The science of direct-acting antiviral and host-targeted agent therapy

Antiviral Therapy

Volumn 17, Issue 6 PART B, 2012, Pages 1109-1117

  Pawlotsky, Jean Michel ^a,b  

^a HENRI MONDOR HOSPITAL   (France)

^b INSERM U955   (France)

Author keywords

[No Author keywords available]

Indexed keywords

ANTIINFECTIVE AGENT; ANTIVIRUS AGENT; BOCEPREVIR; CYCLOPHILIN INHIBITOR; MICRORNA 122 ANTAGONIST; NON NUCLEOSIDE INHIBITOR; NONSTRUCTURAL PROTEIN 3; NONSTRUCTURAL PROTEIN 4A; NONSTRUCTURAL PROTEIN 5A INHIBITOR; NUCLEOSIDE DERIVATIVE; NUCLEOTIDE DERIVATIVE; PEGINTERFERON ALPHA; POLYPROTEIN; RIBAVIRIN; RNA DIRECTED RNA POLYMERASE; SCAVENGER RECEPTOR B 1 INHIBITOR; TELAPREVIR; UNCLASSIFIED DRUG; VIRUS RNA;

ANTIVIRAL RESISTANCE; BINDING AFFINITY; BINDING SITE; DRUG EFFICACY; DRUG POTENCY; DRUG PROTEIN BINDING; DRUG TARGETING; HEPATITIS C; HEPATITIS C VIRUS; HUMAN; LIFE CYCLE; MEMBRANE FUSION; MOLECULAR DYNAMICS; NONHUMAN; PRIORITY JOURNAL; PROTEIN PROCESSING; REVIEW; RNA TRANSLATION; VIRAL CLEARANCE; VIRUS ASSEMBLY; VIRUS ATTACHMENT; VIRUS ENTRY; VIRUS REPLICATION;

ADMINISTRATION, ORAL; ANTIVIRAL AGENTS; CYCLOPHILIN A; DRUG THERAPY, COMBINATION; HEPACIVIRUS; HEPATITIS C, CHRONIC; HUMANS; MICRORNAS; PROTEASE INHIBITORS; RNA REPLICASE; RNA, VIRAL; VIRAL NONSTRUCTURAL PROTEINS; VIRUS ASSEMBLY; VIRUS ATTACHMENT; VIRUS INTERNALIZATION; VIRUS RELEASE; VIRUS REPLICATION;

EID: 84867241787     PISSN: 13596535     EISSN: 20402058     Source Type: Journal    
DOI: 10.3851/IMP2423     Document Type: Review

References (84)

1. Pawlotsky JM, Chevaliez S, McHutchison JG. The hepatitis C virus life cycle as a target for new antiviral therapies. Gastroenterology 2007; 132: 1979-1998. Medline doi:10.1053/j.gastro.2007.03.116
2. Sarrazin C, Hezode C, Zeuzem S, Pawlotsky JM. Antiviral strategies in hepatitis C virus infection. J Hepatol 2012; 56 Suppl 1: S88- S100. Medline doi:10.1016/S0168-8278(12)60010-5
3. Hildebrandt-Eriksen ES, Aarup V, Persson R, Hansen HF, Munk ME, Orum H. A locked nucleic acid oligonucleotide targeting microRNA-122 is well-tolerated in Cynomolgus monkeys. Nucleic Acid Ther 2012; 22: 152-161. Medline
4. Barth H, Schafer C, Adah MI, et al. Cellular binding of hepatitis C virus envelope glycoprotein E2 requires cell surface heparan sulfate. J Biol Chem 2003; 278: 41003-41012. Medline doi:10.1074/jbc.M302267200
5. Barth H, Schnober EK, Zhang F, et al. Viral and cellular determinants of the hepatitis C virus envelope-heparan sulfate interaction. J Virol 2006; 80: 10579-10590. Medline doi:10.1128/JVI.00941-06
6. Agnello V, Abel G, Elfahal M, Knight GB, Zhang QX. Hepatitis C virus and other flaviviridae viruses enter cells via low density lipoprotein receptor. Proc Natl Acad Sci U S A 1999; 96: 12766-12771. Medline doi:10.1073/pnas.96.22. 12766
7. Albecka A, Belouzard S, de Beeck AO, et al. Role of low-density lipoprotein receptor in the hepatitis C virus life cycle. Hepatology 2012; 55: 998-1007. Medline doi:10.1002/hep.25501
8. Cormier EG, Tsamis F, Kajumo F, Durso RJ, Gardner JP, Dragic T. CD81 is an entry coreceptor for hepatitis C virus. Proc Natl Acad Sci U S A 2004; 101: 7270-7274. Medline doi:10.1073/pnas.0402253101
9. Pileri P, Uematsu Y, Campagnoli S, et al. Binding of hepatitis C virus to CD81. Science 1998; 282: 938-941. Medline doi:10.1126/science.282.5390.938
10. Bartosch B, Vitelli A, Granier C, et al. Cell entry of hepatitis C virus requires a set of co-receptors that include the CD81 tetraspanin and the SR-B1 scavenger receptor. J Biol Chem 2003; 278: 41624-41630. Medline doi:10.1074/jbc.M305289200
11. Scarselli E, Ansuini H, Cerino R, et al. The human scavenger receptor class B type I is a novel candidate receptor for the hepatitis C virus. EMBO J 2002; 21: 5017-5025. Medline doi:10.1093/emboj/cdf529
12. Voisset C, Callens N, Blanchard E, Op De Beeck A, Dubuisson J, Vu-Dac N. High density lipoproteins facilitate hepatitis C virus entry through the scavenger receptor class B type I. J Biol Chem 2005; 280: 7793-7799. Medline doi:10.1074/jbc.M411600200
13. Evans MJ, von Hahn T, Tscherne DM, et al . Claudin-1 is a hepatitis C virus co-receptor required for a late step in entry. Nature 2007; 446: 801-805. Medline doi:10.1038/nature05654
14. Ploss A, Evans MJ, Gaysinskaya VA, et al. Human occludin is a hepatitis C virus entry factor required for infection of mouse cells. Nature 2009; 457: 882-886. Medline doi:10.1038/nature07684
15. Lupberger J, Zeisel MB, Xiao F, et al. EGFR and EphA2 are host factors for hepatitis C virus entry and possible targets for antiviral therapy. Nat Med 2011; 17: 589-595. Medline doi:10.1038/nm.2341
16. Sainz B, Barretto N, Martin DN, et al. Identification of the Niemann-Pick C1-like 1 cholesterol absorption receptor as a new hepatitis C virus entry factor. Nat Med 2012; 18: 281-285. Medline doi:10.1038/nm.2581
17. Honda M, Beard MR, Ping LH, Lemon SM. A phylogenetically conserved stem-loop structure at the 5′ border of the internal ribosome entry site of hepatitis C virus is required for cap-independent viral translation. J Virol 1999; 73: 1165-1174. Medline (Pubitemid 29036768)
18. Moradpour D, Penin F, Rice CM. Replication of hepatitis C virus. Nat Rev Microbiol 2007; 5: 453-463. Medline doi:10.1038/nrmicro1645
19. Gwack Y, Kim DW, Han JH, Choe J. DNA helicase activity of the hepatitis C virus nonstructural protein 3. Eur J Biochem 1997; 250: 47-54. Medline doi:10.1111/j.1432-1033.1997.00047.x
20. Tai CL, Chi WK, Chen DS, Hwang LH. The helicase activity associated with hepatitis C virus nonstructural protein 3 (NS3). J Virol 1996; 70: 8477-8484. Medline
21. Egger D, Wolk B, Gosert R, et al. Expression of hepatitis C virus proteins induces distinct membrane alterations including a candidate viral replication complex. J Virol 2002; 76: 5974-5984. Medline doi:10.1128/JVI.76.12. 5974-5984.2002
22. Elazar M, Liu P, Rice CM, Glenn JS. An N-terminal amphipathic helix in hepatitis C virus (HCV) NS4B mediates membrane association, correct localization of replication complex proteins, and HCV RNA replication. J Virol 2004; 78: 11393-11400. Medline doi:10.1128/JVI.78.20.11393-11400.2004
23. Gretton SN, Taylor AI, McLauchlan J. Mobility of the hepatitis C virus NS4B protein on the endoplasmic reticulum membrane and membrane-associated foci. J Gen Virol 2005; 86: 1415-1421. Medline doi:10.1099/vir.0.80768-0
24. Bartenschlager R, Frese M, Pietschmann T. Novel insights into hepatitis C virus replication and persistence. Adv Virus Res 2004; 63: 71-180. Medline doi:10.1016/S0065-3527(04)63002-8
25. Nagy PD, Pogany J. The dependence of viral RNA replication on co-opted host factors. Nat Rev Microbiol 2012; 10: 137-149. Medline
26. Shimoike T, Mimori S, Tani H, Matsuura Y, Miyamura T. Interaction of hepatitis C virus core protein with viral sense RNA and suppression of its translation. J Virol 1999; 73: 9718-9725. Medline
27. Tanaka Y, Shimoike T, Ishii K, et al. Selective binding of hepatitis C virus core protein to synthetic oligonucleotides corresponding to the 5′ untranslated region of the viral genome. Virology 2000; 270: 229-236. Medline doi:10.1006/viro.2000.0252
28. Bartenschlager R, Penin F, Lohmann V, Andre P. Assembly of infectious hepatitis C virus particles. Trends Microbiol 2011; 19: 95-103. Medline doi:10.1016/j.tim.2010.11.005
29. Bacon BR, Gordon SC, Lawitz E, et al. Boceprevir for previously treated chronic HCV genotype 1 infection. N Engl J Med 2011; 364: 1207-1217. Medline doi:10.1056/NEJMoa1009482
30. Jacobson IM, McHutchison JG, Dusheiko G, et al. Telaprevir for previously untreated chronic hepatitis C virus infection. N Engl J Med 2011; 364: 2405-2416. Medline doi:10.1056/NEJMoa1012912
31. Poordad F, McCone J, Bacon BR, et al. Boceprevir for untreated chronic HCV genotype 1 infection. N Engl J Med 2011; 364: 1195-1206. Medline doi:10.1056/NEJMoa1010494
32. Zeuzem S, Andreone P, Pol S, et al. Telaprevir for retreatment of HCV infection. N Engl J Med 2011; 364: 2417-2428. Medline doi:10.1056/NEJMoa1013086
33. Reesink H, Bergmann J, de Bruijne J, et al. Safety and antiviral activity of SCH 900518 administered as monotherapy and in combination with peginterferon alfa-2b to naive and treatment-experienced HCV-1 infected patients. J Hepatol 2009; 50 Suppl 1: S35- S36. doi:10.1016/S0168-8278(09)60088-X
34. Detishin V, Haazen W, Robison H, Robarge L, Olek E. Virological response, safety and pharmacokinetic profile following single- and multiple-dose administration of ACH-0141625 protease inhibitor to healthy volunteers and HCV genotype 1 patients. J Hepatol 2010; 52 Suppl 1: S468. doi:10.1016/S0168- 8278(10)61203-2
35. Forestier N, Larrey D, Guyader D, et al. Treatment of chronic hepatitis C patients with the NS3/4A protease inhibitor danoprevir (ITMN-191/RG7227) leads to robust reductions in viral RNA: a Phase 1b multiple ascending dose study. J Hepatol 2011; 54: 1130-1136. Medline doi:10.1016/j.jhep.2010.11.001
36. Manns MP, Bourliere M, Benhamou Y, et al. Potency, safety, and pharmacokinetics of the NS3/4A protease inhibitor BI201335 in patients with chronic HCV genotype-1 infection. J Hepatol 2011; 54: 1114-1122. Medline doi:10.1016/j.jhep.2010.08.040
37. Manns MP, Reesink H, Moreno C, et al. Safety and antiviral activity of TMC435350 in treatment-naive genotype 1 HCV infected patients. Hepatology 2008; 48 Suppl 1: 1023A.
38. Lawitz E, Sulkowski M, Jacobson I, et al. Safety, tolerability and antiviral activity of MK-7009, a novel inhibitor of the hepatitis C virus NS3/4A protease, in patients with chronic HCV genotype 1 infection. Hepatology 2008; 48 Suppl 1: 403A.
39. Goldwater R, DeMicco M, Zong JA, et al. Safety, pharmacokinetics and antiviral activity of single oral doses of the HCV NS3 protease inhibitor GS-9256. Hepatology 2010; 52 Suppl 1: 717A-718A.
40. Hotho D, de Bruijne J, O'Farrell A, et al. Accelerated clinical trial design to assess the safety, tolerability and antiviral activity of PHX1766, a novel HCV NS3/4A protease inhibitor in healthy volunteers and chronic hepatitis C patients. Hepatology 2009; 50 Suppl 1: 1031A-1032A.
41. Lawitz E, Gaultier I, Poordad F, et al. 4-week virologic response and safety of ABT-450 given with low-dose ritonavir (ABT-450r) in combination with pegylated interferon alfa-2a and ribavirin after 3-day monotherapy in genotype 1 HCV-infected treatment-naive subjects. Hepatology 2010; 52 Suppl 1: 878A-879A.
42. Lawitz E, Hill JM, Marbury TC, et al. Three-day, dose-ranging study of the HCV NS3 protease inhibitor GS-9451. Hepatology 2010; 52 Suppl 1: 714A-715A.
43. Silva M, Kasserra C, Gupta S, Treitel M, Hughes E, O'Mara E. Antiviral activity of boceprevir monotherapy in treatment-naive subjects with chronic hepatitis C genotype 2/3. Hepatol Int 2011; 5: 558.
44. Rouzier R, Larrey D, Gane EJ, et al. Activity of danoprevir plus low-dose ritonavir in combination with peginterferon alfa-2a plus ribavirin in previous null-responders. J Hepatol 2011; 54 Suppl 1: S28. doi:10.1016/S0168-8278(11) 60064-0
45. Kieffer TL, Sarrazin C, Miller JS, et al . Telaprevir and pegylated interferon-alpha-2a inhibit wild-type and resistant genotype 1 hepatitis C virus replication in patients. Hepatology 2007; 46: 631-639. Medline doi:10.1002/hep.21781
46. Sarrazin C, Kieffer TL, Bartels D, et al. Dynamic HCV genotypic and phenotypic changes in patients treated with the protease inhibitor telaprevir (VX-950). Gastroenterology 2007; 132: 1767-1777. Medline doi:10.1053/j.gastro. 2007.02.037
47. Chevaliez S, Rodriguez C, Soulier A, Ahmed-Belkacem A, Hézode C, Pawlotsky JM. Molecular characterization of HCV resistance to telaprevir by means of ultra-deep pyrosequencing: preexisting resistant variants and dynamics of resistant populations. J Hepatol 2011; 54 Suppl 1: S30. doi:10.1016/S0168- 8278(11)60069-X
48. Brainard DM, Perty A, van Dyck K, et al. Safety and antiviral activity of MK-5172, a novel HCV NS3/4A protease inhibitor with potent activity against known resistance mutants, in genotype 1 and 3 HCV-infected patients. Hepatology 2010; 52 Suppl 1: 706A-707A.
49. Reddy R, Rodriguez-Torres M, Gane EJ, et al. Antiviral activity, pharmacokinetics, safety and tolerability of R7128, a novel nucleoside HCV RNA polymerase inhibitor, following multiple, ascending oral doses in patients with HCV genotype 1 infection who have failed prior interferon therapy. Hepatology 2007; 46 Suppl 1: 862A-863A.
50. Lawitz E, Rodriguez-Torres M, Denning J, et al. Once daily dual nucleotide combination of PSI-938 and PSI-7977 provides 94% HCV RNA
51. Powdrill MH, Tchesnokov EP, Kozak RA, et al. Contribution of a mutational bias in hepatitis C virus replication to the genetic barrier in the development of drug resistance. Proc Natl Acad Sci U S A 2011; 108: 20509-20513. Medline doi:10.1073/pnas.1105797108
52. Erhardt A, Deterding K, Benhamou Y, et al. Safety, pharmacokinetics and antiviral effect of BILB 1941, a novel hepatitis C virus RNA polymerase inhibitor, after 5 days oral treatment. Antivir Ther 2009; 14: 23-32. Medline
53. Wagner F, Thompson R, Kantaridis C, et al. Antiviral activity of the hepatitis C virus polymerase inhibitor filibuvir in genotype 1- infected patients. Hepatology 2011; 54: 50-59. Medline doi:10.1002/hep.24342
54. Larrey D, Benhamou Y, Lohse AW, et al. Safety, pharmacokinetics and antiviral effect of BI207127, a novel HCV RNA polymerase inhibitor, after 5 days oral treatment in patients with chronic hepatitis C. J Hepatol 2009; 50 Suppl 1: S383-S384. doi:10.1016/S0168- 8278(09)61056-4
55. Rodriguez-Torres M, Lawitz E, Conway B, et al . Safety and antiviral activity of the HCV non-nucleoside polymerase inhibitor VX- 222 in treatment-naive genotype 1 HCV infected patients. J Hepatol 2010; 52 Suppl 1: S14. doi:10.1016/S0168-8278(10)60033-5
56. Lawitz E, Rodriguez-Torres M, DeMicco M, et al. Antiviral activity of ANA598, a potent non-nucleoside polymerase inhibitor, in chronic hepatitis C patients. J Hepatol 2009; 50 Suppl 1: S384. doi:10.1016/S0168-8278(09)61057-6
57. de Bruijne J, de Rooij JV, van Vliet A, et al . Phase I study in healthy volunteers and patients with IDX-375, a novel non-nucleoside HCV polymerase inhibitor. Hepatology 2010; 52 Suppl 1: 1219A.
58. Fridell RA, Qiu D, Valera L, Wang C, Rose RE, Gao M. Distinct functions of NS5A in hepatitis C virus RNA replication uncovered by studies with the NS5A inhibitor BMS-790052. J Virol 2011; 85: 7312-7320. Medline doi:10.1128/JVI. 00253-11
59. Targett-Adams P, Graham EJ, Middleton J, et al . Small molecules targeting hepatitis C virus-encoded NS5A cause subcellular redistribution of their target: insights into compound modes of action. J Virol 2011; 85: 6353-6368. Medline doi:10.1128/JVI.00215-11
60. Gao M, Nettles RE, Belema M, et al . Chemical genetics strategy identifies an HCV NS5A inhibitor with a potent clinical effect. Nature 2010; 465: 96-100. Medline doi:10.1038/nature08960
61. Nettles R, Chien C, Chung E, et al. BMS-790052 is a first-in-class potent hepatitis C virus NS5A inhibitor for patients with chronic HCV infection: results from a proof-of-concept study. Hepatology 2008; 48 Suppl 1: 1025A.
62. Brown NA, Vig P, Ruby E, et al. Safety and pharmacokinetics of PPI-461, a potent new hepatitis C virus NS5A inhibitor with pangenotype activity. Hepatology 2010; 52 Suppl 1: S464.
63. Nettles R, Wang XD, Quadri S, et al. BMS-824393 is a potent HCV NS5A inhibitor with substantial antiviral activity when given as monotherapy in subjects with chronic genotype 1 HCV infection. Hepatology 2010; 52 Suppl 1: 1203A-1204A.
64. Lawitz E, Gruener D, Hill J, et al. Three-day dose ranging study of the HCV NS5A inhibitor GS-5885. J Hepatol 2011; 54 Suppl 1: S481-S482. doi:10.1016/S0168-8278(11)61221-X
65. Coelmont L, Kaptein S, Paeshuyse J, et al. Debio-025, a cyclophilin binding molecule, is highly efficient in clearing HCV replicon containing cells, alone or when combined with Specifically Targeted Antiviral Therapy for HCV (STAT-C) inhibitors. Antimicrob Agents Chemother 2009; 53: 967-976. Medline doi:10.1128/AAC.00939-08
66. Coelmont L, Gallay P, Bobardt M, et al. Particular in vitro anti-HCV activities and resistance profile of the cyclophylin inhibitor DEBIO-025. J Hepatol 2009; 50 Suppl 1: S36. doi:10.1016/S0168-8278(09)60090-8
67. Neumann AU, Lam NP, Dahari H, et al. Hepatitis C viral dynamics in vivo and the antiviral efficacy of interferon-alpha therapy. Science 1998; 282: 103-107. Medline doi:10.1126/science.282.5386.103
68. Dahari H, Guedj J, Perelson AS, Layden TJ. Hepatitis C viral kinetics in the era of direct acting antiviral agents and IL28B. Curr Hepat Rep 2011; 10: 214-227. Medline doi:10.1007/s11901-011-0101-7
69. Bronowicki JP, Ouzan D, Asselah T, et al. Effect of ribavirin in genotype 1 patients with hepatitis C responding to pegylated interferon alfa-2a plus ribavirin. Gastroenterology 2006; 131: 1040-1048. Medline doi:10.1053/j.gastro. 2006.07.022
70. Herrmann E, Lee HJ, Marinos G, Modi M, Zeuzem S. Effect of ribavirin on hepatitis C viral kinetics in patients treated with pegylated interferon. Hepatology 2003; 37: 1351-1358. Medline doi:10.1053/jhep.2003.50218
71. Pawlotsky JM, Dahari H, Neumann AU, et al. Antiviral action of ribavirin in chronic hepatitis C. Gastroenterology 2004; 126: 703-714. Medline doi:10.1053/j.gastro.2003.12.002
72. Clavel F, Hance AJ. HIV drug resistance. N Engl J Med 2004; 350: 1023-1035. Medline (Pubitemid 38269279)
73. Forestier N, Reesink HW, Weegink CJ, et al. Antiviral activity of telaprevir (VX-950) and peginterferon alfa-2a in patients with hepatitis C. Hepatology 2007; 46: 640-648. Medline doi:10.1002/hep.21774
74. Hézode C, Forestier N, Dusheiko G, et al . Telaprevir and peginterferon with or without ribavirin for chronic HCV infection. N Engl J Med 2009; 360: 1839-1850. Medline doi:10.1056/NEJMoa0807650
75. McHutchison JG, Everson GT, Gordon SC, et al. Telaprevir with peginterferon and ribavirin for chronic HCV genotype 1 infection. N Engl J Med 2009; 360: 1827-1838. Medline doi:10.1056/NEJMoa0806104
76. Lok AS, Gardiner DF, Lawitz E, et al. Preliminary study of two antiviral agents for hepatitis C genotype 1. N Engl J Med 2012; 366: 216-224. Medline doi:10.1056/NEJMoa1104430
77. Pawlotsky JM. Treatment failure and resistance with direct-acting antiviral drugs against hepatitis C virus. Hepatology 2011; 53: 1742-1751. Medline doi:10.1002/hep.24262
78. Zeuzem S, Buggisch P, Agarwal K, et al. The protease inhibitor, GS-9256, and non-nucleoside polymerase inhibitor tegobuvir alone, with ribavirin, or pegylated interferon plus ribavirin in hepatitis C. Hepatology 2012; 55: 749-758. Medline doi:10.1002/hep.24744
79. Gane EJ, Roberts SK, Stedman CA, et al. Oral combination therapy with a nucleoside polymerase inhibitor (RG7128) and danoprevir for chronic hepatitis C genotype 1 infection (INFORM-1): a randomised, double-blind, placebo-controlled, dose-escalation trial. Lancet 2010; 376: 1467-1475. Medline doi:10.1016/S0140-6736(10)61384-0
80. Gane EJ, Stedman CA, Hyland RH, et al. Once daily PSI-7977 plus RBV: pegylated interferon alfa not required for complete rapid viral response in treatment-naive patients with HCV GT2 or GT3. Hepatology 2011; 54 Suppl 1: 377A.
81. Chayama K, Takahashi S, Kawakami Y, et al. Dual oral combination therapy with the NS5A inhibitor BMS-790052 and the NS3 protease inhibitor BMS-650032 achieved 90% sustained virologic response (SVR12) in HCV genotype 1b-infected null responders. Hepatology 2011; 54 Suppl 1: 1428A.
82. Guedj J, Perelson AS. Second-phase hepatitis C virus RNA decline during telaprevir-based therapy increases with drug effectiveness: implications for treatment duration. Hepatology 2011; 53: 1801-1808. Medline doi:10.1002/hep. 24272
83. Chu TW, Kulkarni R, Gane EJ, et al. Effect of IL28B genotype on early viral kinetics during interferon-free treatment of patients with chronic hepatitis C. Gastroenterology 2012; 142: 790-795. Medline doi:10.1053/j.gastro. 2011.12.057
84. Thomas E, Ghany MG, Liang TJ. The application and mechanism of action of ribavirin in therapy of hepatitis C. Antivir Chem Chemother 2012; doi:10.3851/IMP2125Medline doi:10.3851/IMP2125