Review Article

Potential Drug Targets Against Hepatitis B Virus Based on Both Virus and Host Factors

Author(s): Bing-Yi Zhang, Dan-Ping Chai, Yi-Hang Wu*, Li-Peng Qiu, Yong-Yong Zhang, Zi-Hong Ye and Xiao-Ping Yu

Volume 20, Issue 16, 2019

Page: [1636 - 1651] Pages: 16

DOI: 10.2174/1389450120666190729115646

Price: $65

Abstract

Background: Hepatitis B is a very harmful and epidemic disease caused by hepatitis B virus (HBV). Although an effective anti-HBV vaccine is available, chronic infection poses still a huge health burden in the whole world. The present anti-HBV drugs including nucleoside analogues and interferonalpha have their limitations without exception. There is no effective drug and therapeutic method that can really and truly cure hepatitis B so far. The variability of HBV genome results in that a significant number of patients develop drug resistance during the long-term use of anti-HBV drugs. Hence, it is urgently needed to discover novel targets and develop new drugs against hepatitis B.

Objective: The review aims to provide the theory support for designing of the anti-HBV innovative drugs by offering a summary of the current situation of antiviral potential targets.

Results and Conclusion: Since HBV is obligate intracellular parasite, and as such it depends on host cellular components and functions to replicate itself. The targeting both virus and host might be a novel therapeutic option for hepatitis B. Accordingly, we analyse the advances in the study of the potential drug targets for anti-HBV infection, focusing on targeting virus genome, on targeting host cellular functions and on targeting virus-host proteins interactions, respectively. Meanwhile, the immune targets against chronic hepatitis B are also emphasized. In short, the review provides a summary of antiviral therapeutic strategies to target virus factors, host factors and immune factors for future designing of the innovative drug against HBV infection.

Keywords: Hepatitis B virus, viral target, host target, virus-host interactions, immune target, drug design.

Graphical Abstract

[1]
Venkatakrishnan B, Zlotnick A. The structural biology of hepatitis B virus: form and function. Annu Rev Virol 2016; 3(1): 429-51.
[http://dx.doi.org/10.1146/annurev-virology-110615-042238] [PMID: 27482896]
[2]
Trépo C, Chan HL, Lok A. Hepatitis B virus infection. Lancet 2014; 384(9959): 2053-63.
[http://dx.doi.org/10.1016/S0140-6736(14)60220-8] [PMID: 24954675]
[3]
Schweitzer A, Horn J, Mikolajczyk RT, Krause G, Ott JJ. Estimations of worldwide prevalence of chronic hepatitis B virus infection: a systematic review of data published between 1965 and 2013. Lancet 2015; 386(10003): 1546-55.
[http://dx.doi.org/10.1016/S0140-6736(15)61412-X] [PMID: 26231459]
[4]
Wong GL, Wong VW. Eliminating hepatitis B virus as a global health threat. Lancet Infect Dis 2016; 16(12): 1313-4.
[http://dx.doi.org/10.1016/S1473-3099(16)30214-6] [PMID: 27638359]
[5]
Brahmania M, Feld J, Arif A, Janssen HL. New therapeutic agents for chronic hepatitis B. Lancet Infect Dis 2016; 16(2): e10-21.
[http://dx.doi.org/10.1016/S1473-3099(15)00436-3] [PMID: 26795693]
[6]
Yang J, Ding X, Zhang Y, Bo X, Zhang M, Wang S. Fibronectin is essential for hepatitis B virus propagation in vitro: may be a potential cellular target? Biochem Biophys Res Commun 2006; 344(3): 757-64.
[http://dx.doi.org/10.1016/j.bbrc.2006.03.204] [PMID: 16631116]
[7]
Clark DN, Hu J. Hepatitis B virus reverse transcriptase - Target of current antiviral therapy and future drug development. Antiviral Res 2015; 123: 132-7.
[http://dx.doi.org/10.1016/j.antiviral.2015.09.011] [PMID: 26408354]
[8]
Khungar V, Han SH. A systematic review of side effects of nucleoside and nucleotide drugs used for treatment of chronic hepatitis B. Curr Hepat Rep 2010; 9(2): 75-90.
[http://dx.doi.org/10.1007/s11901-010-0039-1] [PMID: 20461127]
[9]
Vörös J, Urbanek A, Rautureau GJ, et al. Large-scale production and structural and biophysical characterizations of the human hepatitis B virus polymerase. J Virol 2014; 88(5): 2584-99.
[http://dx.doi.org/10.1128/JVI.02575-13] [PMID: 24352439]
[10]
Villa JA, Pike DP, Patel KB, et al. Purification and enzymatic characterization of the hepatitis B virus ribonuclease H, a new target for antiviral inhibitors. Antiviral Res 2016; 132: 186-95.
[http://dx.doi.org/10.1016/j.antiviral.2016.06.005] [PMID: 27321664]
[11]
Hayer J, Rodriguez C, Germanidis G, et al. Ultradeep pyrosequencing and molecular modeling identify key structural features of hepatitis B virus RNase H, a putative target for antiviral intervention. J Virol 2014; 88(1): 574-82.
[http://dx.doi.org/10.1128/JVI.03000-13] [PMID: 24173223]
[12]
Lomonosova E, Tavis JE. In vitro enzymatic and cell culture-based assays for measuring activity of HBV RNaseH inhibitors. Methods Mol Biol 2017; 1540: 179-92.
[http://dx.doi.org/10.1007/978-1-4939-6700-1_14] [PMID: 27975316]
[13]
Tavis JE, Lomonosova E. The hepatitis B virus ribonuclease H as a drug target. Antiviral Res 2015; 118: 132-8.
[http://dx.doi.org/10.1016/j.antiviral.2015.04.002] [PMID: 25862291]
[14]
Hu Y, Cheng X, Cao F, Huang A, Tavis JE. β-Thujaplicinol inhibits hepatitis B virus replication by blocking the viral ribonuclease H activity. Antiviral Res 2013; 99(3): 221-9.
[http://dx.doi.org/10.1016/j.antiviral.2013.06.007] [PMID: 23796982]
[15]
Cai CW, Lomonosova E, Moran EA, et al. Hepatitis B virus replication is blocked by a 2-hydroxyisoquinoline-1,3(2H,4H)-dione (HID) inhibitor of the viral ribonuclease H activity. Antiviral Res 2014; 108: 48-55.
[http://dx.doi.org/10.1016/j.antiviral.2014.05.007] [PMID: 24858512]
[16]
Lu G, Lomonosova E, Cheng X, et al. Hydroxylated tropolones inhibit hepatitis B virus replication by blocking viral ribonuclease H activity. Antimicrob Agents Chemother 2015; 59(2): 1070-9.
[http://dx.doi.org/10.1128/AAC.04617-14] [PMID: 25451058]
[17]
Venkatakrishnan B, Katen SP, Francis S, Chirapu S, Finn MG, Zlotnick A. Hepatitis B virus capsids have diverse structural responses to small-molecule ligands bound to the heteroaryldihydropyrimidine pocket. J Virol 2016; 90(8): 3994-4004.
[http://dx.doi.org/10.1128/JVI.03058-15] [PMID: 26842475]
[18]
Mak LY, Wong DK, Seto WK, Lai CL, Yuen MF. Hepatitis B core protein as a therapeutic target. Expert Opin Ther Targets 2017; 21(12): 1153-9.
[http://dx.doi.org/10.1080/14728222.2017.1397134] [PMID: 29065733]
[19]
Zhang W, Ke W, Wu SS, et al. An adenovirus-delivered peptide aptamer C1-1 targeting the core protein of hepatitis B virus inhibits viral DNA replication and production in vitro and in vivo. Peptides 2009; 30(10): 1816-21.
[http://dx.doi.org/10.1016/j.peptides.2009.07.006] [PMID: 19619601]
[20]
Butz K, Denk C, Fitscher B, et al. Peptide aptamers targeting the hepatitis B virus core protein: a new class of molecules with antiviral activity. Oncogene 2001; 20(45): 6579-86.
[http://dx.doi.org/10.1038/sj.onc.1204805] [PMID: 11641783]
[21]
Cheng YC, Ying CX, Leung CH, Li Y. New targets and inhibitors of HBV replication to combat drug resistance. J Clin Virol 2005; 34(Suppl. 1): S147-50.
[http://dx.doi.org/10.1016/S1386-6532(05)80026-5] [PMID: 16461217]
[22]
Zhu X, Zhao G, Zhou X, et al. 2,4-Diaryl-4,6,7,8-tetrahydroquinazolin-5(1H)-one derivatives as anti-HBV agents targeting at capsid assembly. Bioorg Med Chem Lett 2010; 20(1): 299-301.
[http://dx.doi.org/10.1016/j.bmcl.2009.10.119] [PMID: 19897363]
[23]
Yang XY, Xu XQ, Guan H, et al. A new series of HAPs as anti-HBV agents targeting at capsid assembly. Bioorg Med Chem Lett 2014; 24(17): 4247-9.
[http://dx.doi.org/10.1016/j.bmcl.2014.07.032] [PMID: 25127104]
[24]
Ren Q, Liu X, Luo Z, et al. Discovery of hepatitis B virus capsid assembly inhibitors leading to a heteroaryldihydropyrimidine based clinical candidate (GLS4). Bioorg Med Chem 2017; 25(3): 1042-56.
[http://dx.doi.org/10.1016/j.bmc.2016.12.017] [PMID: 28082068]
[25]
Stray SJ, Zlotnick A. BAY 41-4109 has multiple effects on Hepatitis B virus capsid assembly. J Mol Recognit 2006; 19(6): 542-8.
[http://dx.doi.org/10.1002/jmr.801] [PMID: 17006877]
[26]
Campagna MR, Liu F, Mao R, et al. Sulfamoylbenzamide derivatives inhibit the assembly of hepatitis B virus nucleocapsids. J Virol 2013; 87(12): 6931-42.
[http://dx.doi.org/10.1128/JVI.00582-13] [PMID: 23576513]
[27]
Deres K, Schröder CH, Paessens A, et al. Inhibition of hepatitis B virus replication by drug-induced depletion of nucleocapsids. Science 2003; 299(5608): 893-6.
[http://dx.doi.org/10.1126/science.1077215] [PMID: 12574631]
[28]
Soriano V. Hot news: Hepatitis B gene therapy coming to age. AIDS Rev 2018; 20(2): 125-7.
[PMID: 29938706]
[29]
Kumar R, Pérez-Del-Pulgar S, Testoni B, Lebossé F, Zoulim F. Clinical relevance of the study of hepatitis B virus covalently closed circular DNA. Liver Int 2016; 36(Suppl. 1): 72-7.
[http://dx.doi.org/10.1111/liv.13001] [PMID: 26725901]
[30]
Lucifora J, Protzer U. Attacking hepatitis B virus cccDNA--The holy grail to hepatitis B cure. J Hepatol 2016; 64(1)(Suppl.): S41-8.
[http://dx.doi.org/10.1016/j.jhep.2016.02.009] [PMID: 27084036]
[31]
Kennedy EM, Kornepati AV, Cullen BR. Targeting hepatitis B virus cccDNA using CRISPR/Cas9. Antiviral Res 2015; 123: 188-92.
[http://dx.doi.org/10.1016/j.antiviral.2015.10.004] [PMID: 26476375]
[32]
Lin SR, Yang HC, Kuo YT, et al. The CRISPR/Cas9 System Facilitates Clearance of the Intrahepatic HBV Templates In Vivo. Mol Ther Nucleic Acids 2014; 3e186..
[http://dx.doi.org/10.1038/mtna.2014.38] [PMID: 25137139]
[33]
Moyo B, Bloom K, Scott T, Ely A, Arbuthnot P. Advances with using CRISPR/Cas-mediated gene editing to treat infections with hepatitis B virus and hepatitis C virus. Virus Res 2017. pii: S0168-1702(16)30733-X.
[34]
Chinnappan M, Singh AK, Kakumani PK, et al. Key elements of the RNAi pathway are regulated by hepatitis B virus replication and HBx acts as a viral suppressor of RNA silencing. Biochem J 2014; 462(2): 347-58.
[http://dx.doi.org/10.1042/BJ20140316] [PMID: 24902849]
[35]
Chen Y, Du D, Wu J, et al. Inhibition of hepatitis B virus replication by stably expressed shRNA. Biochem Biophys Res Commun 2003; 311(2): 398-404.
[http://dx.doi.org/10.1016/j.bbrc.2003.10.009] [PMID: 14592428]
[36]
Li GQ, Gu HX, Li D, Xu WZ. Inhibition of Hepatitis B virus cccDNA replication by siRNA. Biochem Biophys Res Commun 2007; 355(2): 404-8.
[http://dx.doi.org/10.1016/j.bbrc.2007.01.163] [PMID: 17300745]
[37]
Li G, Jiang G, Lu J, et al. Inhibition of hepatitis B virus cccDNA by siRNA in transgenic mice. Cell Biochem Biophys 2014; 69(3): 649-54.
[http://dx.doi.org/10.1007/s12013-014-9847-1] [PMID: 24569930]
[38]
Xie Q, Zhang S, Wang W, et al. Inhibition of hepatitis B virus gene expression by small interfering RNAs targeting cccDNA and X antigen. Acta Virol 2012; 56(1): 49-55.
[http://dx.doi.org/10.4149/av_2012_01_49] [PMID: 22404609]
[39]
Ebert G, Poeck H, Lucifora J, et al. 5′-Triphosphorylated small interfering RNAs control replication of hepatitis B virus and induce an interferon response in human liver cells and mice. Gastroenterology 2011; 141(2): 696-706.
[40]
van de Klundert MA, Zaaijer HL, Kootstra NA. Identification of FDA-approved drugs that target hepatitis B virus transcription. J Viral Hepat 2016; 23(3): 191-201.
[http://dx.doi.org/10.1111/jvh.12479] [PMID: 26456011]
[41]
Asif-Ullah M, Choi KJ, Choi KI, Jeong YJ, Yu YG. Identification of compounds that inhibit the interaction between core and surface protein of hepatitis B virus. Antiviral Res 2006; 70(2): 85-90.
[http://dx.doi.org/10.1016/j.antiviral.2006.01.003] [PMID: 16487605]
[42]
Suresh V, Krishnakumar KA, Asha VV. A new fluorescent based screening system for high throughput screening of drugs targeting HBV-core and HBsAg interaction. Biomed Pharmacother 2015; 70: 305-16.
[http://dx.doi.org/10.1016/j.biopha.2015.02.002] [PMID: 25776516]
[43]
Yang L, Shi LP, Chen HJ, et al. Isothiafludine, a novel non-nucleoside compound, inhibits hepatitis B virus replication through blocking pregenomic RNA encapsidation. Acta Pharmacol Sin 2014; 35(3): 410-8.
[http://dx.doi.org/10.1038/aps.2013.175] [PMID: 24487969]
[44]
Orabi A, Bieringer M, Geerlof A, Bruss V. An Aptamer against the Matrix Binding Domain on the Hepatitis B Virus Capsid Impairs Virion Formation. J Virol 2015; 89(18): 9281-7.
[http://dx.doi.org/10.1128/JVI.00466-15] [PMID: 26136564]
[45]
Vaillant A. REP 2139: Antiviral mechanisms and applications in achieving functional control of HBV and HDV infection. ACS Infect Dis 2019; 5(5): 675-87.
[http://dx.doi.org/10.1021/acsinfecdis.8b00156] [PMID: 30199230]
[46]
Baumert TF, Verrier ER, Nassal M, Chung RT, Zeisel MB. Host-targeting agents for treatment of hepatitis B virus infection. Curr Opin Virol 2015; 14: 41-6.
[http://dx.doi.org/10.1016/j.coviro.2015.07.009] [PMID: 26262886]
[47]
Engelke M, Mills K, Seitz S, et al. Characterization of a hepatitis B and hepatitis delta virus receptor binding site. Hepatology 2006; 43(4): 750-60.
[http://dx.doi.org/10.1002/hep.21112] [PMID: 16557545]
[48]
Iwamoto M, Watashi K, Tsukuda S, et al. Evaluation and identification of hepatitis B virus entry inhibitors using HepG2 cells overexpressing a membrane transporter NTCP. Biochem Biophys Res Commun 2014; 443(3): 808-13.
[http://dx.doi.org/10.1016/j.bbrc.2013.12.052] [PMID: 24342612]
[49]
Anwer MS, Stieger B. Sodium-dependent bile salt transporters of the SLC10A transporter family: more than solute transporters. Pflugers Arch 2014; 466(1): 77-89.
[http://dx.doi.org/10.1007/s00424-013-1367-0] [PMID: 24196564]
[50]
Seeger C, Mason WS. Sodium-dependent taurocholic cotransporting polypeptide: a candidate receptor for human hepatitis B virus. Gut 2013; 62(8): 1093-5.
[http://dx.doi.org/10.1136/gutjnl-2013-304594] [PMID: 23542357]
[51]
Yan H, Liu Y, Sui J, Li W. NTCP opens the door for hepatitis B virus infection. Antiviral Res 2015; 121: 24-30.
[http://dx.doi.org/10.1016/j.antiviral.2015.06.002] [PMID: 26071008]
[52]
Sun Y, Qi Y, Peng B, Li W. NTCP-reconstituted in vitro hbv infection system. Methods Mol Biol 2017; 1540: 1-14.
[http://dx.doi.org/10.1007/978-1-4939-6700-1_1] [PMID: 27975303]
[53]
Yan H, Zhong G, Xu G, et al. Sodium taurocholate cotransporting polypeptide is a functional receptor for human hepatitis B and D virus eLife. 2012; 1e00049..
[http://dx.doi.org/10.7554/eLife.00049] [PMID: 23150796]
[54]
Ni Y, Lempp FA, Mehrle S, et al. Hepatitis B and D viruses exploit sodium taurocholate co-transporting polypeptide for species-specific entry into hepatocytes. Gastroenterology 2014; 146(4): 1070-83.
[http://dx.doi.org/10.1053/j.gastro.2013.12.024] [PMID: 24361467]
[55]
Tong S, Li J. Identification of NTCP as an HBV receptor: the beginning of the end or the end of the beginning? Gastroenterology 2014; 146(4): 902-5.
[http://dx.doi.org/10.1053/j.gastro.2014.02.024] [PMID: 24576732]
[56]
Yan H, Li W. Sodium taurocholate cotransporting polypeptide acts as a receptor for hepatitis B and D virus. Dig Dis 2015; 33(3): 388-96.
[http://dx.doi.org/10.1159/000371692] [PMID: 26045274]
[57]
Li W, Urban S. Entry of hepatitis B and hepatitis D virus into hepatocytes: Basic insights and clinical implications. J Hepatol 2016; 64(1)(Suppl.): S32-40.
[http://dx.doi.org/10.1016/j.jhep.2016.02.011] [PMID: 27084034]
[58]
Petersen J, Dandri M, Mier W, et al. Prevention of hepatitis B virus infection in vivo by entry inhibitors derived from the large envelope protein. Nat Biotechnol 2008; 26(3): 335-41.
[http://dx.doi.org/10.1038/nbt1389] [PMID: 18297057]
[59]
Schieck A, Müller T, Schulze A, Haberkorn U, Urban S, Mier W. Solid-phase synthesis of the lipopeptide Myr-HBVpreS/2-78, a hepatitis B virus entry inhibitor. Molecules 2010; 15(7): 4773-83.
[http://dx.doi.org/10.3390/molecules15074773] [PMID: 20657392]
[60]
Blank A, Markert C, Hohmann N, et al. First-in-human application of the novel hepatitis B and hepatitis D virus entry inhibitor myrcludex B. J Hepatol 2016; 65(3): 483-9.
[http://dx.doi.org/10.1016/j.jhep.2016.04.013] [PMID: 27132172]
[61]
Huang HC, Tao MH, Hung TM, Chen JC, Lin ZJ, Huang C. (-)-Epigallocatechin-3-gallate inhibits entry of hepatitis B virus into hepatocytes. Antiviral Res 2014; 111: 100-11.
[http://dx.doi.org/10.1016/j.antiviral.2014.09.009] [PMID: 25260897]
[62]
Watashi K, Sluder A, Daito T, et al. Cyclosporin A and its analogs inhibit hepatitis B virus entry into cultured hepatocytes through targeting a membrane transporter, sodium taurocholate cotransporting polypeptide (NTCP). Hepatology 2014; 59(5): 1726-37.
[http://dx.doi.org/10.1002/hep.26982] [PMID: 24375637]
[63]
Jin WB, Wu FL, Kong D, Guo AG. HBV-encoded microRNA candidate and its target. Comput Biol Chem 2007; 31(2): 124-6.
[http://dx.doi.org/10.1016/j.compbiolchem.2007.01.005] [PMID: 17350341]
[64]
Potenza N, Papa U, Mosca N, Zerbini F, Nobile V, Russo A. Human microRNA hsa-miR-125a-5p interferes with expression of hepatitis B virus surface antigen. Nucleic Acids Res 2011; 39(12): 5157-63.
[http://dx.doi.org/10.1093/nar/gkr067] [PMID: 21317190]
[65]
Kohno T, Tsuge M, Murakami E, et al. Human microRNA hsa-miR-1231 suppresses hepatitis B virus replication by targeting core mRNA. J Viral Hepat 2014; 21(9): e89-97.
[http://dx.doi.org/10.1111/jvh.12240] [PMID: 24835118]
[66]
Zhang GL, Li YX, Zheng SQ, Liu M, Li X, Tang H. Suppression of hepatitis B virus replication by microRNA-199a-3p and microRNA-210. Antiviral Res 2010; 88(2): 169-75.
[http://dx.doi.org/10.1016/j.antiviral.2010.08.008] [PMID: 20728471]
[67]
Zhao F, Xu G, Zhou Y, et al. MicroRNA-26b inhibits hepatitis B virus transcription and replication by targeting the host factor CHORDC1 protein. J Biol Chem 2014; 289(50): 35029-41.
[http://dx.doi.org/10.1074/jbc.M114.589978] [PMID: 25342750]
[68]
Qiu L, Fan H, Jin W, et al. miR-122-induced down-regulation of HO-1 negatively affects miR-122-mediated suppression of HBV. Biochem Biophys Res Commun 2010; 398(4): 771-7.
[http://dx.doi.org/10.1016/j.bbrc.2010.07.021] [PMID: 20633528]
[69]
Chen Y, Shen A, Rider PJ, et al. A liver-specific microRNA binds to a highly conserved RNA sequence of hepatitis B virus and negatively regulates viral gene expression and replication. FASEB J 2011; 25(12): 4511-21.
[http://dx.doi.org/10.1096/fj.11-187781] [PMID: 21903935]
[70]
Wang S, Qiu L, Yan X, et al. Loss of microRNA 122 expression in patients with hepatitis B enhances hepatitis B virus replication through cyclin G(1) -modulated P53 activity. Hepatology 2012; 55(3): 730-41.
[http://dx.doi.org/10.1002/hep.24809] [PMID: 22105316]
[71]
Li C, Wang Y, Wang S, et al. Hepatitis B virus mRNA-mediated miR-122 inhibition upregulates PTTG1-binding protein, which promotes hepatocellular carcinoma tumor growth and cell invasion. J Virol 2013; 87(4): 2193-205.
[http://dx.doi.org/10.1128/JVI.02831-12] [PMID: 23221562]
[72]
Hayes CN, Chayama K. MicroRNAs as biomarkers for liver disease and hepatocellular carcinoma. Int J Mol Sci 2016; 17(3): 280.
[http://dx.doi.org/10.3390/ijms17030280] [PMID: 26927063]
[73]
Wu FL, Jin WB, Li JH, Guo AG. Targets for human encoded microRNAs in HBV genes. Virus Genes 2011; 42(2): 157-61.
[http://dx.doi.org/10.1007/s11262-010-0555-7] [PMID: 21113793]
[74]
Bao XQ, Liu GT. Bicyclol: a novel antihepatitis drug with hepatic heat shock protein 27/70-inducing activity and cytoprotective effects in mice. Cell Stress Chaperones 2008; 13(3): 347-55.
[http://dx.doi.org/10.1007/s12192-008-0034-4] [PMID: 18392951]
[75]
Hu J, Seeger C. Hsp90 is required for the activity of a hepatitis B virus reverse transcriptase. Proc Natl Acad Sci USA 1996; 93(3): 1060-4.
[http://dx.doi.org/10.1073/pnas.93.3.1060] [PMID: 8577714]
[76]
Park SG, Lee SM, Jung G. Antisense oligodeoxynucleotides targeted against molecular chaperonin Hsp60 block human hepatitis B virus replication. J Biol Chem 2003; 278(41): 39851-7.
[http://dx.doi.org/10.1074/jbc.M301618200] [PMID: 12869561]
[77]
Tenhunen R, Marver HS, Schmid R. The enzymatic conversion of heme to bilirubin by microsomal heme oxygenase. Proc Natl Acad Sci USA 1968; 61(2): 748-55.
[http://dx.doi.org/10.1073/pnas.61.2.748] [PMID: 4386763]
[78]
Protzer U, Seyfried S, Quasdorff M, et al. Antiviral activity and hepatoprotection by heme oxygenase-1 in hepatitis B virus infection. Gastroenterology 2007; 133(4): 1156-65.
[http://dx.doi.org/10.1053/j.gastro.2007.07.021] [PMID: 17919491]
[79]
Yang J, Bo XC, Yao J, Yang NM, Wang SQ. Differentially expressed cellular genes following HBV: potential targets of anti-HBV drugs? J Viral Hepat 2005; 12(4): 357-63.
[http://dx.doi.org/10.1111/j.1365-2893.2005.00611.x] [PMID: 15985005]
[80]
Budkowska A, Bedossa P, Groh F, Louise A, Pillot J. Fibronectin of human liver sinusoids binds hepatitis B virus: identification by an anti-idiotypic antibody bearing the internal image of the pre-S2 domain. J Virol 1995; 69(2): 840-8.
[PMID: 7815551]
[81]
Chen Z, Zhu M, Pan X, et al. Inhibition of Hepatitis B virus replication by SAMHD1. Biochem Biophys Res Commun 2014; 450(4): 1462-8.
[http://dx.doi.org/10.1016/j.bbrc.2014.07.023] [PMID: 25019997]
[82]
Jeong GU, Park IH, Ahn K, Ahn BY. Inhibition of hepatitis B virus replication by a dNTPase-dependent function of the host restriction factor SAMHD1. Virology 2016; 495: 71-8.
[http://dx.doi.org/10.1016/j.virol.2016.05.001] [PMID: 27179347]
[83]
Wang YP, Liu F, He HW, et al. Heat stress cognate 70 host protein as a potential drug target against drug resistance in hepatitis B virus. Antimicrob Agents Chemother 2010; 54(5): 2070-7.
[http://dx.doi.org/10.1128/AAC.01764-09] [PMID: 20176893]
[84]
Du NN, Li X, Wang YP, et al. Synthesis, structure-activity relationship and biological evaluation of novel N-substituted matrinic acid derivatives as host heat-stress cognate 70 (Hsc70) down-regulators. Bioorg Med Chem Lett 2011; 21(16): 4732-5.
[http://dx.doi.org/10.1016/j.bmcl.2011.06.071] [PMID: 21757347]
[85]
Ying C, Li Y, Leung CH, Robek MD, Cheng YC. Unique antiviral mechanism discovered in anti-hepatitis B virus research with a natural product analogue. Proc Natl Acad Sci USA 2007; 104(20): 8526-31.
[http://dx.doi.org/10.1073/pnas.0609883104] [PMID: 17488817]
[86]
Yoon JC, Puigserver P, Chen G, et al. Control of hepatic gluconeogenesis through the transcriptional coactivator PGC-1. Nature 2001; 413(6852): 131-8.
[http://dx.doi.org/10.1038/35093050] [PMID: 11557972]
[87]
Shlomai A, Paran N, Shaul Y. PGC-1alpha controls hepatitis B virus through nutritional signals. Proc Natl Acad Sci USA 2006; 103(43): 16003-8.
[http://dx.doi.org/10.1073/pnas.0607837103] [PMID: 17043229]
[88]
Shlomai A, Shaul Y. The metabolic activator FOXO1 binds hepatitis B virus DNA and activates its transcription. Biochem Biophys Res Commun 2009; 381(4): 544-8.
[http://dx.doi.org/10.1016/j.bbrc.2009.02.078] [PMID: 19233123]
[89]
Shlomai A, Shaul Y. The “metabolovirus” model of hepatitis B virus suggests nutritional therapy as an effective anti-viral weapon. Med Hypotheses 2008; 71(1): 53-7.
[http://dx.doi.org/10.1016/j.mehy.2007.08.032] [PMID: 18334285]
[90]
Rechtman MM, Har-Noy O, Bar-Yishay I, et al. Curcumin inhibits hepatitis B virus via down-regulation of the metabolic coactivator PGC-1alpha. FEBS Lett 2010; 584(11): 2485-90.
[http://dx.doi.org/10.1016/j.febslet.2010.04.067] [PMID: 20434445]
[91]
Ren JH, Tao Y, Zhang ZZ, et al. Sirtuin 1 regulates hepatitis B virus transcription and replication by targeting transcription factor AP-1. J Virol 2014; 88(5): 2442-51.
[http://dx.doi.org/10.1128/JVI.02861-13] [PMID: 24335313]
[92]
Yang J, Bo XC, Ding XR, et al. Antisense oligonucleotides targeted against asialoglycoprotein receptor 1 block human hepatitis B virus replication. J Viral Hepat 2006; 13(3): 158-65.
[http://dx.doi.org/10.1111/j.1365-2893.2005.00666.x] [PMID: 16475991]
[93]
Cohen D, Adamovich Y, Reuven N, Shaul Y. Hepatitis B virus activates deoxynucleotide synthesis in nondividing hepatocytes by targeting the R2 gene. Hepatology 2010; 51(5): 1538-46.
[http://dx.doi.org/10.1002/hep.23519] [PMID: 20155784]
[94]
Lucifora J, Xia Y, Reisinger F, et al. Specific and nonhepatotoxic degradation of nuclear hepatitis B virus cccDNA. Science 2014; 343(6176): 1221-8.
[http://dx.doi.org/10.1126/science.1243462] [PMID: 24557838]
[95]
Pollock S, Nichita NB, Böhmer A, Radulescu C, Dwek RA, Zitzmann N. Polyunsaturated liposomes are antiviral against hepatitis B and C viruses and HIV by decreasing cholesterol levels in infected cells. Proc Natl Acad Sci USA 2010; 107(40): 17176-81.
[http://dx.doi.org/10.1073/pnas.1009445107] [PMID: 20855621]
[96]
Li H, Zhu W, Zhang L, et al. The metabolic responses to hepatitis B virus infection shed new light on pathogenesis and targets for treatment. Sci Rep 2015; 5: 8421.
[http://dx.doi.org/10.1038/srep08421] [PMID: 25672227]
[97]
Okamura H, Nio Y, Akahori Y, et al. Fatty acid biosynthesis is involved in the production of hepatitis B virus particles. Biochem Biophys Res Commun 2016; 475(1): 87-92.
[http://dx.doi.org/10.1016/j.bbrc.2016.05.043] [PMID: 27178211]
[98]
Liu X, Xu Z, Hou C, et al. Inhibition of hepatitis B virus replication by targeting ribonucleotide reductase M2 protein. Biochem Pharmacol 2016; 103: 118-28.
[http://dx.doi.org/10.1016/j.bcp.2016.01.003] [PMID: 26774458]
[99]
Chen EQ, Dai J, Bai L, Tang H. The efficacy of zinc finger antiviral protein against hepatitis B virus transcription and replication in tansgenic mouse model. Virol J 2015; 12: 25.
[http://dx.doi.org/10.1186/s12985-015-0245-0] [PMID: 25889209]
[100]
Richters A. Targeting protein arginine methyltransferase 5 in disease. Future Med Chem 2017; 9(17): 2081-98.
[http://dx.doi.org/10.4155/fmc-2017-0089] [PMID: 29076773]
[101]
Lubyova B, Hodek J, Zabransky A, et al. PRMT5: A novel regulator of Hepatitis B virus replication and an arginine methylase of HBV core. PLoS One 2017; 12(10)e0186982
[http://dx.doi.org/10.1371/journal.pone.0186982] [PMID: 29065155]
[102]
Zhang W, Chen J, Wu M, et al. PRMT5 restricts hepatitis B virus replication through epigenetic repression of covalently closed circular DNA transcription and interference with pregenomic RNA encapsidation. Hepatology 2017; 66(2): 398-415.
[http://dx.doi.org/10.1002/hep.29133] [PMID: 28236308]
[103]
Benhenda S, Ducroux A, Rivière L, et al. Methyltransferase PRMT1 is a binding partner of HBx and a negative regulator of hepatitis B virus transcription. J Virol 2013; 87(8): 4360-71.
[http://dx.doi.org/10.1128/JVI.02574-12] [PMID: 23388725]
[104]
Saso W, Tsukuda S, Ohashi H, et al. A new strategy to identify hepatitis B virus entry inhibitors by AlphaScreen technology targeting the envelope-receptor interaction. Biochem Biophys Res Commun 2018; 501(2): 374-9.
[http://dx.doi.org/10.1016/j.bbrc.2018.04.187] [PMID: 29730285]
[105]
Li N, Zhang L, Chen L, et al. MxA inhibits hepatitis B virus replication by interaction with hepatitis B core antigen. Hepatology 2012; 56(3): 803-11.
[http://dx.doi.org/10.1002/hep.25608] [PMID: 22271421]
[106]
Michel ML. Towards immunotherapy for chronic hepatitis B virus infections. Vaccine 2002; 20(Suppl. 4): A83-8.
[http://dx.doi.org/10.1016/S0264-410X(02)00393-6] [PMID: 12477434]
[107]
Grimm D, Heeg M, Thimme R. Hepatitis B virus: from immunobiology to immunotherapy. Clin Sci (Lond) 2013; 124(2): 77-85.
[http://dx.doi.org/10.1042/CS20120169] [PMID: 23013042]
[108]
Liu D, Ni B, Wang L, Zhang M, Liu W, Wu Y. Hepatitis B virus core protein interacts with CD59 to promote complement-mediated liver inflammation during chronic hepatitis B virus infection. FEBS Lett 2013; 587(20): 3314-20.
[http://dx.doi.org/10.1016/j.febslet.2013.08.044] [PMID: 24036449]
[109]
Wang S, Qiu L, Liu G, et al. Heat shock protein gp96 enhances humoral and T cell responses, decreases Treg frequency and potentiates the anti-HBV activity in BALB/c and transgenic mice. Vaccine 2011; 29(37): 6342-51.
[http://dx.doi.org/10.1016/j.vaccine.2011.05.008] [PMID: 21600951]
[110]
Meng SD, Gao T, Gao GF, Tien P. HBV-specific peptide associated with heat-shock protein gp96. Lancet 2001; 357(9255): 528-9.
[http://dx.doi.org/10.1016/S0140-6736(00)04050-2] [PMID: 11229675]
[111]
Liu Z, Li X, Qiu L, et al. Treg suppress CTL responses upon immunization with HSP gp96. Eur J Immunol 2009; 39(11): 3110-20.
[http://dx.doi.org/10.1002/eji.200939593] [PMID: 19839010]
[112]
Shahrakyvahed A, Sanchooli J, Sanadgol N, Arababadi MK, Kennedy D. TLR9: an important molecule in the fight against hepatitis B virus. Postgrad Med J 2014; 90(1065): 396-401.
[http://dx.doi.org/10.1136/postgradmedj-2013-132309] [PMID: 24942353]
[113]
Chang WW, Su IJ, Lai MD, Chang WT, Huang W, Lei HY. Toll-like receptor 4 plays an anti-HBV role in a murine model of acute hepatitis B virus expression. World J Gastroenterol 2005; 11(42): 6631-7.
[http://dx.doi.org/10.3748/wjg.v11.i42.6631] [PMID: 16425356]
[114]
Lanford RE, Guerra B, Chavez D, et al. GS-9620, an oral agonist of Toll-like receptor-7, induces prolonged suppression of hepatitis B virus in chronically infected chimpanzees. Gastroenterology 2013; 144(7): 1508-7. 1517.e1-10
[115]
Liu Y, Gao LF, Liang XH, Ma CH. Role of Tim-3 in hepatitis B virus infection: An overview. World J Gastroenterol 2016; 22(7): 2294-303.
[http://dx.doi.org/10.3748/wjg.v22.i7.2294] [PMID: 26900291]
[116]
Shabani Z, Bagheri M, Zare-Bidaki M, et al. NK cells in hepatitis B virus infection: a potent target for immunotherapy. Arch Virol 2014; 159(7): 1555-65.
[http://dx.doi.org/10.1007/s00705-013-1965-3] [PMID: 24445811]
[117]
Wu SF, Wang WJ, Gao YQ. Natural killer cells in hepatitis B virus infection. Braz J Infect Dis 2015; 19(4): 417-25.
[http://dx.doi.org/10.1016/j.bjid.2015.05.006] [PMID: 26119852]
[118]
Yoshio S, Kanto T. Host-virus interactions in hepatitis B and hepatitis C infection. J Gastroenterol 2016; 51(5): 409-20.
[http://dx.doi.org/10.1007/s00535-016-1183-3] [PMID: 26894594]
[119]
Xiang XG, Xie Q. IL-35: a potential therapeutic target for controlling hepatitis B virus infection. J Dig Dis 2015; 16(1): 1-6.
[http://dx.doi.org/10.1111/1751-2980.12218] [PMID: 25476593]
[120]
Li X, Liu X, Tian L, Chen Y. Cytokine-Mediated Immunopathogenesis of Hepatitis B Virus Infections. Clin Rev Allergy Immunol 2016; 50(1): 41-54.
[http://dx.doi.org/10.1007/s12016-014-8465-4] [PMID: 25480494]
[121]
Xia Y, Protzer U. Control of Hepatitis B Virus by Cytokines. Viruses 2017; 9(1)E18
[http://dx.doi.org/10.3390/v9010018] [PMID: 28117695]
[122]
Xia C, Liu Y, Chen Z, Zheng M. Involvement of interleukin 6 in hepatitis B viral infection. Cell Physiol Biochem 2015; 37(2): 677-86.
[http://dx.doi.org/10.1159/000430386] [PMID: 26343270]
[123]
Lin CL, Kao JH. Review article: novel therapies for hepatitis B virus cure - advances and perspectives. Aliment Pharmacol Ther 2016; 44(3): 213-22.
[http://dx.doi.org/10.1111/apt.13694] [PMID: 27302653]
[124]
Wilson EM, Tang L, Kottilil S. Eradication strategies for chronic hepatitis B infection. Clin Infect Dis 2016; 62(Suppl. 4): S318-25.
[http://dx.doi.org/10.1093/cid/ciw044] [PMID: 27190322]
[125]
Shih C, Chou SF, Yang CC, Huang JY, Choijilsuren G, Jhou RS. Control and eradication strategies of hepatitis B virus. Trends Microbiol 2016; 24(9): 739-49.
[http://dx.doi.org/10.1016/j.tim.2016.05.006] [PMID: 27287929]
[126]
Kao JH. Hepatitis B vaccination and prevention of hepatocellular carcinoma. Best Pract Res Clin Gastroenterol 2015; 29(6): 907-17.
[http://dx.doi.org/10.1016/j.bpg.2015.09.011] [PMID: 26651252]
[127]
You CR, Lee SW, Jang JW, Yoon SK. Update on hepatitis B virus infection. World J Gastroenterol 2014; 20(37): 13293-305.
[http://dx.doi.org/10.3748/wjg.v20.i37.13293] [PMID: 25309066]
[128]
Zheng Z, Li J, Sun J, et al. Inhibition of HBV replication by theophylline. Antiviral Res 2011; 89(2): 149-55.
[http://dx.doi.org/10.1016/j.antiviral.2010.12.004] [PMID: 21167867]
[129]
van Campenhout MJ, Janssen HL. How to achieve immune control in chronic hepatitis B? Hepatol Int 2015; 9(1): 9-16.
[http://dx.doi.org/10.1007/s12072-014-9571-3] [PMID: 25788374]

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy