Strategies for the identification of inhibitors of West Nile virus and other flaviviruses

Current Opinion in Investigational Drugs

Volumn 3, Issue 11, 2002, Pages 1567-1573

  Shi, Pei Yong ^a  

^a STATE UNIVERSITY OF NEW YORK   (United States)

Author keywords

Flavivirus; RNase L; West Nile virus

Indexed keywords

1 (2' O METHYL BETA DEXTRO RIBOFURANOSYL)IMIDAZO[4,5 D]PYRIDAZINE 4,7(5H,6H) DIONE; 1 (4,5 DIHYDROXY 3 HYDROXYMETHYL 2 CYCLOPENTEN 1 YL)CYTOSINE; ALPHA GLUCOSIDASE INHIBITOR; ANTIVIRUS AGENT; AZARIBINE; AZAURIDINE; AZAURIDINE DERIVATIVE; HELICASE INHIBITOR; INOSINATE DEHYDROGENASE INHIBITOR; INTERFERON; MYCOPHENOLIC ACID; N NONYL DEOXYNOJIRIMYCIN; NUCLEOSIDE ANALOG; NUCLEOSIDE TRIPHOSPHATE; OROTIDINE MONOPHOSPHATE DECARBOXYLASE INHIBITOR; PIRAZOFURIN; PROTEINASE INHIBITOR; RIBAVIRIN; RIBONUCLEASE; RNA DIRECTED RNA POLYMERASE; RNA HELICASE; SERINE PROTEINASE INHIBITOR; UNCLASSIFIED DRUG; VIRUS RNA; VIRUS VACCINE;

AMINO ACID SEQUENCE; ANTIVIRAL ACTIVITY; ASSAY; DRUG DESIGN; DRUG MECHANISM; DRUG SCREENING; DRUG SENSITIVITY; DRUG TARGETING; ENZYME ACTIVITY; ENZYME INHIBITION; FLAVIVIRUS; GENE LIBRARY; GENE STRUCTURE; GENETIC ORGANIZATION; HUMAN; NONHUMAN; NUCLEOTIDE SEQUENCE; PUBLIC HEALTH; REVIEW; SIDE EFFECT; VIRION; VIRUS GENOME; VIRUS IDENTIFICATION; VIRUS INFECTION; VIRUS REPLICATION; WEST NILE FLAVIVIRUS;

ANIMALS; ANTIVIRAL AGENTS; DRUG DELIVERY SYSTEMS; FLAVIVIRUS; GENOME, VIRAL; HUMANS; WEST NILE VIRUS;

EID: 0036881355     PISSN: 14724472     EISSN: None     Source Type: Journal    
DOI: None     Document Type: Review

References (71)

1. Burke DS, Monath TP: Flaviviruses. In: Fields Virology, 4th Edition. Knipe DM, Howley PM (Eds), Lippincott William & Wilkins, Philadelphia, PA, USA (2001) 1:1043-1126. A comprehensive review of flavivirus evolution, pathogenesis and disease outcomes.
2. Petersen LR, Roehrig JT: West Nile virus: A reemerging global pathogen. Emerging Infect Dis (2001) 7(4):611-614.
3. Centers for Disease Control and Prevention: Guidelines for surveillance, prevention and control of West Nile virus infection - United States. Morbid Mortal Weekly Rep (2000) 49:25-28.
4. Marfin AA, Petersen LR, Eidson M, Miller J, Hadler J, Farello C, Werner B, Campbell GL, Layton M, Smith P, Bresnitz E et al: Widespread West Nile virus activity, eastern United States, 2000. Emerging Infect Dis (200) 7(4):730-735.
5. Centers for Disease Control and Prevention: Weekly update: West Nile virus activity - United States, November 14-20, 2001. Morbid Mortal Weekly Rep (2001) 50:1061-1062.
6. Hubalek Z, Halouzka J: West Nile fever - A reemerging mosquito-borne viral disease in Europe. Emerging Infect Dis (1999) 5(5):643-650.
7. Asnis DS, Conetta R, Teixeira AA, Waldman G, Sampson BA: The West Nile Virus outbreak of 1999 in New York: The Flushing Hospital experience. Clin Infect Dis (2000) 30(3):413-418.
8. Taylor R, Work T, Hurlbut H, Rizk F: A study of the ecology of West Nile virus in Egypt. Am J Trop Med Hyg (1956) 5:579-620.
9. Work T, Hurlbut H, Taylor R: Indigenous wildbirds of the Nile Delta as potential West Nile virus circulating reservoir. Am J Trop Med Hyg (1955) 4:872-878.
10. Cleaves GR, Dubin DT: Methylation status of intracellular dengue type 2 40S RNA. Virology (1979) 96(1):159-165.
11. Wengler G, Wengler G: Terminal sequences of the genome and replicative-from RNA of the flavivirus West Nile virus: Absence of poly(A) and possible role in RNA replication. Virology Virology (1981) 113(2):544-555.
12. Chambers TJ, Hahn CS, Galler R, Rice CM: Flavivirus genome organization, expression and replication. Annu Rev Microbiol (1990) 44:649-688. A comprehensive review of flavivirus gene expression and replication.
13. Muylaert IR, Galler R, Rice CM: Genetic analysis of the yellow fever virus NS1 protein: Identification of a temperature-sensitive mutation which blocks RNA accumulation. J Virol (1997) 71(1):291-298.
14. Lindenbach B, Rice C: Trans-complementation of yellow fever virus NS1 reveals a role in early RNA replication. J Virol (1997) 71(12):9608-9617.
15. Lindenbach BD, Rice CM: Genetic interaction of flavivirus nonstructural proteins NS1 and NS4A as a determinant of replicase function. J Virol (1999) 73(6):4611-4621.
16. Kummerer BM, Rice CM: Mutations in the yellow fever virus nonstructural protein NS2A selectivity block production of infectious particles. J Virol (2002) 76(10):4773-4784.
17. 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(11):6042-6050.
18. Chambers TJ, Nestorowicz A, Amberg SM, Rice CM: Mutagenesis of the yellow fever virus NS2B protein: Effects on proteolytic processing, NS2B-NS3 complex formation and viral replication. J Virol (1993) 67(11):6797-6807.
19. Arias CF, Preugschat F, Strauss JH: Dengue 2 virus NS2B and NS3 form a stable complex that can cleave NS3 within the helicase domain. Virology (1993) 193(2):888-899.
20. Falgout B, Miller RH, Lai CJ: Deletion analysis of dengue virus type 4 nonstructural protein NS2B: Identification of a domain required for NS2B-NS3 protease activity. J Virol (1993) 67(4):2034-2042.
21. Warrener P, Tamura JK, Collett MS: RNA-stimulated NTPase activity associated with yellow fever virus NS3 protein expressed in bacteria. J Virol (1993) 67(2):989-996.
22. Wengler G, Wengler G: The carboxy-terminal part of the NS3 protein of the West Nile flavivirus can be isolated as a soluble protein after proteolytic cleavage and represents an RNA-stimulated NTPase. Virology (1991) 184(2):707-715.
23. Li H, Clum S, You S, Ebner KE, Padmanabhan R: 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 (1999) 73(4):3108-3116.
24. Tan BH, Fu J, Sugrue RJ, Yap EH, Chan YC, Tan YH: Recombinant dengue type 1 virus NS5 protein expressed in Escherichia coli exhibits RNA-dependent RNA polymerase activity. Virology (1996) 216(2):317-325. This paper reported the RNA-dependent RNA polymerase activity of the NS5 protein of dengue virus, which could be used to develop an antiviral assay.
25. Ackermann M, Padmanabhan R: 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 (2001) 276:39926-39937. The RNA-dependent RNA polymerase activity of dengue virus NS5, described in this paper, could be modified to create an assay for screening flavivirus polymerase inhibitors.
26. Guyatt KJ, Westaway EG, Khromykh AA: Expression and purification of enzymatically active recombinant RNA-dependent RN polymerase (NS5) of the flavivirus Kunjin. J Virol Methods (2001) 92(1):37-44.
27. Koonin EV: Computer-assisted identification of a putative methyltransferase domain in NS5 protein of flaviviruses and lambda 2 protein of reovirus. J Gen Virol (1993) 74(Pt 4):733-740.
28. Muylaert IR, Chambers TJ, Galler R, Rice CM: Mutagenesis of the N-linked glycosylation sites of the yellow fever virus NS1 protein: Effects on virus replication and mouse neurovirulence. Virology (1996) 222(1):159-168.
29. Diamond MS, Edgil D, Roberts TG, Lu B, Harris E: Infection of human cells by dengue virus is modulated by different cell types and viral strains. J Virol (2000) 74(17):7814-7823.
30. Heinz FX, Allison SL: Structures and mechanisms in flavivirus fusion. Adv Virus Res (2000) 55:231-269.
31. Rey FA, Heinz FX, Mandl C, Kunz C, Harrison SC: The envelope glycoprotein from tick-borne encephalitis virus at 2Å resolution. Nature (1995) 375(6529):291-298. This is the first paper to report the crystal structure of the ectodomain of the E protein of flavivirus.
32. Murthy HM, Judge K, DeLucas L, Padmanabhan R: Crystal structure of dengue virus NS3 protease in complex with a Bowman-Birk inhibitor: Implications for flaviviral polyprotein processing and drug design. J Mol Biol (2000) 301(4):759-767. This paper reported the crystal structure of the NS3 protease domain complexed with a Bowman-Birk inhibitor. When compared with the NS3 alone, the inhibitor-ligand protease had a similar overall structure, but with significant differences in regions interacting with the inhibitor.
33. Murthy HM, Clum S, Padmanabhan P: Dengue virus NS3 serine protease. Crystical structure and insights into interaction of the active site with substrates by molecular modeling and structural analysis of mutational effects. J Biol Chem (1999) 274(9):5573-5580. This paper first reported the crystal structure of the NS3 protease domain that could be used for the rational design of flavivirus inhibitors.
34. Egloff MP, Benarroch D, Selisko B, Romette JL, Canard B: An RNA cap (nucleoside-2′-O-)-methyltransferase in th flavivirus RNA polymerase NS5: Crystal structure and functional characterization. EMBO J (2002) 21(11):2757-2768. This paper describes the crystal structure of the methyltransferase domain of NS5. In addition, the paper demonstrated, for the first time, the methyltransferase activity of NS5.
35. Wilkinson KF, Rush BD, Sharma SK, Evans DB, Ruwart MJ, Friis JM, Bohanon MJ, Tomich PK: Development of activity assays for high-volume evaluation of human immunodeficiency virus (HIV) protease inhibitors in rat serum: Results with ditekiren. Pharm Res (1993) 10(4):562-566.
36. Ingravallo P, Lahser F, Xia E, Sodowich B, Lai VC, Hong Z, Zhong W: Characterization of monoclonal antibodies that specifically recognize the palm subdomain of hepatitis C virus nonstructural protein 5B polymerase. Virus Res (2001) 75(2):179-187.
37. Morrey JD, Smee DF, Sidwell RW, Tseng C: Identification of active antiviral compounds against a New York isolate of West Nile virus. Antiviral Res (2002) 55(1):107-116. A panel of 34 compounds was tested for anti-WNV activity in a viral infection assay. The compounds 6-azauridine triacetate, cyclopententylcytosine, mycophenolic acid and pyrazofurin had good antiviral activity.
38. Jordan I, Briese T, Fischer N, Lau JY, Lipkin WI: Ribavirin inhibits West Nile virus replication and cytoplasmic effect in neuronal cells. J Infect Dis (2000) 182(4):1214-1217. Ribavirin displayed anti-WNV activity in a viral infection assay.
39. Wu S-F, Lee C-J, Liao C-L, Dwek R, Zitzmann N, Lin Y-L: Antiviral effects of an iminosugar derivative on flavivirus infections. J Virol (2002) 76(8):3596-3604. ER α-glucosidase inhibitors, which block the trimming stem in N-linked glycosylation, eliminated the production of several ER-budding viruses. One such inhibitor, N-nonyl-deoxynojirimycin, inhibited both JE and DEN viruses at micromolar levels.
40. Khromykh AA, Westaway EG: Subgenomic replicons of the flavivirus Kunjin: Construction and applications. J Virol (1997) 71(2):1497-1505.
41. Campbell MS, Pletnev AG: Infectious cDNA clones of Langat tick-borne flavivirus that differ from their parent in peripheral neurovirulence. Virology (2000) 269(1):225-237.
42. Hurrelbrink RJ, Nestorowicz A, McMinn PC: Characterization of infectious Murray Valley encephalitis virus derived from a stably cloned genome-length cDNA. J Gen Virol (1999) 80(Pt 12):3115-3125.
43. Kapoor M, Zhang L, Mohan PM, Padmanabhan R: Synthesis and characterization of an infectious dengue virus type-2 RNA genome (New Guinea C strain). Gene (1995) 162(2):175-180.
44. Khromykh AA, Westaway EG: Completion of Kunjin virus RNA sequence and recovery of an infectious RNA transcribed from stably cloned full-length cDNA. J Virol (1994) 68(7):4580-4588.
45. Lai CJ, Zhao BR, Hori H, Bray M: Infectious RNA transcribed from stably cloned full-length cDNA of dengue type 4 virus. Proc Natl Acad Sci USA (1991) 88(12):5139-5143.
46. Mandl CW, Ecker M, Holzmann H, Kunz C, Heinz FX: Infectious cDNA clones of tick-borne encephalitis virus European subtype prototypic strain Neudoerfl and high virulence strain Hypr. J Gen Virol (1997) 78(Pt 5):1049-1057.
47. Rice CM, Lenches EM, Eddy SR, Shin SJ, Sheets RL, Strauss JH: Nucleotide sequence of yellow fever virus: Implications for flavivirus gene expression and evolution. Science (1985) 229(4715):726-733.
48. Sumiyoshi H, Hoke CH, Trent DW: Infectious Japanese encephalitis virus RNA can be synthesized from in vitro-ligated cDNA templates. J Virol (1992) 66(9):5425-5431.
49. Polo S, Ketner G, Levis R, Falgout B: Infectious RNA transcripts from full-length dengue virus type 2 cDNA clones made in yeast. J Virol (1997) 71(7):5366-5374.
50. Shi PY, Tilgner M, Lo MK, Kent KA, Bernard KA: Infectious cDNA clone of the epidemic West Nile virus from New York city. J Virol (2002) 76(12):5847-5856. The first full-length infectious clone of the human epidemic strain of West Nile virus is produced.
51. Shi PY, Tilgner M, Lo MK: Construction and characterization of subgenomic replicons of New York strain of West Nile virus. Virology (2002) 296(2):219-233.
52. Yamshchikov VF, Wengler G, Perelygin AA, Brinton MA, Compans RW: An infectious clone of the West Nile flavivirus. Virology (2001) 281(2):294-304.
53. Khromykh AA, Varnavski AN, Westaway EG: Encapsidation of the flavivirus Kunjin replication RNA by using a complementation system providing Kunjin virus structural proteins in trans. J Virol (1998) 72(7):5967-5977.
54. Lanciotti RS, Roehrig JT, Deubel V, Smith J, Parker M, Steele K, Crise B, Volpe KE, Crabtree MB, Scherret JH, Hall RA et al: Origin of the West Nile virus responsible for an outbreak of encephalitis in the northeastern United States. Science (1999) 286(5448):2333-2337.
55. Berthet FX, Zeller HG, Drouet MT, Rauzier J, Digoutte JP, Duebel V: Extensive nucleotide changes and deletions within the envelope glycoprotein gene of Euro-African West Nile viruses. J Gen Virol (1997) 78(Pt 9):2293-2297.
56. Jordan I, Briese T, Lipkin WI: Discovery and molecular characterization of West Nile virus NY 1999. Viral Immunol (2000) 13(4):435-446.
57. Player MR, Torrence PF: The 2-5A system: Modulation of viral and cellular processes through acceleration of RNA degradation. Pharmacol Ther (1998) 78(2):55-113.
58. Perelygin AA, Scherbik SV, Zhulin IB, Stockman BM, Li Y, Brinton MA: Positional cloning of the murine flavivirus resistance gene. Proc Natl Acad Sci USA (2002) 99(14):9322-9327. The flavivirus resistance gene was identified as 2′-5′-oligoadenylate synthetase. This result indicated that the 2′-5′-oligoadenylate synthetase/RNase L pathway could be exploited to develop antiviral therapies.
59. Sabin AB: Genetic, hormonal and age factors in natural resistance to certain viruses. Ann NY Acad Sci (1952) 54:936-944.
60. Leaman DW, Longano FJ, Okicki JR, Soike KF, Torrence PF, Silverman RH, Cramer H: Targeted therapy of respiratory syncytial virus in African green monkeys by intranasally administered 2-5A antisense. Virology (2002) 292(1):70-77. This paper used the 2′-5′-oligoadenylate/RNase L pathway was used to develop antiviral therapy against respiratory syncytial virus.
61. Han J-Q, Barton DJ: Activation and evasion of the antiviral 2′-5′-oligoadenylate synthetase/ribonuclease L pathway by hepatitis C virus mRNA. RNA (2002) 8(4):512-525.
62. Koff WC, Elm JL Jr, Halstead SB: Antiviral effects of ribavirin and 6-mercapto-9-tetrahydro-2-furylpurine against dengue viruses in vitro. Antiviral Res (1982) 2(1-2):69-79. Ribavirin has antiviral activity against dengue virus.
63. Crotty S, Cameron CE, Andino R. RNA virus error catastrophe: Direct molecular test by using ribavirin. Proc Natl Acad Sci USA (2001) 98(12):6895-6900.
64. Graci JD, Cameron CE: Quasispecies, error catastrophe and the antiviral activity of ribavirin. Virology (2002) 298(2):175-180.
65. 50 value of approximately 30 μM in both enzyme and viral infection assays.
66. Leung D, Schroder K, White H, Fang N-X, Stoermer M, Abbenante G, Martin JL, Young PR, Fairlie DP: Activity of recombinant dengue 2 virus NS3 protease in the presence of a truncated NS2B co-factor, small peptide substrates and inhibitors. J Biol Chem (2001) 276(49):45762-45771. Peptidic compounds with α-keto amide backbones that mimicked the conserved cleavage sites (basic residues at the P2 and P1 positions and a residue with a small side chain at the P1′ position) of the substrates of the DEN NS3 protease, inhibited its activity and micromolar concentrations.
67. Jacob G: Glycosylation inhibitors in biology and medicine. Curr Opin Struct Biol (1995) 5(5):605-611.
68. McBride WJ, Bielefeldt-Ohmann H: Dengue viral infections: Pathogenesis and epidemiology. Microbes Infect (2000) 2(9):1041-1050.
69. Rosen L: Comments on the epidemiology, pathogenesis and control of dengue. Med Trop (1999) 59(4 Pt 2):495-498.
70. Lam PY, Jadhav PK, Eyermann CJ, Hodge CN, Ru Y, Bachelere LT, Meek JL, Otto MJ, Rayner MM, Wong YN et al: Rational design of potent, bioavailable, nonpeptide cyclic ureas as HIV protease inhibitors. Science (1994) 263(5145):380-384.
71. Ingallinella P, Fattori D, Altamura S, Steinkühler C, Koch U, Cicero D, Bazzo R, Cortese R, Bianchi E, Pessi A: Prime site binding inhibitors of a serine protease: NS3/4A of hepatitis C virus. Biochemistry (2002) 41(17):5483-5492.