Targeting dengue virus NS4B protein for drug discovery

Antiviral Research

Volumn 118, Issue , 2015, Pages 39-45

  Xie, Xuping ^a   Zou, Jing ^a,b,c   Wang, Qing Yin ^a   Shi, Pei Yong ^a  

^a NOVARTIS INSTITUTE FOR TROPICAL DISEASES   (Singapore)

^b WUHAN INSTITUTE OF VIROLOGY   (China)

^c UNIVERSITY OF CHINESE ACADEMY OF SCIENCES   (China)

Author keywords

Antivirals; Dengue; Flavivirus; Nonstructural protein 4B; NS4B

Indexed keywords

2 AMINOTHIAZOLE; ANTIVIRUS AGENT; NONSTRUCTURAL PROTEIN 1; NONSTRUCTURAL PROTEIN 2B; NONSTRUCTURAL PROTEIN 4A; NONSTRUCTURAL PROTEIN 4B; PROTEIN INHIBITOR; SPIROPYRAZOLOPYRIDONE; UNCLASSIFIED DRUG; ENZYME INHIBITOR; NS4B PROTEIN, FLAVIVIRUS; VIRAL PROTEIN;

ANTIVIRAL THERAPY; ARTICLE; CHEMICAL STRUCTURE; DENGUE VIRUS; DIMERIZATION; DRUG DESIGN; DRUG TARGETING; INNATE IMMUNITY; MEMBRANE STRUCTURE; NONHUMAN; PRIORITY JOURNAL; PROTEIN PROTEIN INTERACTION; VIRUS REPLICATION; ANTAGONISTS AND INHIBITORS; CHEMISTRY; DRUG DEVELOPMENT; DRUG EFFECTS; HUMAN; ISOLATION AND PURIFICATION; METABOLISM; PHYSIOLOGY; PROCEDURES; TRENDS;

DENGUE VIRUS; FLAVIVIRUS;

ANTIVIRAL AGENTS; DENGUE VIRUS; DRUG DISCOVERY; ENZYME INHIBITORS; HUMANS; VIRAL NONSTRUCTURAL PROTEINS; VIRUS REPLICATION;

EID: 84925855875     PISSN: 01663542     EISSN: 18729096     Source Type: Journal    
DOI: 10.1016/j.antiviral.2015.03.007     Document Type: Review

References (59)

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. R.L. Ambrose, and J.M. Mackenzie West Nile virus differentially modulates the unfolded protein response to facilitate replication and immune evasion J. Virol. 85 2011 2723 2732
3. 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
4. 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
5. A. Cahour, B. Falgout, and C.J. Lai Cleavage of the dengue virus polyprotein at the NS3/NS4A and NS4B/NS5 junctions is mediated by viral protease NS2B-NS3, whereas NS4A/NS4B may be processed by a cellular protease J. Virol. 66 1992 1535 1542
6. M. Choi, S. Lee, T. Choi, and C. Lee A hepatitis C virus NS4B inhibitor suppresses viral genome replication by disrupting NS4B's dimerization/multimerization as well as its interaction with NS5A Virus Genes 47 2013 395 407
7. H. Dong, B. Zhang, and P.-Y. Shi Flavivirus methyltransferase: a novel antiviral target Antiviral Res. 80 2008 1 10
8. D. Egger, B. Wölk, R. Gosert, L. Bianchi, H.E. Blum, D. Moradpour, and K. Bienz Expression of hepatitis C virus proteins induces distinct membrane alterations including a candidate viral replication complex J. Virol. 76 2002 5974 5984
9. 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
10. M. Gao, R.E. Nettles, M. Belema, L.B. Snyder, V.N. Nguyen, R.A. Fridell, M.H. Serrano-Wu, D.R. Langley, J.H. Sun, D.R. O'Boyle, J.A. Lemm, C. Wang, J.O. Knipe, C. Chien, R.J. Colonno, D.M. Grasela, N.A. Meanwell, and L.G. Hamann Chemical genetics strategy identifies an HCV NS5A inhibitor with a potent clinical effect Nature 465 2010 96 100
11. R. Gosert, D. Egger, V. Lohmann, R. Bartenschlager, H.E. Blum, K. Bienz, and D. Moradpour Identification of the hepatitis C virus RNA replication complex in Huh-7 cells harboring subgenomic replicons J. Virol. 77 2003 5487 5492
12. J. Gouttenoire, R. Montserret, D. Paul, R. Castillo, S. Meister, R. Bartenschlager, F. Penin, and D. Moradpour Aminoterminal amphipathic α-helix AH1 of hepatitis C virus nonstructural protein 4B possesses a dual role in RNA replication and virus production PLoS Pathog. 10 2014 e1004501
13. J. Gouttenoire, P. Roingeard, F. Penin, and D. Moradpour Amphipathic α-helix AH2 Is a major determinant for the oligomerization of hepatitis C virus nonstructural protein 4B J. Virol. 84 2010 12529 12537
14. D. Grant, G.K. Tan, M. Qing, J.K.W. Ng, A. Yip, G. Zou, X. Xie, Z. Yuan, M.J. Schreiber, W. Schul, P.-Y. Shi, and S. Alonso A single amino acid in nonstructural protein NS4B confers virulence to dengue virus in AG129 mice through enhancement of viral RNA synthesis J. Virol. 85 2011 7775 7787
15. P.K. Kakumani, S.S. Ponia, R.K. S, V. Sood, M. Chinnappan, A.C. Banerjea, G.R. Medigeshi, P. Malhotra, S.K. Mukherjee, and R.K. Bhatnagar Role of RNA interference (RNAi) in dengue virus replication and identification of NS4B as an RNAi suppressor J. Virol. 87 2013 8870 8883
16. P.H. Kaufusi, J.F. Kelley, R. Yanagihara, and V.R. Nerurkar Induction of endoplasmic reticulum-derived replication-competent membrane structures by West Nile Virus non-structural protein 4B PLoS One 9 2014 e84040
17. S. Khadka, A.D. Vangeloff, C. Zhang, P. Siddavatam, N.S. Heaton, L. Wang, R. Sengupta, S. Sahasrabudhe, G. Randall, M. Gribskov, R.J. Kuhn, R. Perera, and D.J. LaCount A physical interaction network of dengue virus and human proteins Mol. Cell. Proteomics 2011 10 2011
18. R.J. Kuhn, W. Zhang, M.G. Rossmann, S.V. Pletnev, J. Corver, E. Lenches, C.T. Jones, S. Mukhopadhyay, P.R. Chipman, E.G. Strauss, T.S. Baker, and J.H. Strauss Structure of dengue virus: implications for flavivirus organization, maturation, and fusion Cell 108 2002 717 725
19. B.M. Kümmerer, and C.M. Rice Mutations in the Yellow fever virus nonstructural protein NS2A selectively block production of infectious particles J. Virol. 76 2002 4773 4784
20. J. Lescar, D. Luo, T. Xu, A. Sampath, S.P. Lim, B. Canard, and S.G. Vasudevan Towards the design of antiviral inhibitors against flaviviruses: the case for the multifunctional NS3 protein from Dengue virus as a target Antiviral Res. 80 2008 94 101
21. X.-D. Li, H.-Q. Ye, C.-L. Deng, S.-Q. Liu, H.-L. Zhang, B.-D. Shang, P.-Y. Shi, Z.-M. Yuan, and B. Zhang Genetic interaction between NS4A and NS4B for replication of Japanese encephalitis virus J. Gen. Virol. 2015 10.1099/vir.0.000044
22. C. Lin, S.M. Amberg, T.J. Chambers, and C.M. Rice Cleavage at a novel site in the NS4A region by the yellow fever virus NS2B-3 proteinase is a prerequisite for processing at the downstream 4A/4B signalase site J. Virol. 67 1993 2327 2335
23. B.D. Lindenbach, H.-J. Thiel, and C.M. Rice Flaviviridae: the viruses and their replication P.M. Howley, D.M. Knipe, Fields Virol. 5th ed. 2007 Lippincott William & Wilkins Philadelphia, PA 1101 1152
24. W.J. Liu, X.J. Wang, V.V. Mokhonov, P.-Y. Shi, R. Randall, and A.A. Khromykh Inhibition of interferon signaling by the New York 99 Strain and Kunjin subtype of West Nile virus involves blockage of STAT1 and STAT2 activation by nonstructural proteins J. Virol. 79 2005 1934 1942
25. D. Luo, T. Xu, C. Hunke, G. Grüber, S.G. Vasudevan, and J. Lescar Crystal structure of the NS3 protease-helicase from dengue virus J. Virol. 82 2008 173 183
26. D. Mairiang, H. Zhang, A. Sodja, T. Murali, P. Suriyaphol, P. Malasit, T. Limjindaporn, and R.L. Finley Jr. Identification of new protein interactions between dengue fever virus and its hosts human and mosquito. PLoS One 8 2013 e53535
27. S. Miller, S. Kastner, J. Krijnse-Locker, S. Bühler, and R. Bartenschlager The non-structural protein 4A of dengue virus is an integral membrane protein inducing membrane alterations in a 2K-regulated manner J. Biol. Chem. 282 2007 8873 8882
28. S. Miller, S. Sparacio, and R. Bartenschlager Subcellular localization and membrane topology of the dengue virus type 2 non-structural protein 4B J. Biol. Chem. 281 2006 8854 8863
29. J.L. Muñoz-Jordán, M. Laurent-Rolle, J. Ashour, L. Martínez-Sobrido, M. Ashok, W.I. Lipkin, and A. García-Sastre Inhibition of alpha/beta interferon signaling by the NS4B protein of flaviviruses J. Virol. 79 2005 8004 8013
30. J.L. Muñoz-Jordán, G.G. Sánchez-Burgos, M. Laurent-Rolle, and A. García-Sastre Inhibition of interferon signaling by dengue virus Proc. Natl. Acad. Sci. 100 2003 14333 14338
31. 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
32. C.G. Noble, and P.Y. Shi Structural biology of dengue virus enzymes: towards rational design of therapeutics Antiviral Res. 96 2012 115 126
33. C.G. Patkar, M. Larsen, M. Owston, J.L. Smith, and R.J. Kuhn Identification of inhibitors of yellow fever virus replication using a replicon-based high-throughput assay Antimicrob. Agents Chemother. 53 2009 4103 4114
34. R. Perera, and R.J. Kuhn Structural proteomics of dengue virus Curr. Opin. Microbiol. 11 2008 369 377
35. R. Rai, and J. Deval New opportunities in anti-hepatitis C virus drug discovery: targeting NS4B Antiviral Res. 90 2011 93 101
36. D. Ray, A. Shah, M. Tilgner, Y. Guo, Y. Zhao, H. Dong, T.S. Deas, Y. Zhou, H. Li, and P.-Y. Shi West Nile virus 5′-cap structure is formed by sequential guanine N-7 and ribose 2′-O methylations by nonstructural protein 5 J. Virol. 80 2006 8362 8370
37. Roberts, C.D., and Peat, A.J., 2013. HCV replication inhibitors that interact with NS4B, In: Manoj C. Desai, N.A.M., David, E. Thurston (Eds.), Successful Strategies for the Discovery of Antiviral Drugs. Royal Society of Chemistry.
38. Suk-Fong Lok, A., 2013. HCV NS5A Inhibitors in Development, Clinics in Liver Disease Novel and Combination Therapies for Hepatitis C Virus, pp. 111-121.
39. S. Tajima, T. Takasaki, and I. Kurane Restoration of replication-defective dengue type 1 virus bearing mutations in the N-terminal cytoplasmic portion of NS4A by additional mutations in NS4B Arch. Virol. 156 2011 63 69
40. I. Umareddy, A. Chao, A. Sampath, F. Gu, and S.G. Vasudevan Dengue virus NS4B interacts with NS3 and dissociates it from single-stranded RNA J. Gen. Virol. 87 2006 2605 2614
41. K.W.R. van Cleef, G.J. Overheul, M.C. Thomassen, S.J.F. Kaptein, A.D. Davidson, M. Jacobs, J. Neyts, F.J.M. van Kuppeveld, and R.P. van Rij Identification of a new dengue virus inhibitor that targets the viral NS4B protein and restricts genomic RNA replication Antiviral Res. 99 2013 165 171
42. Wang, Q., Dong, H., Zou, B., Karuna, R., Wan, K.F., Zou, J., Susila, A., Yip, J.T., Xu, H., Ding, M., Chan, W.L., Gu, F., Seah, P.G., Liu, W., Lakshminarayana, S.B., Kang, C., Julien, L., Blasco, F., Smith, P.W., Shi, P.-Y., 2015. Discovery of dengue virus NS4B inhibitors. Submitted for publication.
43. 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
44. E.G. Westaway, A.A. Khromykh, M.T. Kenney, J.M. Mackenzie, and M.K. Jones Proteins C and NS4B of the flavivirus Kunjin translocate independently into the nucleus Virology 234 1997 31 41
45. 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
46. J. Whitehorn, S. Yacoub, K.L. Anders, L.R. Macareo, M.C. Cassetti, V.C. Nguyen Van, P.-Y. Shi, B. Wills, and C.P. Simmons Dengue therapeutics, chemoprophylaxis, and allied tools: state of the art and future directions PLoS. Negl. Trop. Dis. 8 2014 e3025
47. J.A. Wicker, M.C. Whiteman, D.W.C. Beasley, C.T. Davis, C.E. McGee, J.C. Lee, S. Higgs, R.M. Kinney, C.Y.H. Huang, and A.D.T. Barrett Mutational analysis of the West Nile virus NS4B protein Virology 426 2012 22 33
48. J.A. Wicker, M.C. Whiteman, D.W.C. Beasley, C.T. Davis, S. Zhang, B.S. Schneider, S. Higgs, R.M. Kinney, and A.D.T. Barrett A single amino acid substitution in the central portion of the West Nile virus NS4B protein confers a highly attenuated phenotype in mice Virology 349 2006 245 253
49. G. Xie, T. Welte, J. Wang, M.C. Whiteman, J.A. Wicker, V. Saxena, Y. Cong, A.D.T. Barrett, and T. Wang A West Nile virus NS4B-P38G mutant strain induces adaptive immunity via TLR7-MyD88-dependent and independent signaling pathways Vaccine 31 2013 4143 4151
50. X. Xie, Q.-Y. Wang, H.Y. Xu, M. Qing, L. Kramer, Z. Yuan, and P.-Y. Shi Inhibition of dengue virus by targeting viral ns4b protein J. Virol. 85 2011 11183 11195
51. X. Xie, J. Zou, Q.-Y. Wang, C.G. Noble, J. Lescar, and P.-Y. Shi Generation and characterization of mouse monoclonal antibodies against NS4B protein of dengue virus Virology 450-451 2014 250 257
52. 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 Å J. Virol. 79 2005 10278 10288
53. 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
54. S. Youn, T. Li, B.T. McCune, M.A. Edeling, D.H. Fremont, I.M. Cristea, and M.S. Diamond Evidence for a genetic and physical interaction between nonstructural proteins ns1 and ns4b that modulates replication of West Nile virus J. Virol. 86 2012 7360 7371
55. G.-Y. Yu, K.-J. Lee, L. Gao, and M.M.C. Lai Palmitoylation and polymerization of hepatitis C virus NS4B protein J. Virol. 80 2006 6013 6023
56. L. Yu, K. Takeda, and L. Markoff Protein-protein interactions among West Nile non-structural proteins and transmembrane complex formation in mammalian cells Virology 446 2013 365 377
57. J. Zou, L.T. Lee, Q.-Y. Wang, X. Xie, S. Lu, Y.H. Yau, S.G. Shochat, C. Kang, P.-Y. Shi, and J. Lescar Mapping the interactions between the NS4B and NS3 proteins of dengue virus J. Virol. 2015 (in press)
58. J. Zou, X. Xie, L.T. Lee, R. Chandrasekaran, A. Reynaud, L. Yap, Q.-Y. Wang, H. Dong, C. Kang, Z. Yuan, J. Lescar, and P.-Y. Shi Dimerization of flavivirus NS4B protein J. Virol. 88 2014 3379 3391
59. J. Zou, X. Xie, Q. Wang, H. Dong, M.Y. Lee, C. Kang, Z. Yuan, and P.-Y. Shi Characterization of dengue virus NS4A and NS4B protein interaction J. Virol. 2015 (in press)