The small molecules AZD0530 and dasatinib inhibit dengue virus RNA replication via Fyn kinase

Journal of Virology

Volumn 87, Issue 13, 2013, Pages 7367-7381

  De Wispelaere, Melissanne ^a,b   LaCroix, Amy J ^a   Yang, Priscilla L ^a  

^a HARVARD MEDICAL SCHOOL   (United States)

^b INSTITUT PASTEUR   (France)

Author keywords

[No Author keywords available]

Indexed keywords

DASATINIB; NONSTRUCTURAL PROTEIN 4B; PROTEIN KINASE FYN; SARACATINIB;

ANIMAL CELL; ANTIVIRAL ACTIVITY; ARTICLE; CONTROLLED STUDY; DENGUE VIRUS 2; DRUG POTENCY; DRUG TARGETING; EMBRYO; GENE MUTATION; HUMAN; HUMAN CELL; MOUSE; NONHUMAN; PRIORITY JOURNAL; PROTEIN DEPLETION; PROTEIN DOMAIN; PROTEIN FUNCTION; RNA INTERFERENCE; RNA REPLICATION; VIRUS INHIBITION; VIRUS PARTICLE;

ANTIBODIES, MONOCLONAL; BENZODIOXOLES; BLOTTING, NORTHERN; BLOTTING, WESTERN; CELL SURVIVAL; DENGUE VIRUS; DIMETHYL SULFOXIDE; DNA PRIMERS; HEK293 CELLS; HUMANS; MYCOPHENOLIC ACID; POLYMERASE CHAIN REACTION; PROTEIN KINASE INHIBITORS; PROTO-ONCOGENE PROTEINS C-FYN; PYRIMIDINES; QUINAZOLINES; REPLICON; RNA INTERFERENCE; RNA, VIRAL; THIAZOLES; VIRUS REPLICATION;

EID: 84880385563     PISSN: 0022538X     EISSN: 10985514     Source Type: Journal    
DOI: 10.1128/JVI.00632-13     Document Type: Article

References (74)

1. Welsch S, Miller S, Romero-Brey I, Merz A, Bleck CKE, Walther P, Fuller SD, Antony C, Krijnse-Locker J, Bartenschlager R. 2009. Composition and three-dimensional architecture of the dengue virus replication and assembly sites. Cell Host Microbe 5:365-375.
2. Wengler G, Wengler G. 1993. The NS 3 nonstructural protein of flaviviruses contains an RNA triphosphatase activity. Virology 197:265-273.
3. Wengler G, Czaya G, Färber PM, Hegemann JH. 1991. In vitro synthesis of West Nile virus proteins indicates that the amino-terminal segment of the NS3 protein contains the active centre of the protease which cleaves the viral polyprotein after multiple basic amino acids. J. Gen. Virol. 72(Pt 4):851- 858.
4. Li H, Clum S, You S, Ebner KE, Padmanabhan R. 1999. The serine protease and RNA-stimulated nucleoside triphosphatase and RNA helicase functional domains of dengue virus type 2 NS3 converge within a region of 20 amino acids. J. Virol. 73:3108 -3116.
5. Khromykh AA, Kenney MT, Westaway EG. 1998. trans-Complementation of flavivirus RNA polymerase gene NS5 by using Kunjin virus repliconexpressing BHK cells. J. Virol. 72:7270-7279.
6. Ackermann M, Padmanabhan R. 2001. 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: 39926-39937.
7. Tan BH, Fu J, Sugrue RJ, Yap EH, Chan YC, Tan YH. 1996. Recombinant dengue type 1 virus NS5 protein expressed in Escherichia coli exhibits RNA-dependent RNA polymerase activity. Virology 216:317-325.
8. Egloff M-P, Decroly E, Malet H, Selisko B, Benarroch D, Ferron F, Canard B. 2007. 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. 372:723-736.
9. Khromykh AA, Sedlak PL, Guyatt KJ, Hall RA, Westaway EG. 1999. Efficient trans-complementation of the flavivirus Kunjin NS5 protein but not of the NS1 protein requires its coexpression with other components of the viral replicase. J. Virol. 73:10272-10280.
10. Lindenbach BD, Rice CM. 1999. Genetic interaction of flavivirus nonstructural proteins NS1 and NS4A as a determinant of replicase function. J. Virol. 73:4611- 4621.
11. Youn S, Li T, McCune BT, Edeling MA, Fremont DH, Cristea IM, Diamond MS. 2012. Evidence for a genetic and physical interaction between nonstructural proteins NS1 and NS4B that modulates replication of West Nile virus. J. Virol. 86:7360 -7371.
12. Miller S, Kastner S, Krijnse-Locker J, Buhler S, Bartenschlager R. 2007. The non-structural protein 4A of dengue virus is an integral membrane protein inducing membrane alterations in a 2K-regulated manner. J. Biol. Chem. 282:8873- 8882.
13. Kim JM, Yun SI, Song BH, Hahn YS, Lee CH, Oh HW, Lee YM. 2008. A single N-linked glycosylation site in the Japanese encephalitis virus prM protein is critical for cell type-specific prM protein biogenesis, virus particle release, and pathogenicity in mice. J. Virol. 82:7846 -7862.
14. Goto A, Yoshii K, Obara M, Ueki T, Mizutani T, Kariwa H, Takashima I. 2005. Role of the N-linked glycans of the prM and E envelope proteins in tick-borne encephalitis virus particle secretion. Vaccine 23:3043-3052.
15. Lee E, Leang SK, Davidson A, Lobigs M. 2010. Both E protein glycans adversely affect dengue virus infectivity but are beneficial for virion release. J. Virol. 84:5171-5180.
16. Schmidt AG, Yang PL, Harrison SC. 2010. Peptide inhibitors of denguevirus entry target a late-stage fusion intermediate. PLoS Pathog. 6:e1000851. doi:10.1371/journal.ppat.1000851.
17. Niyomrattanakit P, Chen YL, Dong H, Yin Z, Qing M, Glickman JF, Lin K, Mueller D, Voshol H, Lim JYH, Nilar S, Keller TH, Shi PY. 2010. Inhibition of dengue virus polymerase by blocking of the RNA tunnel. J. Virol. 84:5678 -5686.
18. Chu JJH, Yang PL. 2007. c-Src protein kinase inhibitors block assembly and maturation of dengue virus. Proc. Natl. Acad. Sci. U. S. A. 104:3520- 3525.
19. Karaman MW, Herrgard S, Treiber DK, Gallant P, Atteridge CE, Campbell BT, Chan KW, Ciceri P, Davis MI, Edeen PT, Faraoni R, Floyd M, Hunt JP, Lockhart DJ, Milanov ZV, Morrison MJ, Pallares G, Patel HK, Pritchard S, Wodicka LM, Zarrinkar PP. 2008. A quantitative analysis of kinase inhibitor selectivity. Nat. Biotechnol. 26:127-132.
20. Polo S, Ketner G, Levis R, Falgout B. 1997. Infectious RNA transcripts from full-length dengue virus type 2 cDNA clones made in yeast. J. Virol. 71:5366 -5374.
21. de Wispelaere M, Yang PL. 2012. Mutagenesis of the DI/DIII linker in dengue virus envelope protein impairs viral particle assembly. J. Virol. 86:7072-7083.
22. Holden KL, Stein DA, Pierson TC, Ahmed AA, Clyde K, Iversen PL, Harris E. 2006. Inhibition of dengue virus translation and RNA synthesis by a morpholino oligomer targeted to the top of the terminal 3= stem-loop structure. Virology 344:439-452.
23. Bulich R, Aaskov JG. 1992. Nuclear localization of dengue 2 virus core protein detected with monoclonal antibodies. J. Gen. Virol. 73(Pt 11): 2999-3003.
24. Balsitis SJ, Coloma J, Castro G, Alava A, Flores D, McKerrow JH, Beatty PR, Harris E. 2009. Tropism of dengue virus in mice and humans defined by viral nonstructural protein 3-specific immunostaining. Am. J. Trop. Med. Hyg. 80:416-424.
25. Ansarah-Sobrinho C, Nelson S, Jost CA, Whitehead SS, Pierson TC. 2008. Temperature-dependent production of pseudoinfectious dengue reporter virus particles by complementation. Virology 381:67-74.
26. Pierson TC, Sánchez MD, Puffer BA, Ahmed AA, Geiss BJ, Valentine LE, Altamura LA, Diamond MS, Doms RW. 2006. A rapid and quantitative assay for measuring antibody-mediated neutralization of West Nile virus infection. Virology 346:53- 65.
27. Wang P-G, Kudelko M, Lo J, Siu LYL, Kwok KTH, Sachse M, Nicholls JM, Bruzzone R, Altmeyer RM, Nal B. 2009. Efficient assembly and secretion of recombinant subviral particles of the four dengue serotypes using native prM and E proteins. PLoS One 4:e8325. doi:10.1371/journal .pone.0008325.
28. Snead JL, O'Hare T, Adrian LT, Eide CA, Lange T, Druker BJ, Deininger MW. 2009. Acute dasatinib exposure commits Bcr-Abl-dependent cells to apoptosis. Blood 114:3459 -3463.
29. Allison AC, Kowalski WJ, Muller CD, Eugui EM. 1993. Mechanisms of action of mycophenolic acid. Ann. N. Y. Acad. Sci. 696:63- 87.
30. Diamond MS, Zachariah M, Harris E. 2002. Mycophenolic acid inhibits dengue virus infection by preventing replication of viral RNA. Virology 304:211-221.
31. Miller S, Sparacio S, Bartenschlager R. 2006. Subcellular localization and membrane topology of the dengue virus type 2 non-structural protein 4B. J. Biol. Chem. 281:8854-8863.
32. Muñoz-Jordán JL, Sánchez-Burgos GG, Laurent-Rolle M, Garcia-Sastre A. 2003. Inhibition of interferon signaling by dengue virus. Proc. Natl. Acad. Sci. U. S. A. 100:14333-14338.
33. Muñoz-Jordán JL, Laurent-Rolle M, Ashour J, Martínez-Sobrido L, Ashok M, Lipkin WI, Garcia-Sastre A. 2005. Inhibition of alpha/beta interferon signaling by the NS4B protein of flaviviruses. J. Virol. 79:8004- 8013.
34. Patkar CG, Larsen M, Owston M, Smith JL, Kuhn RJ. 2009. Identification of inhibitors of Yellow Fever virus replication using a replicon-based high-throughput assay. Antimicrob. Agents Chemother. 53:4103- 4114.
35. Puig-Basagoiti F, Tilgner M, Bennett CJ, Zhou Y, Muñoz-Jordán JL, Garcia-Sastre A, Bernard KA, Shi P-Y. 2007. A mouse cell-adapted NS4B mutation attenuates West Nile virus RNA synthesis. Virology 361:229- 241.
36. Kelly EP, Puri B, Sun W, Falgout B. 2010. Identification of mutations in a candidate dengue 4 vaccine strain 341750 PDK20 and construction of a full-length cDNA clone of the PDK20 vaccine candidate. Vaccine 28: 3030-3037.
37. Xie X, Wang QY, Xu HY, Qing M, Kramer L, Yuan Z, Shi PY. 2011. Inhibition of dengue virus by targeting viral NS4B protein. J. Virol. 85: 11183-11195.
38. Lombardo LJ, Lee FY, Chen P, Norris D, Barrish JC, Behnia K, Castaneda S, Cornelius LAM, Das J, Doweyko AM, Fairchild C, Hunt JT, Inigo I, Johnston K, Kamath A, Kan D, Klei H, Marathe P, Pang S, Peterson R, Pitt S, Schieven GL, Schmidt RJ, Tokarski J, Wen M-L, Wityak J, Borzilleri RM. 2004. Discovery of N-(2-chloro-6-methylphenyl)-2-(6-(4-(2-hydroxyethyl)-piperazin-1-yl)-2-methylpyrimidin-4-ylamino)thiazole-5-carboxamide (BMS-354825), a dual Src/Abl kinase inhibitor with potent antitumor activity in preclinical assays. J. Med. Chem. 47:6658-6661.
39. Hennequin LF, Allen J, Breed J, Curwen J, Fennell M, Green TP, Lambert-van der Brempt C, Morgentin R, Norman RA, Olivier A, Otterbein L, PIE PA, Warin N, Costello G. 2006. N-(5-Chloro-1,3-benzodioxol-4-yl)-7-[2-(4-methylpiperazin-1-yl)ethoxy]-5-(tetrahydro-2H-pyran-4-yloxy)quinazolin-4-amine, a novel, highly selective, orally available, dual-specific c-Src/Abl kinase inhibitor. J. Med. Chem. 49: 6465-6488.
40. Green TP, Fennell M, Whittaker R, Curwen J, Jacobs V, Allen J, Logie A, Hargreaves J, Hickinson DM, Wilkinson RW, Elvin P, Boyer B, Carragher N, PlE PA, Bermingham A, Holdgate GA, Ward WHJ, Hennequin LF, Davies BR, Costello GF. 2009. Preclinical anticancer activity of the potent, oral Src inhibitor AZD0530. Mol. Oncol. 3:248 -261.
41. Parsons SJ, Parsons JT. 2004. Src family kinases, key regulators of signal transduction. Oncogene 23:7906 -7909.
42. Pulvirenti T, Giannotta M, Capestrano M, Capitani M, Pisanu A, Polishchuk RS, Pietro ES, Beznoussenko GV, Mironov AA, Turacchio G, Hsu VW, Sallese M, Luini A. 2008. A traffic-activated Golgi-based signaling circuit coordinates the secretory pathway. Nat. Cell Biol. 10:912- 922.
43. Johnsen IB, Nguyen TT, Bergstroem B, Fitzgerald KA, Anthonsen MW. 2009. The tyrosine kinase c-Src enhances RIG-I (retinoic acid-inducible gene I)-elicited antiviral signaling. J. Biol. Chem. 284:19122-19131.
44. Johnsen IB, Nguyen TT, Ringdal M, Tryggestad AM, Bakke O, Lien E, Espevik T, Anthonsen MW. 2006. Toll-like receptor 3 associates with c-Src tyrosine kinase on endosomes to initiate antiviral signaling.EMBOJ. 25:3335-3346.
45. Manukyan M, Nalbant P, Luxen S, Hahn KM, Knaus UG. 2009. RhoA GTPase activation by TLR2 and TLR3 ligands: connecting via Src to NF-B. J. Immunol. 182:3522-3529.
46. Coyne CB, Bergelson JM. 2006. Virus-induced Abl and Fyn kinase signals permit coxsackievirus entry through epithelial tight junctions. Cell 124: 119-131.
47. Pfannkuche A, Büther K, Karthe J, Poenisch M, Bartenschlager R, Trilling M, Hengel H, Willbold D, Häussinger D, Bode JG. 2011. C-Src is required for complex formation between the hepatitis C virus-encoded proteins NS5A and NS5B: a prerequisite for replication. Hepatology 53: 1127-1136.
48. Supekova L, Supek F, Lee J, Chen S, Gray N, Pezacki JP, Schlapbach A, Schultz PG. 2008. Identification of human kinases involved in hepatitis C virus replication by small interference RNA library screening. J. Biol. Chem. 283:29 -36.
49. Hirsch AJ, Medigeshi GR, Meyers HL, DeFilippis V, Früh K, Briese T, Lipkin WI, Nelson JA. 2005. The Src family kinase c-Yes is required for maturation of West Nile virus particles. J. Virol. 79:11943-11951.
50. Thomas SM, Brugge JS. 1997. Cellular functions regulated by Src family kinases. Annu. Rev. Cell Dev. Biol. 13:513- 609.
51. Sandilands E, Brunton VG, Frame MC. 2007. The membrane targeting and spatial activation of Src, Yes and Fyn is influenced by palmitoylation and distinct RhoB/RhoD endosome requirements. J. Cell Sci. 120:2555- 2564.
52. Kapoor M, Zhang L, Ramachandra M, Kusukawa J, Ebner KE, Padmanabhan R. 1995. Association between NS3 and NS5 proteins of dengue virus type 2 in the putative RNA replicase is linked to differential phosphorylation of NS5. J. Biol. Chem. 270:19100 -19106.
53. Bhattacharya D, Mayuri Best SM, Perera R, Kuhn RJ, Striker R. 2009. Protein kinase G phosphorylates mosquito-borne flavivirus NS5. J. Virol. 83:9195-9205.
54. Raung S-L, Chen S-Y, Liao S-L, Chen J-H, Chen C-J. 2007. Japanese encephalitis virus infection stimulates Src tyrosine kinase in neuron/glia. Neurosci. Lett. 419:263-268.
55. Shimakami T, Hijikata M, Luo H, Ma YY, Kaneko S, Shimotohno K, Murakami S. 2004. Effect of interaction between hepatitis C virus NS5A and NS5B on hepatitis C virus RNA replication with the hepatitis C virus replicon. J. Virol. 78:2738 -2748.
56. Frasson M, Vitadello M, Brunati AM, La Rocca N, Tibaldi E, Pinna LA, Gorza L, Donella-Deana A. 2009. Grp94 is Tyr-phosphorylated by Fyn in the lumen of the endoplasmic reticulum and translocates to Golgi in differentiating myoblasts. BBA Mol. Cell Res. 1793:239 -252.
57. Blaney JE, Manipon GG, Firestone CY, Johnson DH, Hanson CT, Murphy BR, Whitehead SS. 2003. Mutations which enhance the replication of dengue virus type 4 and an antigenic chimeric dengue virus type 2/4 vaccine candidate in Vero cells. Vaccine 21:4317- 4327.
58. Tajima S, Takasaki T, Kurane I. 2010. Restoration of replicationdefective dengue type 1 virus bearing mutations in the N-terminal cytoplasmic portion of NS4A by additional mutations in NS4B. Arch. Virol. 156:63- 69.
59. Tang W-F, Eshita Y, Tadano M, Morita K, Makino Y. 2005. Molecular basis for adaptation of a chimeric dengue type-4/Japanese encephalitis virus to Vero cells. Microbiol. Immunol. 49:285-294.
60. Zou G, Xu HY, Qing M, Wang Q-Y, Shi P-Y. 2011. Development and characterization of a stable luciferase dengue virus for high-throughput screening. Antivir. Res. 91:11-19.
61. Umareddy I, Chao A, Sampath A, Gu F, Vasudevan SG. 2006. Dengue virus NS4B interacts with NS3 and dissociates it from single-stranded RNA. J. Gen. Virol. 87:2605-2614.
62. Hanley KA, Manlucu LR, Gilmore LE, Blaney JE, Jr, Hanson CT, Murphy BR, Whitehead SS. 2003. A trade-off in replication in mosquito versus mammalian systems conferred by a point mutation in the NS4B protein of dengue virus type 4. Virology 312:222-232.
63. Coffey LL, Beeharry Y, Borderia AV, Blanc H, Vignuzzi M. 2011. Arbovirus high-fidelity variant loses fitness in mosquitoes and mice. Proc. Natl. Acad. Sci. U. S. A. 108:16038 -16043.
64. Bain J, Plater L, Elliott M, Shpiro N, Hastie CJ, McLauchlan H, Klevernic I, Arthur JSC, Alessi DR, Cohen P. 2007. The selectivity of protein kinase inhibitors: a further update. Biochem. J. 408:297-315.
65. Brandvold KR, Steffey ME, Fox CC, Soellner MB. 2012. Development of a highly selective c-Src kinase inhibitor. ACS Chem. Biol. 7:1393-1398.
66. Chang G-JJ, Hunt AR, Holmes DA, Springfield T, Chiueh T-S, Roehrig JT, Gubler DJ. 2003. Enhancing biosynthesis and secretion of premembrane and envelope proteins by the chimeric plasmid of dengue virus type 2 and Japanese encephalitis virus. Virology 306:170 -180.
67. Purdy DE, Chang G-JJ. 2005. Secretion of noninfectious dengue viruslike particles and identification of amino acids in the stem region involved in intracellular retention of envelope protein. Virology 333:239 -250.
68. Puls LN, Eadens M, Messersmith W. 2011. Current status of SRC inhibitors in solid tumor malignancies. Oncologist 16:566 -578.
69. Knight ZA, Lin H, Shokat KM. 2010. Targeting the cancer kinome through polypharmacology Nat. Rev. Cancer 10:130 -137.
70. Apsel B, Blair JA, Gonzalez B, Nazif TM, Feldman ME, Aizenstein B, Hoffman R, Williams RL, Shokat KM, Knight ZA. 2008. Targeted polypharmacology: discovery of dual inhibitors of tyrosine and phosphoinositide kinases. Nat. Chem. Biol. 4:691- 699.
71. Balfour HH. 1984. Acyclovir and other chemotherapy for herpes group viral infections. Annu. Rev. Med. 35:279 -291.
72. Yang PL, Gao M, Lin K, Liu Q, Villareal VA. 2011. Anti-HCV drugs in the pipeline. Curr. Opin. Virol. 1:607- 616.
73. Mocroft A, Phillips AN, Ledergerber B, Katlama C, Chiesi A, Goebel F-D, Knysz B, Antunes F, Reiss P, Lundgren JD. 2006. Relationship between antiretrovirals used as part of a cART regimen and CD4 cell count increases in patients with suppressed viremia. AIDS 20:1141- 1150.
74. Dar AC, Das TK, Shokat KM, Cagan RL. 2012. Chemical genetic discovery of targets and anti-targets for cancer polypharmacology. Nature 486:80-84.