Hepatitis C drug discovery: in vitro and in vivo systems and drugs in the pipeline

References

• Cohen J. The scientific challenge of hepatitis C. Science 285,26–30 (1999).
   PubMed Web of Science ®Google Scholar
• Alter MJ. Epidemiology of hepatitis C. Hepatology 26\(Suppl. 1), 62–65 (1997).
   Web of Science ®Google Scholar
• WHO. Hepatitis C: global prevalence. Wkly EpidemioL Rec. 72,341–344 (1997).
   PubMedGoogle Scholar
• Hoofnagle JH, Mullen KD, Jones DB, et al Treatment of chronic non-A, non-B hepatitis with recombinant human a-interferon. A preliminary report. N EngL J. Med 315(25), 1575–1578 (1986).
   PubMed Web of Science ®Google Scholar
• McHutchison JG, Gordon SC, Schiff ER, et al Interferon-a2b alone or in combination with ribavirin as initial treatment for chronic hepatitis C. Hepatitis Interventional Therapy Group. N EngL J. Med. 339(21), 1485–1492 (1998).
   PubMed Web of Science ®Google Scholar
• Poynard T, Marcellin P, Lee SS, et al Randomised trial of interferon-a2b plus ribavirin for 48 weeks or for 24 weeks versus interferon-a2b plus placebo for 48 weeks for treatment of chronic infection with hepatitis C virus. International Hepatitis Interventional Therapy Group (IHIT). Lancet 352 (9138), 1426–1432 (1998).
   PubMed Web of Science ®Google Scholar
• Manns MP, McHutchison JG, Gordon SC, et al Peginterferon-am plus ribavirin compared with interferon-a2b plus ribavirin for initial treatment of chronic hepatitis C: a randomised trial. Lancet 358(9286), 958–965 (2001).
   PubMed Web of Science ®Google Scholar
• Fried MW, Shiffman ML, Reddy KR, et al Peginterferon-a2a plus ribavirin for chronic hepatitis C virus infection. N EngL J. Med. 347(13), 975–982 (2002).
   PubMed Web of Science ®Google Scholar
• Ahn J, Flamm S. Peginterferon-am and ribavirin. Expert Rev. Anti-infect. Ther 2(1), 17–25 (2004).
   PubMedGoogle Scholar
• Griffin SD, Reales LP, Clarke DS, et al The p7 protein of hepatitis C virus forms an ion channel that is blocked by the antiviral drug, amantadine. FEBS Lett. 535,34–38 (2003).
   PubMed Web of Science ®Google Scholar
• Sakai A, Claire MS, Faulk K, et al. The p7 protein of hepatitis C virus is critical for infectivity and contains functionally important genotype-specific sequences. 10th International Meeting on Hepatitis C Virus and Related Viruses. (2003) (Abstract 040).
   Google Scholar
• 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 76, 5974–5984 (2002).
   PubMed Web of Science ®Google Scholar
• Hugle T, Fehrmann F, Bieck E, et al. The hepatitis C virus nonstructural protein 4B is an integral endoplasmic reticulum membrane protein. Virology 284,70–81 (2001).
   PubMed Web of Science ®Google Scholar
• Einav S, Elazar M, Glann J. A nucleotide binding motif in HCV NS4B mediates HCV RNA replication. 10th International Meeting on Hepatitis C Virus and Relate d Viruses. (2003) (Abstract 041).
   Google Scholar
• He Y, Katze MG. To interfere and to anti-interfere: the interplay between hepatitis C virus and interferon. Viral Immunol. 15,95–119 (2002).
   PubMed Web of Science ®Google Scholar
• Xu Z, Choi J, Yen TS, et al Synthesis of a novel hepatitis C virus protein by ribosomal frameshift. EMBO J. 20(14), 3840–3848 (2001).
   PubMed Web of Science ®Google Scholar
• Varaklioti A, Vassilaki N, Georgopoulou U, et al. Alternate translation occurs within the core-coding region of the hepatitis C viral genome. J. Biol. Chem. 277(20), 17713–17721 (2002).
   PubMed Web of Science ®Google Scholar
• Vassilaki N, Mavromara P. Two alternative translation mechanisms are responsible for the expression of the HCV ARFP/F/core+1 coding open reading frame. J. Biol. Chem. 278(42), 40503–40513 (2003).
   PubMed Web of Science ®Google Scholar
• Lu HH, Wimmer E. Poliovirus chimeras replicating under the translational control of genetic elements of hepatitis C virus reveal unusual properties of the internal ribosomal entry site of hepatitis C virus. Proc. Nati Acad. Sci. USA 93, 1412–1417 (1996).
   PubMed Web of Science ®Google Scholar
• Zhao WD, Wimmer E, Lahser FC. Poliovirus/Hepatitis C virus (internal ribosomal entry site—core) chimeric viruses: improved growth properties through modification of a proteolytic cleavage site and requirement for core RNA sequences but not for core-related polypeptides. J. ViroL 73(2), 1546–1554 (1999).
   PubMed Web of Science ®Google Scholar
• Troxell J, Wenzel M, Huang M. A system for evaluation of compounds against HCV internal ribosomal entry site (IRES) activity. Antivir. Res. 46, A64 (1999).
   Google Scholar
• Jubin R. Targeting hepatitis C virus translation: stopping HCV where it starts. Curr. Opin. Investig. Drugs 4(2), 162–167 (2003).
   PubMedGoogle Scholar
• Thibeault D, Maurice R, Pilote L, et al. In vitro characterization of a purified N52/3 protease variant of hepatitis C virus. J. Biol. Chem. 276(49), 46678–46684 (2001).
   Google Scholar
• Pallaoro M, Lahm A, Biasiol G, et al. Characterization of the hepatitis C virus N52/3 processing reaction by using a purified precursor protein. J. ViroL 75(20), 9939–9946 (2001).
   PubMed Web of Science ®Google Scholar
• Wenzel M, Troxell J, Buckheit R, Huang M. Establishment of a cell based assay for evaluation of compounds against HCV NS2-3 protease activity. Antivir. Ther. 4(Suppl.), A95 (1999).
   Google Scholar
• Whitney M, Stack JH, Darke PL, et al. A collaborative screening program for the discovery of inhibitors of HCV N52/3 cis-cleaving protease activity. J. BiomoL Screen. 7(2), 149–154 (2002).
   Google Scholar
• Flint M, Maidens C, Loomis-Price LD, et al Characterization of hepatitis C virus E2 glycoprotein interaction with a putative cellular receptor, CD81. J. ViroL 73, 6235–6244 (1999).
   PubMed Web of Science ®Google Scholar
• Pileri P, Uematsu Y, Compagnoli S, et al Binding of hepatitis C virus to CD81. Science 282,938–941 (1998).
   PubMed Web of Science ®Google Scholar
• Zhang J, Randall G, Higginbottom A, et al CD81 is required for hepatitis C virus glycoprotein-mediated viral infection. J. ViroL 78(3), 1448–1455 (2004).
   PubMed Web of Science ®Google Scholar
• 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. EMBOJ. 21,5017–5025 (2002).
   PubMed Web of Science ®Google Scholar
• Gardner JP, Durso RJ, Arrigale RR, et al L-SIGN (CD 209L) is a liver-specific capture receptor for hepatitis C virus. Proc. Nad Acad Sci. USA 100,4498–4503 (2003).
   PubMed Web of Science ®Google Scholar
• Lozach PY, Lortat-Jacob H, Lacroix De Lavalette, et al DC-SIGN and L-SIGN are high-affinity binding receptors for hepatitis C virus glycoprotein E2. J. Biol. Chem. 278, 20358–20366 (2003).
   PubMed Web of Science ®Google Scholar
• Pohlmann S, Zhang J, Baribaud F, et al. Hepatitis C virus glycoproteins interact with DC-SIGN and DC-SIGNR. J. ViroL 77, 4070–4080 (2003).
   Google Scholar
• Agnello V, Abel G, Elfahal M, et al. Hepatitis C virus and other flaviviridae viruses enter cells via low density lipoprotein receptor. Proc. Nad Acad. Sci. USA 96,12766–12771 (1999).
   PubMed Web of Science ®Google Scholar
• Wunschmann S, Medh JD, Klinzmann D, et al Characterization of hepatitis C virus (HCV) and HCV E2 interactions with CD81 and the low-density lipoprotein receptor. J. Vito/. 74,10055–10062 (2000).
   Google Scholar
• Bartosch B, Dubuisson J, Cosset FL. Infectious hepatitis C virus pseudopartides containing functional E1—E2 envelope protein complexes. J. Exp. Med. 197, 633–642 (2003).
   PubMed Web of Science ®Google Scholar
• Pietschmann T, Lohmann V, Kaul A, et al. Persistent and transient replication of full length hepatitis C virus genomes in cell
   Google Scholar
• Hsu MJ, Zhang M, Flint C, et al. Hepatitis C virus glycoproteins mediate pH-dependent cell entry of pseudotyped retroviral particles. Proc. Natl Acad. Sci. USA 100,7271–7276 (2003).
   PubMed Web of Science ®Google Scholar
• Lohmann V, Korner F, Koch J, et al. Replication of subgenomic hepatitis C virus RNAs in a hepatoma cell line. Science 285(5424), 110–113 (1999).
   PubMed Web of Science ®Google Scholar
• •First paper to report the establishment of the hepatitis C virus (HCV) replicon.
   Google Scholar
• Behrens SE, Grassmann CW, Thiel HJ, et al. Characterization of an autonomous subgenomic pestivirus RNA replicon. J. Vito/. 72(3), 2364–2372 (1998).
   Google Scholar
• Blight KJ, Kolykhalov AA, Rice CM. Efficient initiation of HCV RNA replication in cell culture. Science 290, 1972–1974 (2000).
   PubMed Web of Science ®Google Scholar
• •Confirms Lohmann's original findings and describes the adaptive mutations for the first time.
   Google Scholar
• Krieger N, Lohmann V, Bartenschlager R. Enhancement of hepatitis C virus RNA replication by cell culture-adaptive mutations. J. ViroL 75,4614–4624 (2001).
   PubMed Web of Science ®Google Scholar
• Lohmann V, Körner F, Dobierzewska A, Bartenschlager R. Mutations in hepatitis C virus RNAs conferring cell culture adaptation. J. Viral. 75,1437–1449 (2001).
   PubMed Web of Science ®Google Scholar
• Guo JT, Bichko VV, Seeger C. Effect of a-interferon on the hepatitis C virus replicon. J. Vito/. 75,8516–8523 (2001).
   Google Scholar
• Lohmann V, Hoffmann S, Herian U, et al. Viral and cellular determinants of hepatitis C virus RNA replication in cell culture. J. Viral. 77(5), 3007–3019 (2003).
   PubMed Web of Science ®Google Scholar
• Murray EM, Grobler JA, Markel EJ, et al. Persistent replication of hepatitis C virus replicons expressing the 8-lactamase reporter in subpopulations of highly permissive Huh7 cells. J. ViroL 77(5), 2928–2935 (2003).
   PubMed Web of Science ®Google Scholar
• Yi M, Bodola F, Lemon SM. Subgenomic hepatitis C virus replicons inducing expression of a secreted enzymatic reporter protein. Virology 304(2), 197–210 (2002).
   PubMed Web of Science ®Google Scholar
• Ikeda M, Yi M, Li K, Lemon SM. Selectable subgenomic and genome-length dicistronic RNAs derived from an infectious molecular clone of the HCV-N strain of hepatitis C virus replicate efficiently in cultured Huh7 cells. J. ViroL 76,2997–3006 (2002).
   PubMed Web of Science ®Google Scholar
• •First paper to demonstrate the establishment of the functional replicon from a non-Con-1 strain.
   Google Scholar
• Kishine H, Sugiyama K, Hijikata M, et al. Subgenomic replicon derived from a cell line infected with the hepatitis C virus. Biochem. Biophys. Res. Commun. 293, 993–999 (2002).
   PubMed Web of Science ®Google Scholar
• Kato N, Sugiyama K, Namba K, et al. Establishment of a hepatitis C virus subgenomic replicon derived from human hepatocytes infected in vitro. Biochem. Biophys. Res. Commun. 306,756–766 (2003).
   PubMed Web of Science ®Google Scholar
• Blight KJ, McKeating JA, Marcotrigiano J, Rice CM. Efficient replication of hepatitis C virus genotype la RNAs in cell culture. J. Viral. 77, 3181–3190 (2003).
   Google Scholar
• Kato T, Date T, Miyamoto M, et al. Efficient replication of the genotype 2a hepatitis C virus subgenomic replicon. Gastroenterology 125,1808–1817 (2003).
   PubMed Web of Science ®Google Scholar
• Flores O. Impact of HCV Genetic heterogenecity on efficacy of next generation of antiviral agents. HEP DART 2003. Kauai, Hawaii, USA. 14th-18th December 2003.
   Google Scholar
• Zhu Q, Guo JT, Seeger C. Replication of hepatitis C virus subgenomes in nonhepatic epithelial and mouse hepatoma cells. J. Viral. 77(17), 9204–9210 (2003).
   PubMed Web of Science ®Google Scholar
• Carroll SS, Tomassini JE, Bosserman M, et al Inhibition of hepatitis C virus RNA replication by 2'-modified nucleoside analogs. J. BiaL Chem. 278,11979–11984 (2003).
   PubMed Web of Science ®Google Scholar
• Trozzi C, Bartholomew L, Ceccacci A, et al. In vitro selection and characterization of hepatitis C virus serine protease variants resistant to an active-site peptide inhibitor. J. Viral. 77(6), 3669–3679 (2003).
   Google Scholar
• •First paper that describes resistant induction studies using a replicon system.
   Google Scholar
• Yang W, Liu D, Sun Y, et al. Two simple, inexpensive and medium to high throughput methods to quantify the amount of HCV RNA and NPTII in HCV replicon containing cells. 10th International Meeting on Hepatitis C Virus and Relate d Viruses. Kyoto, Japan. (2003) (Abstract P–211).
   Google Scholar
• Nguyen TT, Gates AT, Gutshall LL, et al. Resistance profile of a hepatitis C virus RNA-dependent RNA polymerase benzothiadiazine inhibitor. Antimicrob. Agents Chemother. 47(11), 3525–3530 (2003).
   PubMed Web of Science ®Google Scholar
• Migliaccio G, Tomassini JE, Carroll SS, et al Characterization of resistance to nonobligate chain-terminating ribonucleoside analogs that inhibit hepatitis C virus replication in vitro. J. Bid Chem. 278(49), 49164–49170 (2003).
   PubMed Web of Science ®Google Scholar
• Tomei L, Altamura S, Bartholomew L, et al. Mechanism of action and antiviral activity of benzimidazole-based allosteric inhibitors of the hepatitis C virus RNA-dependent RNA polymerase. j Viral. 77(24), 13225–13231 (2003).
   PubMed Web of Science ®Google Scholar
• Tomei L, Altamura S, Bartholomew L, et al. Characterization of the inhibition of hepatitis C virus RNA replication by non-nucleosides. J. Viral. 78(2), 938–946 (2004).
   PubMed Web of Science ®Google Scholar
• Lin C, Lin K, Luong YP, et al. In vitro resistance studies of hepatitis C virus serine protease inhibitors, VX-950 and BILN 2061: structural analysis indicates different resistance mechanisms. J. Bid Chem. (Epub ahead of print) (2004).
   Google Scholar
• Lamarre D, Anderson PC, Bailey M, et al An NS3 protease inhibitor with antiviral effects in humans infected with hepatitis C virus. Nature 426(6963), 186–189 (2003).
   PubMed Web of Science ®Google Scholar
• •Demonstrates the efficacy of a HCV-specific small molecule in humans for the first time.
   Google Scholar
• Lin K, Pemi RB, Kwong AD, et al. Synergistic inhibition of HCV replication by a HCV N53 4A protease inhibitor and interferon-a in replicon cells. 10th International Meeting on Hepatitis C Virus and Related Viruses. Kyoto, Japan. 2nd — 6th December 2003.
   Google Scholar
• Carloni G, Iacovacci S, Sargiacomo M, et al Susceptibility of human liver cell cultures to hepatitis C virus infection. Arch. ViroL 8(Suppl.), 31–39 (1993).
   Google Scholar
• Iacovacci S, Manzin A, Barca S, et al Molecular characterization and dynamics of hepatitis C virus replication in human fetal hepatocytes infected in vitro. Hepatology 26, 1328–1337 (1997).
   Google Scholar
• Fournier C, Sureau C, Coste J, et al In vitro infection of adult normal human hepatocytes in primary culture by hepatitis C virus. J. Gen. Viral. 79\(Part 10), 2367–2374 (1998).
   PubMedGoogle Scholar
• Rumin S, Berthillon P, Tanaka E, et al Dynamic analysis of hepatitis C virus replication and quasispecies selection in long-term cultures of adult human hepatocytes infected in vitro. J. Gen. Viral. 80\(Pt 11), 3007–3018 (1999).
   PubMedGoogle Scholar
• Castet VC, Fournier A, Soulier R, et al Alpha interferon inhibits hepatitis C virus replication in primary human hepatocytes infected in vitro. J ViroL 76,8189–8199 (2002).
   PubMed Web of Science ®Google Scholar
• Kwong A, Bym R, Alford J, et al Development of a hepatitis C virus infection virus assay for drug discovery. 10th Internal Meeting on HCV and Related Viruses. (2003) (Abstract P167).
   Google Scholar
• Sung VM, Shimodaira S, Doughty AL, et al Establishment of B-cell lymphoma cell lines persistently infected with hepatitis C virus in vivo and in vitro: the apoptotic effects of virus infection. J. Viral. 77(3), 2134–2146 (2003).
   Google Scholar
• Mercer DF, Schiller DE, Elliott JF, et al Hepatitis C virus replication in mice with chimeric human livers. Nature Med. 7, 727–933 (2001).
   Web of Science ®Google Scholar
• •Describes a small animal model demonstrating robust HCV replication for the first time.
   Google Scholar
• Kneteman NM, His B, Schiller D, et al Validation of Alb/uPA mouse model for treatment and prevention of viral hepatitis. 10th internal meeting on HCV and Related Viruses. (2003) (Abstract P–187).
   Google Scholar
• Beames B, Chavez D, Lanford RE. GB virus B as a model for hepatitis C virus. ILARJ 42, 152–160 (2001).
   PubMedGoogle Scholar
• Bukh J, Apgar CL, Govindarajan S, Purcell RH. Host range studies of GB virus-B hepatitis agent, the closest relative of hepatitis C virus, in New World monkeys and chimpanzees. J. Med Viral 6,694–697 (2001).
   Google Scholar
• Lanford RE, Chavez D, Notvall L, Brasky KM. Comparison of tamarins and marmosets as hosts for GBV-B infections and the effect of immune suppression on the duration of viremia. Virology 311,72–80 (2003).
   PubMed Web of Science ®Google Scholar
• Bright H, Carroll AR, Watts PA, Fenton RJ. Development of a GB virus B marmoset model and its validation with a novel series of hepatitis C virus NS3 protease inhibitors. J. Viral 78(4), 2062–2071 (2004).
   PubMed Web of Science ®Google Scholar
• Tomassi De, Pizzuti AM, Graziani A, et al Cell clones selected from the Huh7 human hepatoma cell line support efficient replication of a subgenomic GB virus B replicon.J. Viral 76,7736–7746 (2002).
   PubMed Web of Science ®Google Scholar
• Tomassi A, Pizzuti M, Traboni C. Hep3B human hepatoma cells support replication of the wild type and a 5'-end deletion mutant GB virus B replicon.J. Viral. 77(22), 11875–11881 (2003).
   PubMed Web of Science ®Google Scholar
• Thibeault D, Bousquet C, Gingras R, et al. Sensitivity of N53 Serine Proteases from Various Hepatitis C Virus Genotypes to the Antiviral Compound BILN 2061. 54th Annual Meeting of the American Association for the Study of Liver Diseases. (2003) (Abstract 300A).
   Google Scholar
• Benhamou Yves. Short-term anti-HCV activity and safety of BILN 2061 a novel oral HCV serine protease inhibitor. HEP DART 2003 Frontiers In Drug Development For Viral Hepatitis Conference. Kauai, Hawaii, USA. 14th-18th December 2003.
   Google Scholar
• Reiser M, Hinrichsen H, Benhamous Y, et al. Antiviral effect of BILN 2061, a novel HCV serine protease inhibitor, after oral treatment over 2 days in patients with chronic hepatitis C, nongenotype 1. 54th Annual Meeting of the American Association for the Study of Liver Diseases. (2003) (Abstract 136A).
   Google Scholar
• Wedemeyer H, Hochschule M, Erhardt A, et al. Safety and antiviral effect of BILN 2061, a novel HCV serine protease inhibitor, after oral treatment over 2 days in patients with chronic hepatitis C, genotype 1 and liver cirrhosis. 54th Annual Meeting of the American Association for the Study of Liver Diseases. (2003) (Abstract 294A).
   Google Scholar
• Perni RB, Chandorkar G, Chaturvedi PR, et al. VX-950: the discovery of an inhibitor of the hepatitis C N53•4a protease and a potential heptitis C virus therapeutic. 54th Annual Meeting of the American Association for the Study of Liver Diseases. (2003) (Abstract 972A).
   Google Scholar
• Lin K, Gates CA, Luong YP, et al. VX-950: a tight-binding HCV protease inhibitor with a superior sustained inhibitory response in HCV replicon cells. 54th Annual Meeting of the American Association for the Study of Liver Diseases. (2003) (Abstract 137A).
   Google Scholar
• Standring DN, Lanford R, Wright T, et al. NM283 has potent antiviral activity against chronic hepatitis C virus genotype 1 infection in the chimpanzee. HEP DART 2003 Frontiers In Drug Development For Viral Hepatitis Conference. Kauai, Hawaii, USA. 14th-18th December 2003.
   Google Scholar
• Godofsky E, Afdhal N, Rustgi V, et al First clinical results for a novel antiviral treatment for hepatitis C: a Phase I/II dose escalation trial assessing tolerance, pharmacokinetics and antiviral activity of NM283.39th Annual Meeting of the European Association fir the Study of the Liver. Berlin, Germany. 14–18 April 2004.
   Google Scholar
• •Clinical results of first-in-class nucleoside inhibitor.
   Google Scholar
• McHutchison JG, Patel K Future therapy of hepatitis C. Hepatology 36, S245—S252 (2002).
   PubMedGoogle Scholar
• McHutchison JG, Pockros PJ, Patel K, et al A Phase lb dose escalation trial of ISIS 14803, an antisense inhibitor of HCV, in patients with chronic HCV: final report. Hepatology 36,303A (2002).
   Web of Science ®Google Scholar
• Gordon SC, Bacon BR, Jacobson IM, et al A, Phase II, 12-week study of ISIS 14803, an antisense inhibitor of HCV for the treatment of chronic hepatitis C. Hepatology 36 (2002) (Abstract 362A).
   Web of Science ®Google Scholar
• Gordon SC, Bacon BR, Jacobson IM, et al Treatment of chronic hepatitis C with ISIS 14803, an antisense inhibitor of HCV, given for 12 weeks. 54th Annual Meeting of the American Association for the Study of Liver Diseases. (2003) (Abstract 312A).
   Google Scholar
• Bartenschlager R. Hepatitis C virus replicons: potential role for drug development. Naure Rev. Drug Discou 1(11), 911–916 (2002).
   PubMed Web of Science ®Google Scholar