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
[http://dx.doi.org/10.1146/annurev-virology-110615-042238] [PMID: 27482896]
[http://dx.doi.org/10.1016/S0140-6736(14)60220-8] [PMID: 24954675]
[http://dx.doi.org/10.1016/S0140-6736(15)61412-X] [PMID: 26231459]
[http://dx.doi.org/10.1016/S1473-3099(16)30214-6] [PMID: 27638359]
[http://dx.doi.org/10.1016/S1473-3099(15)00436-3] [PMID: 26795693]
[http://dx.doi.org/10.1016/j.bbrc.2006.03.204] [PMID: 16631116]
[http://dx.doi.org/10.1016/j.antiviral.2015.09.011] [PMID: 26408354]
[http://dx.doi.org/10.1007/s11901-010-0039-1] [PMID: 20461127]
[http://dx.doi.org/10.1128/JVI.02575-13] [PMID: 24352439]
[http://dx.doi.org/10.1016/j.antiviral.2016.06.005] [PMID: 27321664]
[http://dx.doi.org/10.1128/JVI.03000-13] [PMID: 24173223]
[http://dx.doi.org/10.1007/978-1-4939-6700-1_14] [PMID: 27975316]
[http://dx.doi.org/10.1016/j.antiviral.2015.04.002] [PMID: 25862291]
[http://dx.doi.org/10.1016/j.antiviral.2013.06.007] [PMID: 23796982]
[http://dx.doi.org/10.1016/j.antiviral.2014.05.007] [PMID: 24858512]
[http://dx.doi.org/10.1128/AAC.04617-14] [PMID: 25451058]
[http://dx.doi.org/10.1128/JVI.03058-15] [PMID: 26842475]
[http://dx.doi.org/10.1080/14728222.2017.1397134] [PMID: 29065733]
[http://dx.doi.org/10.1016/j.peptides.2009.07.006] [PMID: 19619601]
[http://dx.doi.org/10.1038/sj.onc.1204805] [PMID: 11641783]
[http://dx.doi.org/10.1016/S1386-6532(05)80026-5] [PMID: 16461217]
[http://dx.doi.org/10.1016/j.bmcl.2009.10.119] [PMID: 19897363]
[http://dx.doi.org/10.1016/j.bmcl.2014.07.032] [PMID: 25127104]
[http://dx.doi.org/10.1016/j.bmc.2016.12.017] [PMID: 28082068]
[http://dx.doi.org/10.1002/jmr.801] [PMID: 17006877]
[http://dx.doi.org/10.1128/JVI.00582-13] [PMID: 23576513]
[http://dx.doi.org/10.1126/science.1077215] [PMID: 12574631]
[PMID: 29938706]
[http://dx.doi.org/10.1111/liv.13001] [PMID: 26725901]
[http://dx.doi.org/10.1016/j.jhep.2016.02.009] [PMID: 27084036]
[http://dx.doi.org/10.1016/j.antiviral.2015.10.004] [PMID: 26476375]
[http://dx.doi.org/10.1038/mtna.2014.38] [PMID: 25137139]
[http://dx.doi.org/10.1042/BJ20140316] [PMID: 24902849]
[http://dx.doi.org/10.1016/j.bbrc.2003.10.009] [PMID: 14592428]
[http://dx.doi.org/10.1016/j.bbrc.2007.01.163] [PMID: 17300745]
[http://dx.doi.org/10.1007/s12013-014-9847-1] [PMID: 24569930]
[http://dx.doi.org/10.4149/av_2012_01_49] [PMID: 22404609]
[http://dx.doi.org/10.1111/jvh.12479] [PMID: 26456011]
[http://dx.doi.org/10.1016/j.antiviral.2006.01.003] [PMID: 16487605]
[http://dx.doi.org/10.1016/j.biopha.2015.02.002] [PMID: 25776516]
[http://dx.doi.org/10.1038/aps.2013.175] [PMID: 24487969]
[http://dx.doi.org/10.1128/JVI.00466-15] [PMID: 26136564]
[http://dx.doi.org/10.1021/acsinfecdis.8b00156] [PMID: 30199230]
[http://dx.doi.org/10.1016/j.coviro.2015.07.009] [PMID: 26262886]
[http://dx.doi.org/10.1002/hep.21112] [PMID: 16557545]
[http://dx.doi.org/10.1016/j.bbrc.2013.12.052] [PMID: 24342612]
[http://dx.doi.org/10.1007/s00424-013-1367-0] [PMID: 24196564]
[http://dx.doi.org/10.1136/gutjnl-2013-304594] [PMID: 23542357]
[http://dx.doi.org/10.1016/j.antiviral.2015.06.002] [PMID: 26071008]
[http://dx.doi.org/10.1007/978-1-4939-6700-1_1] [PMID: 27975303]
[http://dx.doi.org/10.7554/eLife.00049] [PMID: 23150796]
[http://dx.doi.org/10.1053/j.gastro.2013.12.024] [PMID: 24361467]
[http://dx.doi.org/10.1053/j.gastro.2014.02.024] [PMID: 24576732]
[http://dx.doi.org/10.1159/000371692] [PMID: 26045274]
[http://dx.doi.org/10.1016/j.jhep.2016.02.011] [PMID: 27084034]
[http://dx.doi.org/10.1038/nbt1389] [PMID: 18297057]
[http://dx.doi.org/10.3390/molecules15074773] [PMID: 20657392]
[http://dx.doi.org/10.1016/j.jhep.2016.04.013] [PMID: 27132172]
[http://dx.doi.org/10.1016/j.antiviral.2014.09.009] [PMID: 25260897]
[http://dx.doi.org/10.1002/hep.26982] [PMID: 24375637]
[http://dx.doi.org/10.1016/j.compbiolchem.2007.01.005] [PMID: 17350341]
[http://dx.doi.org/10.1093/nar/gkr067] [PMID: 21317190]
[http://dx.doi.org/10.1111/jvh.12240] [PMID: 24835118]
[http://dx.doi.org/10.1016/j.antiviral.2010.08.008] [PMID: 20728471]
[http://dx.doi.org/10.1074/jbc.M114.589978] [PMID: 25342750]
[http://dx.doi.org/10.1016/j.bbrc.2010.07.021] [PMID: 20633528]
[http://dx.doi.org/10.1096/fj.11-187781] [PMID: 21903935]
[http://dx.doi.org/10.1002/hep.24809] [PMID: 22105316]
[http://dx.doi.org/10.1128/JVI.02831-12] [PMID: 23221562]
[http://dx.doi.org/10.3390/ijms17030280] [PMID: 26927063]
[http://dx.doi.org/10.1007/s11262-010-0555-7] [PMID: 21113793]
[http://dx.doi.org/10.1007/s12192-008-0034-4] [PMID: 18392951]
[http://dx.doi.org/10.1073/pnas.93.3.1060] [PMID: 8577714]
[http://dx.doi.org/10.1074/jbc.M301618200] [PMID: 12869561]
[http://dx.doi.org/10.1073/pnas.61.2.748] [PMID: 4386763]
[http://dx.doi.org/10.1053/j.gastro.2007.07.021] [PMID: 17919491]
[http://dx.doi.org/10.1111/j.1365-2893.2005.00611.x] [PMID: 15985005]
[PMID: 7815551]
[http://dx.doi.org/10.1016/j.bbrc.2014.07.023] [PMID: 25019997]
[http://dx.doi.org/10.1016/j.virol.2016.05.001] [PMID: 27179347]
[http://dx.doi.org/10.1128/AAC.01764-09] [PMID: 20176893]
[http://dx.doi.org/10.1016/j.bmcl.2011.06.071] [PMID: 21757347]
[http://dx.doi.org/10.1073/pnas.0609883104] [PMID: 17488817]
[http://dx.doi.org/10.1038/35093050] [PMID: 11557972]
[http://dx.doi.org/10.1073/pnas.0607837103] [PMID: 17043229]
[http://dx.doi.org/10.1016/j.bbrc.2009.02.078] [PMID: 19233123]
[http://dx.doi.org/10.1016/j.mehy.2007.08.032] [PMID: 18334285]
[http://dx.doi.org/10.1016/j.febslet.2010.04.067] [PMID: 20434445]
[http://dx.doi.org/10.1128/JVI.02861-13] [PMID: 24335313]
[http://dx.doi.org/10.1111/j.1365-2893.2005.00666.x] [PMID: 16475991]
[http://dx.doi.org/10.1002/hep.23519] [PMID: 20155784]
[http://dx.doi.org/10.1126/science.1243462] [PMID: 24557838]
[http://dx.doi.org/10.1073/pnas.1009445107] [PMID: 20855621]
[http://dx.doi.org/10.1038/srep08421] [PMID: 25672227]
[http://dx.doi.org/10.1016/j.bbrc.2016.05.043] [PMID: 27178211]
[http://dx.doi.org/10.1016/j.bcp.2016.01.003] [PMID: 26774458]
[http://dx.doi.org/10.1186/s12985-015-0245-0] [PMID: 25889209]
[http://dx.doi.org/10.4155/fmc-2017-0089] [PMID: 29076773]
[http://dx.doi.org/10.1371/journal.pone.0186982] [PMID: 29065155]
[http://dx.doi.org/10.1002/hep.29133] [PMID: 28236308]
[http://dx.doi.org/10.1128/JVI.02574-12] [PMID: 23388725]
[http://dx.doi.org/10.1016/j.bbrc.2018.04.187] [PMID: 29730285]
[http://dx.doi.org/10.1002/hep.25608] [PMID: 22271421]
[http://dx.doi.org/10.1016/S0264-410X(02)00393-6] [PMID: 12477434]
[http://dx.doi.org/10.1042/CS20120169] [PMID: 23013042]
[http://dx.doi.org/10.1016/j.febslet.2013.08.044] [PMID: 24036449]
[http://dx.doi.org/10.1016/j.vaccine.2011.05.008] [PMID: 21600951]
[http://dx.doi.org/10.1016/S0140-6736(00)04050-2] [PMID: 11229675]
[http://dx.doi.org/10.1002/eji.200939593] [PMID: 19839010]
[http://dx.doi.org/10.1136/postgradmedj-2013-132309] [PMID: 24942353]
[http://dx.doi.org/10.3748/wjg.v11.i42.6631] [PMID: 16425356]
[http://dx.doi.org/10.3748/wjg.v22.i7.2294] [PMID: 26900291]
[http://dx.doi.org/10.1007/s00705-013-1965-3] [PMID: 24445811]
[http://dx.doi.org/10.1016/j.bjid.2015.05.006] [PMID: 26119852]
[http://dx.doi.org/10.1007/s00535-016-1183-3] [PMID: 26894594]
[http://dx.doi.org/10.1111/1751-2980.12218] [PMID: 25476593]
[http://dx.doi.org/10.1007/s12016-014-8465-4] [PMID: 25480494]
[http://dx.doi.org/10.3390/v9010018] [PMID: 28117695]
[http://dx.doi.org/10.1159/000430386] [PMID: 26343270]
[http://dx.doi.org/10.1111/apt.13694] [PMID: 27302653]
[http://dx.doi.org/10.1093/cid/ciw044] [PMID: 27190322]
[http://dx.doi.org/10.1016/j.tim.2016.05.006] [PMID: 27287929]
[http://dx.doi.org/10.1016/j.bpg.2015.09.011] [PMID: 26651252]
[http://dx.doi.org/10.3748/wjg.v20.i37.13293] [PMID: 25309066]
[http://dx.doi.org/10.1016/j.antiviral.2010.12.004] [PMID: 21167867]
[http://dx.doi.org/10.1007/s12072-014-9571-3] [PMID: 25788374]