Assessment of Dengue virus helicase and methyltransferase as targets for fragment-based drug discovery

Antiviral Research

Volumn 106, Issue 1, 2014, Pages 61-70

  Coutard, Bruno ^a,b   Decroly, Etienne ^a,b   Li, Changqing ^a,b   Sharff, Andrew ^c   Lescar, Julien ^a,b   Bricogne, Gérard ^c   Barral, Karine ^a,b  

^a AIX MARSEILLE UNIVERSITY   (France)

^b CNRS   (France)

^c GLOBAL PHASING LTD   (United Kingdom)

Author keywords

Antiviral screening; Dengue virus; Fragment based drug discovery; Keywords; NS3 helicase; NS5 methyltransferase

Indexed keywords

ANTIVIRUS AGENT; LIGAND; MESSENGER RNA; METHYLTRANSFERASE; NONSTRUCTURAL PROTEIN 3; NONSTRUCTURAL PROTEIN 5; RNA HELICASE; HELICASE; S ADENOSYLMETHIONINE; ENZYME INHIBITOR; PROTEIN BINDING;

ARTICLE; BINDING AFFINITY; BINDING SITE; CONTROLLED STUDY; DENGUE VIRUS; DRUG DEVELOPMENT; ENZYMATIC ASSAY; ENZYME ACTIVITY; FLAVIVIRUS; MOLECULAR LIBRARY; NONHUMAN; PRIORITY JOURNAL; PROTEIN ANALYSIS; PROTEIN DOMAIN; VALIDATION PROCESS; VIRUS REPLICATION; X RAY CRYSTALLOGRAPHY; ANTIVIRAL ACTIVITY; DENGUE VIRUS 3; DRUG DESIGN; DRUG SCREENING; DRUG TARGETING; ENZYME ASSAY; ENZYME BINDING; FRAGMENT BASED DRUG DISCOVERY; FRAGMENT BASED X RAY CRYSTALLOGRAPHY; GENETIC PROCEDURES; IC 50; IN VITRO STUDY; MOLECULAR DOCKING; THERMAL SHIFT ASSAY; VIRUS STRAIN; ANTAGONISTS AND INHIBITORS; DRUG EFFECTS; ENZYMOLOGY; HUMAN; IC50; ISOLATION AND PURIFICATION; PROCEDURES;

ANTIVIRAL AGENTS; CRYSTALLOGRAPHY, X-RAY; DENGUE VIRUS; DRUG DISCOVERY; ENZYME INHIBITORS; HUMANS; INHIBITORY CONCENTRATION 50; METHYLTRANSFERASES; PROTEIN BINDING; RNA HELICASES;

EID: 84901012308     PISSN: 01663542     EISSN: 18729096     Source Type: Journal    
DOI: 10.1016/j.antiviral.2014.03.013     Document Type: Article

References (73)

1. C. Abad-Zapatero Ligand efficiency indices for effective drug discovery Expert Opin. Drug Discov. 2 2007 469 488
2. S.S. Antonysamy, B. Aubol, J. Blaney, M.F. Browner, A.M. Giannetti, S.F. Harris, N. Hebert, J. Hendle, S. Hopkins, E. Jefferson, C. Kissinger, V. Leveque, D. Marciano, E. McGee, I. Najera, B. Nolan, M. Tomimoto, E. Torres, and T. Wright Fragment-based discovery of hepatitis C virus NS5b RNA polymerase inhibitors Bioorg. Med. Chem. Lett. 18 2008 2990 2995
3. R. Assenberg, E. Mastrangelo, T.S. Walter, A. Verma, M. Milani, R.J. Owens, D.I. Stuart, J.M. Grimes, and E.J. Mancini Crystal structure of a novel conformational state of the flavivirus NS3 protein: implications for polyprotein processing and viral replication J. Virol. 83 2009 12895 12906
4. K. Barral, C. Sallamand, C. Petzold, B. Coutard, A. Collet, Y. Thillier, J. Zimmermann, J.J. Vasseur, B. Canard, J. Rohayem, F. Debart, and E. Decroly Development of specific dengue virus 2′-O- and N7-methyltransferase assays for antiviral drug screening Antiviral Res. 99 2013 292 300
5. S.D. Bembenek, B.A. Tounge, and C.H. Reynolds Ligand efficiency and fragment-based drug discovery Drug Discov. Today 14 2009 278 283
6. D. Benarroch, M.P. Egloff, L. Mulard, C. Guerreiro, J.L. Romette, and B. Canard A structural basis for the inhibition of the NS5 dengue virus mRNA 2′-O-methyltransferase domain by ribavirin 5′-triphosphate J. Biol. Chem. 279 2004 35638 35643
7. D. Benarroch, B. Selisko, G.A. Locatelli, G. Maga, J.L. Romette, and B. Canard The RNA helicase, nucleotide 5′-triphosphatase, and RNA 5′-triphosphatase activities of Dengue virus protein NS3 are Mg2+dependent and require a functional Walker B motif in the helicase catalytic core Virology 328 2004 208 218
8. M. Bollati, K. Alvarez, R. Assenberg, C. Baronti, B. Canard, S. Cook, B. Coutard, E. Decroly, X. de Lamballerie, E.A. Gould, G. Grard, J.M. Grimes, R. Hilgenfeld, A.M. Jansson, H. Malet, E.J. Mancini, E. Mastrangelo, A. Mattevi, M. Milani, G. Moureau, J. Neyts, R.J. Owens, J. Ren, B. Selisko, S. Speroni, H. Steuber, D.I. Stuart, T. Unge, and M. Bolognesi Structure and functionality in flavivirus NS-proteins: perspectives for drug design Antiviral Res. 87 2010 125 148
9. G. Bricogne, E. Blanc, M. Brandl, C. Flensburg, P. Keller, W. Paciorek, P. Roversi, A. Sharff, O.S. Smart, C. Vonrhein, and T.O. Womack BUSTER Version 2.11.2 2011 Global Phasing Ltd. Cambridge, United Kingdom
10. I.J. Bruno, J.C. Cole, M. Kessler, J. Luo, W.D. Motherwell, L.H. Purkis, B.R. Smith, R. Taylor, R.I. Cooper, S.E. Harris, and A.G. Orpen Retrieval of crystallographically-derived molecular geometry information J. Chem. Inf. Comput. Sci. 44 2004 2133 2144
11. C.M. Byrd, D.W. Grosenbach, A. Berhanu, D. Dai, K.F. Jones, K.B. Cardwell, C. Schneider, G. Yang, S. Tyavanagimatt, C. Harver, K.A. Wineinger, J. Page, E. Stavale, M.A. Stone, K.P. Fuller, C. Lovejoy, J.M. Leeds, D.E. Hruby, and R. Jordan Novel benzoxazole inhibitor of dengue virus replication that targets the NS3 helicase Antimicrob. Agents Chemother. 57 2013 1902 1912
12. C.S. Chen, C.T. Chiou, G.S. Chen, S.C. Chen, C.Y. Hu, W.K. Chi, Y.D. Chu, L.H. Hwang, P.J. Chen, D.S. Chen, S.H. Liaw, and J.W. Chern Structure-based discovery of triphenylmethane derivatives as inhibitors of hepatitis C virus helicase J. Med. Chem. 52 2009 2716 2723
13. A. Ciulli, and C. Abell Fragment-based approaches to enzyme inhibition Curr. Opin. Biotechnol. 18 2007 489 496
14. M. Congreve, G. Chessari, D. Tisi, and A.J. Woodhead Recent developments in fragment-based drug discovery J. Med. Chem. 51 2008 3661 3680
15. S. Daffis, K.J. Szretter, J. Schriewer, J. Li, S. Youn, J. Errett, T.Y. Lin, S. Schneller, R. Zust, H. Dong, V. Thiel, G.C. Sen, V. Fensterl, W.B. Klimstra, T.C. Pierson, R.M. Buller, M. Gale Jr., P.Y. Shi, and M.S. Diamond 2′-O methylation of the viral mRNA cap evades host restriction by IFIT family members Nature 468 2010 452 456
16. I.W. Davis, A. Leaver-Fay, V.B. Chen, J.N. Block, G.J. Kapral, X. Wang, L.W. Murray, W.B. Arendall III, J. Snoeyink, J.S. Richardson, and D.C. Richardson MolProbity: all-atom contacts and structure validation for proteins and nucleic acids Nucleic Acids Res. 35 2007 W375 W383
17. G.E. de Kloe, D. Bailey, R. Leurs, and I.J. de Esch Transforming fragments into candidates: small becomes big in medicinal chemistry Drug Discov. Today 14 2009 630 646
18. A. Delean, P.J. Munson, and D. Rodbard Simultaneous analysis of families of sigmoidal curves - application to bioassay, radioligand assay, and physiological dose-response curves Am. J. Physiol. 235 1978 E97 E102
19. H.P. Dong, B. Zhang, and P.Y. Shi Flavivirus methyltransferase: A novel antiviral target Antiviral Res. 80 2008 1 10
20. H.P. Dong, D.C. Chang, X.P. Xie, Y.X. Toh, K.Y. Chung, G. Zou, J. Lescar, S.P. Lim, and P.Y. Shi Biochemical and genetic characterization of dengue virus methyltransferase Virology 405 2010 568 578
21. M.P. Egloff, D. Benarroch, B. Selisko, J.L. Romette, and B. Canard An RNA cap (nucleoside-2′-O-)-methyltransferase in the flavivirus RNA polymerase NS5: crystal structure and functional characterization EMBO J. 21 2002 2757 2768
22. M.P. Egloff, E. Decroly, H. Malet, B. Selisko, D. Benarroch, F. Ferron, and B. Canard Structural and functional analysis of methylation and 5′-RNA sequence requirements of short capped RNAs by the methyltransferase domain of dengue virus NS5 J. Mol. Biol. 372 2007 723 736
23. D. Ekonomiuk, X.C. Su, K. Ozawa, C. Bodenreider, S.P. Lim, G. Otting, D. Huang, and A. Caflisch Flaviviral protease inhibitors identified by fragment-based library docking into a structure generated by molecular dynamics J. Med. Chem. 52 2009 4860 4868
24. D. Ekonomiuk, X.C. Su, K. Ozawa, C. Bodenreider, S.P. Lim, Z. Yin, T.H. Keller, D. Beer, V. Patel, G. Otting, A. Caflisch, and D. Huang Discovery of a non-peptidic inhibitor of west nile virus NS3 protease by high-throughput docking PLoS Negl. Trop. Dis, 3 2009 e356
25. P. Emsley, B. Lohkamp, W.G. Scott, and K. Cowtan Features and development of Coot Acta Crystallogr. D Biol. Crystallogr. 66 2010 486 501
26. D.A. Erlanson Introduction to fragment-based drug discovery Top. Curr. Chem. 317 2012 1 32
27. P. Evans Scaling and assessment of data quality Acta Crystallogr. D Biol. Crystallogr. 62 2006 72 82
28. B.J. Geiss, A.A. Thompson, A.J. Andrews, R.L. Sons, H.H. Gari, S.M. Keenan, and O.B. Peersen Analysis of flavivirus NS5 methyltransferase cap binding J. Mol. Biol. 385 2009 1643 1654
29. A.M. Giannetti, B.D. Koch, and M.F. Browner Surface plasmon resonance based assay for the detection and characterization of promiscuous inhibitors J. Med. Chem. 51 2008 574 580
30. P.J. Hajduk, and J. Greer A decade of fragment-based drug design: strategic advances and lessons learned Nat. Rev. Drug Discov. 6 2007 211 219
31. R.D. Henkel, J.L. VandeBerg, and R.A. Walsh A microassay for ATPase Anal. Biochem. 169 1988 312 318
32. A.L. Hopkins, C.R. Groom, and A. Alex Ligand efficiency: A useful metric for lead selection Drug Discov. Today 9 2004 430 431
33. Y. Hu, and J. Bajorath Molecular scaffolds with high propensity to form multi-target activity cliffs J. Chem. Inf. Model. 50 2010 500 510
34. M.A. Ismail, D.A. Abou El Ella, K.A. Abouzid, and A.H. Mahmoud Integrated structure-based activity prediction model of benzothiadiazines on various genotypes of HCV NS5b polymerase (1a, 1b and 4) and its application in the discovery of new derivatives Bioorg. Med. Chem. 20 2012 2455 2478
35. W. Kabsch Xds Acta Crystallogr. D Biol. Crystallogr. 66 2010 125 132
36. M. Karelson, D.A. Dobchev, G. Karelson, T. Tamm, K. Tamm, A. Nikonov, M. Mutso, and A. Merits Fragment-based development of HCV protease inhibitors for the treatment of hepatitis C Curr. Comput. Aided Drug Des. 8 2012 55 61
37. T. Knehans, A. Schuller, D.N. Doan, K. Nacro, J. Hill, P. Guntert, M.S. Madhusudhan, T. Weil, and S.G. Vasudevan Structure-guided fragment-based in silico drug design of dengue protease inhibitors J. Comput. Aided Mol. Des. 25 2011 263 274
38. L.C. Kuo Fragment-based drug design - tools, practical approaches, and examples. Preface Methods Enzymol. 493 2011 xxi xxii
39. V. Lantez, K. Dalle, R. Charrel, C. Baronti, B. Canard, and B. Coutard Comparative production analysis of three phlebovirus nucleoproteins under denaturing or non-denaturing conditions for crystallographic studies PLoS Negl. Trop. Dis. 5 2011 e936
40. S.P. Lim, L.S. Sonntag, C. Noble, S.H. Nilar, R.H. Ng, G. Zou, P. Monaghan, K.Y. Chung, H.P. Dong, B.P. Liu, C. Bodenreider, G. Lee, M. Ding, W.L. Chan, G. Wang, Y.L. Jian, A.T. Chao, J. Lescar, Z. Yin, T.R. Vedananda, T.H. Keller, and P.Y. Shi Small molecule inhibitors that selectively block dengue virus methyltransferase J. Biol. Chem. 286 2011 6233 6240
41. S.P. Lim, J.H. Koh, C.C. Seh, C.W. Liew, A.D. Davidson, L.S. Chua, R. Chandrasekaran, T.C. Cornvik, P.Y. Shi, and J. Lescar A crystal structure of the dengue virus non-structural protein 5 (ns5) polymerase delineates interdomain amino acid residues that enhance its thermostability and de novo initiation activities J. Biol. Chem. 288 2013 31105 31114
42. S.P. Lim, Q.Y. Wang, C.G. Noble, Y.L. Chen, H. Dong, B. Zou, F. Yokokawa, S. Nilar, P. Smith, D. Beer, J. Lescar, and P.Y. Shi Ten years of dengue drug discovery: progress and prospects Antiviral Res. 100 2013 500 519
43. T. Lundqvist The devil is still in the details - driving early drug discovery forward with biophysical experimental methods Curr. Opin. Drug Discov. Devel. 8 2005 513 519
44. D. Luo, T. Xu, C. Hunke, G. Gruber, S.G. Vasudevan, and J. Lescar Crystal structure of the NS3 protease-helicase from dengue virus J. Virol. 82 2008 173 183
45. D. Luo, N. Wei, D.N. Doan, P.N. Paradkar, Y. Chong, A.D. Davidson, M. Kotaka, J. Lescar, and S.G. Vasudevan 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. 285 2010 18817 18827
46. E. Mastrangelo, M. Pezzullo, T. De Burghgraeve, S. Kaptein, B. Pastorino, K. Dallmeier, X. de Lamballerie, J. Neyts, A.M. Hanson, D.N. Frick, M. Bolognesi, and M. Milani Ivermectin is a potent inhibitor of flavivirus replication specifically targeting NS3 helicase activity: new prospects for an old drug J. Antimicrob. Chemother. 67 2012 1884 1894
47. A.J. McCoy, R.W. Grosse-Kunstleve, P.D. Adams, M.D. Winn, L.C. Storoni, and R.J. Read Phaser crystallographic software J. Appl. Crystallogr. 40 2007 658 674
48. T. Mendgen, C. Steuer, and C.D. Klein Privileged scaffolds or promiscuous binders: A comparative study on rhodanines and related heterocycles in medicinal chemistry J. Med. Chem. 55 2012 743 753
49. M. Milani, E. Mastrangelo, M. Bollati, B. Selisko, E. Decroly, M. Bouvet, B. Canard, and M. Bolognesi Flaviviral methyltransferase/RNA interaction: structural basis for enzyme inhibition Antiviral Res. 83 2009 28 34
50. C.W. Murray, and D.C. Rees The rise of fragment-based drug discovery Nat. Chem. 1 2009 187 192
51. J.E. Nettleship, J. Brown, M.R. Groves, and A. Geerlof Methods for protein characterization by mass spectrometry, thermal shift (ThermoFluor) assay, and multiangle or static light scattering Methods Mol. Biol. 426 2008 299 318
52. C.G. Noble, C.C. Seh, A.T. Chao, and P.Y. Shi Ligand-bound structures of the dengue virus protease reveal the active conformation J. Virol. 86 2012 438 446
53. N. Papageorgiou, B. Coutard, V. Lantez, E. Gautron, O. Chauvet, C. Baronti, H. Norder, X. de Lamballerie, V. Heresanu, N. Ferte, S. Veesler, A.E. Gorbalenya, and B. Canard The 2C putative helicase of echovirus 30 adopts a hexameric ring-shaped structure Acta Crystallogr. D Biol. Crystallogr. 66 2010 1116 1120
54. R.C. Schoenfeld, D.L. Bourdet, K.A. Brameld, E. Chin, J. de Vicente, A. Fung, S.F. Harris, E.K. Lee, S. Le Pogam, V. Leveque, J. Li, A.S. Lui, I. Najera, S. Rajyaguru, M. Sangi, S. Steiner, F.X. Talamas, J.P. Taygerly, and J. Zhao Discovery of a novel series of potent non-nucleoside inhibitors of hepatitis C virus NS5B J. Med. Chem. 56 2013 8163 8182
55. M.N. Schulz, J. Landstrom, and R.E. Hubbard MTSA - a Matlab program to fit thermal shift data Anal. Biochem. 433 2012 43 47
56. D.E. Scott, A.G. Coyne, S.A. Hudson, and C. Abell Fragment-based approaches in drug discovery and chemical biology Biochemistry 51 2012 4990 5003
57. B. Selisko, F.F. Peyrane, B. Canard, K. Alvarez, and E. Decroly Biochemical characterization of the (nucleoside-2′O)-methyltransferase activity of dengue virus protein NS5 using purified capped RNA oligonucleotides (7Me)GpppAC(n) and GpppAC(n) J. Gen. Virol. 91 2010 112 121
58. A. Sharff, P. Keller, C. Vonrhein, O. Smart, T. Womack, C. Flensburg, C. Paciorek, and G. Bricogne Pipedream, Version 0.1.4 2011 Global Phasing Ltd. Cambridge, United Kingdom
59. G. Siegal, E. Ab, and J. Schultz Integration of fragment screening and library design Drug Discov. Today 12 2007 1032 1039
60. O.S. Smart, T.O. Womack, A. Sharff, C. Flensburg, P. Keller, W. Paciorek, C. Vonrhein, and G. Bricogne Grade, Version 1.1.1 2011 Global Phasing Ltd. Cambridge, United Kingdom
61. T.A. Stammers, R. Coulombe, J. Rancourt, B. Thavonekham, G. Fazal, S. Goulet, A. Jakalian, D. Wernic, Y. Tsantrizos, M.A. Poupart, M. Bos, G. McKercher, L. Thauvette, G. Kukolj, and P.L. Beaulieu Discovery of a novel series of non-nucleoside thumb pocket 2 HCV NS5B polymerase inhibitors Bioorg. Med. Chem. Lett. 23 2013 2585 2589
62. C. Steuer, C. Gege, W. Fischl, K.H. Heinonen, R. Bartenschlager, and C.D. Klein Synthesis and biological evaluation of alpha-ketoamides as inhibitors of the Dengue virus protease with antiviral activity in cell-culture Bioorg. Med. Chem. 19 2011 4067 4074
63. F.X. Talamas, G. Ao-Ieong, K.A. Brameld, E. Chin, J. de Vicente, J.P. Dunn, M. Ghate, A.M. Giannetti, S.F. Harris, S.S. Labadie, V. Leveque, J. Li, A.S. Lui, K.L. McCaleb, I. Najera, R.C. Schoenfeld, B. Wang, and A. Wong De novo fragment design: A medicinal chemistry approach to fragment-based lead generation J. Med. Chem. 56 2013 3115 3119
64. S.J. Thomas, and T.P. Endy Current issues in dengue vaccination Curr. Opin. Infect. Dis. 26 2013 429 434
65. C. Vonrhein, C. Flensburg, P. Keller, A. Sharff, O. Smart, W. Paciorek, T. Womack, and G. Bricogne Data processing and analysis with the autoPROC toolbox Acta Crystallogr. D Biol. Crystallogr. 67 2011 293 303
66. T. Womack, O. Smart, A. Sharff, C. Flensburg, P. Keller, W. Paciorek, C. Vonrhein, and G. Bricogne Rhofit, Version 1.2.3 2011 Global Phasing Ltd. Cambridge, United Kingdom
67. D.F. Wyss, A. Arasappan, M.M. Senior, Y.S. Wang, B.M. Beyer, F.G. Njoroge, and M.A. McCoy Non-peptidic small-molecule inhibitors of the single-chain hepatitis C virus NS3 protease/NS4A cofactor complex discovered by structure-based NMR screening J. Med. Chem. 47 2004 2486 2498
68. T. Xu, A. Sampath, A. Chao, D. Wen, M. Nanao, P. Chene, S.G. Vasudevan, and J. Lescar Structure of the Dengue virus helicase/nucleoside triphosphatase catalytic domain at a resolution of 2.4 A J. Virol. 79 2005 10278 10288
69. T. Xu, A. Sampath, A. Chao, D. Wen, M. Nanao, D. Luo, P. Chene, S.G. Vasudevan, and J. Lescar Towards the design of flavivirus helicase/NTPase inhibitors: crystallographic and mutagenesis studies of the dengue virus NS3 helicase catalytic domain Novartis Found. Symp. 277 2006 87 97
70. L.J. Yap, D. Luo, K.Y. Chung, S.P. Lim, C. Bodenreider, C. Noble, P.Y. Shi, and J. Lescar Crystal structure of the dengue virus methyltransferase bound to a 5′-capped octameric RNA PLoS ONE 5 2010
71. C. Yon, T. Teramoto, N. Mueller, J. Phelan, V.K. Ganesh, K.H. Murthy, and R. Padmanabhan Modulation of the nucleoside triphosphatase/RNA helicase and 5′-RNA triphosphatase activities of Dengue virus type 2 nonstructural protein 3 (NS3) by interaction with NS5, the RNA-dependent RNA polymerase J. Biol. Chem. 280 2005 27412 27419
72. R. Zust, L. Cervantes-Barragan, M. Habjan, R. Maier, B.W. Neuman, J. Ziebuhr, K.J. Szretter, S.C. Baker, W. Barchet, M.S. Diamond, S.G. Siddell, B. Ludewig, and V. Thiel Ribose 2′-O-methylation provides a molecular signature for the distinction of self and non-self mRNA dependent on the RNA sensor Mda5 Nat. Immunol. 12 2011 137 143
73. R. Zust, H. Dong, X.F. Li, D.C. Chang, B. Zhang, T. Balakrishnan, Y.X. Toh, T. Jiang, S.H. Li, Y.Q. Deng, B.R. Ellis, E.M. Ellis, M. Poidinger, F. Zolezzi, C.F. Qin, P.Y. Shi, and K. Fink Rational design of a live attenuated dengue vaccine: 2′-O-methyltransferase mutants are highly attenuated and immunogenic in mice and macaques PLoS Pathog. 9 2013 e1003521