Novel small-molecule inhibitors of hepatitis C virus entry block viral spread and promote viral clearance in cell culture

PLoS ONE

Volumn 7, Issue 4, 2012, Pages

  Coburn, Glen A ^a   Fisch, Danielle N ^a   Moorji, Sameer M ^a   de Muys, Jean Marc ^a   Murga, Jose D ^a   Paul, Dorothy ^a   Provoncha, Kathleen P ^a   Rotshteyn, Yakov ^a   Han, Amy Q ^a   Qian, Dapeng ^a   Maddon, Paul J ^a   Olson, William C ^a  

^a A Subsidiary of Lantheus Holdings   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

AMINO ACID; ANTIVIRUS AGENT; JS 81; PR 0371155; PR 0373192; PR 0502647; PR 0502661; PR 0502797; TRIAZINE; UNCLASSIFIED DRUG; VIRUS PROTEIN; TRIAZINE DERIVATIVE; VIRUS ENVELOPE PROTEIN;

ANTIVIRAL SUSCEPTIBILITY; ARTICLE; CELL CULTURE; DRUG EFFICACY; DRUG POTENCY; DRUG SELECTIVITY; DRUG STRUCTURE; DRUG TARGETING; DRUG TOLERABILITY; GENOTYPE; HEPATITIS C; HEPATITIS C VIRUS; HIGH THROUGHPUT SCREENING; HUMAN; HUMAN CELL; IN VITRO STUDY; LONG TERM CARE; MOLECULAR LIBRARY; VIRAL CLEARANCE; VIRUS ENTRY; VIRUS ENVELOPE; VIRUS PARTICLE; VIRUS REPLICATION; VIRUS RESISTANCE; VIRUS TRANSMISSION; ANTIVIRAL RESISTANCE; CELL LINE; CHEMISTRY; DRUG EFFECT; GENETICS;

ANTIVIRAL AGENTS; CELL LINE; DRUG RESISTANCE, VIRAL; GENOTYPE; HEPACIVIRUS; HEPATITIS C; HUMANS; SMALL MOLECULE LIBRARIES; TRIAZINES; VIRAL ENVELOPE PROTEINS; VIRUS INTERNALIZATION;

EID: 84860132481     PISSN: None     EISSN: 19326203     Source Type: Journal    
DOI: 10.1371/journal.pone.0035351     Document Type: Article

References (53)

1. Feld JJ, Hoofnagle JH, (2005) Mechanism of action of interferon and ribavirin in treatment of hepatitis C. Nature 436: 967-972.
2. McHutchison JG, Gordon SC, Schiff ER, Shiffman ML, Lee WM, et al. (1998) Interferon alfa-2b alone or in combination with ribavirin as initial treatment for chronic hepatitis C. Hepatitis Interventional Therapy Group. N Engl J Med 339: 1485-1492.
3. Bacon BR, Gordon SC, Lawitz E, Marcellin P, Vierling JM, et al. (2011) Boceprevir for previously treated chronic HCV genotype 1 infection. N Engl J Med 364: 1207-1217.
4. Jacobson IM, McHutchison JG, Dusheiko G, Di Bisceglie AM, Reddy KR, et al. (2011) Telaprevir for previously untreated chronic hepatitis C virus infection. N Engl J Med 364: 2405-2416.
5. Poordad F, McCone J Jr, Bacon BR, Bruno S, Manns MP, et al. (2011) Boceprevir for untreated chronic HCV genotype 1 infection. N Engl J Med 364: 1195-1206.
6. Zeuzem S, Andreone P, Pol S, Lawitz E, Diago M, et al. (2011) Telaprevir for retreatment of HCV infection. N Engl J Med 364: 2417-2428.
7. Cormier EG, Tsamis F, Kajumo F, Durso RJ, Gardner JP, et al. (2004) CD81 is an entry coreceptor for hepatitis C virus. Proc Natl Acad Sci U S A 101: 7270-7274.
8. Meuleman P, Hesselgesser J, Paulson M, Vanwolleghem T, Desombere I, et al. (2008) Anti-CD81 antibodies can prevent a hepatitis C virus infection in vivo. Hepatology 48: 1761-1768.
9. Grove J, Huby T, Stamataki Z, Vanwolleghem T, Meuleman P, et al. (2007) Scavenger receptor BI and BII expression levels modulate hepatitis C virus infectivity. J Virol 81: 3162-3169.
10. Scarselli E, Ansuini H, Cerino R, Roccasecca RM, Acali S, et al. (2002) The human scavenger receptor class B type I is a novel candidate receptor for the hepatitis C virus. EMBO J 21: 5017-5025.
11. Sainz B Jr, Barretto N, Martin DN, Hiraga N, Imamura M, et al. (2012) Identification of the Niemann-Pick C1-like 1 cholesterol absorption receptor as a new hepatitis C virus entry factor. Nat Med 18: 281-285.
12. Evans MJ, von Hahn T, Tscherne DM, Syder AJ, Panis M, et al. (2007) Claudin-1 is a hepatitis C virus co-receptor required for a late step in entry. Nature 446: 801-805.
13. Ploss A, Evans MJ, Gaysinskaya VA, Panis M, You H, et al. (2009) Human occludin is a hepatitis C virus entry factor required for infection of mouse cells. Nature 457: 882-886.
14. Agnello V, Abel G, Elfahal M, Knight GB, Zhang QX, (1999) Hepatitis C virus and other flaviviridae viruses enter cells via low density lipoprotein receptor. Proc Natl Acad Sci U S A 96: 12766-12771.
15. Dubuisson J, Helle F, Cocquerel L, (2008) Early steps of the hepatitis C virus life cycle. Cell Microbiol 10: 821-827.
16. Germi R, Crance JM, Garin D, Guimet J, Lortat-Jacob H, et al. (2002) Cellular glycosaminoglycans and low density lipoprotein receptor are involved in hepatitis C virus adsorption. J Med Virol 68: 206-215.
17. Voisset C, Callens N, Blanchard E, Op De Beeck A, Dubuisson J, et al. (2005) High density lipoproteins facilitate hepatitis C virus entry through the scavenger receptor class B type I. J Biol Chem 280: 7793-7799.
18. Drummer HE, Wilson KA, Poumbourios P, (2002) Identification of the hepatitis C virus E2 glycoprotein binding site on the large extracellular loop of CD81. J Virol 76: 11143-11147.
19. Flint M, Maidens C, Loomis-Price LD, Shotton C, Dubuisson J, et al. (1999) Characterization of hepatitis C virus E2 glycoprotein interaction with a putative cellular receptor, CD81. J Virol 73: 6235-6244.
20. Owsianka AM, Timms JM, Tarr AW, Brown RJ, Hickling TP, et al. (2006) Identification of conserved residues in the E2 envelope glycoprotein of the hepatitis C virus that are critical for CD81 binding. J Virol 80: 8695-8704.
21. Zeisel MB, Koutsoudakis G, Schnober EK, Haberstroh A, Blum HE, et al. (2007) Scavenger receptor class B type I is a key host factor for hepatitis C virus infection required for an entry step closely linked to CD81. Hepatology 46: 1722-1731.
22. Benedicto I, Molina-Jimenez F, Barreiro O, Maldonado-Rodriguez A, Prieto J, et al. (2008) Hepatitis C virus envelope components alter localization of hepatocyte tight junction-associated proteins and promote occludin retention in the endoplasmic reticulum. Hepatology 48: 1044-1053.
23. Harris HJ, Farquhar MJ, Mee CJ, Davis C, Reynolds GM, et al. (2008) CD81 and claudin 1 coreceptor association: role in hepatitis C virus entry. J Virol 82: 5007-5020.
24. Lupberger J, Zeisel MB, Xiao F, Thumann C, Fofana I, et al. (2011) EGFR and EphA2 are host factors for hepatitis C virus entry and possible targets for anti-viral therapy. Nat Med 17: 589-595.
25. Meertens L, Bertaux C, Dragic T, (2006) Hepatitis C virus entry requires a critical postinternalization step and delivery to early endosomes via clathrin-coated vesicles. J Virol 80: 11571-11578.
26. Hsu M, Zhang J, Flint M, Logvinoff C, Cheng-Mayer C, et al. (2003) Hepatitis C virus glycoproteins mediate pH-dependent cell entry of pseudotyped retroviral particles. PNAS 100: 7271-7276.
27. Tscherne DM, Jones CT, Evans MJ, Lindenbach BD, McKeating JA, et al. (2006) Time- and temperature-dependent activation of hepatitis C virus for low-pH-triggered entry. J Virol 80: 1734-1741.
28. Modis Y, Ogata S, Clements D, Harrison SC, (2004) Structure of the dengue virus envelope protein after membrane fusion. Nature 427: 313-319.
29. Rey FA, Heinz FX, Mandl C, Kunz C, Harrison SC, (1995) The envelope glycoprotein from tick-borne encephalitis virus at 2 A resolution. Nature 375: 291-298.
30. Zhang Y, Zhang W, Ogata S, Clements D, Strauss JH, et al. (2004) Conformational changes of the flavivirus E glycoprotein. Structure 12: 1607-1618.
31. Coburn, GA, Han, AQ, Provoncha, KP, Rotshteyn, Y, (2009) WO2009/091388 Triazines and related compounds having anti-viral activity, compositions and methods thereof.
32. Baldick CJ, Wichroski MJ, Pendri A, Walsh AW, Fang J, et al. (2010) A novel small molecule inhibitor of hepatitis C virus entry. PLoS Pathog 6: e1001086.
33. Lavillette D, Tarr AW, Voisset C, Donot P, Bartosch B, et al. (2005) Characterization of host-range and cell entry properties of the major genotypes and subtypes of hepatitis C virus. Hepatology 41: 265-274.
34. Gottwein JM, Scheel TKH, Jensen TB, Lademann JB, Prentoe JC, et al. (2009) Development and characterization of hepatitis C virus genotype 1-7 cell culture systems: Role of CD81 and scavenger receptor class B type 1 and effect of anti-viral drugs. Hepatology 49: 364-377.
35. Zhang Y, Weady P, Duggal R, Hao W, (2008) Novel chimeric genotype 1b/2a hepatitis C virus suitable for high-throughput screening. Antimicrob Agents Chemother 52: 666-674.
36. Zhong J, Gastaminza P, Cheng G, Kapadia S, Kato T, et al. (2005) Robust hepatitis C virus infection in vitro. Proc Natl Acad Sci U S A 102: 9294-9299.
37. Brimacombe CL, Grove J, Meredith LW, Hu K, Syder AJ, et al. (2011) Neutralizing antibody-resistant hepatitis C virus cell-to-cell transmission. J Virol 85: 596-605.
38. Timpe JM, Stamataki Z, Jennings A, Hu K, Farquhar MJ, et al. (2008) Hepatitis C virus cell-cell transmission in hepatoma cells in the presence of neutralizing antibodies. Hepatology 47: 17-24.
39. Howe AY, Bloom J, Baldick CJ, Benetatos CA, Cheng H, et al. (2004) Novel nonnucleoside inhibitor of hepatitis C virus RNA-dependent RNA polymerase. Antimicrob Agents Chemother 48: 4813-4821.
40. Perni RB, Almquist SJ, Byrn RA, Chandorkar G, Chaturvedi PR, et al. (2006) Preclinical profile of VX-950, a potent, selective, and orally bioavailable inhibitor of hepatitis C virus NS3-4A serine protease. Antimicrob Agents Chemother 50: 899-909.
41. Liang Y, Shilagard T, Xiao SY, Snyder N, Lau D, et al. (2009) Visualizing hepatitis C virus infections in human liver by two-photon microscopy. Gastroenterology 137: 1448-1458.
42. Rodriguez-Inigo E, Lopez-Alcorocho JM, Bartolome J, Ortiz-Movilla N, Pardo M, et al. (2005) Percentage of hepatitis C virus-infected hepatocytes is a better predictor of response than serum viremia levels. J Mol Diagn 7: 535-543.
43. Rong L, Perelson AS, (2010) Treatment of hepatitis C virus infection with interferon and small molecule direct anti-virals: viral kinetics and modeling. Crit Rev Immunol 30: 131-148.
44. Deng L, Adachi T, Kitayama K, Bungyoku Y, Kitazawa S, et al. (2008) Hepatitis C virus infection induces apoptosis through a Bax-triggered, mitochondrion-mediated, caspase 3-dependent pathway. J Virol 82: 10375-10385.
45. Joyce MA, Walters KA, Lamb SE, Yeh MM, Zhu LF, et al. (2009) HCV induces oxidative and ER stress, and sensitizes infected cells to apoptosis in SCID/Alb-uPA mice. PLoS Pathog 5: e1000291.
46. Neumann AU, Lam NP, Dahari H, Gretch DR, Wiley TE, et al. (1998) Hepatitis C viral dynamics in vivo and the anti-viral efficacy of interferon-alpha therapy. Science 282: 103-107.
47. Kuiken C, Hraber P, Thurmond J, Yusim K, (2008) The hepatitis C sequence database in Los Alamos. Nucleic Acids Res 36: D512-D516.
48. Olsen DB, Davies ME, Handt L, Koeplinger K, Zhang NR, et al. (2011) Sustained viral response in a hepatitis C virus-infected chimpanzee via a combination of direct-acting anti-viral agents. Antimicrob Agents Chemother 55: 937-939.
49. Walters KA, Joyce MA, Thompson JC, Smith MW, Yeh MM, et al. (2006) Host-specific response to HCV infection in the chimeric SCID-beige/Alb-uPA mouse model: role of the innate anti-viral immune response. PLoS Pathog 2: e59.
50. Freeman A, Hamid S, Morris L, Vowler S, Rushbrook S, et al. (2003) Improved detection of hepatocyte proliferation using antibody to the pre-replication complex: an association with hepatic fibrosis and viral replication in chronic hepatitis C virus infection. J Viral Hepat 10: 345-350.
51. Syder AJ, Lee H, Zeisel MB, Grove J, Soulier E, et al. (2011) Small molecule scavenger receptor BI antagonists are potent HCV entry inhibitors. J Hepatol 54: 48-55.
52. Dixit NM, Layden-Almer JE, Layden TJ, Perelson AS, (2004) Modelling how ribavirin improves interferon response rates in hepatitis C virus infection. Nature 432: 922-924.
53. Dahari H, Lo A, Ribeiro RM, Perelson AS, (2007) Modeling hepatitis C virus dynamics: liver regeneration and critical drug efficacy. J Theor Biol 247: 371-381.