Polymerases of hepatitis C viruses and flaviviruses: Structural and mechanistic insights and drug development

Antiviral Research

Volumn 105, Issue 1, 2014, Pages 8-16

  Caillet Saguy, Célia ^a   Lim, Siew Pheng ^b   Shi, Pei Yong ^b   Lescar, Julien ^c,d   Bressanelli, Stéphane ^e  

^a INSTITUT PASTEUR   (France)

^b NOVARTIS INSTITUTE FOR TROPICAL DISEASES   (Singapore)

^c NANYANG TECHNOLOGICAL UNIVERSITY   (Singapore)

^d PITIÉ SALPÊTRIÈRE HOSPITAL   (France)

^e CNRS   (France)

Author keywords

Flaviviridae; Non nucleoside inhibitors; Nucleoside inhibitors; RdRp regulation; RNA synthesis; RNA dependent RNA polymerase

Indexed keywords

ANTIVIRUS AGENT; BALAPIRAVIR; NONNUCLEOSIDE REVERSE TRANSCRIPTASE INHIBITOR; PEGINTERFERON; RIBAVIRIN; RNA DIRECTED DNA POLYMERASE INHIBITOR; RNA DIRECTED RNA POLYMERASE; VIRUS RNA; GLYCOPROTEIN E1; NONSTRUCTURAL PROTEIN 2A; NONSTRUCTURAL PROTEIN 4B; NONSTRUCTURAL PROTEIN 5; NONSTRUCTURAL PROTEIN 5B; NUCLEOSIDE; PROTEINASE INHIBITOR; UNCLASSIFIED DRUG; VIRUS PROTEIN; PROTEIN BINDING;

ANTIVIRAL ACTIVITY; CRYSTAL STRUCTURE; DRUG DESIGN; ENZYME ACTIVITY; FLAVIVIRUS; HEPATITIS C; HEPATITIS C VIRUS; HUMAN; NONHUMAN; PRIORITY JOURNAL; REVIEW; RNA SYNTHESIS; VIRUS REPLICATION; PROTEIN CONFORMATION; PROTEIN STRUCTURE; CHEMISTRY; DRUG DEVELOPMENT; ENZYMOLOGY; FLAVIVIRIDAE; METABOLISM; PROCEDURES; X RAY CRYSTALLOGRAPHY;

ANTIVIRAL AGENTS; CRYSTALLOGRAPHY, X-RAY; DRUG DISCOVERY; FLAVIVIRIDAE; HUMANS; PROTEIN BINDING; PROTEIN CONFORMATION; RNA REPLICASE;

EID: 84895822138     PISSN: 01663542     EISSN: 18729096     Source Type: Journal    
DOI: 10.1016/j.antiviral.2014.02.006     Document Type: Review

References (65)

1. M. Ackermann, and R. Padmanabhan De novo synthesis of RNA by the dengue virus RNA-dependent RNA polymerase exhibits temperature dependence at the initiation but not elongation phase J. Biol. Chem. 276 2001 39926 39937
2. T. Adachi, H. Ago, N. Habuka, K. Okuda, M. Komatsu, S. Ikeda, and K. Yatsunami The essential role of C-terminal residues in regulating the activity of hepatitis C virus RNA-dependent RNA polymerase Biochim. Biophys. Acta 1601 2002 38 48 (Pubitemid 38234529)
3. H. Ago, T. Adachi, A. Yoshida, M. Yamamoto, N. Habuka, K. Yatsunami, and M. Miyano Crystal structure of the RNA-dependent RNA polymerase of hepatitis C virus Structure 7 1999 1417 1426 (Pubitemid 29529882)
4. R. Assenberg, J. Ren, A. Verma, T.S. Walter, D. Alderton, R.J. Hurrelbrink, S.D. Fuller, S. Bressanelli, R.J. Owens, D.I. Stuart, and J.M. Grimes Crystal structure of the Murray Valley encephalitis virus NS5 methyltransferase domain in complex with cap analogues J. Gen. Virol 88 2007 2228 2236 (Pubitemid 47194220)
5. R. Bartenschlager, V. Lohmann, and F. Penin The molecular and structural basis of advanced antiviral therapy for hepatitis C virus infection Nat. Rev. Microbiol. 11 2013 482 496
6. S. Bhatt, P.W. Gething, O.J. Brady, J.P. Messina, A.W. Farlow, C.L. Moyes, J.M. Drake, J.S. Brownstein, A.G. Hoen, O. Sankoh, M.F. Myers, D.B. George, T. Jaenisch, G.R.W. Wint, C.P. Simmons, T.W. Scott, J.J. Farrar, and S.I. Hay The global distribution and burden of dengue Nature 496 2013 504 507
7. E. Blanchard, S. Belouzard, L. Goueslain, T. Wakita, J. Dubuisson, C. Wychowski, and Y. Rouillé Hepatitis C virus entry depends on clathrin-mediated endocytosis J. Virol. 80 2006 6964 6972 (Pubitemid 44025195)
8. S. Bressanelli, L. Tomei, A. Roussel, I. Incitti, R.L. Vitale, M. Mathieu, R. De Francesco, and F.A. Rey Crystal structure of the RNA-dependent RNA polymerase of hepatitis C virus Proc. Natl. Acad. Sci. U.S.A. 96 1999 13034 13039
9. S. Bressanelli, L. Tomei, F.A. Rey, and R. De Francesco Structural analysis of the hepatitis C virus RNA polymerase in complex with ribonucleotides J. Virol. 76 2002 3482 3492 (Pubitemid 34224549)
10. S.J. Butcher, J.M. Grimes, E.V. Makeyev, D.H. Bamford, and D.I. Stuart A mechanism for initiating RNA-dependent RNA polymerization Nature 410 2001 235 240 (Pubitemid 32216599)
11. C. Caillet-Saguy, P.C. Simister, and S. Bressanelli An objective assessment of conformational variability in complexes of hepatitis C virus polymerase with non-nucleoside inhibitors J. Mol. Biol. 414 2011 370 384
12. Y.-L. Chen, Z. Yin, S.B. Lakshminarayana, M. Qing, W. Schul, J. Duraiswamy, R.R. Kondreddi, A. Goh, H.Y. Xu, A. Yip, B. Liu, M. Weaver, V. Dartois, T.H. Keller, and P.-Y. Shi Inhibition of dengue virus by an ester prodrug of an adenosine analog Antimicrob. Agents Chemother. 54 2010 3255 3261
13. Y.-L. Chen, N. Abdul Ghafar, R. Karuna, Y. Fu, S.P. Lim, W. Schul, F. Gu, M. Herve, F. Yokohama, G. Wang, D. Cerny, K. Fink, F. Blasco, and P.-Y. Shi Activation of peripheral blood mononuclear cells by dengue virus infection depotentiates balapiravir J. Virol. 88 2014 1740 1747
14. S. Chevaliez, and J.-M. Pawlotsky Interferon-based therapy of hepatitis C Adv. Drug Delivery Rev 59 2007 1222 1241 (Pubitemid 350047513)
15. K.H. Choi, J.M. Groarke, D.C. Young, R.J. Kuhn, J.L. Smith, D.C. Pevear, and M.G. Rossmann The structure of the RNA-dependent RNA polymerase from bovine viral diarrhea virus establishes the role of GTP in de novo initiation Proc. Natl. Acad. Sci. U.S.A. 101 2004 4425 4430 (Pubitemid 38437428)
16. K.H. Choi, A. Gallei, P. Becher, and M.G. Rossmann The structure of bovine viral diarrhea virus RNA-dependent RNA polymerase and its amino-terminal domain Structure 14 2006 1107 1113 (Pubitemid 44037427)
17. E. Decroly, F. Ferron, J. Lescar, and B. Canard Conventional and unconventional mechanisms for capping viral mRNA Nat. Rev. Microbiol. 10 2012 51 65
18. M. Delarue, O. Poch, N. Tordo, D. Moras, and P. Argos An attempt to unify the structure of polymerases Protein Eng. 3 1990 461 467 (Pubitemid 20290022)
19. H. Dong, S. Ren, H. Li, and P.-Y. Shi Separate molecules of West Nile virus methyltransferase can independently catalyze the N7 and 2′-O methylations of viral RNA cap Virology 377 2008 1 6
20. H. Dong, S. Ren, B. Zhang, Y. Zhou, F. Puig-Basagoiti, H. Li, and P.-Y. Shi West Nile virus methyltransferase catalyzes two methylations of the viral RNA cap through a substrate-repositioning mechanism J. Virol. 82 2008 4295 4307 (Pubitemid 351563667)
21. C. Ferrer-Orta, R. Agudo, E. Domingo, and N. Verdaguer Structural insights into replication initiation and elongation processes by the FMDV RNA-dependent RNA polymerase Curr. Opin. Struct. Biol. 19 2009 752 758
22. A.E. Gorbalenya, and E.V. Koonin Birnavirus RNA polymerase is related to polymerases of positive strand RNA viruses Nucleic Acids Res. 16 1988 7735
23. D. Harrus, N. Ahmed-El-Sayed, P.C. Simister, S. Miller, M. Triconnet, C.H. Hagedorn, K. Mahias, F.A. Rey, T. Astier-Gin, and S. Bressanelli Further insights into the roles of GTP and the C terminus of the hepatitis C virus polymerase in the initiation of RNA synthesis J. Biol. Chem. 285 2010 32906 32918
24. F.X. Heinz, and K. Stiasny Flaviviruses and flavivirus vaccines Vaccine 30 2012 4301 4306
25. H. Huang, R. Chopra, G.L. Verdine, and S.C. Harrison Structure of a covalently trapped catalytic complex of HIV-1 reverse transcriptase: implications for drug resistance Science 282 1998 1669 1675 (Pubitemid 28549275)
26. Z. Jin, V. Leveque, H. Ma, K.A. Johnson, and K. Klumpp NTP-mediated nucleotide excision activity of hepatitis C virus RNA-dependent RNA polymerase Proc. Natl. Acad. Sci. U.S.A. 110 2013 E348 E357
27. C.A. Lesburg, M.B. Cable, E. Ferrari, Z. Hong, A.F. Mannarino, and P.C. Weber Crystal structure of the RNA-dependent RNA polymerase from hepatitis C virus reveals a fully encircled active site Nat. Struct. Biol 6 1999 937 943 (Pubitemid 29463307)
28. J. Lescar, and B. Canard RNA-dependent RNA polymerases from flaviviruses and Picornaviridae Curr. Opin. Struct. Biol. 19 2009 759 767
29. D.H. Libraty, T.P. Endy, H.-S.H. Houng, S. Green, S. Kalayanarooj, S. Suntayakorn, W. Chansiriwongs, D.W. Vaughn, A. Nisalak, F.A. Ennis, and A.L. Rothman Differing influences of virus burden and immune activation on disease severity in secondary dengue-3 virus infections J. Infect. Dis. 185 2002 1213 1221 (Pubitemid 34439127)
30. D.H. Libraty, P.R. Young, D. Pickering, T.P. Endy, S. Kalayanarooj, S. Green, D.W. Vaughn, A. Nisalak, F.A. Ennis, and A.L. Rothman High circulating levels of the dengue virus nonstructural protein NS1 early in dengue illness correlate with the development of dengue hemorrhagic fever J. Infect. Dis. 186 2002 1165 1168 (Pubitemid 35177121)
31. 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
32. S.P. Lim, J.H.K. 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
33. B.D. Lindenbach, H.J. Thiel, and C.M. Rice Flaviviridae: the viruses and their replication D.M. Knipe, P.M. Howley, Fields Virology 2007 Lippincott-Raven Publishers Philadelphia 1101 1152
34. G. Lu, and P. Gong Crystal structure of the full-length Japanese encephalitis virus NS5 reveals a conserved methyltransferase-polymerase interface PLoS Pathog. 9 2013 e1003549
35. J.M. Mackenzie, A.A. Khromykh, M.K. Jones, and E.G. Westaway Subcellular localization and some biochemical properties of the flavivirus Kunjin nonstructural proteins NS2A and NS4A Virology 245 1998 203 215 (Pubitemid 28394183)
36. H. Malet, M.-P. Egloff, B. Selisko, R.E. Butcher, P.J. Wright, M. Roberts, A. Gruez, G. Sulzenbacher, C. Vonrhein, G. Bricogne, J.M. Mackenzie, A.A. Khromykh, A.D. Davidson, and B. Canard Crystal structure of the RNA polymerase domain of the West Nile virus non-structural protein 5 J. Biol. Chem. 282 2007 10678 10689 (Pubitemid 47093413)
37. R.T. Mosley, T.E. Edwards, E. Murakami, A.M. Lam, R.L. Grice, J. Du, M.J. Sofia, P.A. Furman, and M.J. Otto Structure of hepatitis C virus polymerase in complex with primer-template RNA J. Virol. 86 2012 6503 6511
38. D.R. Nelson, S. Zeuzem, P. Andreone, P. Ferenci, R. Herring, D.M. Jensen, P. Marcellin, P.J. Pockros, M. Rodríguez-Torres, L. Rossaro, V.K. Rustgi, T. Sepe, M. Sulkowski, I.R. Thomason, E.M. Yoshida, A. Chan, and G. Hill Balapiravir plus peginterferon alfa-2a (40KD)/ribavirin in a randomized trial of hepatitis C genotype 1 patients Ann. Hepatol. 11 2012 15 31
39. N.M. Nguyen, C.N.B. Tran, L.K. Phung, K.T.H. Duong, A. Huynh Hle, J. Farrar, Q.T.H. Nguyen, H.T. Tran, C.V.V. Nguyen, L. Merson, L.T. Hoang, M.L. Hibberd, P.P.K. Aw, A. Wilm, N. Nagarajan, D.T. Nguyen, M.P. Pham, T.T. Nguyen, H. Javanbakht, K. Klumpp, J. Hammond, R. Petric, M. Wolbers, C.T. Nguyen, and C.P. Simmons A randomized, double-blind placebo controlled trial of balapiravir, a polymerase inhibitor, in adult dengue patients J. Infect. Dis. 207 2013 1442 1450
40. P. Niyomrattanakit, Y.-L. Chen, H. Dong, Z. Yin, M. Qing, J.F. Glickman, K. Lin, D. Mueller, H. Voshol, J.Y.H. Lim, S. Nilar, T.H. Keller, and P.-Y. Shi Inhibition of dengue virus polymerase by blocking of the RNA tunnel J. Virol. 84 2010 5678 5686
41. C.G. Noble, S.P. Lim, Y.-L. Chen, C.W. Liew, L. Yap, J. Lescar, and P.-Y. Shi Conformational flexibility of the dengue virus RNA-dependent RNA polymerase revealed by a complex with an inhibitor J. Virol. 87 2013 5291 5295
42. J.W. Oh, T. Ito, and M.M. Lai A recombinant hepatitis C virus RNA-dependent RNA polymerase capable of copying the full-length viral RNA J. Virol. 73 1999 7694 7702 (Pubitemid 29383253)
43. D.L. Ollis, C. Kline, and T.A. Steitz Domain of E. coli DNA polymerase I showing sequence homology to T7 DNA polymerase Nature 313 1985 818 819
44. J.-M. Pawlotsky Treatment of chronic hepatitis C: current and future Curr. Top. Microbiol. Immunol. 369 2013 321 342
45. J. Rohayem, I. Robel, K. Jäger, U. Scheffler, and W. Rudolph Protein-primed and de novo initiation of RNA synthesis by norovirus 3Dpol J. Virol. 80 2006 7060 7069 (Pubitemid 44025203)
46. I. Romero-Brey, A. Merz, A. Chiramel, J.-Y. Lee, P. Chlanda, U. Haselman, R. Santarella-Mellwig, A. Habermann, S. Hoppe, S. Kallis, P. Walther, C. Antony, J. Krijnse-Locker, and R. Bartenschlager Three-dimensional architecture and biogenesis of membrane structures associated with hepatitis C virus replication PLoS Pathog. 8 2012 e1003056
47. A. Sabchareon, D. Wallace, C. Sirivichayakul, K. Limkittikul, P. Chanthavanich, S. Suvannadabba, V. Jiwariyavej, W. Dulyachai, K. Pengsaa, T.A. Wartel, A. Moureau, M. Saville, A. Bouckenooghe, S. Viviani, N.G. Tornieporth, and J. Lang Protective efficacy of the recombinant, live-attenuated, CYD tetravalent dengue vaccine in Thai schoolchildren: a randomised, controlled phase 2b trial Lancet 380 2012 1559 1567
48. M. Schmitt, N. Scrima, D. Radujkovic, C. Caillet-Saguy, P.C. Simister, P. Friebe, O. Wicht, R. Klein, R. Bartenschlager, V. Lohmann, and S. Bressanelli A comprehensive structure-function comparison of hepatitis C virus strain JFH1 and J6 polymerases reveals a key residue stimulating replication in cell culture across genotypes J. Virol. 85 2011 2565 2581
49. N. Scrima, C. Caillet-Saguy, M. Ventura, D. Harrus, T. Astier-Gin, and S. Bressanelli Two crucial early steps in RNA synthesis by the hepatitis C virus polymerase involve a dual role of residue 405 J. Virol. 86 2012 7107 7117
50. B. Selisko, S. Potisopon, R. Agred, S. Priet, I. Varlet, Y. Thillier, C. Sallamand, F. Debart, J.-J. Vasseur, and B. Canard Molecular basis for nucleotide conservation at the ends of the dengue virus genome PLoS Pathog. 8 2012 e1002912
51. P. Simister, M. Schmitt, M. Geitmann, O. Wicht, U.H. Danielson, R. Klein, S. Bressanelli, and V. Lohmann Structural and functional analysis of hepatitis C virus strain JFH1 polymerase J. Virol. 83 2009 11926 11939
52. T.A. Steitz A mechanism for all polymerases Nature 391 1998 231 232
53. T.A. Steitz Visualizing polynucleotide polymerase machines at work EMBO J. 25 2006 3458 3468 (Pubitemid 44264857)
54. Y. Tao, D.L. Farsetta, M.L. Nibert, and S.C. Harrison RNA synthesis in a cage - structural studies of reovirus polymerase lambda3 Cell 111 2002 733 745 (Pubitemid 35452525)
55. H.M. Van der Schaar, M.J. Rust, C. Chen, H. van der Ende-Metselaar, J. Wilschut, X. Zhuang, and J.M. Smit Dissecting the cell entry pathway of dengue virus by single-particle tracking in living cells PLoS Pathog. 4 2008 e1000244
56. M. Vignuzzi, J.K. Stone, J.J. Arnold, C.E. Cameron, and R. Andino Quasispecies diversity determines pathogenesis through cooperative interactions in a viral population Nature 439 2006 344 348 (Pubitemid 43128860)
57. M. Vignuzzi, E. Wendt, and R. Andino Engineering attenuated virus vaccines by controlling replication fidelity Nat. Med. 14 2008 154 161 (Pubitemid 351214560)
58. S. Welsch, S. Miller, I. Romero-Brey, A. Merz, C.K.E. Bleck, P. Walther, S.D. Fuller, C. Antony, J. Krijnse-Locker, and R. Bartenschlager Composition and three-dimensional architecture of the dengue virus replication and assembly sites Cell Host Microbe 5 2009 365 375
59. E.G. Westaway, J.M. Mackenzie, M.T. Kenney, M.K. Jones, and A.A. Khromykh Ultrastructure of Kunjin virus-infected cells: colocalization of NS1 and NS3 with double-stranded RNA, and of NS2B with NS3, in virus-induced membrane structures J. Virol. 71 1997 6650 6661 (Pubitemid 27355323)
60. S. Yang, F.-E. Chen, and E. De Clercq Dihydro-alkoxyl-benzyl- oxopyrimidine derivatives (DABOs) as non-nucleoside reverse transcriptase inhibitors: an update review (2001-2011) Curr. Med. Chem. 19 2012 152 162
61. T.L. Yap, T. Xu, Y.-L. Chen, H. Malet, M.-P. Egloff, B. Canard, S.G. Vasudevan, and J. Lescar Crystal structure of the dengue virus RNA-dependent RNA polymerase catalytic domain at 1.85-angstrom resolution J. Virol. 81 2007 4753 4765 (Pubitemid 46668672)
62. 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
63. Z. Yin, Y.-L. Chen, W. Schul, Q.-Y. Wang, F. Gu, J. Duraiswamy, R.R. Kondreddi, P. Niyomrattanakit, S.B. Lakshminarayana, A. Goh, H.Y. Xu, W. Liu, B. Liu, J.Y.H. Lim, C.Y. Ng, M. Qing, C.C. Lim, A. Yip, G. Wang, W.L. Chan, H.P. Tan, K. Lin, B. Zhang, G. Zou, K.A. Bernard, C. Garrett, K. Beltz, M. Dong, M. Weaver, H. He, A. Pichota, V. Dartois, T.H. Keller, and P.-Y. Shi An adenosine nucleoside inhibitor of dengue virus Proc. Natl. Acad. Sci. U.S.A. 106 2009 20435 20439
64. D.F. Zamyatkin, F. Parra, J.M.M. Alonso, D.A. Harki, B.R. Peterson, P. Grochulski, and K.K.-S. Ng Structural insights into mechanisms of catalysis and inhibition in Norwalk virus polymerase J. Biol. Chem. 283 2008 7705 7712
65. G. Zou, Y.-L. Chen, H. Dong, C.C. Lim, L.J. Yap, Y.H. Yau, S.G. Shochat, J. Lescar, and P.-Y. Shi Functional analysis of two cavities in flavivirus NS5 polymerase J. Biol. Chem. 286 2011 14362 14372