Emerging therapies for hepatitis C virus infection

Emerging Drugs

Volumn 6, Issue 1, 2001, Pages 13-42

  Dymock, B W ^a  

^a ROCHE PRODUCTS LTD   (United Kingdom)

Author keywords

CD81; Hepatitis C virus; IMPDH; Interferon; IRES; NS3 helicase; NS3 serine protease; Peptide inhibitors; RNA dependent RNA polymerase

Indexed keywords

2 OXOACID; ALDEHYDE DERIVATIVE; AMIDE; BENZIMIDAZOLE DERIVATIVE; BORONIC ACID DERIVATIVE; CARBOXYLIC ACID DERIVATIVE; CONSENSUS INTERFERON; HELICASE; HISTAMINE; INOSINATE DEHYDROGENASE; INTERFERON; KETONE DERIVATIVE; MAXAMINE; PEPTIDE DERIVATIVE; PHOSPHONIC ACID DERIVATIVE; RD 3 4082; RD 4 6250; REBETRON; RECOMBINANT ALPHA2A INTERFERON; RECOMBINANT ALPHA2B INTERFERON; RIBAVIRIN; SCH 351633; SCH 68631; SERINE PROTEINASE; THYMOSIN ALPHA1; UNCLASSIFIED DRUG; UNINDEXED DRUG; UREA DERIVATIVE; VIRTRON;

CLINICAL TRIAL; DRUG EFFICACY; DRUG POTENCY; DRUG TARGETING; ENZYME INHIBITION; GENOTYPE; HEPATITIS C; HEPATITIS C VIRUS; HUMAN; NONHUMAN; PHYSICAL CHEMISTRY; PROTEIN STRUCTURE; REVIEW;

EID: 0035027046     PISSN: 13619195     EISSN: None     Source Type: Journal    
DOI: 10.1517/14728214.6.1.13     Document Type: Review

References (173)

1. Epidemiology of viral hepatitis: An overview
2. Hepatitis C: Progress and problems
3. The scientific challenge of hepatitis C
4. Public health effort unwittingly spread HCV
5. The prevalence of hepatitis C virus infection in the United States, 1988 through 1994
6. Replication of hepatitis C virus
7. Molecular targets in inhibition of hepatitis C virus replication
8. Risk factors for the rising rates of primary liver cancer in the United States
9. Hepatitis C virus dynamics in vivo and the antiviral efficacy of interferon-α therapy
10. Hepatitis C virus: Current understanding and prospects for future therapies
11. Hepatitis B and C viruses: Molecular identification and targeted antiviral therapies
12. The treatment of chronic viral hepatitis
13. Broad spectrum antiviral activity of Virazole: 1-β-D-ribofuranosyl-1,2,4-triazole-3-carboxamide
14. Interferon-alpha-2b alone or in combination with ribavirin as initial treatment for chronic hepatitis C
15. Interferon-alpha-2b alone or in combination with ribavirin for the treatment of relapse of chronic hepatitis C
16. Multinational evaluation of the efficacy and safety of once-weekly peginterferon α-2a (PEG-IFN) in patients with chronic hepatitis C (CHC) with compensated cirrhosis
17. A controlled, randomized, multicenter, descending dose Phase II trial of pegylated interferon-alpha-2a (PEG) vs. standard interferon alpha-2a (IFN) for treatment of chronic hepatitis C
18. Peginterferon alpha-2a in patients with chronic hepatitis C
19. Peginterferon alpha-2a in patients with chronic hepatitis C and cirrhosis
20. Hepatitis C virus encoded proteins: Targets for antiviral therapy
21. Cell-based and animal models for hepatitis B and C viruses
22. Hepatitis C virus viremia in SCID BNX mouse chimera
23. The Trimera mouse: An HBV and HCV infection model for the evaluation of antiviral drugs
24. In vitro infection of adult normal human hepatocytes in primary culture by hepatitis C virus
25. Replication of subgenomic hepatitis C virus RNAs in a hepatoma cell line
26. Molecular virology of hepatitis C virus
27. Biosynthesis and biochemical properties of the hepatitis C virus core protein
28. Homotypic interaction and multimerization of hepatitis C core protein
29. Characterization of hepatitis C virus envelope glycoprotein complexes expressed by recombinant vaccinia viruses
30. Formation and intracellular localisation of hepatitis C virus envelope glycoprotein complexes expressed by recombinant vaccinia and sindbis viruses
31. Complex processing and protein: Protein interactions in the E2: NS2 region of HCV
32. Inhibition of the interferon-inducible protein kinase PKR by HCV E2 protein
33. Proteolytic processing and membrane association of putative non-structural proteins of hepatitis C virus
34. A second hepatitis C virus-encoded proteinase
35. Two distinct proteinase activities required for the processing of a putative non-structural precursor protein of hepatitis C virus
36. In vitro study of the NS2-3 protease of hepatitis C virus
37. Mechanism of autoproteolysis at the NS2-NS3 junction of the hepatitis C virus polyprotein
38. Characterization and mutational analysis of the helicase and NTPase activities of hepatitis C virus full-length NS3 protein
39. Complex formation between the NS3 serine-type proteinase of the hepatitis C virus and NS4A and its importance for polyprotein maturation
40. Nonstructural protein 3 of the hepatitis C virus encodes a serine-type proteinase required for cleavage at the NS3/4 and NS4/5 junctions
41. Recombinant baculovirus-expressed NS3 proteinase of hepatitis C virus shows activity in cell-based and in vitro assays
42. Recent progress on NS3 protease as an HCV drug target
43. Mechanisms of hepatitis C virus NS3 proteinase inhibitors
44. Hepatitis C virus NS3/4A protease
45. Erratum to 'Hepatitis C virus NS3/4A protease' [Antiviral Res. (1998) 40:1-18]
46. NS3-4A of hepatitis C virus is a chymotrypsin-like protease
47. Synthetic inhibitors of elastase
48. The design and synthesis of potent inhibitors of hepatitis C virus NS3-4A proteinase
49. Solid phase synthesis of aminoboronic acids: Potent inhibitors of the hepatitis C virus NS3 proteinase
50. The identification of α-ketoamides as potent inhibitors of hepatitis C virus NS3-4A proteinase
51. α-Ketoamides, α-ketoesters and α-diketones as HCV NS3 protease inhibitors
52. α-Ketoacids are potent slow binding inhibitors of the hepatitis C virus NS3 protease
53. Optimization of the P′-region of peptide inhibitors of hepatitis C virus NS3/4A protease
54. Peptide-based inhibitors of the hepatitis C virus serine protease
55. Studies on the C-terminus of hexapeptide inhibitors of the hepatitis C virus serine protease
56. Potent peptide inhibitors of human hepatitis C virus NS3 protease are obtained by optimising the cleavage products
57. Highly potent and selective peptide-based inhibitors of the hepatitis C virus serine protease: Towards smaller inhibitors
58. Novel HCV protease inhibitors: 2,4,6-Trihydroxy-3-nitro-benzamide derivatives
59. Erratum: Novel HCV protease inhibitors: 2,4,6-Trihydroxy-3-nitro-benzamide derivatives
60. Establishment of an in vitro assay system for screening hepatitis C virus protease inhibitors using high performance liquid chromatography
61. Novel HCV protease inhibitors: Thiazolidine derivatives
62. Non-peptide inhibitors of HCV serine proteinase
63. An enzyme-linked immunosorbent assay for detecting proteolytic activity of hepatitis C virus proteinase
64. Structure of SCH 68631: A new HCV proteinase inhibitor from Streptomyces sp.
65. Isolation and structure of SCH 68631: A novel (HCV) NS3 protease inhibitor from the fungus Penicillium griseofulvum
66. Design of selective eglin inhibitors of HCV NS3 proteinase
67. Interscaffolding additivity. Association of P1 variants of eglin c and of turkey ovomucoid third domain with serine proteinases
68. Structure of the elastase-cathepsin G inhibitor of the leech Hirudo medicinalis
69. Characterisation of engineered hepatitis C virus NS3 protease inhibitors affinity selected from human pancreatic secretory trypsin inhibitor and minibody repertoires
70. Isolation and characterisation of monoclonal antibodies that inhibit hepatitis C virus NS3 protease
71. Selection of RNA aptamers that bind specifically to the NS3 protease of hepatitis C virus
72. Isolation of RNA aptamers specific to the NS3 protein of hepatitis C virus from a pool of completely random RNA
73. The crystal structure of hepatitis C virus NS3 proteinase reveals a trypsin-like fold and a structural zinc binding site
74. The conformation of hepatitis C virus NS3 proteinase with and without NS4A: A structural basis for the activation of the enzyme by its cofactor
75. Crystal structure of the hepatitis C virus NS3 protease domain complexed with a synthetic NS4A cofactor peptide
76. Complex of NS3 protease and NS4A peptide of BK strain hepatitis C virus: A 2.2A resolution structure in a hexagonal crystal form
77. Conformation changes in hepatitis C virus NS3 proteinase during NS4A complexation: Correlation with enhanced cleavage and implications for inhibitor design
78. Solution structure of substrate-based ligands when bound to hepatitis C virus NS3 protease domain
79. The solution structure of the N-terminal protease domain of the hepatitis C virus (HCV) NS3 protein provides new insight into its activation and catalytic mechanism
80. Structural characterisation of the interactions of optimized product inhibitors with the N-terminal proteinase domain of the hepatitis C virus (HCV) NS3 protein by NMR and modelling studies
81. Structure-based mutagenesis study of hepatitis C virus NS3 helicase
82. Two related superfamilies of putative helicases involved in replication, recombination, repair and expression of DNA and RNA genomes
83. Similarities in RNA helicases
84. A point mutation abolishes the helicase but not the nucleoside triphosphatase activity of hepatitis C virus NS3 protein
85. Mutational analysis of the hepatitis C virus RNA helicase
86. Functional interactions between conserved motifs of the hepatitis C virus RNA helicase protein NS3
87. DNA helicase activity of the hepatitis C virus nonstructural protein 3
88. The helicase activity associated with hepatitis C virus non-structural protein 3 (NS3)
89. Hepatitis C virus NS3 RNA helicase domain with a bound oligonucleotide: The crystal structure provides insights into the mode of unwinding
90. Construction, expression and characterisation of a novel, fully activated recombinant single-chain hepatitis C virus protease
91. A novel recombinant single-chain hepatitis C virus NS3-NS4A protein with improved helicase activity
92. Polynucleotide modulation of the protease, nucleoside triphosphate and helicase activities of a hepatitis C virus NS3-4A complex isolated from transfected COS cells
93. Modulation of hepatitis C virus NS3 protease and helicase activities through the interaction with NS4A
94. Serine protease of hepatitis C virus expressed in insect cells as the NS3/4A complex
95. Inhibition of hepatitis C virus NS3 protease activity by product-based peptides is dependent on helicase domain
96. Subcellular localisation of NS3 in HCV-infected hepatocytes
97. Molecular views of viral polyprotein processing revealed by the crystal structure of the hepatitis C virus bifunctional protease-helicase
98. Identification of the sequence on NS4A required for enhanced cleavage of the NS5A/5B site by hepatitis C virus NS3 protease
99. Hepatitis C virus non-structural 5A protein as a therapeutic target
100. The NS5A/NS5 proteins of viruses from three genera of the family Flaviridae are phosphorylated by associated serine/threonine kinases
101. Identification of the major phosphorylation site of the hepatitis C virus H strain NS5A protein as serine 2321
102. Phosphorylation of hepatitis C virus-encoded nonstructural protein NS5A
103. The N-terminal region of hepatitis C virus-encoded NS5A is important for NS4A-dependent phosphorylation
104. Hepatitis C virus NS5A binds RNA-dependent RNA polymerase (RdRp) NS5B and augments the RdRp activity
105. Molecular cloning and characterisation of the human double-stranded RNA-activated protein kinase induced by interferon
106. The double-stranded RNA-dependant protein kinase PKR: Structure and function
107. Evidence that hepatitis C virus resistant to interferon is mediated through repression of the PKR protein kinase by the non-structural 5A protein
108. Statistical analysis of combined substitutions in nonstructural 5A region of hepatitis C virus and interferon response
109. Integrity of the NS5A (amino acid 2209 to 2248) region in hepatitis C virus 1b patients non-responsive to interferon therapy
110. Comparison of full-length sequences of interferon sensitive and resistant hepatitis C virus 1b
111. Mutations in the non-structural protein 5A gene and response to interferon in patients with chronic hepatitis C virus lb infection
112. Mutations in the NS5A region of hepatitis C virus genome correlate with presence of NS5A antibodies and response to interferon therapy for most common European hepatitis C virus genotypes
113. Expression of recombinant hepatitis C virus non-structural protein 5B in Escherichia coli
114. Identification and properties of the RNA-dependent RNA polymerase of hepatitis C virus
115. Biochemical properties of hepatitis C virus NS5B RNA-dependent RNA polymerase and identification of amino acid sequence motifs essential for enzymatic activity
116. Biochemical and structural analysis of the NS5B RNA-dependent RNA polymerase of the hepatitis C virus
117. Recent advances in the analysis of HCV NS5B RNA-dependent RNA polymerase
118. Primary structural comparison of RNA-dependent polymerases from plant, animal and bacterial viruses
119. Characterization of soluble hepatitis C virus RNA-dependent RNA polymerase expressed in Escherichia coli
120. Expression of hepatitis C virus NS5B protein: Characterization of its RNA polymerase activity and RNA binding
121. Selective stimulation of hepatitis C virus and pestivirus NS5B RNA polymerase activity by GTP
122. RNA-dependent RNA polymerase activity of the soluble recombinant hepatitis C virus NS5B protein truncated at the C-terminal region
123. Expression, purification and partial characterization of HCV RNA polymerase
124. Hepatitis C virus NS5B protein is a membrane-associated phosphoprotein with a predominately perinuclear localisation
125. Complex formation of NS5B with NS3 and NS4A proteins of hepatitis C virus
126. Template requirement and initiation site selection by hepatitis C virus polymerase on a minimal viral template
127. Specific interaction between the hepatitis C virus NS5B RNA polymerase and the 3′ end of the viral RNA
128. Structure of the RNA-dependent RNA polymerase of poliovirus
129. Analysis of RNA-dependent RNA polymerase structure and function as guided by known polymerase structures and computer predictions of secondary structure
130. Crystal structure of the RNA-dependent RNA polymerase from hepatitis C virus reveals a fully encircled active site
131. Crystal structure of the RNA-dependent RNA polymerase of hepatitis C virus
132. Crystal structure of the RNA-dependent RNA polymerase of hepatitis C virus
133. Biochemical and kinetic analyses of NS5B RNA-dependent RNA polymerase of the hepatitis C virus
134. Diketobutanoic acids as HCV Pol inhibitors
135. Nucleoside analogues with anti-viral activity on bovine viral diarrhoea virus as candidate inhibitors of hepatitis C RNA-dependent RNA polymerase, Poster L14
136. Identification of cellular activators of hepatitis C virus internal ribosome entry site (HCV IRES) - Mediated translation using a randomized hairpin ribozyme library
137. Future directions in the treatment of patients with chronic hepatitis C virus infection
138. Hepatitis C viral IRES inhibition by phenazine and phenazine-like molecules
139. Oligonucleotides surge into clinical trials
140. Antisense oligonucleotides as therapeutic agents
141. Antisense oligonucleotides as therapeutic agents - Is the bullet really magical?
142. Antisense nucleic acids - Prospects for antiviral intervention
143. Phosphorothioate oligodeoxynucleotides - Antisense inhibitors of gene expression
144. Specific inhibition of hepatitis C viral gene expression by anitisense phosphorothioate oligodeoxynucleotides
145. Core specific anitisense phosphorothioate oligodeoxynucleotides as potent and specific inhibitors of hepatitis C viral translation
146. Antiviral effects of antisense RNA on hepatitis C virus RNA translation and expression
147. Antisense oligonucleotide inhibition of hepatitis C virus (HCV) gene expression in livers of mice infected with an HCV-vaccinia virus recombinant
148. Antisense oligonucleotide inhibition of hepatitis C virus gene expression in transformed hepatocytes
149. Comparative inhibitory potential of differently modified antisense oligodeoxynucleotides on hepatitis C virus translation
150. Inhibition of hepatitis C virus (HCV)-RNA-dependent translation and replication of a chimeric HCV poliovirus using synthetic stabilized ribozymes
151. Inhibition of hepatitis C virus-directed expression by a DNA ribonuclease
152. Ribavirin for the respiratory syncytial virus lower respiratory tract infection. A systematic overview
153. Combination treatment for chronic hepatitis C: What is the role of ribavirin
154. The broad spectrum antiviral ribonucleoside ribavirin is an RNA virus mutagen
155. Use of the yellow fever virus vaccine strain 17D for the study of strategies for the treatment of yellow fever virus infections
156. Mode of action of ribavirin: Effect of nucleoside pool alterations on influenza virus ribonucleoprotein synthesis
157. IMP dehydrogenase, an enzyme linked with proliferation and malignancy
158. Enzymes essential for the biosynthesis of nucleic acid guanine; inosine 5′-phosphate dehydrogenase of Aerobacter aerogenes
159. Metabolism of 5-amino-1-β-D-ribofuranosyl-imidazole-4-carboxamide and related five-membered heterocycles to 5′-triphosphates in human blood and L5178Y cells
160. Mechanism of action of 1-β-D-ribofuranosyl-1,2,4triazole-3-carboxamide (Virazole), a new broad spectrum antiviral agent
161. X-ray crystal structure of the antiviral drug ribavirin monophosphate bound to IMP dehydrogenase. Poster 76
162. Antiviral efficacy of VX-497, a novel IMPDH inhibitor, or ribavirin in combination with interferon-α in encephalomyocarditis virus (EMCV) infected L929 cells. Poster 65
163. Broad-spectrum antiviral activity of the IMP dehydrogenase inhibitor VX-497: A comparison with ribavirin and demonstration of antiviral additivity with alpha interferon
164. Hepatitis C virus and other Flaviridae viruses enter cells via low density lipoprotein receptor
165. Binding of hepatitis C virus to CD81
166. Hepatitis C virus envelope protein E2 binds to CD81 of tamarins
167. Characterization of hepatitis C virus E2 glycoprotein interaction with a putative cellular receptor, CD81
168. Crystallisation and preliminary crystallographic studies on the large extracellular domain of human CD81, a tetraspanin receptor for hepatitis C virus