Current approaches in antiviral drug discovery against the Flaviviridae family

Current Pharmaceutical Design

Volumn 20, Issue 21, 2014, Pages 3428-3444

  Baharuddin, Aida ^a   Hassan, Asfarina Amir ^a   Sheng, Gan Chye ^a   Nasir, Shah Bakhtiar ^a   Othman, Shatrah ^a   Yusof, Rohana ^a   Othman, Rozana ^a   Rahman, Noorsaadah Abdul ^a  

^a UNIVERSITY OF MALAYA   (Malaysia)

Author keywords

Antiviral; Dengue virus (DENV); Drug discovery; Hepatitis C virus (HCV); Japanese encephalitis virus (JEV); West Nile virus (WNV); Yellow Fever virus (YFV)

Indexed keywords

1 (4,5 DIHYDROXY 3 HYDROXYMETHYL 2 CYCLOPENTEN 1 YL)CYTOSINE; 2 THIO AZAURIDINE; ANTIVIRUS AGENT; BENZIMIDAZOLE; BI 12202; BOCEPREVIR; CLAUDIN 1; DANOPREVIR; JAPANESE ENCEPHALITIS VACCINE; MYCOPHENOLIC ACID; NONSTRUCTURAL PROTEIN 2; NONSTRUCTURAL PROTEIN 3; NONSTRUCTURAL PROTEIN 4A; PIRAZOFURIN; RIBAVIRIN (BETA RIBOFURANOSYL 1H 1,2,4 TRIAZOLE 3 CARBOXAMIDE); SIMEPREVIR; TELAPREVIR; UNCLASSIFIED DRUG; VANIPREVIR; VIRUS PROTEIN;

ANTIVIRAL ACTIVITY; DENGUE VIRUS; DENGUE VIRUS 1; DRUG DESIGN; FLAVIVIRUS; HEPATITIS C VIRUS; JAPANESE ENCEPHALITIS VIRUS; NONHUMAN; PRIORITY JOURNAL; PROTEIN STRUCTURE; REVIEW; WEST NILE FLAVIVIRUS; YELLOW FEVER FLAVIVIRUS; ANTAGONISTS AND INHIBITORS; DRUG DEVELOPMENT; DRUG EFFECTS; ENZYMOLOGY; FLAVIVIRIDAE; FLAVIVIRIDAE INFECTIONS; HUMAN; MOLECULARLY TARGETED THERAPY; PROCEDURES;

ANTIVIRAL AGENTS; DRUG DESIGN; DRUG DISCOVERY; FLAVIVIRIDAE; FLAVIVIRIDAE INFECTIONS; HUMANS; MOLECULAR TARGETED THERAPY; VIRAL PROTEINS;

EID: 84903695254     PISSN: 13816128     EISSN: 18734286     Source Type: Journal    
DOI: 10.2174/13816128113199990635     Document Type: Review

References (191)

1. Burke DS. Monath TP. Flaviviruses. In Fields Virology, 4th ed, Edited by Knipe DM. Howley PM. Philadelphia, PA: Lippincott Williams & Wilkins 2001.
2. Pugachev KV, Guirakhoo F, Trent DW, Monath TP. Traditional and novelapproaches to flavivirus vaccines. Int J Parasitol 2003; 33: 567-82.
3. Mackenzie JS, Gubler DJ, Petersen LR. Emerging flaviviruses: the spread and resurgence of Japanese encephalitis, West Nile and dengue viruses. Nat Med 2004; 10: S98-S109.
4. Leyssen P, De Clercq E, Neyts J. Molecular strategies to inhibit the replication of RNA viruses. Antiviral Res 2008; 78: 9-25.
5. Hombach J, Barrett ADT, Cardosa MJ, et al. Review on flavivirus vaccine development. Proceedings of a meeting jointly organized by the World Health Organization and the Thai Ministry of Public Health, 26-27 April 2004, Bangkok, Thailand. Vaccine 2005; 23: 2689-95.
6. Guzman MG, Kouri G. Dengue: an update. Lancet Infect Dis 2002; 2: 33-42.
7. Harris E, Holden KL, Edgil D, et al. Molecular Biology of flaviviruses. New Treatment Strategies for Dengue and Other Flaviviral Diseases: Novartis Foundation Symposium 277. John Wiley & Sons 2006.
8. Mukhopadhyay S, Kuhn RJ, Rossmann MG. A structural perspective of the flavivirus life cycle. Nat Rev Microbiol 2006; 3: 13-22.
9. Leung JY, Pijlman GP, Kondratieva N, et al. Role of nonstructural protein NS2A in flavivirus assembly. J Virol 2008; 82: 4731-41.
10. Rice CM, Lenches EM, Reddy SR, et al. Rice Nucleotide sequence of yellow fever virus: implications for flavivirus gene expression and evolution. Science 1985; 229: 726-33.
11. Perera R, Khaliq M, Kuhn RJ. Closing the door on flaviviruses: Entry as a target for antiviral drug design. Antiviral Res 2008; 80: 11-22.
12. Lescar J, Dahai L, Xu T, et al. Towards the design of antiviral inhibitors against flaviviruses: the case for the multifunctional NS3 protein from Dengue virus as a target. Antiviral Res 2008; 80: 94-101.
13. Dong H, Zhang B, Shi PY. Flavivirus methyltransferase: a novel antiviral target. Antiviral Res 2008; 80: 1-10.
14. Malet H, Massé N, Selisko B, et al. The flavivirus polymerase as a target for drug discovery. Antiviral Res 2008; 80: 23-35.
15. Thomas G. Furin at the cutting edge: from protein traffic to embryogenesis and disease Nat Rev Mol Cell Biol 2002; 10: 753-66.
16. Bridges S. Basic science priorities for therapeutics research. Res Initiat Treat Action 2003; 8: 25-27.
17. DeMarco SJ, Henze H, Lederer A, et al. Discovery of novel, highly potent and selective beta-hairpin mimetic CXCR4 inhibitors with excellent anti-HIV activity and pharmacokinetic profiles. Bioorg Med Chem 2006; 14: 8396-404.
18. Daelemens D, Lu R, De Clercq E, et al. Characterization of a replication-competent, integrase-defective human immunodeficiency virus (HIV)/simian virus 40 chimera as a powerful tool for the discovery and validation of HIV integrase inhibitors. J Virol 2007; 81: 4381-5.
19. Deas TS, Binduga-Gajewska I, Tilgner M, et al. Inhibition of flavivirus infections by antisense oligomers specifically suppressing viral translation and RNA replication. J Virol 2005; 79: 4599-609.
20. Ray D, Shi PY. Recent Advances in Flavivirus Antiviral Drug Discovery and Vaccine Development. Recent Patents on Anti-Infective. Drug Discov 2006; 1: 45-55.
21. Deng J, Li N, Hongchuan L, et al. Discovery of novel small molecule inhibitors of dengue viral NS2B-NS3 protease using virtual screening and scaffold hopping. J of Med Chem 2012; 55: 6278-93.
22. Schuller A, Yin Z, Brian Chia CS, et al. Tripeptide inhibitors of dengue and West Nile virus NS2B-NS3 protease. Antiviral Res 2011; 92: 96-101.
23. Noble CG, Seh CC, Chao AT, et al. Ligand-Bound Structures of the Dengue Virus Protease Reveal the Active Conformation. J of Virology 2012; 86: 438-46.
24. Nitsche C, Behnam MAM, Steuer C, et al. Retro peptidehybrids as selective inhibitors of the dengue virus NS2B-NS3 protease, Antiviral Res 2012; 94: 72-79.
25. Cregar-Hernandez L, Jiao GS, Johnson AT, et al. Small molecule pan-Dengue and West Nile Virus NS3 protease inhibitors. Antivir Chem Chemother 2011; 21: 209-18.
26. Knehans T, Schuller A, Doan DN, et al. Structure guided fragmentbased in silico drug design of dengue protease inhibitors. J Comput Aided Mol Des 2011; 25: 263-74.
27. Frimayanti N, Zain SM, Lee VS, et al. Fragment-based molecular design of new competitive dengue Den2 Ns2b/Ns3 inhibits from the components of fingerroot (Boesenbergia rotunda). In Silico Biol 2011-2012; 11: 29-37.
28. Tan SK, Pippen R, Yusof R, et al. Inhibitory activity of cylohexenyl chalcone derivatives and favanoids of fingerroot, Boesenbergia rotunda (l), towards dengue-2 virus ns3 protease. Bioorg Med Chem Lett 2006; 16: 3337-40.
29. Kubinyi H. 3d qsar in drug design: Theory, method and applications. Springer: 1993; Vol. 1.
30. Modis Y, Ogata S, Clements D, et al. A ligand-binding pocket in the dengue virus envelope glycoprotein. Proc Natl Acad Sci USA 2003; 12: 6986-91.
31. Poh MK, Yip A, Zhang S, et al. A small molecule fusion inhibitor of dengue virus. Antiviral Res 2009; 84: 260-6.
32. Wang QY, Patel SJ, Vangrevelinghe E, et al. A small-molecule dengue virus entry inhibibitor. Antimicrob Agents Chemother 2009; 5: 1823-31.
33. Yennamalli R, Subbarao N, Kampmann T, et al. Identification of novel target sites and an inhibitor of the dengue virus E protein. J Comput Aided Mol Des 2009; 23: 333-41.
34. Kampmann T, Yennamalli R, Campbell P, et al. In silico screening of small molecule libraries using the dengue virus envelope E protein has identified compounds with antiviral activity against multiple flaviviruses. Antiviral Res 2009; 84: 234-41.
35. Zhang W, Chipman PR, Corver J, et al. Visualization of membrane protein domains by cryo-electron microscopy of dengue virus. Nat Struct Biol 2003; 10: 907-12.
36. Allison SL, Stiasny K, Stadler K, et al. Mapping of functional elements in the stem-anchor region of tick-borne encephalitis virus envelope protein. Eur J Virol 1999; 73: 5605-12.
37. Schmidt AG, Yang PL, Harrison SC, et al. Peptide inhibitors of dengue-virus entry target a late-stage fusion intermediate. PLoS Pathog 2010; 6: e1000851. Available at doi: 10.1371/journal.ppat.1000851.
38. Schmidt AG, Yang PL, Harrison SC, et al. Peptide inhibitors of flavivirus entry derived from the E protein stem. J Virol 2010; 84: 12549-54.
39. Costin JM, Jenwitheesuk E, Lok SM, et al. Structural optimization and de novo design of dengue virus entry inhibitory peptides. PLoS Negl Trop Dis 2010; 4: e721. Available at doi: 10.1371/journal.pntd.0000721.
40. Nicholson CO, Costin JM, Rowe DK, et al. Viral entry inhibitors block dengue antibody-dependent enhancement in vitro. Antiviral Res 2011; 89: 71-4.
41. Hayes EB, Komar N, Nasci RS, et al. Epideniology and transmission dynamics of West Nile Virus Diseases. Emerg. Infect. Dis Aug 2005; 11(8): 1167-73
42. Jordan I, Briese T, Fischer N, Lau JYN, Lipkin WI. Ribavirin inhibits West Nile virus replication and cytopathic effect in neural cells. J Infect Dis 2000; 182: 1214-7.
43. Anderson JF, Raha JJ. Efficacy of interferon α-2b and ribavirin against West Nile Virus in vitro. Emerg Infect Dis 2002; 8: 107-8.
44. Morrey JD, Smee DF, Sidwell RW, et al. Identification of active antiviral compounds against a New York isolate of West Nile virus. Antiviral Res 2002; 55: 107-16.
45. Leyssen P, Balzarini J, De Clercq E, et al. The predominant mechanism by which ribavirin exerts its antiviral activity in vitro against flaviviruses and paramyxoviruses is mediated by inhibition of IMP dehydrogenase. J of Virol 2005; 79: 1943-7.
46. Murray KO, Walker C, Gould E. The virology, epidemiology, and clinical impact of West Nile virus: a decade of advancements in research since its introduction into the Western Hemisphere. Epidemiol Infect 2011; 139: 810-7.
47. Leyssen P, Balzarini J, De Clercq E, et al. The predominant mechanism by which ribavirin exerts its antiviral activity in vitro against flaviviruses and paramyxoviruses is mediated by inhibition of IMP dehydrogenase. J Virol 2005; 79: 1943-7.
48. Sintchak MD, Fleming MA, Futer O, et al. Structure and mechanism of inosine monophosphate dehydrogenase in complex with the immunosuppressant mycophenolic acid. Cell 1996; 85: 921-30.
49. Diamond MS, Zachariah M, Harris E. Mycophenolic acid inhibits Dengue virus infection by preventing replication of viral RNA. Virology 2002; 304: 211-21.
50. Stamos DP, Inventor; Vertex Pharmaceutical, Inc., assignee. Prodrugs of carbamate inhibitors of IMPDH. United States patent US20046825224. 2004 Nov.
51. Sebastian L, Madhusudana SN, Ravi V, et al. Mycophenolic acid inhibits replication of Japanese encephalitis virus. Chemotherapy 2011; 57: 56-61.
52. Borowski P, Lang M, Haag A, et al. Characterization of imidazo[4,5-d] pyridazine nucleosides as modulators of unwinding reaction mediated by West Nile virus nucleoside triphosphatase/ helicase: evidence for activity on the level of substrate and/or enzyme. Antimicrob Agents Chemother 2002; 46: 1231-9.
53. Migliaccio G, Tomassini JE, Carroll SS, et al. Characterization of resistance to non-obligate chain-terminating ribonucleoside analogs that inhibit hepatitis C virus replication in vitro. J Biol Chem 2003; 278: 49164-70.
54. Chappell KJ, Stoermer MJ, Fairlie DP, et al. West Nile virus NS3 protease: insights into substrate binding and processing through combined modelling, protease mutagenesis and kinetic studies. J Biol Chem 2006; 281: 38448-58.
55. Stoermer MJ, Chappell KJ, Liebscher S, et al. Potent cationic inhibitors of West Nile virus NS2B/NS3 protease with serum stability, cell permeability and antiviral activity. J Med Chem 2008; 51: 5714-21.
56. Shüller A, Yin Z, Chia CSB, et al. Tripeptide inhibitors of dengue and West Nile virus NS2B-NS3 protease. Antiviral Res 2011; 92: 96-101.
57. Moulin A, Martinez J, Fehrentz JA. Synthesis of peptide aldehydes. J Pept Sci 2007; 13: 1-15.
58. Ekonomiuk D, Su XC, Ozawa K, et al. Discovery of a non-peptidic inhibitor of West Nile Virus NS3 Protease by high-throughput docking. PLoS Neglected Tropical Diseases 2009; 3: 1-9.
59. Aqvist J, Medina C, Samuelsson JE. A new method for predicting binding affinity in computer-aided drug design. Protein Eng 1994; 7: 385-91.
60. Brooks BR, Bruccoleri RE, Olafson BD, et al. CHARMM: a program for macromolecular energy, minimization, and dynamics calculations. J Comput Chem 1983; 4: 187-217.
61. Su XC, Ozawa K, Qi R, et al. NMR analysis of the Dynamic Exchange of the NS2B cofactor between open and closed conformations of the west nile virus NS2B-NS3 protease. PLoS Negl Trop Dis 2009; 3: e561. Available at doi: 10.1371/journal.pntd.0000561.
62. Jitendra S, Vinay R. Structure based drug designing of a novel antiflaviviral for nonstructural 3 protein. Bioinformation 2011; 6: 57-60.
63. Tambunan US, Alamudi S. Designing cyclic peptide inhibitor of dengue virus NS3-NS2B protease by using molecular docking approach. Bioinformation 2010; 5: 250-4.
64. Cregar-Hernandez L, Jiao GS, Johnson AT, et al. Small molecule pan-Dengue and West Nile Virus NS3 protease Inhibitors. Antivir Chem Chemother 2011; 21: 209-18.
65. Aravapalli S, Lai H, Teramoto T, et al. Inhibitors of Dengue virus and West Nile virus proteases based on the aminobenzamide scaffold. Bioorg Med Chem 2012; 21: 4140-8.
66. Steuer C, Gege C, Fischl W, et al. Synthesis and biological evaluation of a-ketoamides as inhibitors of the Dengue virus protease with antiviral activity in cell-culture. Bioorg Med Chem 2011; 19: 4067-74.
67. Nitsche C, Steuer C, Klein CD. Arylcyanoacrylamides as inhibitors of the Dengue and West Nile virus proteases. Bioorg Med Chem 2011; 19: 7318-37.
68. Glay SC, Vivian JG, Miguel MDA, et al. inventors; Centro de ingenieria genetica y biotecnologia (Ciudad de la habana, Cuba), assignee. Chimerical peptidic molecules with antiviral properties against the virus of the flaviviridae family. United States patent US 20100273702. 2009 Dec.
69. Knox JE, Ma NL, Yin Z, et al. Peptide inhibitors of West Nile NS3 protease: SAR study of tetrapeptide aldehyde inhibitors. J Med Chem 2006; 49: 6585-90.
70. Johnston PA, Phillips J, Shun TY, et al. HTS identifies novel and specific uncompetitive inhibitors of the two-component NS2B-NS3 proteinase of West Nile virus. Assay Drug Dev Technol 2007; 5: 737-50.
71. Sidique S, Shiryaev SA, Ratnikov BI, et al. Structure-activity relationship and improved hydrolytic stability of pyrazole derivatives that are allosteric inhibitors of West Nile virus NS2B-NS3 proteinase. Bioorg Med Chem Lett 2009; 19: 5773-7.
72. Shiryaev SA, Cheltsov AV, Gawlik K, et al. 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 2011; 9: 69-78.
73. Jorgensen WL, Rives JT. The OPLS [optimized potentials for liquid simulations] potential functions for proteins, energy minimizations for crystals of cyclic peptides and crambin. J Am Chem Soc 1988; 110: 1657-66.
74. Samanta S, Cui T, Lam Y. Discovery, synthesis, and in vitro evaluation of West Nile virus protease inhibitors based on the 9,10-dihydro-3H,4aH-1,3,9,10a-tetraazaphenanthren-4-one scaffold. Chem Med Chem 2012; 7: 1 210-6.
75. Jia F, Zou G, Fan J, Yuan Z. Identification of palmatine as an inhibitor of West Nile virus. Arch Virol 2010; 155: 1325-9.
76. Hrobowski YM, Garry RF, Michael SF. Peptide inhibitors of dengue virus and West Nile virus infectivity. Virol J 2005; 2: 1-10.
77. White SH, Snider C, Jaysinghe S, et al. Membrane ProteinExplorer version 2.2a. http: //blancobiomoluciedu/mpex/ 2003.
78. CDC. Japanese encephalitis among three U.S. Travelers Returning from Asia, 2003-2008. MMWR Morb Mortal Wkly Rep 2009; 58: 737-40.
79. Ghosh D, Basu A. Japanese Encephalitis-A Pathological and Clinical Perspective. PLoS Negl Trop Dis 2009; 3: e437. Available at doi: 10.1371/journal.pntd. 0000437.
80. Erlanger TE, Weiss S, Keiser J, et al. Past, present and future of Japanese encephalitis. Emerg Infect Dis 2012; 15: 1-7.
81. Beasley D, Lewthwaite P, Solomon T. Current use and development of vaccines for Japanese encephalitis. Exp Opinion Biological Therap 2006; 8: 95-106.
82. Solomon T. Recent advances in Japanese encephalitits. J Neuro Virol 2003; 9: 274-83.
83. Solomon T. New vaccines for Japanese encephalitis. Lancet Neurol 2008; 7: 116-8.
84. Solomon T, Ni H, Beasley DW, et al. Origin and evolution of Japanese encephalitis virus in southeast Asia. J Virol 2003; 77: 3091-8.
85. Food and Drug Administration. Product approval information [package insert]. JE-Vax (Japanese encephalitis virus vaccine inactivated). Research Foundation for Microbial Diseases of Osaka University, Osaka, Japan. Available at http: //www.fda.gov/BiologicsBloodVaccines/Vaccines/ApprovedProdu cts/ucm179149.htm.
86. Campbell GL, Hills SL, Fischer M, et al. Estimated global incidence of Japanese encephalitis: a systematic review. Bulletin of the World Health Organization BLT 2011; 10.085233: 1-22.
87. Solomon T. Control of Japanese encephalitis-within our grasp?N Engl J Med 2006; 355: 869-71.
88. World Health Organization. Global Advisory Committee on Vaccine Safety. Wkly Epidemiol Rec 2008; 83: 37-44.
89. Phong MY, Moreland NJ, Lim SP, et al. Dengue protease activity: the structural integrity and interaction of NS2B with NS3 protease and its potential as a drug target. Biosci Rep 2011; 31: art: BSR20100142. doi: 10.1042/BSR2010014
90. Bessaud M, Pastorino BAM, Peyrefitte CN, et al. Functional characterization of the NS2B/NS3 protease complex from seven viruses belonging to different groups inside the genus Flavivirus. Virus Research 2006; 120: 79-90.
91. Yamashita T, Unno H, Mori Y, et al. Crystal structure of the catalytic domain of Japanese encephalitis virus NS3 helicase/ nucleoside triphosphatase at a resolution of 1.8 A. Virology 2008; 373: 426-36.
92. Borowski P, Heising MV, Miranda IB, et al. Viral NS3 helicase activity is inhibited by peptides reproducing the Arg-rich conserved motif of the enzyme (motif VI). Biochme Pharmacol 2008; 76: 28-38
93. Kaczor A, Matosiuk D. Structure-based virtual screening for novel inhibitors of Japanese encephalitis virus NS3 helicase/nucleoside triphosphatase. FEMS Immunol Med Microbiol 2010; 58: 91-101.
94. Zhang N, Chen HM, Koch V et al. Ring-expanded ('fat') nucleoside and nucleotide analogues exhibit potent in vitro activity against flaviviridae NTPases/helicases, including those of the West Nile virus, hepatitis C virus, and Japanese encephalitis virus. J Med Chem 2003; 46: 4149-64.
95. Jain AN. Surflex: fully automatic flexible molecular docking using a molecular similarity-based search engine. J Med Chem 2003; 46: 499-511
96. Krieger E & Vriend G. Models@Home-distributed computing in bioinformatics using a screensaver based approach. Bioinformatics 2002; 18: 315-8.
97. Frick DN, Lam AM. Understanding helicases as a means of virus control. Curr Pharm Design 2006; 12: 1315-38.
98. Irwin JJ & Shoichet BK. ZINC-a free database of commercially available compounds for virtual screening. J Chem Inf Model 2005; 45: 177-82.
99. Feher M. Consensus scoring for protein-ligand interactions. Drug Discov Today 2006; 11: 421-8.
100. Wu KP, Wu CW, Tsao YP, et al. Structural basis of a flavivirus recognized by its neutralizing antibody: solution structure of the domain III of the Japanese encephalitis virus envelope protein. J Biol Chem 2003; 278: 46007-13.
101. Luca VC, Abimansour J, Nelson CA, et al. Crystal structure of the Japanese encephalitis virus envelope protein. J Virol 2012; 86: 2337-46.
102. Li C, Li-ying Zhang LY, Sun MX, et al. Inhibition of Japanese encephalitis virus entry into the cells by the envelope glycoprotein domain III (EDIII) and the loop3 peptide derived from EDIII. Antiviral Res 2012; 94: 179-83.
103. Chu J, Rajamanonmani R, Li J, et al. Inhibition of West Nile virus entry by using a recombinant domain III from the envelope glycoprotein. J Gen Virol 2005; 86: 405-12.
104. Bai F, Town T, Pradhan D, et al. Antiviral peptides targeting the West Nile Virus envelope protein. J Virol 2007; 81: 2047-55.
105. Zhang S, Bovshik EI, Maillard R, et al. Role of BC loop residues in structure, function and antigenicity of the West Nile virus envelope protein receptor-binding domain III. Virology 2010; 403: 85-91.
106. Hung JJ, Hsieh MT, Young MJ, et al. An external loop region of domain III of dengue virus type 2 envelope protein is involved in serotype-specific binding to mosquito but not mammalian cells. J Virol 2004; 78: 378-88.
107. Schmidt AG, Yang PL, Harrison SC. Peptide inhibitors of flavivirus entry derived from the E protein stem. J Virol 2010; 84: 12549-54.
108. Smit JM, Moesker B, Rodenhuis-Zybert I, et al. Flavivirus Cell Entry and Membrane Fusion. Viruses 2011; 3: 160-71.
109. Carter HR. Yellow Fever: An Epidemiological and Historical Study of Its Place of Origin. Baltimore, Maryland: Williams & Wilkins 1931.
110. Monath TP. Yellow fever: Victor, Victoria? conqueror, conquest? Epidemics and research in the last forty years and prospects for the future. Am J Trop Med Hyg 1991; 45: 1-43.
111. Barrett AD, Higgs S. Yellow fever: a disease that has yet to be conquered. Annu Rev Entomol 2007; 52: 209-29.
112. Gubler DJ. The changing epidemiology of yellow fever and dengue, 1900 to 2003: full circle? Comp Immunol Microbiol Infect Dis 2004; 27: 319-30.
113. Khasnatinov MA, Ustanikova K, Frolova TV, et al. Non-Hemagglutinating Flaviviruses: Molecular Mechanisms for the Emergence of New Strains via Adaptation to European Ticks. PLoS ONE 2009; 4: e7295. Available at doi: 10.1371/journal.pone.0007295.
114. Volk DE, Gandham SH, May FJ, et al. Yellow fever envelope protein domain III NMR structure (S288-K398). Virology 2009; 394: 12-8.
115. Thompson AA, Geiss BJ, Peersen OB, et al. Analysis of flavivirus NS5 methyltransferase cap binding. J Mol Biol 2009; 385: 1643-754.
116. Wu J, Bera AK, Kuhn RJ, et al. Structure of the flavivirus helicase: implications for catalytic activity, protein interactions, and proteolytic processing. J Virol 2005; 79: 10268-77.
117. Chambers TJ, Hahn CS, Galler R, et al. Flavivirus genome organization, expression, and replication. Annu Rev Microbiol 1990; 44: 649-88.
118. Falgout B, Pethel M, Zhang YM et al. Both nonstructural proteins NS2B and NS3 are required for the proteolytic processing of dengue virus nonstructural proteins. J Virol 1991; 65: 2467-75.
119. Löhr K, Knox JE, Phong WY, et al. Yellow fever virus NS3 protease: peptide-inhibition studies. J of Gen Virol 2007; 88: 2223-7.
120. Yin Z, Patel SJ, Wang WL, et al. Peptide inhibitors of dengue virus NS3 protease. 1. Warhead. Bioorg Med Chem Lett 2006; 16: 36-9.
121. Yin Z, Patel SJ, Wang WL, et al. Peptide inhibitors of dengue virus NS3 protease. 2. SAR study of tetrapeptide aldehyde inhibitors. Bioorg Med Chem Lett 2006; 16: 40-3.
122. Chambers TJ, Grakoui A, Rice CM. Processing of the yellow fever virus nonstructural polyprotein: a catalytically active NS3 proteinase domain and NS2B are required for cleavages at dibasic sites. J Virol 1991; 65: 6042-50.
123. Copeland RA. Enzymes: a Practical Introduction to Structure, Mechanism and Data Analysis, 2nd ed. New York: Wiley 2000.
124. Yusof R, Clum S, Wetzel M, et al. Purified NS2B/NS3 serine protease of dengue virus type 2 exhibits cofactor NS2B dependence for cleavage of substrates with dibasic amino acids in vitro. J Biol Chem 2000; 275: 9963-9.
125. Bessaud M, Pastorino BAM, Peyrefitte CN, et al. Functional characterization of the N2B/NS3 protease complex from seven viruses belonging to different groups inside the genus Flavivirus. Virus Res 2006; 120: 79-90.
126. Erbel P, Shiering N, D'Arcy A, et al. Structural basis for the activation of flaviviral NS3 proteases from dengue and West Nile virus. Nat Struct Mol Biol 2006; 13: 372-273.
127. Mastrangelo E, Pezzullo M, Burghgrave TD, et al. Ivermectin is a potent inhibitor of flavivirus replication specifically targeting NS3 helicase activity: new prospects for an old drug. J Antimicrob Chemother 2012; 67: 1884-94.
128. Luo D, Xu T, Watson RP, et al. Insights into RNA unwinding and ATP hydrolysis by the flavivirus NS3 protein. EMBO J 2008; 27: 3209-19.
129. Mastrangelo E, Milani M, Bollati M, et al. Crystal structure and activity of Kunjin virus NS3 helicase; protease and helicase domain assembly in the full length NS3 protein. J Mol Biol 2007; 372: 444-55.
130. Velankar SS, Soultanas P, Dillingham MS, et al. Crystal structures of complexes of PcrA DNA helicase with a DNA substrate indicate an inchworm mechanism. Cell 1999; 97: 75-84.
131. Luo DH, Xu T, Watson RP, et al. Dengue virus 4 NS3 helicase in complex with ssRNA. EMBO J 2008; 27: 10278-88.
132. Wu J, Bera AK, Kuhn RJ, et al. Structure of the flavivirus helicase: implications for catalytic activity, protein interactions, and proteolytic processing. J Virol 2005; 79: 10268-77.
133. Boguszewska-Chachulska AM, Krawczyk M, Stankiewicz A, et al. Direct fluorometric measurement of hepatitis C virus helicase activity. FEBS Lett 2004; 567: 253-8.
134. Mukhopadhyay S, Kuhn RJ, Rossmann MG. A structural perspective of the flavivirus life cycle. Nat Rev Microbiol 2005; 3: 13-22
135. Milani De Mayo De Mari et al. inventor; Consiglio Nazionale Delle Richerche, Katholieke Universiteit Leuven-K.U. Leuven R&D, Aix-Marseille Universite, assignee. Avermectins and Milbemycins for the treatment prevention or amelioration of flavivirus infections. United States patent US 20120208778 A1. 2012 Aug.
136. van der Poel, CL. Hepatitis C virus and blood transfusion: past and present risks. Hepatology 1999; 31: 101-6.
137. World Health Organization (WHO). Hepatitis C. Weekly Epidemiological Record 1997; 72: 65-9.
138. World Health Organization (WHO). Global surveillance and control of hepatitis C. Report of a WHO Consultation organized in collaboration with the Viral Hepatitis Prevention Board, Antwerp, Belgium. J Viral Hepat1999; 6: 35-47.
139. Hoofnagle JH. Course and outcome of hepatitis C. Hepatology 2002; 36: S21-29.
140. Liang TJ, Rehermann B, Seeff LB, et al. Pathogenesis, natural history, treatment, and prevention of hepatitis C. Ann Intern Med 2000: 132; 296-305.
141. Kuo G, Choo QL, Alter HJ, et al. An assay for circulating antibodies to a major etiologic virus of human non-a, non-BHepatitis. Science 1989; 244: 362-4.
142. Barazani Y, Hiatt JR, Tong MJ, et al. Chronic viral hepatitis and hepatocellular carcinoma. World J Surg 2007; 31: 1243-8.
143. Das D, Hong J, Chen SH, et al. Recent advances in drug discovery of benzothiadiazine and related analogs as HCV NS5B polymerase inhibitors. Bioorg Med Chem 2011; 19: 4690-703.
144. Rehman S, Ashfaq UA, Javed T. Antiviral drugs against hepatitis C virus. Genet Vaccines Ther 2011; 9: 1-10.
145. Yang PL, Gao M, Lin K, et al. Anti-HCV drugs in the pipeline. Curr Opin Virol 2011; 1: 607-16.
146. Manns MP, Foster GR, Rockstroh JK, et al. The way forward in HCV treatment-finding the right path. Nat Rev Drug Discovery 2008; 6: 991-1000.
147. Lesburg CA, Cable MB, Ferrari E, et al. Crystal structure of the RNA-dependent RNA polymerase from hepatitis C virus reveals a fully encircled active site. Nat Struct Biol 1999; 6: 937-43.
148. Bressanelli S, Tomei L, Roussel A, et al. Crystal structure of the RNA-dependent RNA polymerase of hepatitis C virus. Proc Natl Acad Sci USA 1999; 96: 13034-9.
149. Patel PD, Patel MR, Kaushik-Basu N, et al. 3D QSAR and molecular docking studies of benzimidazole derivatives as hepatitis C virus NS5B polymerase inhibitors. J Chem Inf Model 2008; 48: 42-55.
150. LaPlante SR, Gillard JR, Jakalian A, et al. Importance of ligand bioactive conformation in the discovery of potent indole-diamide inhibitors of the hepatitis C virus NS5B. J Am Chem Soc 2010; 132: 15204-12.
151. McKercher G, Beaulieu PL, Lamarre D, et al. Specific inhibitors of HCV polymerase identified using an NS5B with lower affinity for template/primer substrate. Nucl Acids Res 2004; 32: 422-31.
152. Beaulieu PL, Gillard J, Jolicoeur E, et al. From benzimidazole to indole-5-carboxamide Thumb Pocket I inhibitors of HCV NS5B polymerase. Part 1: Indole C-2 SAR and discovery of diamide derivatives with nanomolar potency in cell-based subgenomic replicons. Bioorg Med Chem Lett 2011; 21: 3658-63.
153. Yao N, Reichert P, Taremi SS, et al. Molecular views of viral poly protein processing revealed by the crystal structure of the hepatitis C virus bifuctional protease-helicase. Structure 1999; 7: 1353-63.
154. Perni RB, Almquist SJ, Bryan RA, et al. Preclinical profile of VX-950, a potent, selective, and orally bioavailable inhibitor of hepatitis C virus NS3-4A serine protease. Antimicrob. Agents Chemother 2006; 50: 899-909.
155. Li X, Zhang S, Zhang YK, et al. Synthesis and SAR of acyclic HCV NS3 protease inhibitors with novel P4-benzoxzborole moieties. Bioorg Med Chem Lett 2011; 21: 2048-54.
156. Rong L, Dahari H, Ribeiro RM, et al. Rapid emergence of protease inhibitor resistance in hepatitis C virus. Sci Transl Med 2010; 2: 30-2.
157. Takaya D, Yamashita A, Kamijo K, et al. A new method for induced fit docking (GENIUS) and its application to virtual screening of novel HCV NS3-4A protease inhibitors. Bioorg Med Chem 2011; 19: 6892-904.
158. Kazmierski WM, Hamatake R, Duan M, et al. Discovery of novel urea-based hepatitis C protease inhibitors with high potency against protease-inhibitor-resistant mutants. J Med Chem 2012; 55: 3021-6.
159. Barbato G, Cicero DO, Cordier F, et al. Inhibitor binding induces active site stabilization of the HCV NS3 protein serine protein domain. EMBO J 2000; 19: 1195-206.
160. Ding CZ, Zhang YK, Li X, et al. Synthesis and biological evaluations of P4-benzoxaborole-substituted macrocyclic inhibitors of HCV NS3 protease. Bioorg Med Chem Lett 2010; 20: 7317-22.
161. Kota S, Coito C, Mousseau G, et al. Peptide inhibitors of hepatitis C virus core oligomerization and virus production. J Genl Virol 2009; 90: 1319-28.
162. Wells JA, McClendon, CL. Reaching for high-hanging fruit in drug discovery at protein-protein interfaces. Nature 2007; 450: 1001-9.
163. Che W, Zhang Z, Chen J, et al. HCV core protein interacts with Dicer to antagonize RNA silencing. Virus Res 2008; 133: 250-8.
164. Si Y, Liu S, Liu X, Jacobs JL, et al. A human claudin-1-derived peptide inhibits hepatitis C virus entry. Hepatology 2012; 56: 507-15.
165. Scarselli E, Ansuini H, Cerino R, et al. The human scavenger receptor class B type I is a novel candi-date receptor for the hepatitis C virus. EMBO J 2002; 21: 5017-25.
166. Evans MJ, von Hahn T, Tscherne DM, et al. Claudin-1 is a hepatitis C virus co-receptor required for a late step in entry. Nature 2007; 446: 801-5.
167. Liu S, Yang W, Shen L, et al. Tight junction proteins claudin-1 and occludin control hepatitis C virus entry and are downregulated during infection to prevent superinfection. J Virol 2009; 83: 2011-4.
168. Ploss A, Evans MJ, Gaysinskaya VA, et al. Human occludin is a hepatitis C virus entry factor required for infection of mouse cells. Nature 2009; 457: 882-6.
169. Montero A, Gastaminaza P, Law M, et al. Self-assembling peptide nanotubes with antiviral activity against hepatitis C virus. Chem Biol 2011; 18: 1453-62.
170. Dartois V, Sanchez-Quesada J, Cabezas E, et al. Systemic antibacterial activity of novel synthetic cyclic peptides. Antimicrob Agents Chemother 2005; 49: 3302-10.
171. Fernandez-Lopez S, Kim HS, Choi EC, et al. Antibacterial agents based on the cyclic D, L-alpha-peptide architecture. Nature 2001; 412: 452-5.
172. Horne WS, Wiethoff CM, Cui C, et al. Antiviral cyclic D, L-alphapeptides: targeting a general biochemical pathway in virus infections. Bioorg Med Chem 2005; 13: 5145-53.
173. Bildick CJ, Wichroski MJ, Pendri A, et al. A novel small molecule inhibitor of hepatitis C virus entry. PLoS Pathog 2010; 6: e1001086. Available at doi: 10.1371/journal.ppat.1001086.
174. Gary RF, Dash S, Coy DH, et al, inventor; The Administrators of the Tulane Educational Fund. The Rockefeller University. Assignee. The Flavivirus fusion inhibitors. United States patent US815336. 2012 April.
175. Chandramouli S, Joseph JS, Daudenarde S, et al. Serotype-specific structural differences in the protease-cofactor complexes of the dengue virus family. J Virol 2010; 84: 3059-67.
176. Luo D, Wei N, Doan DN, et al. Flexibility between the protease and helicase domains of the dengue virus NS3 protein conferred by the linker region and its functional implications. J Biol Chem 2010; 285: 18817-27.
177. Noble CG, Seh CC, Chao AT, et al. Ligand-bound structures of the dengue virus protease reveal the active conformation. J Virol 2011; 86: 438-46.
178. Luo DH, Xu T, Hunke C, et al. Crystal structure of the NS3 protease-helicase from dengue virus. J Virol 2008; 82: 173-83.
179. Aleshin AE, Shiryaev SA, Strongin AY, et al. Structural evidence for regulation and specificity of flaviviral proteases and evolution of the Flaviviridae fold. Protein Sci 2007; 16: 795-806.
180. Robin G, Chappell K, Stoermer MJ, et al. Structure of West Nile virus NS3 protease: ligand stabilization of the catalytic conformation. J Mol Biol 2009; 385: 1568-77.
181. Kaufmann B, Rossmann MG. Molecular mechanisms involved in the early steps of flavivirus cell entry. Microbes Infect 2011; 13: 1-9.
182. Lindenbach BD, Rice CM. Flaviviridae: the viruses and their replication. In Fields Virology, 4th ed. Edited by Knipe DM and Howley PM. Lippincott Williams & Wilkins 2001.
183. Hijikata M, Mizushima H, Akagi T, et al. Two distinct proteinase activities required for the processing of a putative nonstructural precursor protein of hepatitis C virus. J Virol 1993; 67: 4665-75.
184. Popescu C-I, Callens N, Trinel D, et al. NS2 Protein of Hepatitis C Virus Interacts with Structural and Non-Structural Proteins towards Virus Assembly. PLoS Pathog 2011; 7: e1001278. Available at doi: 10.1371/journal.ppat.1001278.
185. Chevaliez S, Pawlotsky JM. HCV Genome and Life Cycle. In: Tan SL, editor. Hepatitis C Viruses: Genomes and Molecular Biology. Norfolk (UK): Horizon Bioscience; 2006. Chapter 1. Available from: http: //www.ncbi.nlm.nih.gov/books/NBK1630/.
186. Matusan AE, Pryor MJ, Davidson AD, et al. Mutagenesis of the Dengue virus type 2 NS3 protein within and outside helicase motifs: effects on enzyme activity and virus replication. J Virol 2001; 75: 9633-43.
187. Miller S, Kastner S, Krijnse-Locker J, et al. The non-structural protein 4A of dengue virus is an integral membrane protein inducing membrane alterations in a 2K-regulated manner. J Biol Chem 2007; 282: 8873-82.
188. Roosendaal J, Westaway EG, Khromykh A, et al. Regulated cleavages at the West Nile virus NS4A-2K-NS4B junctions play a major role in rearranging cytoplasmic membranes and Golgi trafficking of the NS4A protein. J Virol 2006; 80: 4623-32.
189. Munoz-Jordan JL, Laurent-Rolle M, Ashour J, et al. Inhibition of alpha/beta interferon signaling by the NS4B protein of flaviviruses. J Virol 2005; 79: 8004-13.
190. Umareddy I, Chao A, Sampath A, et al. Dengue virus NS4B interacts with NS3 and dissociates it from single-stranded RNA. J Gen Virol 2006; 87: 2605-14.
191. Pastorino B, Nougairéde A, Wurtz N, et al. Role of host cell factors in flavivirus infection: Implications for pathogenesis and development of antiviral drugs. Antiviral Res 2010; 87: 281-94.