 2012.
DOI : 10.1016/j.antiviral.2011.12.003

C. Nitsche, C. Steuer, and C. Klein, Arylcyanoacrylamides as inhibitors of the Dengue and West Nile virus proteases, Bioorganic & Medicinal Chemistry, vol.19, issue.24, pp.7318-7337, 2011.
DOI : 10.1016/j.bmc.2011.10.061

A. Schüller, Z. Yin, B. Chia, C. Doan, D. Kim et al., Tripeptide inhibitors of dengue and West Nile virus NS2B???NS3 protease, Antiviral Research, vol.92, issue.1, pp.96-101, 2011.
DOI : 10.1016/j.antiviral.2011.07.002

L. Cregar-hernandez, G. Jiao, A. Johnson, A. Lehrer, and T. Wong, Small molecule pan-dengue and West Nile virus NS3 protease inhibitors, Antiviral Chemistry and Chemotherapy, vol.21, issue.5, pp.209-217, 2011.
DOI : 10.3851/IMP1767

URL : http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3095516

N. Frimayanti, C. Chee, S. Zain, and N. Rahman, Design of New Competitive Dengue Ns2b/Ns3 Protease Inhibitors???A Computational Approach, International Journal of Molecular Sciences, vol.12, issue.12, p.21541045, 2011.
DOI : 10.3390/ijms12021089

T. Knehans, A. Schüller, D. Doan, K. Nacro, and J. Hill, Structure-guided fragment-based in silico drug design of dengue protease inhibitors, Journal of Computer-Aided Molecular Design, vol.9, issue.3, pp.263-274, 2011.
DOI : 10.1007/s10822-011-9418-0

N. Frimayanti, S. Zain, V. Lee, W. Ha, and R. Yusof, Fragment-based molecular design of new competitive dengue Den2 Ns2b/Ns3 inhibitors from the components of fingerroot (Boesenbergia rotunda), In Silico Biol, vol.11, pp.29-37, 2012.

S. Tomlinson, R. Malmstrom, and S. Watowich, New Approaches to Structure-Based Discovery of Dengue Protease Inhibitors, Infectious Disorders - Drug Targets, vol.9, issue.3, pp.327-343, 2009.
DOI : 10.2174/1871526510909030327

S. Sa, A. Cheltsov, K. Gawlik, B. Ratnikov, and A. Strongin, Virtual ligand screening of the National Cancer Institute (NCI) compound library leads to the allosteric inhibitory scaffolds of the West Nile Virus NS3 proteinase, Assay Drug Dev Technol, vol.9, pp.69-78, 2011.

V. Frecer and S. Miertus, Design, structure-based focusing and in silico screening of combinatorial library of peptidomimetic inhibitors of Dengue virus NS2B-NS3 protease, Journal of Computer-Aided Molecular Design, vol.54, issue.12 suppl, pp.195-212, 2010.
DOI : 10.1007/s10822-010-9326-8

D. Ekonomiuk, X. Su, K. Ozawa, C. Bodenreider, and S. Lim, Discovery of a Non-Peptidic Inhibitor of West Nile Virus NS3 Protease by High-Throughput Docking, PLoS Neglected Tropical Diseases, vol.8, issue.1, 2009.
DOI : 10.1371/journal.pntd.0000356.s006

D. Ekonomiuk, X. Su, K. Ozawa, C. Bodenreider, and S. Lim, Flaviviral Protease Inhibitors Identified by Fragment-Based Library Docking into a Structure Generated by Molecular Dynamics, Journal of Medicinal Chemistry, vol.52, issue.15, pp.4860-4868, 2009.
DOI : 10.1021/jm900448m

F. Spyrakis, A. Bidonchanal, X. Barril, and F. Luque, Protein Flexibility and Ligand Recognition: Challenges for Molecular Modeling, Current Topics in Medicinal Chemistry, vol.11, issue.2, 2011.
DOI : 10.2174/156802611794863571

P. Erbel, N. Schiering, D. Arcy, A. Renatus, M. Kroemer et al., Structural basis for the activation of flaviviral NS3 proteases from dengue and West Nile virus, Nature Structural & Molecular Biology, vol.280, issue.4, pp.372-373, 1073.
DOI : 10.1016/S0092-8674(00)81351-3

D. Luo, T. Xu, C. Hunke, G. Grüber, and S. Vasudevan, Crystal Structure of the NS3 Protease-Helicase from Dengue Virus, Journal of Virology, vol.82, issue.1, pp.173-183, 2008.
DOI : 10.1128/JVI.01788-07

S. Chandramouli, J. Joseph, S. Daudenarde, J. Gatchalian, and C. Cornillez-ty, Serotype-Specific Structural Differences in the Protease-Cofactor Complexes of the Dengue Virus Family, Journal of Virology, vol.84, issue.6, pp.3059-3067, 2010.
DOI : 10.1128/JVI.02044-09

C. Noble, C. Seh, A. Chao, and P. Shi, Ligand-Bound Structures of the Dengue Virus Protease Reveal the Active Conformation, Journal of Virology, vol.86, issue.1, pp.438-446, 2012.
DOI : 10.1128/JVI.06225-11

S. Huang and X. Zou, Ensemble docking of multiple protein structures: Considering protein structural variations in molecular docking, Proteins: Structure, Function, and Bioinformatics, vol.48, issue.2, pp.399-421, 2007.
DOI : 10.1002/prot.21214

O. Korb, T. Olsson, S. Bowden, R. Hall, and M. Verdonk, Potential and Limitations of Ensemble Docking, Journal of Chemical Information and Modeling, vol.52, issue.5, pp.1262-1274, 2012.
DOI : 10.1021/ci2005934

W. Sinko, S. Lindert, and J. Mccammon, Accounting for Receptor Flexibility and Enhanced Sampling Methods in Computer-Aided Drug Design, Chemical Biology & Drug Design, vol.6, issue.(29), pp.41-49, 2013.
DOI : 10.1111/cbdd.12051

R. Amaro and W. Li, Emerging Methods for Ensemble-Based Virtual Screening, Current Topics in Medicinal Chemistry, vol.10, issue.1, 2010.
DOI : 10.2174/156802610790232279

D. Osguthorpe, W. Sherman, and A. Hagler, Exploring Protein Flexibility: Incorporating Structural Ensembles From Crystal Structures and Simulation into Virtual Screening Protocols, The Journal of Physical Chemistry B, vol.116, issue.23, pp.6952-6959, 2012.
DOI : 10.1021/jp3003992

N. Eswar, B. Webb, M. Marti-renom, M. Madhusudhan, and D. Eramian, Comparative protein structure modeling using Modeller. Current protocols in bioinformatics, Chapter, 2006.

R. Laskowski, M. Macarthur, D. Moss, and J. Thornton, PROCHECK: a program to check the stereochemical quality of protein structures, Journal of Applied Crystallography, vol.26, issue.2, pp.283-291, 1993.
DOI : 10.1107/S0021889892009944

W. Humphrey, VMD: Visual molecular dynamics, Journal of Molecular Graphics, vol.14, issue.1, pp.33-38, 1996.
DOI : 10.1016/0263-7855(96)00018-5

B. Brooks, C. Brooks, A. Mackerell, L. Nilsson, and R. Petrella, CHARMM: The biomolecular simulation program, Journal of Computational Chemistry, vol.103, issue.13, pp.1545-1614, 2009.
DOI : 10.1002/jcc.21287

J. Phillips, R. Braun, W. Wang, J. Gumbart, and E. Tajkhorshid, Scalable molecular dynamics with NAMD, Journal of Computational Chemistry, vol.84, issue.16, pp.1781-1802, 2005.
DOI : 10.1002/jcc.20289

URL : http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2486339

T. Darden, D. York, and L. Pedersen, ) method for Ewald sums in large systems, The Journal of Chemical Physics, vol.98, issue.12, 1993.
DOI : 10.1063/1.464397

J. Ryckaert, G. Ciccotti, and H. Berendsen, Numerical integration of the cartesian equations of motion of a system with constraints: molecular dynamics of n-alkanes, Journal of Computational Physics, vol.23, issue.3, pp.327-341, 1977.
DOI : 10.1016/0021-9991(77)90098-5

Z. Zhang, Y. Li, B. Lin, M. Schroeder, and B. Huang, Identification of cavities on protein surface using multiple computational approaches for drug binding site prediction, Bioinformatics, vol.27, issue.15, pp.2083-2088, 2011.
DOI : 10.1093/bioinformatics/btr331

P. Schmidtke, A. Bidon-chanal, F. Luque, and X. Barril, MDpocket: open-source cavity detection and characterization on molecular dynamics trajectories, Bioinformatics, vol.27, issue.23, pp.3276-3285, 2011.
DOI : 10.1093/bioinformatics/btr550

R. Assenberg, E. Mastrangelo, T. Walter, A. Verma, and M. Milani, Crystal Structure of a Novel Conformational State of the Flavivirus NS3 Protein: Implications for Polyprotein Processing and Viral Replication, Journal of Virology, vol.83, issue.24, pp.12895-12906, 2009.
DOI : 10.1128/JVI.00942-09

D. Luo, N. Wei, D. Doan, P. Paradkar, and Y. Chong, Flexibility between the protease and helicase domains of the dengue virus NS3 protein conferred by the linker region and its functional implications, Journal of Biological Chemistry, vol.285, issue.24, pp.18817-18827, 2010.
DOI : 10.1074/jbc.M109.090936

W. Salaemae, M. Junaid, C. Angsuthanasombat, and G. Katzenmeier, Structure-guided mutagenesis of active site residues in the dengue virus two-component protease NS2B-NS3, J Biomed Sci, vol.17, pp.68-78, 2010.

D. Miller and D. Agard, Enzyme specificity under dynamic control: A normal mode analysis of ??-lytic protease, Journal of Molecular Biology, vol.286, issue.1, pp.267-278, 1999.
DOI : 10.1006/jmbi.1998.2445

A. Schmidt and V. Lamzin, Extraction of functional motion in trypsin crystal structures, Acta Crystallographica Section D Biological Crystallography, vol.61, issue.8, pp.1132-1139, 2005.
DOI : 10.1107/S0907444905016732

J. Martin, F. Mulder, Y. Karimi-nejad, J. Van-der-zwan, and M. Mariani, The solution structure of serine protease PB92 from Bacillus alcalophilus presents a rigid fold with a flexible substrate-binding site, Structure, vol.5, issue.4, pp.521-532, 1997.
DOI : 10.1016/S0969-2126(97)00208-6

S. Liu, Z. Meng, Y. Fu, and K. Zhang, Insights derived from molecular dynamics simulation into the molecular motions of serine protease proteinase K, Journal of Molecular Modeling, vol.265, issue.1, pp.17-28, 2009.
DOI : 10.1007/s00894-009-0518-x

S. Tomlinson and S. Watowich, Anthracene-based inhibitors of dengue virus NS2B???NS3 protease???, Antiviral Research, vol.89, issue.2, pp.127-135, 2011.
DOI : 10.1016/j.antiviral.2010.12.006

URL : http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3026091

V. Ganesh, N. Muller, K. Judge, C. Luan, and R. Padmanabhan, Identification and characterization of nonsubstrate based inhibitors of the essential dengue and West Nile virus proteases, Bioorganic & Medicinal Chemistry, vol.13, issue.1, pp.257-264, 2005.
DOI : 10.1016/j.bmc.2004.09.036

S. Chanprapaph, P. Saparpakorn, C. Sangma, P. Niyomrattanakit, and S. Hannongbua, Competitive inhibition of the dengue virus NS3 serine protease by synthetic peptides representing polyprotein cleavage sites, Biochemical and Biophysical Research Communications, vol.330, issue.4, pp.1237-1246, 2005.
DOI : 10.1016/j.bbrc.2005.03.107

R. Brinkworth, D. Fairlie, D. Leung, and P. Young, Homology model of the dengue 2 virus NS3 protease: putative interactions with both substrate and NS2B cofactor., Journal of General Virology, vol.80, issue.5, pp.1167-1177, 1999.
DOI : 10.1099/0022-1317-80-5-1167

Y. Yan, Y. Li, S. Munshi, V. Sardana, and J. Cole, Complex of NS3 protease and NS4A peptide of BK strain hepatitis C virus: A 2.2 ?? resolution structure in a hexagonal crystal form, Protein Science, vol.4, issue.4, pp.837-847, 1998.
DOI : 10.1002/pro.5560070402

A. Aleshin, S. Shiryaev, A. Strongin, and R. Liddington, fold, Protein Science, vol.7, issue.5, pp.795-806, 2007.
DOI : 10.1110/ps.072753207

Y. Lee, S. Tan, H. Wahab, R. Yusof, and N. Rahman, Nonsubstrate Based Inhibitors of Dengue Virus Serine Protease: A Molecular Docking Approach to Study Binding Interactions between Protease and Inhibitors, Asia Pac J Mol Biol Biotechnol, vol.15, pp.53-59, 2007.

P. Niyomrattanakit, P. Winoyanuwattikun, S. Chanprapaph, C. Angsuthanasombat, and S. Panyim, Identification of Residues in the Dengue Virus Type 2 NS2B Cofactor That Are Critical for NS3 Protease Activation, Journal of Virology, vol.78, issue.24, pp.13708-13716, 2004.
DOI : 10.1128/JVI.78.24.13708-13716.2004

L. Rosales-león, G. Ortega-lule, and B. Ruiz-ordaz, Analysis of the domain interactions between the protease and helicase of NS3 in dengue and hepatitis C virus, Journal of Molecular Graphics and Modelling, vol.25, issue.5, pp.585-594, 2007.
DOI : 10.1016/j.jmgm.2006.04.001

K. Wichapong, S. Pianwanit, W. Sippl, and S. Kokpol, Homology modeling and molecular dynamics simulations of Dengue virus NS2B/NS3 protease: insight into molecular interaction, Journal of Molecular Recognition, vol.83, issue.2, 2010.
DOI : 10.1002/jmr.977

J. Eargle, D. Wright, and Z. Luthey-schulten, Multiple Alignment of protein structures and sequences for VMD, Bioinformatics, vol.22, issue.4, pp.504-506, 2006.
DOI : 10.1093/bioinformatics/bti825

G. Robin, K. Chappell, M. Stoermer, S. Hu, and P. Young, Structure of West Nile Virus NS3 Protease: Ligand Stabilization of the Catalytic Conformation, Journal of Molecular Biology, vol.385, issue.5, pp.1568-1577, 2009.
DOI : 10.1016/j.jmb.2008.11.026