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Review Article

To Explore the Potential Targets and Current Structure-based Design Strategies Utilizing Co-crystallized Ligand to Combat HCV

Author(s): Heena Tarannum, Bhumika Chauhan, Asmita Samadder, Harekrishna Roy and Sisir Nandi*

Volume 22, Issue 5, 2021

Published on: 27 July, 2020

Page: [590 - 604] Pages: 15

DOI: 10.2174/1389450121999200727215020

Price: $65

Abstract

Background: Hepatitis C Virus (HCV) belongs to the Hepacivirus family. HCV has been designated as a very dreadful virus as it can attack the liver, causing inflammation and even may lead to cancer in chronic conditions. It was estimated that 71 million people around the world have chronic HCV infection. World Health Organization (WHO) reported that about 399000 people died because of chronic cirrhosis and liver cancer globally. In spite of the abundance of availability of drugs for the treatment of HCV, however, the issue of drug resistance surpasses all the possibilities of therapeutic management of HCV. Therefore, to address this issue of ‘drug-resistance’, various HCV targets were explored to quest the evaluation of the mechanism of the disease progression.

Methods: An attempt has been made in the present study to explore the various targets of HCV involved in the mechanism(s) of the disease initiation and progression and to focus on the mode of binding of ligands, which are co-crystallized at the active cavity of different HCV targets.

Conclusion: The present study could predict some crucial features of these ligands, which possibly interacted with various amino acid residues responsible for their biological activity and molecular signaling pathway(s). Such binding mode may be considered as a template for the high throughput screening and designing of active congeneric ligands to combat HCV.

Keywords: Hepatitis C virus, various potential HCV targets, co-crystallized ligand, mode of binding, structure-based design, drug resistance in HCV target.

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[1]
Mohan H. Textbook of pathology6th ed published by Jaypee brother’s medical publisher’s pvtltd 2010.
[http://dx.doi.org/10.5005/jp/books/11091]
[2]
World health organization [WHO] 2019.
[3]
Rusyn I, Lemon SM. Mechanisms of HCV-induced liver cancer: what did we learn from in vitro and animal studies? Cancer Lett 2014; 345(2): 210-5.
[http://dx.doi.org/10.1016/j.canlet.2013.06.028] [PMID: 23871966]
[4]
Ferri C. Sebastiani.; Giuggioli, D.; Colaci, M.; Fallahi, P.; Piluso, A.; Antonelli, A.; Zignego, A.N. HCV syndrome: A constellation of organ- and non-organ specific autoimmune disorders, B-cell non-Hodgkin’s lymphoma, and cancer. World J Hepatol 2015; 7(3): 327-43.
[http://dx.doi.org/10.4254/wjh.v7.i3.327] [PMID: 25848462]
[5]
Dubuisson J, Cosset FL. Virology and cell biology of the hepatitis C virus life cycle: an update. J Hepatol 2014; 61(1)(Suppl.): S3-S13.
[http://dx.doi.org/10.1016/j.jhep.2014.06.031] [PMID: 25443344]
[6]
Kaito M, Ishida S, Tanaka H, et al. Morphology of hepatitis C and hepatitis B virus particles as detected by immunogold electron microscopy. Med Mol Morphol 2006; 39(2): 63-71.
[http://dx.doi.org/10.1007/s00795-006-0317-8] [PMID: 16821143]
[7]
Op De Beeck A, Dubuisson J. Topology of hepatitis C virus envelope glycoproteins. Rev Med Virol 2003; 13(4): 233-41.
[http://dx.doi.org/10.1002/rmv.391] [PMID: 12820185]
[8]
Castelli M, Clementi N, Pfaff J, et al. A Biologically-validated HCV E1E2 Heterodimer Structural Model. Sci Rep 2017; 7(1): 214.
[http://dx.doi.org/10.1038/s41598-017-00320-7] [PMID: 28303031]
[9]
Basu A, Beyene A, Meyer K, Ray R. The hypervariable region 1 of the E2 glycoprotein of hepatitis C virus binds to glycosaminoglycans, but this binding does not lead to infection in a pseudotype system. J Virol 2004; 78(9): 4478-86.
[http://dx.doi.org/10.1128/JVI.78.9.4478-4486.2004] [PMID: 15078928]
[10]
Kato N. Genome of human hepatitis C virus (HCV): gene organization, sequence diversity, and variation. Microb Comp Genomics 2000; 5(3): 129-51.
[http://dx.doi.org/10.1089/omi.1.2000.5.129] [PMID: 11252351]
[11]
Jubin R. Hepatitis C IRES: translating translation into a therapeutic target. Curr Opin Mol Ther 2001; 3(3): 278-87.
[PMID: 11497352]
[12]
Berry KE, Waghray S, Mortimer SA, Bai Y, Doudna JA. Crystal structure of the HCV IRES central domain reveals strategy for start-codon positioning. Structure 2011; 19(10): 1456-66.
[http://dx.doi.org/10.1016/j.str.2011.08.002] [PMID: 22000514]
[13]
Dubuisson J. Hepatitis C virus proteins. World J Gastroenterol 2007; 13(17): 2406-15.
[http://dx.doi.org/10.3748/wjg.v13.i17.2406] [PMID: 17552023]
[14]
Simmonds P. The origin of hepatitis C virus. Curr Top Microbiol Immunol 2013; 369: 1-15.
[http://dx.doi.org/10.1007/978-3-642-27340-7_1] [PMID: 23463195]
[15]
Choumet V, Despres Ph. Dengue and other flavivirus infections. Rev Sci Tech 2015; 34(2): 473-8.
[16]
Maggi F, Focosi D, Pistello M. How current direct-acting antiviral and novel cell culture systems for HCV are shaping therapy and molecular diagnosis of chronic HCV infection. Curr Drug Targets 2017; 18(7): 811-25.
[http://dx.doi.org/10.2174/1389450116666150806123119] [PMID: 26245474]
[17]
Paul D, Madan V, Bartenschlager R. Hepatitis C virus RNA replication and assembly: living on the fat of the land. Cell Host Microbe 2014; 16(5): 569-79.
[http://dx.doi.org/10.1016/j.chom.2014.10.008] [PMID: 25525790]
[18]
André P, Komurian-Pradel F, Deforges S, et al. Characterization of low- and very-low-density hepatitis C virus RNA-containing particles. J Virol 2002; 76(14): 6919-28.
[http://dx.doi.org/10.1128/JVI.76.14.6919-6928.2002] [PMID: 12072493]
[19]
Lohmann V. Hepatitis C virus RNA replication. Curr Top Microbiol Immunol 2013; 369: 167-98.
[http://dx.doi.org/10.1007/978-3-642-27340-7_7] [PMID: 23463201]
[20]
Niepmann M. Hepatitis C virus RNA translation. Curr Top Microbiol Immunol 2013; 369: 143-66.
[http://dx.doi.org/10.1007/978-3-642-27340-7_6] [PMID: 23463200]
[21]
Ball JK, Tarr AW, McKeating JA. The past, present and future of neutralizing antibodies for hepatitis C virus. Antiviral Res 2014; 105: 100-11.
[http://dx.doi.org/10.1016/j.antiviral.2014.02.013] [PMID: 24583033]
[22]
Timpe JM, Stamataki Z, Jennings A, et al. Hepatitis C virus cell-cell transmission in hepatoma cells in the presence of neutralizing antibodies. Hepatology 2008; 47(1): 17-24.
[http://dx.doi.org/10.1002/hep.21959] [PMID: 17941058]
[23]
Xiao F, Fofana I, Heydmann L, et al. Hepatitis C virus cell-cell transmission and resistance to direct-acting antiviral agents. PLoS Pathog 2014; 10(5)e1004128
[http://dx.doi.org/10.1371/journal.ppat.1004128] [PMID: 24830295]
[24]
Yoon JC, Lim JB, Park JH, Lee JM. Cell-to-cell contact with hepatitis C virus-infected cells reduces functional capacity of natural killer cells. J Virol 2011; 85(23): 12557-69.
[http://dx.doi.org/10.1128/JVI.00838-11] [PMID: 21937646]
[25]
Barretto N, Sainz B Jr, Hussain S, Uprichard SL. Determining the involvement and therapeutic implications of host cellular factors in hepatitis C virus cell-to-cell spread. J Virol 2014; 88(9): 5050-61.
[http://dx.doi.org/10.1128/JVI.03241-13] [PMID: 24554660]
[26]
Lindenbach BD, Evans MJ, Syder AJ, et al. Complete replication of hepatitis C virus in cell culture. Science 2005; 309(5734): 623-6.
[http://dx.doi.org/10.1126/science.1114016] [PMID: 15947137]
[27]
Wakita T, Pietschmann T, Kato T, et al. Production of infectious hepatitis C virus in tissue culture from a cloned viral genome. Nat Med 2005; 11(7): 791-6.
[http://dx.doi.org/10.1038/nm1268] [PMID: 15951748]
[28]
Steinmann E, Brohm C, Kallis S, Bartenschlager R, Pietschmann T. Efficient trans-encapsidation of hepatitis C virus RNAs into infectious virus-like particles. J Virol 2008; 82(14): 7034-46.
[http://dx.doi.org/10.1128/JVI.00118-08] [PMID: 18480457]
[29]
Suzuki R, Saito K, Kato T, et al. Trans-complemented hepatitis C virus particles as a versatile tool for study of virus assembly and infection. Virology 2012; 432(1): 29-38.
[http://dx.doi.org/10.1016/j.virol.2012.05.033] [PMID: 22727832]
[30]
Mina MM, Luciani F, Cameron B, et al. Resistance to hepatitis C virus: potential genetic and immunological determinants. Lancet Infect Dis 2015; 15(4): 451-60.
[http://dx.doi.org/10.1016/S1473-3099(14)70965-X] [PMID: 25703062]
[31]
Yang DR, Zhu HZ. Hepatitis C virus and antiviral innate immunity: who wins at tug-of-war? World J Gastroenterol 2015; 21(13): 3786-800.
[http://dx.doi.org/10.3748/wjg.v21.i13.3786] [PMID: 25852264]
[32]
Baugh JM, Garcia-Rivera JA, Gallay PA. Host-targeting agents in the treatment of hepatitis C: a beginning and an end? Antiviral Res 2013; 100(2): 555-61.
[http://dx.doi.org/10.1016/j.antiviral.2013.09.020] [PMID: 24091203]
[33]
Dustin LB, Bartolini B, Capobianchi MR, Pistello M. Hepatitis C virus: life cycle in cells, infection and host response, and analysis of molecular markers influencing the outcome of infection and response to therapy. Clin Microbiol Infect 2016; 22(10): 826-32.
[http://dx.doi.org/10.1016/j.cmi.2016.08.025] [PMID: 27592089]
[34]
Freedman H, Logan MR, Law JL, Houghton M. Structure and Function of the Hepatitis C Virus Envelope Glycoproteins E1 and E2: Antiviral and Vaccine Targets. ACS Infect Dis 2016; 2(11): 749-62.
[http://dx.doi.org/10.1021/acsinfecdis.6b00110] [PMID: 27933781]
[35]
Kong L, Giang E, Nieusma T, et al. Hepatitis C virus E2 envelope glycoprotein core structure. Science 2013; 342(6162): 1090-4.
[http://dx.doi.org/10.1126/science.1243876] [PMID: 24288331]
[36]
Khan AG, Whidby J, Miller MT, et al. Structure of the core ectodomain of the hepatitis C virus envelope glycoprotein 2. Nature 2014; 509(7500): 381-4.
[http://dx.doi.org/10.1038/nature13117] [PMID: 24553139]
[37]
Gonzalez ME, Carrasco L. Viroporins. FEBS Lett 2003; 552(1): 28-34.
[http://dx.doi.org/10.1016/S0014-5793(03)00780-4] [PMID: 12972148]
[38]
Lin C, Lindenbach BD, Prágai BM, McCourt DW, Rice CM. Processing in the hepatitis C virus E2-NS2 region: identification of p7 and two distinct E2-specific products with different C termini. J Virol 1994; 68(8): 5063-73.
[http://dx.doi.org/10.1128/JVI.68.8.5063-5073.1994] [PMID: 7518529]
[39]
Jones CT, Murray CL, Eastman DK, Tassello J, Rice CM. Hepatitis C virus p7 and NS2 proteins are essential for production of infectious virus. J Virol 2007; 81(16): 8374-83.
[http://dx.doi.org/10.1128/JVI.00690-07] [PMID: 17537845]
[40]
Steinmann E, Penin F, Kallis S, Patel AH, Bartenschlager R, Pietschmann T. Hepatitis C virus p7 protein is crucial for assembly and release of infectious virions PLoS Pathog 2007; 3(7): 962-71.
[41]
Carrère-Kremer S, Montpellier-Pala C, Cocquerel L, Wychowski C, Penin F, Dubuisson J. Subcellular localization and topology of the p7 polypeptide of hepatitis C virus. J Virol 2002; 76(8): 3720-30.
[http://dx.doi.org/10.1128/JVI.76.8.3720-3730.2002] [PMID: 11907211]
[42]
Clarke D, Griffin S, Beales L, et al. Evidence for the formation of a heptameric ion channel complex by the hepatitis C virus p7 protein in vitro. J Biol Chem 2006; 281(48): 37057-68.
[http://dx.doi.org/10.1074/jbc.M602434200] [PMID: 17032656]
[43]
Luik P, Chew C, Aittoniemi J, et al. The 3-dimensional structure of a hepatitis C virus p7 ion channel by electron microscopy. Proc Natl Acad Sci USA 2009; 106(31): 12712-6.
[http://dx.doi.org/10.1073/pnas.0905966106] [PMID: 19590017]
[44]
Pavlović D, Neville DC, Argaud O, et al. The hepatitis C virus p7 protein forms an ion channel that is inhibited by long-alkyl-chain iminosugar derivatives. Proc Natl Acad Sci USA 2003; 100(10): 6104-8.
[http://dx.doi.org/10.1073/pnas.1031527100] [PMID: 12719519]
[45]
Montserret R, Saint N, Vanbelle C, et al. NMR structure and ion channel activity of the p7 protein from hepatitis C virus. J Biol Chem 2010; 285(41): 31446-61.
[http://dx.doi.org/10.1074/jbc.M110.122895] [PMID: 20667830]
[46]
Erdtmann L, Franck N, Lerat H, et al. The hepatitis C virus NS2 protein is an inhibitor of CIDE-B-induced apoptosis. J Biol Chem 2003; 278(20): 18256-64.
[http://dx.doi.org/10.1074/jbc.M209732200] [PMID: 12595532]
[47]
Suarez DL. Influenza AVirusAnimal Influenza. 2016; p. 3.
[48]
Lorenz IC. The Hepatitis C Virus Nonstructural Protein 2 (NS2): An Up-and-Coming Antiviral Drug Target. Viruses 2010; 2(8): 1635-46.
[http://dx.doi.org/10.3390/v2081635] [PMID: 21994698]
[49]
Grakoui A, McCourt DW, Wychowski C, Feinstone SM, Rice CM. A second hepatitis C virus-encoded proteinase. Proc Natl Acad Sci USA 1993; 90(22): 10583-7.
[http://dx.doi.org/10.1073/pnas.90.22.10583] [PMID: 8248148]
[50]
Schregel V, Jacobi S, Penin F, Tautz N. Hepatitis C virus NS2 is a protease stimulated by cofactor domains in NS3. Proc Natl Acad Sci USA 2009; 106(13): 5342-7.
[http://dx.doi.org/10.1073/pnas.0810950106] [PMID: 19282477]
[51]
Blight KJ, McKeating JA, Rice CM. Highly permissive cell lines for subgenomic and genomic hepatitis C virus RNA replication. J Virol 2002; 76(24): 13001-14.
[http://dx.doi.org/10.1128/JVI.76.24.13001-13014.2002] [PMID: 12438626]
[52]
Lohmann V, Körner F, Koch J, Herian U, Theilmann L, Bartenschlager R. Replication of subgenomic hepatitis C virus RNAs in a hepatoma cell line. Science 1999; 285(5424): 110-3.
[http://dx.doi.org/10.1126/science.285.5424.110] [PMID: 10390360]
[53]
Welbourn S, Green R, Gamache I, et al. Hepatitis C virus NS2/3 processing is required for NS3 stability and viral RNA replication. J Biol Chem 2005; 280(33): 29604-11.
[http://dx.doi.org/10.1074/jbc.M505019200] [PMID: 15980068]
[54]
Popescu CI, Callens N, Trinel D, et al. NS2 protein of hepatitis C virus interacts with structural and non-structural proteins towards virus assembly. PLoS Pathog 2011; 7(2)e1001278
[http://dx.doi.org/10.1371/journal.ppat.1001278] [PMID: 21347350]
[55]
Jirasko V, Montserret R, Appel N, et al. Structural and functional characterization of nonstructural protein 2 for its role in hepatitis C virus assembly. J Biol Chem 2008; 283(42): 28546-62.
[http://dx.doi.org/10.1074/jbc.M803981200] [PMID: 18644781]
[56]
Pietschmann T, Kaul A, Koutsoudakis G, et al. Construction and characterization of infectious intragenotypic and intergenotypic hepatitis C virus chimeras. Proc Natl Acad Sci USA 2006; 103(19): 7408-13.
[http://dx.doi.org/10.1073/pnas.0504877103] [PMID: 16651538]
[57]
Yi M, Ma Y, Yates J, Lemon SM. Trans-complementation of an NS2 defect in a late step in hepatitis C virus (HCV) particle assembly and maturation. PLoS Pathog 2009; 5(5)e1000403
[http://dx.doi.org/10.1371/journal.ppat.1000403] [PMID: 19412343]
[58]
Lorenz IC, Marcotrigiano J, Dentzer TG, Rice CM. Structure of the catalytic domain of the hepatitis C virus NS2-3 protease. Nature 2006; 442(7104): 831-5.
[http://dx.doi.org/10.1038/nature04975] [PMID: 16862121]
[59]
Weiser BM, Tellinghuisen TL. Structural biology of the hepatitis C virus proteins. Drug Discov Today Technol 2012; 9(3): e175-226.
[http://dx.doi.org/10.1016/j.ddtec.2011.11.002] [PMID: 24064309]
[60]
Hijikata M, Mizushima H, Tanji Y, et al. Proteolytic processing and membrane association of putative nonstructural proteins of hepatitis C virus. Proc Natl Acad Sci USA 1993; 90(22): 10773-7.
[http://dx.doi.org/10.1073/pnas.90.22.10773] [PMID: 7504283]
[61]
Raney KD, Sharma SD, Moustafa IM, Cameron CE, Hepatitis C. Hepatitis C virus non-structural protein 3 (HCV NS3): a multifunctional antiviral target. J Biol Chem 2010; 285(30): 22725-31.
[http://dx.doi.org/10.1074/jbc.R110.125294] [PMID: 20457607]
[62]
LaPlante SR, Padyana AK, Abeywardane A, et al. Integrated strategies for identifying leads that target the NS3 helicase of the hepatitis C virus. J Med Chem 2014; 57(5): 2074-90.
[http://dx.doi.org/10.1021/jm401432c] [PMID: 24467709]
[63]
Beran RK, Lindenbach BD, Pyle AM, Pyle AM. The NS4A protein of hepatitis C virus promotes RNA-coupled ATP hydrolysis by the NS3 helicase. J Virol 2009; 83(7): 3268-75.
[http://dx.doi.org/10.1128/JVI.01849-08] [PMID: 19153239]
[64]
Failla C, Tomei L, De Francesco R. Both NS3 and NS4A are required for proteolytic processing of hepatitis C virus nonstructural proteins. J Virol 1994; 68(6): 3753-60.
[http://dx.doi.org/10.1128/JVI.68.6.3753-3760.1994] [PMID: 8189513]
[65]
Pang PS, Jankowsky E, Planet PJ, Pyle AM. The hepatitis C viral NS3 protein is a processive DNA helicase with cofactor enhanced RNA unwinding. EMBO J 2002; 21(5): 1168-76.
[http://dx.doi.org/10.1093/emboj/21.5.1168] [PMID: 11867545]
[66]
Tanji Y, Hijikata M, Satoh S, Kaneko T, Shimotohno K. Hepatitis C virus-encoded nonstructural protein NS4A has versatile functions in viral protein processing. J Virol 1995; 69(3): 1575-81.
[http://dx.doi.org/10.1128/JVI.69.3.1575-1581.1995] [PMID: 7853491]
[67]
Wölk B, Sansonno D, Kräusslich HG, et al. Subcellular localization, stability, and trans-cleavage competence of the hepatitis C virus NS3-NS4A complex expressed in tetracycline-regulated cell lines. J Virol 2000; 74(5): 2293-304.
[http://dx.doi.org/10.1128/JVI.74.5.2293-2304.2000] [PMID: 10666260]
[68]
Andrews DM, Chaignot H, Coomber BA, et al. Pyrrolidine-5,5-trans-lactams. 2. The use of X-ray crystal structure data in the optimization of P3 and P4 substituents. Org Lett 2002; 4(25): 4479-82.
[http://dx.doi.org/10.1021/ol027014p] [PMID: 12465917]
[69]
Bartenschlager R, Ahlborn-Laake L, Mous J, Jacobsen H. Kinetic and structural analyses of hepatitis C virus polyprotein processing. J Virol 1994; 68(8): 5045-55.
[http://dx.doi.org/10.1128/JVI.68.8.5045-5055.1994] [PMID: 8035505]
[70]
Lin C, Rice CM. The hepatitis C virus NS3 serine proteinase and NS4A cofactor: establishment of a cell-free trans-processing assay. Proc Natl Acad Sci USA 1995; 92(17): 7622-6.
[http://dx.doi.org/10.1073/pnas.92.17.7622] [PMID: 7644466]
[71]
Ma Y, Yates J, Liang Y, Lemon SM, Yi M. NS3 helicase domains involved in infectious intracellular hepatitis C virus particle assembly. J Virol 2008; 82(15): 7624-39.
[http://dx.doi.org/10.1128/JVI.00724-08] [PMID: 18508894]
[72]
Yao N, Reichert P, Taremi SS, Prosise WW, Weber PC. Molecular views of viral polyprotein processing revealed by the crystal structure of the hepatitis C virus bifunctional protease-helicase. Structure 1999; 7(11): 1353-63.
[http://dx.doi.org/10.1016/S0969-2126(00)80025-8] [PMID: 10574797]
[73]
Jiang Y, Andrews SW, Condroski KR, et al. Discovery of danoprevir (ITMN-191/R7227), a highly selective and potent inhibitor of hepatitis C virus (HCV) NS3/4A protease. J Med Chem 2014; 57(5): 1753-69.
[http://dx.doi.org/10.1021/jm400164c] [PMID: 23672640]
[74]
Slater MJ, Amphlett EM, Andrews DM, et al. Pyrrolidine-5,5-trans-lactams. 4. Incorporation of a P3/P4 urea leads to potent intracellular inhibitors of hepatitis C virus NS3/4A protease. Org Lett 2003; 5(24): 4627-30.
[http://dx.doi.org/10.1021/ol035826v] [PMID: 14627400]
[75]
Bartenschlager R, Ahlborn-Laake L, Mous J, Jacobsen H. Nonstructural protein 3 of the hepatitis C virus encodes a serine-type proteinase required for cleavage at the NS3/4 and NS4/5 junctions. J Virol 1993; 67(7): 3835-44.
[http://dx.doi.org/10.1128/JVI.67.7.3835-3844.1993] [PMID: 8389908]
[76]
Bartenschlager R, Ahlborn-Laake L, Yasargil K, Mous J, Jacobsen H. Substrate determinants for cleavage in cis and in trans by the hepatitis C virus NS3 proteinase. J Virol 1995; 69(1): 198-205.
[http://dx.doi.org/10.1128/JVI.69.1.198-205.1995] [PMID: 7983710]
[77]
Failla C, Tomei L, De Francesco R. An amino-terminal domain of the hepatitis C virus NS3 protease is essential for interaction with NS4A. J Virol 1995; 69(3): 1769-77.
[http://dx.doi.org/10.1128/JVI.69.3.1769-1777.1995] [PMID: 7853516]
[78]
Lin C, Prágai BM, Grakoui A, Xu J, Rice CM. Hepatitis C virus NS3 serine proteinase: trans-cleavage requirements and processing kinetics. J Virol 1994; 68(12): 8147-57.
[http://dx.doi.org/10.1128/JVI.68.12.8147-8157.1994] [PMID: 7966606]
[79]
Penin F, Dubuisson J, Rey FA, Moradpour D, Pawlotsky JM. Structural biology of hepatitis C virus. Hepatology 2004; 39(1): 5-19.
[http://dx.doi.org/10.1002/hep.20032] [PMID: 14752815]
[80]
De Francesco R, Tomei L, Altamura S, Summa V, Migliaccio G. Approaching a new era for hepatitis C virus therapy: inhibitors of the NS3-4A serine protease and the NS5B RNA-dependent RNA polymerase. Antiviral Res 2003; 58(1): 1-16.
[http://dx.doi.org/10.1016/S0166-3542(03)00028-7] [PMID: 12719002]
[81]
Love RA, Parge HE, Wickersham JA, et al. The crystal structure of hepatitis C virus NS3 proteinase reveals a trypsin-like fold and a structural zinc binding site. Cell 1996; 87(2): 331-42.
[http://dx.doi.org/10.1016/S0092-8674(00)81350-1] [PMID: 8861916]
[82]
Stempniak M, Hostomska Z, Nodes BR, Hostomsky Z. The NS3 proteinase domain of hepatitis C virus is a zinc-containing enzyme. J Virol 1997; 71(4): 2881-6.
[http://dx.doi.org/10.1128/JVI.71.4.2881-2886.1997] [PMID: 9060645]
[83]
Li K, Foy E, Ferreon JC, et al. Jr.Gale, M.; Lemon, S.M. Immune evasions by hepatitis C virus NS3/4A protease mediate cleavage of the Toll-like receptor 3 adaptor protein TRIF. Proc Natl Acad Sci USA 2005; 102(8): 2992-7.
[http://dx.doi.org/10.1073/pnas.0408824102] [PMID: 15710891]
[84]
Meylan E, Curran J, Hofmann K, et al. Cardif is an adaptor protein in the RIG-I antiviral pathway and is targeted by hepatitis C virus. Nature 2005; 437(7062): 1167-72.
[http://dx.doi.org/10.1038/nature04193] [PMID: 16177806]
[85]
Cho HS, Ha NC, Kang LW, et al. Crystal structure of RNA helicase from genotype 1b hepatitis C virus. A feasible mechanism of unwinding duplex RNA. J Biol Chem 1998; 273(24): 15045-52.
[http://dx.doi.org/10.1074/jbc.273.24.15045] [PMID: 9614113]
[86]
Kim JL, Morgenstern KA, Griffith JP, et al. Hepatitis C virus NS3 RNA helicase domain with a bound oligonucleotide: the crystal structure provides insights into the mode of unwinding. Structure 1998; 6(1): 89-100.
[http://dx.doi.org/10.1016/S0969-2126(98)00010-0] [PMID: 9493270]
[87]
Yao N, Hesson T, Cable M, et al. Structure of the hepatitis C virus RNA helicase domain. Nat Struct Biol 1997; 4(6): 463-7.
[http://dx.doi.org/10.1038/nsb0697-463] [PMID: 9187654]
[88]
Romano KP, Laine JM, Deveau LM, Cao H, Massi F, Schiffer CA. Molecular mechanisms of viral and host cell substrate recognition by hepatitis C virus NS3/4A protease. J Virol 2011; 85(13): 6106-16.
[http://dx.doi.org/10.1128/JVI.00377-11] [PMID: 21507982]
[89]
Dumont S, Cheng W, Serebrov V, et al. RNA translocation and unwinding mechanism of HCV NS3 helicase and its coordination by ATP. Nature 2006; 439(7072): 105-8.
[http://dx.doi.org/10.1038/nature04331] [PMID: 16397502]
[90]
Levin MK, Gurjar M, Patel SS. A Brownian motor mechanism of translocation and strand separation by hepatitis C virus helicase. Nat Struct Mol Biol 2005; 12(5): 429-35.
[http://dx.doi.org/10.1038/nsmb920] [PMID: 15806107]
[91]
Levin MK, Wang YH, Patel SS. The functional interaction of the hepatitis C virus helicase molecules is responsible for unwinding processivity. J Biol Chem 2004; 279(25): 26005-12.
[http://dx.doi.org/10.1074/jbc.M403257200] [PMID: 15087464]
[92]
Serebrov V, Pyle AM. Periodic cycles of RNA unwinding and pausing by hepatitis C virus NS3 helicase. Nature 2004; 430(6998): 476-80.
[http://dx.doi.org/10.1038/nature02704] [PMID: 15269774]
[93]
Locatelli GA, Spadari S, Maga G. Hepatitis C virus NS3 ATPase/helicase: an ATP switch regulates the cooperativity among the different substrate binding sites. Biochemistry 2002; 41(32): 10332-42.
[http://dx.doi.org/10.1021/bi026082g] [PMID: 12162749]
[94]
Mackintosh SG, Lu JZ, Jordan JB, et al. Structural and biological identification of residues on the surface of NS3 helicase required for optimal replication of the hepatitis C virus. J Biol Chem 2006; 281(6): 3528-35.
[http://dx.doi.org/10.1074/jbc.M512100200] [PMID: 16306038]
[95]
Kwong AD, Rao BG, Jeang KT. Viral and cellular RNA helicases as antiviral targets. Nat Rev Drug Discov 2005; 4(10): 845-53.
[http://dx.doi.org/10.1038/nrd1853] [PMID: 16184083]
[96]
Beld M, Penning M, van Putten M, et al. Hepatitis C virus serotype-specific core and NS4 antibodies in injecting drug users participating in the Amsterdam cohort studies. J Clin Microbiol 1998; 36(10): 3002-6.
[http://dx.doi.org/10.1128/JCM.36.10.3002-3006.1998] [PMID: 9738057]
[97]
Sklan EH, Glenn JS. Chapter8 HCV NS4B: From Obscurity to Central Stage in Hepatitis C Viruses: Genomes and Molecular Biology Tan SL. Norfolk: Horizon Bioscience 2006.
[98]
Egger D, Wölk 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(12): 5974-84.
[http://dx.doi.org/10.1128/JVI.76.12.5974-5984.2002] [PMID: 12021330]
[99]
Lundin M, Lindström H, Grönwall C, Persson MA. Dual topology of the processed hepatitis C virus protein NS4B is influenced by the NS5A protein. J Gen Virol 2006; 87(Pt 11): 3263-72.
[http://dx.doi.org/10.1099/vir.0.82211-0] [PMID: 17030859]
[100]
Gouttenoire J, Castet V, Montserret R, et al. Identification of a novel determinant for membrane association in hepatitis C virus nonstructural protein 4B. J Virol 2009; 83(12): 6257-68.
[http://dx.doi.org/10.1128/JVI.02663-08] [PMID: 19357161]
[101]
Einav S, Elazar M, Danieli T, Glenn JS. A nucleotide binding motif in hepatitis C virus (HCV) NS4B mediates HCV RNA replication. J Virol 2004; 78(20): 11288-95.
[http://dx.doi.org/10.1128/JVI.78.20.11288-11295.2004] [PMID: 15452248]
[102]
Gouttenoire J, Montserret R, Kennel A, Penin F, Moradpour D. An amphipathic alpha-helix at the C terminus of hepatitis C virus nonstructural protein 4B mediates membrane association. J Virol 2009; 83(21): 11378-84.
[http://dx.doi.org/10.1128/JVI.01122-09] [PMID: 19692468]
[103]
Belda O, Targett-Adams P. Small molecule inhibitors of the hepatitis C virus-encoded NS5A protein. Virus Res 2012; 170(1-2): 1-14.
[http://dx.doi.org/10.1016/j.virusres.2012.09.007] [PMID: 23009750]
[104]
Huang Y, Staschke K, De Francesco R, Tan SL. Phosphorylation of hepatitis C virus NS5A nonstructural protein: a new paradigm for phosphorylation-dependent viral RNA replication? Virology 2007; 364(1): 1-9.
[http://dx.doi.org/10.1016/j.virol.2007.01.042] [PMID: 17400273]
[105]
Macdonald A, Harris M. Hepatitis C virus NS5A: tales of a promiscuous protein. J Gen Virol 2004; 85(Pt 9): 2485-502.
[http://dx.doi.org/10.1099/vir.0.80204-0] [PMID: 15302943]
[106]
He Y, Staschke KA, Tan SL. HCV NS5A: A multifunctional Regulator of Cellular Pathways and Virus ReplicationHepatitis C Viruses: Genomes and Molecular Biology. Norfolk, UK: Horizon Bioscience 2006.
[107]
Tellinghuisen TL, Marcotrigiano J, Gorbalenya AE, Rice CM. The NS5A protein of hepatitis C virus is a zinc metalloprotein. J Biol Chem 2004; 279(47): 48576-87.
[http://dx.doi.org/10.1074/jbc.M407787200] [PMID: 15339921]
[108]
Foster TL, Belyaeva T, Stonehouse NJ, Pearson AR, Harris M. All three domains of the hepatitis C virus nonstructural NS5A protein contribute to RNA binding. J Virol 2010; 84(18): 9267-77.
[http://dx.doi.org/10.1128/JVI.00616-10] [PMID: 20592076]
[109]
Huang L, Hwang J, Sharma SD, et al. Hepatitis C virus nonstructural protein 5A (NS5A) is an RNA-binding protein. J Biol Chem 2005; 280(43): 36417-28.
[http://dx.doi.org/10.1074/jbc.M508175200] [PMID: 16126720]
[110]
Love RA, Brodsky O, Hickey MJ, Wells PA, Cronin CN. Crystal structure of a novel dimeric form of NS5A domain I protein from hepatitis C virus. J Virol 2009; 83(9): 4395-403.
[http://dx.doi.org/10.1128/JVI.02352-08] [PMID: 19244328]
[111]
Tellinghuisen TL, Marcotrigiano J, Rice CM. Structure of the zinc-binding domain of an essential component of the hepatitis C virus replicase. Nature 2005; 435(7040): 374-9.
[http://dx.doi.org/10.1038/nature03580] [PMID: 15902263]
[112]
Blight KJ, Kolykhalov AA, Rice CM. Efficient initiation of HCV RNA replication in cell culture. Science 2000; 290(5498): 1972-4.
[http://dx.doi.org/10.1126/science.290.5498.1972] [PMID: 11110665]
[113]
Kolykhalov AA, Mihalik K, Feinstone SM, Rice CM. Hepatitis C virus-encoded enzymatic activities and conserved RNA elements in the 3′ nontranslated region are essential for virus replication in vivo. J Virol 2000; 74(4): 2046-51.
[http://dx.doi.org/10.1128/JVI.74.4.2046-2051.2000] [PMID: 10644379]
[114]
Lévêque VJ, Wang QM. RNA-dependent RNA polymerase encoded by hepatitis C virus: biomedical applications. Cell Mol Life Sci 2002; 59(6): 909-19.
[http://dx.doi.org/10.1007/s00018-002-8478-7] [PMID: 12169021]
[115]
Gehring S, Gregory SH, Wintermeyer P, Aloman C, Wands JR. Generation of immune responses against hepatitis C virus by dendritic cells containing NS5 protein-coated microparticles. Clin Vaccine Immunol 2009; 16(2): 163-71.
[http://dx.doi.org/10.1128/CVI.00287-08] [PMID: 19091993]
[116]
Moradpour D, Brass V, Bieck E, et al. Membrane association of the RNA-dependent RNA polymerase is essential for hepatitis C virus RNA replication. J Virol 2004; 78(23): 13278-84.
[http://dx.doi.org/10.1128/JVI.78.23.13278-13284.2004] [PMID: 15542678]
[117]
Schmidt-Mende J, Bieck E, Hugle T, et al. Determinants for membrane association of the hepatitis C virus RNA-dependent RNA polymerase. J Biol Chem 2001; 276(47): 44052-63.
[http://dx.doi.org/10.1074/jbc.M103358200] [PMID: 11557752]
[118]
Ivashkina N, Wölk B, Lohmann V, et al. The hepatitis C virus RNA-dependent RNA polymerase membrane insertion sequence is a transmembrane segment. J Virol 2002; 76(24): 13088-93.
[http://dx.doi.org/10.1128/JVI.76.24.13088-13093.2002] [PMID: 12438637]
[119]
Jin Z, Leveque V, Ma H, Johnson KA, Klumpp K. Assembly, purification, and pre-steady-state kinetic analysis of active RNA-dependent RNA polymerase elongation complex. J Biol Chem 2012; 287(13): 10674-83.
[http://dx.doi.org/10.1074/jbc.M111.325530] [PMID: 22303022]
[120]
Moradpour D, Penin F, Rice CM. Replication of hepatitis C virus. Nat Rev Microbiol 2007; 5(6): 453-63.
[http://dx.doi.org/10.1038/nrmicro1645] [PMID: 17487147]
[121]
Rigat K, Wang Y, Hudyma TW, et al. Ligand-induced changes in hepatitis C virus NS5B polymerase structure. Antiviral Res 2010; 88(2): 197-206.
[http://dx.doi.org/10.1016/j.antiviral.2010.08.014] [PMID: 20813137]
[122]
Biswal BK, Cherney MM, Wang M, et al. Crystal structures of the RNA-dependent RNA polymerase genotype 2a of hepatitis C virus reveal two conformations and suggest mechanisms of inhibition by non-nucleoside inhibitors. J Biol Chem 2005; 280(18): 18202-10.
[http://dx.doi.org/10.1074/jbc.M413410200] [PMID: 15746101]
[123]
O’Farrell D, Trowbridge R, Rowlands D, Jäger J. Substrate complexes of hepatitis C virus RNA polymerase (HC-J4): structural evidence for nucleotide import and de-novo initiation. J Mol Biol 2003; 326(4): 1025-35.
[http://dx.doi.org/10.1016/S0022-2836(02)01439-0] [PMID: 12589751]
[124]
Ago H, Adachi T, Yoshida A, et al. Crystal structure of the RNA-dependent RNA polymerase of hepatitis C virus. Structure 1999; 7(11): 1417-26.
[http://dx.doi.org/10.1016/S0969-2126(00)80031-3] [PMID: 10574802]
[125]
Lesburg CA, Cable MB, Ferrari E, Hong Z, Mannarino AF, Weber PC. Crystal structure of the RNA-dependent RNA polymerase from hepatitis C virus reveals a fully encircled active site. Nat Struct Biol 1999; 6(10): 937-43.
[http://dx.doi.org/10.1038/13305] [PMID: 10504728]
[126]
Bressanelli S, Tomei L, Roussel A, et al. Crystal structure of the RNA-dependent RNA polymerase of hepatitis C virus. Proc Natl Acad Sci USA 1999; 96(23): 13034-9.
[http://dx.doi.org/10.1073/pnas.96.23.13034] [PMID: 10557268]
[127]
Bressanelli S, Tomei L, Rey FA, De Francesco R. Structural analysis of the hepatitis C virus RNA polymerase in complex with ribonucleotides. J Virol 2002; 76(7): 3482-92.
[http://dx.doi.org/10.1128/JVI.76.7.3482-3492.2002] [PMID: 11884572]
[128]
Hong Z, Cameron CE, Walker MP, et al. A novel mechanism to ensure terminal initiation by hepatitis C virus NS5B polymerase. Virology 2001; 285(1): 6-11.
[http://dx.doi.org/10.1006/viro.2001.0948] [PMID: 11414800]
[129]
Kim YC, Russell WK, Ranjith-Kumar CT, Thomson M, Russell DH, Kao CC. Functional analysis of RNA binding by the hepatitis C virus RNA-dependent RNA polymerase. J Biol Chem 2005; 280(45): 38011-9.
[http://dx.doi.org/10.1074/jbc.M508145200] [PMID: 16166071]
[130]
Ranjith-Kumar CT, Gutshall L, Sarisky RT, Kao CC. Multiple interactions within the hepatitis C virus RNA polymerase repress primer-dependent RNA synthesis. J Mol Biol 2003; 330(4): 675-85.
[http://dx.doi.org/10.1016/S0022-2836(03)00613-2] [PMID: 12850139]
[131]
Cai Z, Yi M, Zhang C, Luo G. Mutagenesis analysis of the rGTP-specific binding site of hepatitis C virus RNA-dependent RNA polymerase. J Virol 2005; 79(18): 11607-17.
[http://dx.doi.org/10.1128/JVI.79.18.11607-11617.2005] [PMID: 16140738]
[132]
Lévêque VJ, Johnson RB, Parsons S, et al. Identification of a C-terminal regulatory motif in hepatitis C virus RNA-dependent RNA polymerase: structural and biochemical analysis. J Virol 2003; 77(16): 9020-8.
[http://dx.doi.org/10.1128/JVI.77.16.9020-9028.2003] [PMID: 12885918]
[133]
Wang QM, Hockman MA, Staschke K, et al. Oligomerization and cooperative RNA synthesis activity of hepatitis C virus RNA-dependent RNA polymerase. J Virol 2002; 76(8): 3865-72.
[http://dx.doi.org/10.1128/JVI.76.8.3865-3872.2002] [PMID: 11907226]
[134]
Piccininni S, Varaklioti A, Nardelli M, Dave B, Raney KD, McCarthy JE. Modulation of the hepatitis C virus RNA-dependent RNA polymerase activity by the non-structural (NS) 3 helicase and the NS4B membrane protein. J Biol Chem 2002; 277(47): 45670-9.
[http://dx.doi.org/10.1074/jbc.M204124200] [PMID: 12235135]
[135]
Shirota Y, Luo H, Qin W, et al. Hepatitis C virus (HCV) NS5A binds RNA-dependent RNA polymerase (RdRP) NS5B and modulates RNA-dependent RNA polymerase activity. J Biol Chem 2002; 277(13): 11149-55..
[http://dx.doi.org/10.1074/jbc.M111392200] [PMID: 11801599]

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