{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,31]],"date-time":"2025-12-31T00:21:44Z","timestamp":1767140504727,"version":"build-2238731810"},"reference-count":128,"publisher":"Springer Science and Business Media LLC","issue":"5","license":[{"start":{"date-parts":[[2013,8,25]],"date-time":"2013-08-25T00:00:00Z","timestamp":1377388800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/www.springer.com\/tdm"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Arch Virol"],"published-print":{"date-parts":[[2014,5]]},"DOI":"10.1007\/s00705-013-1803-7","type":"journal-article","created":{"date-parts":[[2013,8,24]],"date-time":"2013-08-24T02:53:21Z","timestamp":1377312801000},"page":"831-846","source":"Crossref","is-referenced-by-count":12,"title":["Current and future therapies for hepatitis C virus infection: from viral proteins to host targets"],"prefix":"10.1007","volume":"159","author":[{"given":"Muhammad","family":"Imran","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sobia","family":"Manzoor","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nasir Mahmood","family":"Khattak","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Madiha","family":"Khalid","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qazi Laeeque","family":"Ahmed","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fahed","family":"Parvaiz","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Muqddas","family":"Tariq","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Javed","family":"Ashraf","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Waseem","family":"Ashraf","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sikandar","family":"Azam","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Muhammad","family":"Ashraf","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2013,8,25]]},"reference":[{"key":"1803_CR1","doi-asserted-by":"crossref","first-page":"1567","DOI":"10.1056\/NEJMe048237","volume":"351","author":"JR Wands","year":"2004","unstructured":"Wands JR (2004) Prevention of hepatocellular carcinoma. N Engl J Med 351:1567\u20131570","journal-title":"N Engl J Med"},{"key":"1803_CR2","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1177\/0091270003258669","volume":"44","author":"Global Burden of Hepatitis C Working Group","year":"2004","unstructured":"Global Burden of Hepatitis C Working Group (2004) Global burden of disease (GBD) for hepatitis C. J Clin Pharmacol 44:20\u201329","journal-title":"J Clin Pharmacol"},{"key":"1803_CR3","doi-asserted-by":"crossref","first-page":"2057","DOI":"10.1073\/pnas.87.6.2057","volume":"87","author":"RH Miller","year":"1990","unstructured":"Miller RH, Purcell RH (1990) Hepatitis C virus shares amino acid sequence similarity with pestiviruses and flaviviruses as well as members of two plant virus supergroups. Proc Natl Acad Sci USA 87:2057\u20132061","journal-title":"Proc Natl Acad Sci USA"},{"key":"1803_CR4","doi-asserted-by":"crossref","first-page":"8853","DOI":"10.1128\/JVI.00753-07","volume":"8","author":"TL Tellinghuisen","year":"2007","unstructured":"Tellinghuisen TL, Evans MJ, von Hahn T, You S, Rice CM (2007) Studying hepatitis C virus: making the best of a bad virus. J Virol 8:8853\u20138867","journal-title":"J Virol"},{"key":"1803_CR5","first-page":"17","volume":"131","author":"SD Sharma","year":"2010","unstructured":"Sharma SD (2010) Hepatitis C virus: molecular biology & current therapeutic options. Indian J Med Res 131:17\u201334","journal-title":"Indian J Med Res"},{"key":"1803_CR6","doi-asserted-by":"crossref","first-page":"631","DOI":"10.1002\/hep.21781","volume":"46","author":"TL Kieffer","year":"2007","unstructured":"Kieffer TL, Sarrazin C, Miller JS, Welker MW, Forestier N, Reesink HW, Kwong AD, Zeuzem S (2007) Telaprevir and pegylated interferon-alpha-2a inhibit wild-type and resistant genotype 1 hepatitis C virus replication in patients. Hepatology 46:631\u2013639","journal-title":"Hepatology"},{"key":"1803_CR7","doi-asserted-by":"crossref","first-page":"993","DOI":"10.1016\/j.jhep.2004.02.007","volume":"40","author":"S Zeuzem","year":"2004","unstructured":"Zeuzem S, Hultcrantz R, Bourliere M et al (2004) Peginterferon alfa-2b plus ribavirin for treatment of chronic hepatitis C in previously untreated patients infected with HCV genotypes 2 or 3. J Hepatol 40:993\u2013999","journal-title":"J Hepatol"},{"key":"1803_CR8","doi-asserted-by":"crossref","first-page":"884","DOI":"10.1016\/j.cgh.2010.06.019","volume":"8","author":"H Farnik","year":"2010","unstructured":"Farnik H, Lange CM, Sarrazin C et al (2010) Meta-analysis shows extended therapy improves response of patients with chronic hepatitis C virus genotype 1 infection. Clin Gastroenterol Hepatol 8:884\u2013890","journal-title":"Clin Gastroenterol Hepatol"},{"key":"1803_CR9","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1053\/j.gastro.2009.11.055","volume":"138","author":"C Sarrazin","year":"2010","unstructured":"Sarrazin C, Zeuzem S (2010) Resistance to direct antiviral agents in patients with hepatitis C virus infection. Gastroenterology 138:447\u2013462","journal-title":"Gastroenterology"},{"key":"1803_CR10","doi-asserted-by":"crossref","first-page":"2623","DOI":"10.1093\/nar\/gkh579","volume":"32","author":"G Cristofari","year":"2004","unstructured":"Cristofari G, Ivanyi-Nagy R, Gabus C et al (2004) The hepatitis C virus Core protein is a potent nucleic acid chaperone that directs dimerization of the viral (+) strand RNA in vitro. Nucleic Acids Res 32:2623\u20132631","journal-title":"Nucleic Acids Res"},{"key":"1803_CR11","doi-asserted-by":"crossref","first-page":"2618","DOI":"10.1093\/nar\/gkl240","volume":"34","author":"R Ivanyi-Nagy","year":"2006","unstructured":"Ivanyi-Nagy R, Kanevsky I, Gabus C, Lavergne JP, Ficheux D, Penin F, Fosse P, Darlix JL (2006) Analysis of hepatitis C virus RNA dimerization and core-RNA interactions. Nucleic Acids Res 34:2618\u20132633","journal-title":"Nucleic Acids Res"},{"key":"1803_CR12","doi-asserted-by":"crossref","first-page":"1666","DOI":"10.1128\/JVI.02043-09","volume":"84","author":"M Kopp","year":"2010","unstructured":"Kopp M, Murray CL, Jones CT, Rice CM (2010) Genetic analysis of the carboxy-terminal region of the Hepatitis C virus core protein. J Virol 84:1666\u20131673","journal-title":"J Virol"},{"key":"1803_CR13","doi-asserted-by":"crossref","first-page":"8349","DOI":"10.1128\/JVI.00306-08","volume":"82","author":"K Okamoto","year":"2008","unstructured":"Okamoto K, Mori Y, Komoda Y et al (2008) Intramembrane processing by signal peptide peptidase regulates the membrane localization of hepatitis C virus core protein and viral propagation. J Virol 82:8349\u20138361","journal-title":"J Virol"},{"key":"1803_CR14","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1006\/viro.1996.0510","volume":"224","author":"P H\u00fcssy","year":"1996","unstructured":"H\u00fcssy P, Langen H, Mous J, Jacobsen H (1996) Hepatitis C virus core protein: carboxy-terminal boundaries of two processed species suggest cleavage by a signal peptide peptidase. Virology 224:93\u2013104","journal-title":"Virology"},{"key":"1803_CR15","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1016\/j.virusres.2007.02.023","volume":"127","author":"J Cristina","year":"2007","unstructured":"Cristina J, Moreno-del PM, Moratorio G (2007) Hepatitis C virus genetic variability in patients undergoing antiviral therapy. Virus Res 127:185\u2013194","journal-title":"Virus Res"},{"key":"1803_CR16","doi-asserted-by":"crossref","first-page":"1001","DOI":"10.1038\/nature06526","volume":"450","author":"JA Wells","year":"2007","unstructured":"Wells JA, McClendon CL (2007) Reaching for high-hanging fruit in drug discovery at protein-protein interfaces. Nature 450:1001\u20131009","journal-title":"Nature"},{"key":"1803_CR17","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1089\/adt.2009.0217","volume":"8","author":"S Kota","year":"2010","unstructured":"Kota S, Scampavia L, Spicer T, Beeler AB, Takahashi V, Snyder JK, Porco JA Jr, Hodder P, Strosberg AD (2010) A homogeneous time resolved fluorescence assay for identifying inhibitors of Hepatitis C virus dimerization. Assay Drug Dev Technol 8:96\u2013105","journal-title":"Assay Drug Dev Technol"},{"key":"1803_CR18","doi-asserted-by":"crossref","first-page":"1734","DOI":"10.3390\/v2081734","volume":"2","author":"AD Strosberg","year":"2010","unstructured":"Strosberg AD, Kota S, Takahashi V, Snyder JK, Mousseau G (2010) Core as a novel viral target for hepatitis C drugs. Viruses 2:1734\u20131751","journal-title":"Viruses"},{"key":"1803_CR19","doi-asserted-by":"crossref","first-page":"550","DOI":"10.1126\/science.1068999","volume":"296","author":"TR Brummelkamp","year":"2002","unstructured":"Brummelkamp TR, Bernards R, Agami R (2002) A system for stable expression of short interfering RNAs in mammalian cells. Science 296:550\u2013553","journal-title":"Science"},{"key":"1803_CR20","doi-asserted-by":"crossref","first-page":"494","DOI":"10.1038\/35078107","volume":"411","author":"SM Elbashir","year":"2001","unstructured":"Elbashir SM, Harborth J, Lendeckel W, Yalcin A, Weber K, Tuschl T (2001) Duplexes of 21-nucleotide RNAs mediate RNA interference in cultured mammalian cells. Nature 411:494\u2013498","journal-title":"Nature"},{"key":"1803_CR21","doi-asserted-by":"crossref","first-page":"318","DOI":"10.1186\/1743-422X-7-318","volume":"7","author":"S Khaliq","year":"2010","unstructured":"Khaliq S, Jahan S, Ijaz B, Ahmad W, Asad S, Pervaiz A, Samreen B, Khan M, Hassan S (2010) Inhibition of core gene of HCV 3a genotype using synthetic and vector derived siRNAs. Virol J 7:318","journal-title":"Virol J"},{"key":"1803_CR22","doi-asserted-by":"crossref","first-page":"2049","DOI":"10.1271\/bbb.60001","volume":"70","author":"M Liu","year":"2006","unstructured":"Liu M, Ding H, Zhao P, Qin ZL, Gao J, Cao MM, Luan J, Wu WB, Qi ZT (2006) RNA interference effectively inhibits mRNA accumulation and protein expression of hepatitis C virus core and E2 genes in human cells. Biosci Biotechnol Biochem 70:2049\u20132055","journal-title":"Biosci Biotechnol Biochem"},{"key":"1803_CR23","doi-asserted-by":"crossref","first-page":"692","DOI":"10.3390\/v2030692","volume":"2","author":"B Bartosch","year":"2010","unstructured":"Bartosch B, Dubuisson J (2010) Recent advances in Hepatitis C virus cell entry. Viruses 2:692\u2013709","journal-title":"Viruses"},{"key":"1803_CR24","doi-asserted-by":"crossref","first-page":"6964","DOI":"10.1128\/JVI.00024-06","volume":"80","author":"E Blanchard","year":"2006","unstructured":"Blanchard E, Belouzard S, Goueslain L, Wakita T, Dubuisson J, Wychowski C, Rouill\u00e9 Y (2006) Hepatitis C virus entry depends on clathrin-mediated endocytosis. J Virol 80:6964\u20136972","journal-title":"J Virol"},{"key":"1803_CR25","doi-asserted-by":"crossref","first-page":"519","DOI":"10.1016\/j.lfs.2007.06.011","volume":"8","author":"N Khan","year":"2007","unstructured":"Khan N, Mukhtar H (2007) Tea polyphenols for health promotion. Life Sci 8:519\u2013533","journal-title":"Life Sci"},{"key":"1803_CR26","doi-asserted-by":"crossref","first-page":"459","DOI":"10.1016\/j.jaci.2008.12.024","volume":"123","author":"CL Nance","year":"2009","unstructured":"Nance CL, Siwak EB, Shearer WT (2009) Preclinical development of the green tea catechin, epigallocatechin gallate, as an HIV-1 therapy. J Allergy Clin Immunol 123:459\u2013465","journal-title":"J Allergy Clin Immunol"},{"key":"1803_CR27","doi-asserted-by":"crossref","first-page":"720","DOI":"10.1002\/hep.24803","volume":"55","author":"N Calland","year":"2012","unstructured":"Calland N, Albecka A, Belouzard S et al (2012) Epigallocatechin-3-gallate is a new inhibitor of hepatitis C virus entry. Hepatology 55:720\u2013729","journal-title":"Hepatology"},{"key":"1803_CR28","doi-asserted-by":"crossref","first-page":"7271","DOI":"10.1073\/pnas.0832180100","volume":"100","author":"M Hsu","year":"2003","unstructured":"Hsu M, Zhang J, Flint M, Logvinoff C, Cheng MC, Rice CM, McKeating A (2003) Hepatitis C virus glycoproteins mediate pH-dependent cell entry of pseudotyped retroviral particles. PNAS 100:7271\u20137276","journal-title":"PNAS"},{"key":"1803_CR29","doi-asserted-by":"crossref","first-page":"e1001086","DOI":"10.1371\/journal.ppat.1001086","volume":"6","author":"CJ Baldick","year":"2010","unstructured":"Baldick CJ, Wichroski MJ, Pendri A et al (2010) A novel small molecule inhibitor of hepatitis C virus entry. PLoS Pathog 6:e1001086","journal-title":"PLoS Pathog"},{"key":"1803_CR30","doi-asserted-by":"crossref","first-page":"172","DOI":"10.1016\/j.antiviral.2010.02.316","volume":"86","author":"R Liua","year":"2010","unstructured":"Liua R, Tewari M, Konga R et al (2010) A peptide derived from hepatitis C virus E2 envelope protein inhibits post-binding step in HCV entry. Antiviral Res 86:172\u2013179","journal-title":"Antiviral Res"},{"key":"1803_CR31","doi-asserted-by":"crossref","first-page":"31446","DOI":"10.1074\/jbc.M110.122895","volume":"285","author":"R Montserret","year":"2010","unstructured":"Montserret R, Saint N, Vanbelle C et al (2010) NMR structure and ion channel activity of the p7 protein from hepatitis C virus. J Biol Chem 285:31446\u201331461","journal-title":"J Biol Chem"},{"key":"1803_CR32","doi-asserted-by":"crossref","first-page":"L10","DOI":"10.1016\/j.bpj.2008.10.004","volume":"96","author":"CF Chew","year":"2009","unstructured":"Chew CF, Vijayan R, Chang J, Zitzmann N, Biggin PC (2009) Determination of pore-lining residues in the hepatitis C virus p7 protein. Biophys J 96:L10\u2013L12","journal-title":"Biophys J"},{"key":"1803_CR33","doi-asserted-by":"crossref","first-page":"31038","DOI":"10.1074\/jbc.M003663200","volume":"275","author":"JA Mould","year":"2000","unstructured":"Mould JA, Drury JE, Frings SM, Kaupp UB, Pekosz A, Lamb RA, Pinto LH (2000) Permeation and activation of the M2 ion channel of influenza A virus. J Bio Chem 275:31038\u201331050","journal-title":"J Bio Chem"},{"key":"1803_CR34","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1007\/s002490100177","volume":"31","author":"GD Ewart","year":"2002","unstructured":"Ewart GD, Mills K, Cox GB, Gage PW (2002) Amiloride derivatives block ion channel activity and enhancement of virus-like particle budding caused by HIV-1 protein Vpu. Eur Biophys J 31:26\u201335","journal-title":"Eur Biophys J"},{"key":"1803_CR35","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1016\/j.antiviral.2010.02.312","volume":"86","author":"CA Luscombe","year":"2010","unstructured":"Luscombe CA, Huang Z, Murray MG, Miller M, Wilkinson J, Ewart GD (2010) A novel Hepatitis C virus p7 ion channel inhibitor, BIT225, inhibits bovine viral diarrhea virus in vitro and shows synergism with recombinant interferon-alpha-2b and nucleoside analogues. Antivir Res 86:144\u2013153","journal-title":"Antivir Res"},{"key":"1803_CR36","doi-asserted-by":"crossref","first-page":"1173","DOI":"10.1091\/mbc.6.9.1173","volume":"6","author":"JR Peterson","year":"1995","unstructured":"Peterson JR, Ora A, Van PN, Helenius A (1995) Transient, lectin-like association of calreticulin with folding intermediates of cellular and viral glycoproteins. Mol Biol Cell 6:1173\u20131184","journal-title":"Mol Biol Cell"},{"key":"1803_CR37","doi-asserted-by":"crossref","first-page":"8987","DOI":"10.1128\/JVI.75.19.8987-8998.2001","volume":"75","author":"D Durantel","year":"2001","unstructured":"Durantel D, Branza-Nichita N, Carrou\u00e9e-Durantel S, Butters TD, Dwek RA, Zitzmann N (2001) Study of the mechanism of antiviral action of iminosugar derivatives against bovine viral diarrhea virus. J Virol 75:8987\u20138998","journal-title":"J Virol"},{"key":"1803_CR38","doi-asserted-by":"crossref","unstructured":"Pavlovi\u0107 D, Neville DC, Argaud O, Blumberg B, Dwek RA, Fischer WB, Zitzmann N (2003) The hepatitis C virus p7 protein forms an ion channel that is inhibited by long-alkyl-chain iminosugar derivatives. Proc Natl Acad Sci USA 100:6104-6108. Epub 2003 Apr 28","DOI":"10.1073\/pnas.1031527100"},{"key":"1803_CR39","doi-asserted-by":"crossref","first-page":"18256","DOI":"10.1074\/jbc.M209732200","volume":"278","author":"L Erdtmann","year":"2003","unstructured":"Erdtmann L, Franck N, Lerat H et al (2003) The hepatitis C virus NS2 protein is an inhibitor of CIDE-B-induced apoptosis. J Biol Chem 278:18256\u201318264","journal-title":"J Biol Chem"},{"key":"1803_CR40","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1016\/j.virusres.2006.02.004","volume":"121","author":"XJ Yang","year":"2006","unstructured":"Yang XJ, Liu J, Ye L, Liao QJ et al (2006) HCV NS2 protein inhibits cell proliferation and induces cell cycle arrest in the S-phase in mammalian cells through down-regulation of cyclin A expression. Virus Res 121:134\u2013143","journal-title":"Virus Res"},{"key":"1803_CR41","doi-asserted-by":"crossref","first-page":"948","DOI":"10.1016\/j.bbrc.2007.03.070","volume":"356","author":"KM Kim","year":"2007","unstructured":"Kim KM, Kwon SN, Kang JI, Lee SH, Jang SK, Ahn BY, Kim YK (2007) Hepatitis C virus NS2 protein activates cellular cyclic AMP-dependent pathways. Biochem Biophys Res Commun 356:948\u2013954","journal-title":"Biochem Biophys Res Commun"},{"key":"1803_CR42","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1007\/s00705-007-1103-1","volume":"153","author":"JK Oem","year":"2008","unstructured":"Oem JK, Jackel CC, Li YP, Kang HN, Zhou Y, Babiuk LA, Liu Q (2008) Hepatitis C virus non-structural protein-2 activates CXCL-8 transcription through NF-kappaB. Arch Virol 153:293\u2013301","journal-title":"Arch Virol"},{"key":"1803_CR43","doi-asserted-by":"crossref","first-page":"1225","DOI":"10.1099\/vir.0.83491-0","volume":"89","author":"JK Oem","year":"2008","unstructured":"Oem JK, Jackel CC, Li YP, Zhou Y, Zhong J, Shimano H, Babiuk LA, Liu Q (2008) Activation of sterol regulatory element-binding protein 1c and fatty acid synthase transcription by hepatitis C virus non-structural protein 2. J Gen Virol 89:1225\u20131230","journal-title":"J Gen Virol"},{"key":"1803_CR44","doi-asserted-by":"crossref","first-page":"1635","DOI":"10.3390\/v2081635","volume":"2","author":"IC Lorenz","year":"2010","unstructured":"Lorenz IC (2010) The Hepatitis C virus nonstructural protein 2 (NS2): an up-and-coming antiviral drug target. Viruses 2:1635\u20131646","journal-title":"Viruses"},{"key":"1803_CR45","doi-asserted-by":"crossref","first-page":"46678","DOI":"10.1074\/jbc.M108266200","volume":"276","author":"D Thibeault","year":"2001","unstructured":"Thibeault D, Maurice R, Pilote L, Lamarre D, Pause A (2001) In vitro characterization of a purified NS2\/3 protease variant of hepatitis C virus. J Biol Chem 276:46678\u201346684","journal-title":"J Biol Chem"},{"key":"1803_CR46","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1016\/S0092-8674(00)81351-3","volume":"87","author":"JL Kim","year":"1996","unstructured":"Kim JL, Morgenstern KA, Lin C, Fox T et al (1996) Crystal structure of the hepatitis C virus NS3 protease domain complexed with a synthetic NS4A cofactor peptide. Cell 87:343\u2013355","journal-title":"Cell"},{"key":"1803_CR47","first-page":"132","volume":"18","author":"DL Wyles","year":"2010","unstructured":"Wyles DL (2010) Moving beyond interferon alfa: investigational drugs for hepatitis C virus infection. Top HIV Med 18:132\u2013136","journal-title":"Top HIV Med"},{"key":"1803_CR48","doi-asserted-by":"crossref","first-page":"1822","DOI":"10.1021\/bi901974a","volume":"49","author":"CA Belon","year":"2010","unstructured":"Belon CA, High YD, Lin TI, Pauwels F, Frick DN (2010) Mechanism and specificity of a symmetrical benzimidazolephenylcarboxamide helicase inhibitor. Biochemistry 49:1822\u20131832","journal-title":"Biochemistry"},{"key":"1803_CR49","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1186\/1479-0556-9-11","volume":"9","author":"S Rehman","year":"2011","unstructured":"Rehman S, Ashfaq UA, Javed T (2011) Antiviral drugs against hepatitis C virus. Genet Vaccines Ther 9:11","journal-title":"Genet Vaccines Ther"},{"key":"1803_CR50","doi-asserted-by":"crossref","first-page":"1130","DOI":"10.1016\/j.jhep.2010.11.001","volume":"54","author":"N Forestier","year":"2011","unstructured":"Forestier N, Larrey D, Guyader D, Marcellin P, Rouzier R, Patat A, Smith P, Bradford W, Porter S, Blatt L, Seiwert SD, Zeuzem S (2011) 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. Hepatol 54:1130\u20131136","journal-title":"Hepatol"},{"key":"1803_CR51","first-page":"606","volume":"9","author":"JA Thomson","year":"2006","unstructured":"Thomson JA, Perni RB (2006) Hepatitis C virus NS3\/4A protease inhibitors: countering viral subversion in vitro and showing promise in the clinic. Curr Opin Drug Discov Dev 9:606\u2013617","journal-title":"Curr Opin Drug Discov Dev"},{"key":"1803_CR52","first-page":"871","volume":"10","author":"YS Tsantrizos","year":"2009","unstructured":"Tsantrizos YS (2009) TMC-435, an NS3\/4A protease inhibitor for the treatment of HCV infection. Curr Opin Investig Drugs 10:871\u2013881","journal-title":"Curr Opin Investig Drugs"},{"key":"1803_CR53","doi-asserted-by":"crossref","first-page":"1021","DOI":"10.3851\/IMP1894","volume":"16","author":"M Manns","year":"2011","unstructured":"Manns M, Reesink H, Berg T, Dusheiko G, Flisiak R, Marcellin P, Moreno C, Lenz O, Meyvisch P, Peeters M, Sekar V, Simmen K, Verloes R (2011) Rapid viral response of once-daily TMC435 plus pegylated interferon\/ribavirin in hepatitis C genotype-1 patients: a randomized trial. Antivir Ther 16:1021\u20131033","journal-title":"Antivir Ther"},{"key":"1803_CR54","doi-asserted-by":"crossref","first-page":"6466","DOI":"10.1021\/jm100690x","volume":"53","author":"M Llin\u00e0s-Brunet","year":"2010","unstructured":"Llin\u00e0s-Brunet M, Bailey MD, Goudreau N, Bhardwaj PK, Bordeleau J, B\u00f6s M, Bousquet Y, Cordingley MG, Duan J, Forgione P, Garneau M, Ghiro E, Gorys V, Goulet S, Halmos T, Kawai SH, Naud J, Poupart MA, White PW (2010) Discovery of a potent and selective noncovalent linear inhibitor of the hepatitis C virus NS3 protease (BI 201335). J Med Chem 53:6466\u20136476","journal-title":"J Med Chem"},{"key":"1803_CR55","doi-asserted-by":"crossref","first-page":"164","DOI":"10.3109\/00498254.2011.611546","volume":"42","author":"J Duan","year":"2012","unstructured":"Duan J, Yong CL, Garneau M, Amad M, Bolger G, De Marte J, Montpetit H, Otis F, Jutras M, Rh\u00e9aume M, White PW, Llin\u00e0s-Brunet M, Bethell RC, Cordingley MG (2012) Cross-species absorption, metabolism, distribution and pharmacokinetics of BI 201335, a potent HCV genotype 1 NS3\/4A protease inhibitor. Xenobiotica 42:164\u2013172","journal-title":"Xenobiotica"},{"key":"1803_CR56","doi-asserted-by":"crossref","first-page":"2047","DOI":"10.1053\/j.gastro.2011.08.051","volume":"14","author":"S Zeuzem","year":"2011","unstructured":"Zeuzem S, Asselah T, Angus P, Zarski JP, Larrey D, M\u00fcllhaupt B, Gane E, Schuchmann M, Lohse A, Pol S, Bronowicki JP, Roberts S, Arasteh K, Zoulim F, Heim M, Stern JO, Kukolj G, Nehmiz G, Haefner C, Boecher WO (2011) Efficacy of the protease inhibitor BI 201335, polymerase inhibitor BI 207127, and ribavirin in patients with chronic HCV infection. Gastroenterology 14:2047\u20132055","journal-title":"Gastroenterology"},{"key":"1803_CR57","first-page":"G847","volume":"290","author":"J Choi","year":"2006","unstructured":"Choi J, Ou JHJ (2006) Mechanisms of liver injury III. Oxidative stress in the pathogenesis of hepatitis C virus. American Journal of Physiology-Gastrointestinal and Liver. Physiology 290:G847\u2013G851","journal-title":"Physiology"},{"key":"1803_CR58","doi-asserted-by":"crossref","first-page":"1430","DOI":"10.1002\/hep.22491","volume":"48","author":"ZW Zhu","year":"2008","unstructured":"Zhu ZW, Wilson AT, Mathahs MM et al (2008) Heme Oxygenase-1 Suppresses Hepatitis C Virus Replication and Increases Resistance of Hepatocytes to Oxidant Injury. Hepatology 48:1430\u20131439","journal-title":"Hepatology"},{"key":"1803_CR59","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1165\/rcmb.2006-0333TR","volume":"36","author":"SW Ryter","year":"2007","unstructured":"Ryter SW, Morse D, Choi AMK (2007) Carbon monoxide and bilirubin-Potential therapies for pulmonary\/vascular injury and disease. Am J Resp Cell Mol Biol 36:175\u2013182","journal-title":"Am J Resp Cell Mol Biol"},{"key":"1803_CR60","doi-asserted-by":"crossref","first-page":"9049","DOI":"10.1074\/jbc.M412687200","volume":"280","author":"C Fillebeen","year":"2005","unstructured":"Fillebeen C, Rivas-Estilla AM, Bisaillon M et al (2005) Iron inactivates the RNA polymerase NS5B and suppresses subgenomic replication of hepatitis C virus. J Biol Chem 280:9049\u20139057","journal-title":"J Biol Chem"},{"key":"1803_CR61","doi-asserted-by":"crossref","first-page":"398","DOI":"10.1002\/hep.23339","volume":"51","author":"E Lehmann","year":"2010","unstructured":"Lehmann E, EL-Tantawy WH, Ocker M et al (2010) The Heme Oxygenase 1 product biliverdin interferes with Hepatitis C virus replication by increasing antiviral interferon response. Hepatology 51:398\u2013404","journal-title":"Hepatology"},{"key":"1803_CR62","doi-asserted-by":"crossref","first-page":"1897","DOI":"10.1002\/hep.23921","volume":"52","author":"Z Zhu","year":"2010","unstructured":"Zhu Z, Wilson AT, Luxon BA, Brown KE, Mathahs MM, Bandyopadhyay S, McCaffrey AP, Schmidt WN (2010) Biliverdin inhibits hepatitis C virus nonstructural 3\/4A protease activity: mechanism for the antiviral effects of heme oxygenase? Hepatology 52:1897\u20131905","journal-title":"Hepatology"},{"key":"1803_CR63","doi-asserted-by":"crossref","first-page":"2559","DOI":"10.1021\/bi900038p","volume":"48","author":"R Rajagopalan","year":"2009","unstructured":"Rajagopalan R, Misialek S, Stevens S, Myszka D, Brandhuber B, Ballard J et al (2009) Inhibition and binding kinetics of the hepatitis C virus NS3 protease inhibitor ITMN-191 reveals tight binding and slow dissociative behavior. Biochemistry 48:2559\u20132568","journal-title":"Biochemistry"},{"key":"1803_CR64","first-page":"1146A","volume":"48","author":"WZ Bradford","year":"2008","unstructured":"Bradford WZ, Rubino C, Porter S, Forrest A, Blatt LM, Patat A (2008) A phase 1 study of the safety, tolerability, and pharmacokinetics of single ascending oral doses of the NS3\/4A protease inhibitor ITMN-191 in healthy subjects. Hepatology 48:1146A","journal-title":"Hepatology"},{"key":"1803_CR65","doi-asserted-by":"crossref","first-page":"S380","DOI":"10.1016\/S0168-8278(09)61048-5","volume":"50","author":"EJ Gane","year":"2009","unstructured":"Gane EJ, Roberts SK, Stedman C et al (2009) First-in-man demonstration of potent antiviral activity with a nucleoside polymerase (R7128) and protease (R7227\/ITMN-191) inhibitor combination in HCV: safety, pharmacokinetics, and virologic results from INFORM-1. J Hepatol 50:S380","journal-title":"J Hepatol"},{"key":"1803_CR66","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1128\/AAC.00677-09","volume":"54","author":"NJ Liverton","year":"2010","unstructured":"Liverton NJ, Carroll SS, Dimuzio J, Fandozzi C, Graham DJ, Hazuda D, Holloway MK, Ludmerer SW, McCauley JA, McIntyre CJ, Olsen DB, Rudd MT, Stahlhut M, Vacca JP (2010) MK-7009, a potent and selective inhibitor of hepatitis C virus NS3\/4A protease. Antimicrob Agents Chemother 54:305\u2013311","journal-title":"Antimicrob Agents Chemother"},{"key":"1803_CR67","doi-asserted-by":"crossref","first-page":"884","DOI":"10.1002\/hep.25743","volume":"56","author":"MP Manns","year":"2012","unstructured":"Manns MP, Gane E, Rodriguez-Torres M, Stoehr A, Yeh CT, Marcellin P, Wiedmann RT, Hwang PM, Caro L, Barnard RJ, Lee AW (2012) MK-7009 Protocol 007 Study Group. Vaniprevir with pegylated interferon alpha-2a and ribavirin in treatment-na\u00efve patients with chronic hepatitis C: a randomized phase II study. Hepatology 56:884\u2013893","journal-title":"Hepatology"},{"key":"1803_CR68","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1053\/j.gastro.2009.11.055","volume":"138","author":"C Sarrazin","year":"2010","unstructured":"Sarrazin C, Zeuzem S (2010) Resistance to direct antiviral agents in patients with hepatitis C virus infection. Gastroenterology 138:447\u2013462","journal-title":"Gastroenterology"},{"key":"1803_CR69","first-page":"181","volume":"10","author":"I Mederacke","year":"2009","unstructured":"Mederacke I, Wedemeyer H, Manns MP (2009) Boceprevir, an NS3 serine protease inhibitor of hepatitis C virus, for the treatment of HCV infection. Curr Opin Investig Drugs 10:181\u2013189","journal-title":"Curr Opin Investig Drugs"},{"key":"1803_CR70","doi-asserted-by":"crossref","first-page":"1013","DOI":"10.1128\/AAC.50.3.1013-1020.2006","volume":"50","author":"BA Malcolm","year":"2006","unstructured":"Malcolm BA, Liu R, Lahser F, Agrawal S, Belanger B et al (2006) SCH 503034, a mechanism-based inhibitor of hepatitis C virus NS3 protease, suppresses polyprotein maturation and enhances the antiviral activity of alpha interferon in replicon cells. Antimicrob Agents Chemother 50:1013\u20131020","journal-title":"Antimicrob Agents Chemother"},{"key":"1803_CR71","doi-asserted-by":"crossref","first-page":"1195","DOI":"10.1056\/NEJMoa1010494","volume":"364","author":"F Poordad","year":"2011","unstructured":"Poordad F, McCone J Jr, Bacon BR, Bruno S, Manns MP, Sulkowski MS, Jacobson IM, Reddy KR, Goodman ZD, Boparai N, DiNubile MJ, Sniukiene V, Brass CA, Albrecht JK, Bronowicki JP, SPRINT-2 Investigators (2011) Boceprevir for untreated chronic HCV genotype 1 infection. N Engl J Med 364:1195\u20131206","journal-title":"N Engl J Med"},{"key":"1803_CR72","doi-asserted-by":"crossref","first-page":"1195","DOI":"10.1056\/NEJMoa1010494","volume":"364","author":"F Poordad","year":"2011","unstructured":"Poordad F, McCone J Jr, Bacon BR, Bruno S, Manns MP, Sulkowski MS, Jacobson IM, Reddy KR, Goodman ZD, Boparai N, DiNubile MJ, Sniukiene V, Brass CA, Albrecht JK, Bronowicki JP, SPRINT-2 Investigators (2011) Boceprevir for untreated chronic HCV genotype 1 infection. N Engl J Med 364:1195\u20131206","journal-title":"N Engl J Med"},{"key":"1803_CR73","doi-asserted-by":"crossref","first-page":"1292","DOI":"10.1056\/NEJMoa0908014","volume":"362","author":"JG McHutchison","year":"2010","unstructured":"McHutchison JG, Manns MP, Muir AJ, Terrault NA, Jacobson IM, Afdhal NH, Heathcote EJ, Zeuzem S, Reesink HW, Garg J, Bsharat M, George S, Kauffman RS, Adda N, Di Bisceglie AM, PROVE3 Study Team (2010) Telaprevir for previously treated chronic HCV infection. N Engl J Med 362:1292\u20131303","journal-title":"N Engl J Med"},{"key":"1803_CR74","doi-asserted-by":"crossref","first-page":"2405","DOI":"10.1056\/NEJMoa1012912","volume":"364","author":"IM Jacobson","year":"2011","unstructured":"Jacobson IM, McHutchison JG, Dusheiko G, Di Bisceglie AM, Reddy KR, Bzowej NH, Marcellin P, Muir AJ, Ferenci P, Flisiak R, George J, Rizzetto M, Shouval D, Sola R, Terg RA, Yoshida EM, Adda N, Bengtsson L, Sankoh AJ, Kieffer TL, George S, Kauffman RS, Zeuzem S, ADVANCE Study Team (2011) Telaprevir for previously untreated chronic hepatitis C virus infection. N Engl J Med 364:2405\u20132416","journal-title":"N Engl J Med"},{"key":"1803_CR75","doi-asserted-by":"crossref","first-page":"1014","DOI":"10.1056\/NEJMoa1014463","volume":"365","author":"KE Sherman","year":"2011","unstructured":"Sherman KE, Flamm SL, Afdhal NH, Nelson DR, Sulkowski MS, Everson GT, Fried MW, Adler M, Reesink HW, Martin M, Sankoh AJ, Adda N, Kauffman RS, George S, Wright CI, Poordad F, ILLUMINATE Study Team (2011) Response-guided telaprevir combination treatment for hepatitis C virus infection. N Engl J Med 365:1014\u20131024","journal-title":"N Engl J Med"},{"key":"1803_CR76","doi-asserted-by":"crossref","first-page":"1752","DOI":"10.3390\/v2081752","volume":"2","author":"CL Chatel","year":"2010","unstructured":"Chatel CL, Baril M, Lamarre D (2010) Hepatitis C virus NS3\/4A protease inhibitors: a light at the end of the tunnel. Viruses 2:1752\u20131765","journal-title":"Viruses"},{"key":"1803_CR77","doi-asserted-by":"crossref","first-page":"2417","DOI":"10.1056\/NEJMoa1013086","volume":"364","author":"S Zeuzem","year":"2011","unstructured":"Zeuzem S, Andreone P, Pol S, Lawitz E, Diago M, Roberts S, Focaccia R, Younossi Z, Foster GR, Horban A, Ferenci P, Nevens F, M\u00fcllhaupt B, Pockros P, Terg R, Shouval D, van Hoek B, Weiland O, Van Heeswijk R, De Meyer S, Luo D, Boogaerts G, Polo R, Picchio G, Beumont M, REALIZE Study Team (2011) Telaprevir for retreatment of HCV infection. N Engl J Med 364:2417\u20132428","journal-title":"N Engl J Med"},{"key":"1803_CR78","doi-asserted-by":"crossref","first-page":"3319","DOI":"10.1021\/jm300021v","volume":"55","author":"K Li","year":"2012","unstructured":"Li K, Frankowski KJ, Belon CA, Neuenswander B, Ndjomou J, Hanson AM, Shanahan MA, Schoenen FJ, Blagg BS, Aub\u00e9 J, Frick DN (2012) Optimization of potent Hepatitis C Virus NS3 helicase inhibitors isolated from the yellow dyes thioflavine S and primuline. J Med Chem 55:3319\u20133330","journal-title":"J Med Chem"},{"key":"1803_CR79","doi-asserted-by":"crossref","first-page":"650","DOI":"10.1021\/np200883s","volume":"75","author":"KA Salam","year":"2012","unstructured":"Salam KA, Furuta A, Noda N, Tsuneda S, Sekiguchi Y, Yamashita A, Moriishi K, Nakakoshi M, Tsubuki M, Tani H, Tanaka J, Akimitsu N (2012) Inhibition of hepatitis C virus\u00a0NS3\u00a0helicase\u00a0by manoalide. J Nat Prod 75:650\u2013654","journal-title":"J Nat Prod"},{"key":"1803_CR80","doi-asserted-by":"crossref","first-page":"2293","DOI":"10.1128\/JVI.74.5.2293-2304.2000","volume":"74","author":"B Wolk","year":"2000","unstructured":"Wolk B, Sansonno D, Krausslich HG, Dammacco F, Rice CM, Blum HE, Moradpour D (2000) Subcellular localization, stability, and trans-cleavage competence of the hepatitis C virus NS3-NS4A complex expressed in tetracycline-regulated cell lines. J Virol 74:2293\u20132304","journal-title":"J Virol"},{"key":"1803_CR81","doi-asserted-by":"crossref","first-page":"790","DOI":"10.1128\/JVI.71.1.790-796.1997","volume":"71","author":"SI Asabe","year":"1997","unstructured":"Asabe SI, Tanji Y, Satoh S, Kaneko T, Kimura K, Shimotohno K (1997) The N-terminal region of hepatitis C virus-encoded NS5A is important for NS4A-dependent phosphorylation. J Virol 71:790\u2013796","journal-title":"J Virol"},{"key":"1803_CR82","doi-asserted-by":"crossref","first-page":"S221","DOI":"10.1016\/S0168-8278(07)62181-3","volume":"46","author":"M Huang","year":"2007","unstructured":"Huang M, Sun Y, Yang W et al (2007) ACH-806: a potent inhibitor of HCV replication with a novel mechanism of action. J Hepatol 46:S221","journal-title":"J Hepatol"},{"key":"1803_CR83","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1002\/rmv.640","volume":"20","author":"J Gouttenoire","year":"2010","unstructured":"Gouttenoire J, Penin F, Moradpour D (2010) Hepatitis C virus nonstructural protein 4B: a journey into unexplored territory. Rev Med Virol 20:117\u2013129","journal-title":"Rev Med Virol"},{"key":"1803_CR84","doi-asserted-by":"crossref","first-page":"1019","DOI":"10.1038\/nbt.1490","volume":"26","author":"S Einav","year":"2008","unstructured":"Einav S, Gerber D, Bryson P, Sklan E, Elazar M, Glenn JS, Quake S (2008) Inhibitors of a new hepatitis C target discovered bymicrofluidic affinity analysis. Nat Biotechnol 26:1019\u20131027","journal-title":"Nat Biotechnol"},{"key":"1803_CR85","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.antiviral.2010.03.013","volume":"87","author":"S Einav","year":"2010","unstructured":"Einav S, Dvory SH, Gehrig EG (2010) The Hepatitis C virus (HCV) NS4B RNA binding inhibitor, clemizole, is highly synergistic with HCV protease inhibitors, submitted for publication. Antiviral Res 87:1\u20138","journal-title":"Antiviral Res"},{"key":"1803_CR86","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.antiviral.2010.03.013","volume":"87","author":"PD Bryson","year":"2010","unstructured":"Bryson PD, Cho NJ, Einav S, Lee C, Tai V, Bechtel J, Sivaraja M, Roberts C, Schmitz U, Glenn JS (2010) A small molecule inhibits HCV replication and alters NS4B\u2019s subcellular distribution. Antiviral Res 87:1\u20138","journal-title":"Antiviral Res"},{"key":"1803_CR87","doi-asserted-by":"crossref","first-page":"3263","DOI":"10.1099\/vir.0.82211-0","volume":"87","author":"M Lundin","year":"2006","unstructured":"Lundin M, Lindstr\u00f6m H, Gr\u00f6nwall C, Persson MA (2006) Dual topology of the processed hepatitis C virus protein NS4B is influenced by the NS5A protein. J Gen Virol 87:3263\u20133272","journal-title":"J Gen Virol"},{"key":"1803_CR88","doi-asserted-by":"crossref","unstructured":"Cho NJ, Dvory-Sobol H, Lee C, Cho SJ, Bryson P, Masek M, Elazar M, Frank CW, Glenn JS (2010) Identification of a class of HCV inhibitors directed against the nonstructural protein NS4B. Sci Transl Med 2:15ra6","DOI":"10.1126\/scitranslmed.3000331"},{"key":"1803_CR89","doi-asserted-by":"crossref","first-page":"192","DOI":"10.1002\/hep.510280125","volume":"28","author":"D Moradpour","year":"1998","unstructured":"Moradpour D, Kary P, Rice CM, Blum HE (1998) Continuous human cell lines inducibly expressing hepatitis C virus structural and nonstructural proteins. Hepatology 28:192\u2013201","journal-title":"Hepatology"},{"key":"1803_CR90","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1038\/nature08960","volume":"465","author":"M Gao","year":"2010","unstructured":"Gao M, Nettles RE, Belema M, Snyder LB et al (2010) Chemical genetics strategy identifies an HCV NS5A inhibitor with a potent clinical effect. Nature 465:96\u2013100","journal-title":"Nature"},{"key":"1803_CR91","unstructured":"Elicker J (2011) BMS-790052 Plus Peginterferon Alfa and Ribavirin Demonstrated up to 83% Sustained Virologic Response 24 Weeks Post-Treatment (SVR24) in Phase II Study of Genotype 1 Hepatitis C Patients. Bristol-Myers Squibb. http:\/\/news.bms.com\/press-release\/rd-news\/bms-790052-plus-peginterferon-alfa-and-ribavirin-demonstrated-83-sustained-vir , September 17, 2011"},{"key":"1803_CR92","doi-asserted-by":"crossref","first-page":"482","DOI":"10.1128\/JVI.01360-09","volume":"84","author":"JA Lemm","year":"2010","unstructured":"Lemm JA, O\u2019Boyle D, Liu M et al (2010) Identification of hepatitis C virus NS5A inhibitors. J Virol 84:482\u2013491","journal-title":"J Virol"},{"key":"1803_CR93","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1016\/j.virol.2011.03.026","volume":"414","author":"C Lee","year":"2011","unstructured":"Lee C, Ma H, Hang JQ, Leveque V, Sklan EH, Elazar M, Klumpp K, Glenn JS (2011) The hepatitis C virus NS5A inhibitor (BMS-790052) alters the subcellular localization of the NS5A non-structural viral protein. Virology 414:10\u201318","journal-title":"Virology"},{"key":"1803_CR94","unstructured":"Obrein P (2013) Gilead Announces Update on Phase 3 Study of Oral Fixed-Dose Combination of Sofosbuvir and Ledipasvir for Genotype 1 Hepatitis C Patient. Gilead Sciences, Inc. http:\/\/investors.gilead.com\/phoenix.zhtml?c=69964&p=irol-newsArticle&id=1800517 . Accessed 26 Mar 2013"},{"key":"1803_CR95","unstructured":"Spreen W, Wilfret D, Bechtel J, Adkison K, Lou Y, Jones L, Willsie S, Glass S, Roberts C (2011) GSK2336805 HCV NS5A Inhibitor Demonstrates Potent Antiviral Activity in Chronic Hepatitis C (CHC) Genotype 1 Infection: Results from a First Time in Human (FTIH) Single and Repeat Dose Study. 62th Annual Meeting of the American Association for the Study of liver diseases. http:\/\/www.natap.org\/2011\/AASLD\/AASLD_30.htm . Accessed 5\u20139 Nov 2011"},{"key":"1803_CR96","unstructured":"Kevin G (2013) Boehringer signs hep C pact with Presidio. World News. http:\/\/www.pharmatimes.com\/article\/13-03-4\/Boehringer_signs_hep_C_pact_with_Presidio.aspx . Accessed 5\u20139 Nov 2011"},{"key":"1803_CR97","doi-asserted-by":"crossref","first-page":"394A","DOI":"10.1016\/j.jhep.2008.09.018","volume":"50","author":"EJ Gane","year":"2009","unstructured":"Gane EJ, Roberts SK, Stedman CA et al (2009) Combination therapy with a nucleoside polymerase (R7128) and protease (R7227\/ITMN-191) Inhibitor in HCV: Safety, pharmacokinetics, and virologic results from INFORM-1. Hepatology 50:394A\u2013395A","journal-title":"Hepatology"},{"key":"1803_CR98","doi-asserted-by":"crossref","first-page":"2057","DOI":"10.1073\/pnas.87.6.2057","volume":"87","author":"RH Miller","year":"1990","unstructured":"Miller RH, Purcell RH (1990) Hepatitis C virus shares amino acid sequence similarity with pestiviruses and flaviviruses as well as members of two plant virus supergroups. Proc Natl Acad Sci USA 87:2057\u20132061","journal-title":"Proc Natl Acad Sci USA"},{"key":"1803_CR99","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1038\/34593","volume":"391","author":"S Doubli\u00e9","year":"1998","unstructured":"Doubli\u00e9 S, Tabor S, Long AM, Richardson CC, Ellenberger T (1998) Crystal structure of a bacteriophage T7 DNA replication complex at 2.2 A resolution. Nature 391:251\u2013258","journal-title":"Nature"},{"key":"1803_CR100","doi-asserted-by":"crossref","first-page":"2046","DOI":"10.1128\/JVI.74.4.2046-2051.2000","volume":"74","author":"AA Kolykhalov","year":"2000","unstructured":"Kolykhalov AA, Mihalik K, Feinstone SM, Rice CM (2000) Hepatitis C virus-encoded enzymatic activities and conserved RNA elements in the 3\u2032 nontranslated region are essential for virus replication in vivo. J Virol 74:2046\u20132051","journal-title":"J Virol"},{"key":"1803_CR101","doi-asserted-by":"crossref","first-page":"1901","DOI":"10.1128\/AAC.01496-07","volume":"52","author":"JA Heck","year":"2008","unstructured":"Heck JA, Lam AM, Narayanan N, Frick DN (2008) Effects of mutagenic and chain-terminating nucleotide analogs on enzymes isolated from hepatitis C virus strains of various genotypes. Antimicrob Agents Chemother 52:1901\u20131911","journal-title":"Antimicrob Agents Chemother"},{"key":"1803_CR102","doi-asserted-by":"crossref","first-page":"1604","DOI":"10.1128\/AAC.01317-07","volume":"52","author":"MF McCown","year":"2008","unstructured":"McCown MF, Rajyaguru S, Pogam SL et al (2008) The hepatitis C virus replicon presents a higher barrier to resistance to nucleoside analogs than to non-nucleoside polymerase or protease inhibitors. Antimicrob Agents Chemother 52:1604\u20131612","journal-title":"Antimicrob Agents Chemother"},{"key":"1803_CR103","doi-asserted-by":"crossref","first-page":"4356","DOI":"10.1128\/AAC.00444-08","volume":"52","author":"S Ali","year":"2008","unstructured":"Ali S, Leveque V, Le Pogam S et al (2008) Selected replicon variants with low-level in vitro resistance to the hepatitis C virus NS5B polymerase inhibitor PSI-6130 lack cross-resistance with R1479. Antimicrob Agents Chemother 52:4356\u20134369","journal-title":"Antimicrob Agents Chemother"},{"key":"1803_CR104","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1177\/135965350901400104","volume":"14","author":"A Erhardt","year":"2009","unstructured":"Erhardt A, Deterding K, Benhamou Y, Reiser M, Forns X et al (2009) Safety, pharmacokinetics and antiviral effect of BILB 1941, a novel hepatitis C virus RNA polymerase inhibitor, after 5\u00a0days oral treatment. Antivir Ther 14:23\u201332","journal-title":"Antivir Ther"},{"key":"1803_CR105","doi-asserted-by":"crossref","first-page":"3187","DOI":"10.1128\/AAC.00399-10","volume":"54","author":"AM Lam","year":"2010","unstructured":"Lam AM, Murakami E, Espiritu C, Steuer HM, Niu C, Keilman M et al (2010) PSI-7851, a pronucleotide of beta-D-2\u2019-deoxy-2\u2019-fluoro-2\u2019-C-methyluridine monophosphate, is a potent and pan-genotype inhibitor of hepatitis C virus replication. Antimicrob Agents Chemother 54:3187\u20133196","journal-title":"Antimicrob Agents Chemother"},{"key":"1803_CR106","doi-asserted-by":"crossref","first-page":"4850","DOI":"10.1016\/j.bmcl.2010.06.094","volume":"20","author":"C McGuigan","year":"2010","unstructured":"McGuigan C, Madela K, Aljarah M, Gilles A, Brancale A et al (2010) Design, synthesis and evaluation of a novel double pro-drug: INX-08189. A new clinical candidate for hepatitis C virus. Bioorg Med Chem Lett 20:4850\u20134854","journal-title":"Bioorg Med Chem Lett"},{"key":"1803_CR107","doi-asserted-by":"crossref","first-page":"1843","DOI":"10.1128\/AAC.01335-10","volume":"55","author":"JH Vernachio","year":"2011","unstructured":"Vernachio JH, Bleiman B, Bryant KD et al (2011) INX-08189, a phosphoramidate prodrug of 6-O-methyl-2\u2019-C-methyl guanosine, is a potent inhibitor of hepatitis C virus replication with excellent pharmacokinetic and pharmacodynamic properties. Antimicrob Agents Chemother 55:1843\u20131851","journal-title":"Antimicrob Agents Chemother"},{"key":"1803_CR108","unstructured":"Peepo L (2012) Abbott Presents Positive Results from Phase 2 \u201cPilot\u201d Study of an interferon-free combination regimen for the treatment of Hepatitis C http:\/\/www.abbott.com\/news-media\/press-releases\/abbott-presents-positive-results-from-phase-2-pilot-study-of-an-interferonfree-combination-regime.htm . Accessed 19 Apr 2012"},{"key":"1803_CR109","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/j.virusres.2007.03.020","volume":"128","author":"L Kong","year":"2007","unstructured":"Kong L, Li S, Han X, Xiang Z, Fang X, Li B, Wang W, Zhong H, Gao J, Ye L (2007) Inhibition of HCV RNA-dependent RNA polymerase activity by aqueous extract from Fructus Ligustri Lucidi. Virus Res 128:9\u201317","journal-title":"Virus Res"},{"key":"1803_CR110","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1016\/j.antiviral.2013.02.003","volume":"98","author":"L Kong","year":"2013","unstructured":"Kong L, Li S, Liao Q, Zhang Y, Sun R, Zhu X, Zhang Q, Wang J, Wu X, Fang X, Zhu Y (2013) Oleanolic acid and ursolic acid: Novel hepatitis C virus antivirals that inhibit NS5B activity. Antiviral Res 98:44\u201353","journal-title":"Antiviral Res"},{"key":"1803_CR111","doi-asserted-by":"crossref","first-page":"282","DOI":"10.1016\/j.jhep.2011.06.020","volume":"56","author":"N Jilg","year":"2012","unstructured":"Jilg N, Chung RT (2012) Adding to the toolbox: Receptor tyrosine kinases as potential targets in the treatment of hepatitis C. J Hepatol 56:282\u2013284","journal-title":"J Hepatol"},{"key":"1803_CR112","doi-asserted-by":"crossref","first-page":"326","DOI":"10.1016\/j.bbrc.2013.01.103","volume":"432","author":"Y Shinohara","year":"2013","unstructured":"Shinohara Y, Imajo K, Yoneda M, Tomeno W, Ogawa Y, Kirikoshi H, Funakoshi K, Ikeda M, Kato N, Nakajima A, Saito S (2013) Unfolded protein response pathways regulate Hepatitis C virus replication via modulation of autophagy. Biochem Biophys Res Commun 432:326\u2013332","journal-title":"Biochem Biophys Res Commun"},{"key":"1803_CR113","doi-asserted-by":"crossref","first-page":"44249","DOI":"10.1074\/jbc.M112.392209","volume":"287","author":"C Rosnoblet","year":"2012","unstructured":"Rosnoblet C, Fritzinger B, Legrand D, Launay H, Wieruszeski JM, Lippens G, Hanoulle X (2012) Hepatitis C virus NS5B and host cyclophilin A share a common binding site on NS5A. J Biol Chem 287:44249\u201344260","journal-title":"J Biol Chem"},{"key":"1803_CR114","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1016\/j.jhep.2010.01.041","volume":"53","author":"U Chatterji","year":"2010","unstructured":"Chatterji U, Lim P, Bobardt MD et al (2010) HCV resistance to cyclosporin A does not correlate with a resistance of the NS5A cyclophilin A interaction to cyclophilin inhibitors. J Hepatol 53:50\u201356","journal-title":"J Hepatol"},{"key":"1803_CR115","doi-asserted-by":"crossref","first-page":"2976","DOI":"10.1128\/AAC.00310-06","volume":"50","author":"S Ma","year":"2006","unstructured":"Ma S, Boerner JE, TiongYip C et al (2006) NIM811, a cyclophilin inhibitor, exhibits potent in vitro activity against hepatitis C virus alone or in combination with alpha interferon. Antimicrob Agents Chemother 50:2976\u20132982","journal-title":"Antimicrob Agents Chemother"},{"key":"1803_CR116","doi-asserted-by":"crossref","first-page":"660","DOI":"10.1128\/AAC.00660-09","volume":"54","author":"S Hopkins","year":"2010","unstructured":"Hopkins S, Scorneaux B, Huang Z et al (2010) SCY-635: A Novel Non-Immunosuppressive Analog of Cyclosporin A that Exhibits Potent Inhibition of Hepatitis C Virus RNA Replication in vitro. Antimicrob Agents Chemother 54:660\u2013672","journal-title":"Antimicrob Agents Chemother"},{"key":"1803_CR117","doi-asserted-by":"crossref","first-page":"4679","DOI":"10.1021\/bi1003266","volume":"49","author":"I Landrieu","year":"2010","unstructured":"Landrieu I, Hanoulle X, Bonachera F et al (2010) Structural basis for the non-immunosuppressive character of the Cyclosporin A analog Debio 025. Biochemistry 49:4679\u20134686","journal-title":"Biochemistry"},{"key":"1803_CR118","doi-asserted-by":"crossref","first-page":"1460","DOI":"10.1002\/hep.22835","volume":"49","author":"R Flisiak","year":"2009","unstructured":"Flisiak R, Feinman SV, Jablkowski M et al (2009) The cyclophilin inhibitor Debio 025 combined with PEG IFNalpha2a significantly reduces viral load in treatment-naive hepatitis C patients. Hepatology 49:1460\u20131468","journal-title":"Hepatology"},{"key":"1803_CR119","doi-asserted-by":"crossref","first-page":"623","DOI":"10.1111\/j.1365-2893.2012.01586.x","volume":"19","author":"S Pianko","year":"2012","unstructured":"Pianko S, Zeuzem S, Chuang WL, Foster GR, Sarin SK, Flisiak R, Lee CM, Andreone P, Piratvisuth T, Shah S, Sood A, George J, Gould M, Komolmit P (2012) Randomized trial of albinterferon alfa-2b every 4\u00a0weeks for chronic hepatitis C virus genotype 2\/3. J Viral Hepat 19:623\u2013634","journal-title":"J Viral Hepat"},{"key":"1803_CR120","doi-asserted-by":"crossref","first-page":"1827","DOI":"10.1053\/j.gastro.2009.07.056","volume":"137","author":"M Elazar","year":"2009","unstructured":"Elazar M, Liu M, McKenna SA et al (2009) The antihepatitis C agent nitazoxanide induces phosphorylation of eukaryotic initiation factor 2alpha via protein kinase activated by double-stranded RNA activation. Gastroenterology 137:1827\u20131835","journal-title":"Gastroenterology"},{"key":"1803_CR121","doi-asserted-by":"crossref","first-page":"574","DOI":"10.1111\/j.1365-2036.2008.03781.x","volume":"28","author":"JF Rossignol","year":"2008","unstructured":"Rossignol JF, Kabil SM, El Gohary Y et al (2008) Clinical trial: randomized, double-blind, placebo-controlled study of nitazoxanide monotherapy for the treatment of patients with chronic hepatitis C genotype 4. Aliment Pharmacol Ther 28:574\u2013580","journal-title":"Aliment Pharmacol Ther"},{"key":"1803_CR122","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1016\/S1665-2681(19)31800-9","volume":"8","author":"I Mederacke","year":"2009","unstructured":"Mederacke I, Wedemeyer H (2009) Nitazoxanide for the treatment of chronic hepatitis C New opportunities but new challenges? Ann Hepatol 8:166\u2013168","journal-title":"Ann Hepatol"},{"key":"1803_CR123","doi-asserted-by":"crossref","first-page":"559","DOI":"10.1517\/14712598.4.4.559","volume":"4","author":"AL Goldstein","year":"2004","unstructured":"Goldstein AL, Thymosins Badamchian M (2004) Chemistry and biological properties in health and disease. Expert Opin Biol Ther 4:559\u2013573","journal-title":"Expert Opin Biol Ther"},{"issue":"Suppl 1","key":"1803_CR124","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1111\/j.1365-2893.2011.01524.x","volume":"19","author":"A Ciancio","year":"2012","unstructured":"Ciancio A, Andreone P, Kaiser S, Mangia A, Milella M, Sol\u00e0 R, Pol S, Tsianos E, De Rosa A, Camerini R, McBeath R, Rizzetto M (2012) Thymosin alpha-1 with peginterferon alfa-2a\/ribavirin for chronic hepatitis C not responsive to IFN\/ribavirin: an adjuvant role? J Viral Hepat 19(Suppl 1):52\u201359","journal-title":"J Viral Hepat"},{"key":"1803_CR125","doi-asserted-by":"crossref","first-page":"1473","DOI":"10.4161\/cc.8.10.8349","volume":"8","author":"M Niepmann","year":"2009","unstructured":"Niepmann M (2009) Activation of hepatitis C virus translation by liver-specific microRNA. Cell Cycle 8:1473\u20131477","journal-title":"Cell Cycle"},{"key":"1803_CR126","doi-asserted-by":"crossref","first-page":"6615","DOI":"10.1128\/JVI.00417-10","volume":"84","author":"RK Jangra","year":"2010","unstructured":"Jangra RK, Yi M, Lemon SM (2010) Regulation of hepatitis C virus translation and infectious virus production by the microRNA miR-122. J Virol 84:6615\u20136625","journal-title":"J Virol"},{"key":"1803_CR127","first-page":"189","volume":"487","author":"K Fluiter","year":"2009","unstructured":"Fluiter K, Mook OR, Baas F (2009) The therapeutic potential of LNA-modified siRNAs: reduction of off-target effects by chemical modification of the siRNA sequence. Methods Mol Biol 487:189\u2013203","journal-title":"Methods Mol Biol"},{"key":"1803_CR128","doi-asserted-by":"crossref","first-page":"198","DOI":"10.1126\/science.1178178","volume":"327","author":"RE Lanford","year":"2010","unstructured":"Lanford RE, Hildebrandt-Eriksen ES, Petri A, Persson R, Lindow M, Munk ME et al (2010) Therapeutic silencing of microRNA-122 in primates with chronic hepatitis C virus infection. Science 327:198\u2013201","journal-title":"Science"}],"updated-by":[{"DOI":"10.1007\/s00705-014-2077-4","type":"correction","label":"Correction","source":"publisher","updated":{"date-parts":[[2014,4,17]],"date-time":"2014-04-17T00:00:00Z","timestamp":1397692800000}}],"container-title":["Archives of Virology"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1007\/s00705-013-1803-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/article\/10.1007\/s00705-013-1803-7\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1007\/s00705-013-1803-7","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,7,3]],"date-time":"2023-07-03T22:30:49Z","timestamp":1688423449000},"score":1,"resource":{"primary":{"URL":"http:\/\/link.springer.com\/10.1007\/s00705-013-1803-7"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2013,8,25]]},"references-count":128,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2014,5]]}},"alternative-id":["1803"],"URL":"https:\/\/doi.org\/10.1007\/s00705-013-1803-7","relation":{},"ISSN":["0304-8608","1432-8798"],"issn-type":[{"value":"0304-8608","type":"print"},{"value":"1432-8798","type":"electronic"}],"subject":[],"published":{"date-parts":[[2013,8,25]]}}}