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Article(id=1239174990747202011, tenantId=1146029695717560320, journalId=1205117082300743687, issueId=1239174986137661844, articleNumber=null, orderNo=null, doi=10.14109/j.cnki.xyylc.2024.04.01, pmid=null, cstr=null, oa=null, hot=null, price=null, onlineType=0, articleFormat=0, articleType=null, articleTypeStr=null, receivedDate=1695052800000, receivedDateStr=2023-09-19, revisedDate=null, revisedDateStr=null, acceptedDate=1706803200000, acceptedDateStr=2024-02-02, onlineDate=1773371940552, onlineDateStr=2026-03-13, pubDate=1713974400000, pubDateStr=2024-04-25, doiRegisterDate=null, doiRegisterDateStr=null, onlineIssueDate=1773371940552, onlineIssueDateStr=2026-03-13, onlineJustAcceptDate=null, onlineJustAcceptDateStr=null, onlineFirstDate=null, onlineFirstDateStr=null, sourceXml=null, magXml=null, createTime=1773371940552, creator=13701087609, updateTime=1773371940552, updator=13701087609, issue=Issue{id=1239174986137661844, tenantId=1146029695717560320, journalId=1205117082300743687, year='2024', volume='43', issue='4', pageStart='241', pageEnd='320', issueExtLink='null', onlineDate='null', pubDate='null', beforeIssueId=null, nextIssueId=null, price=null, status=1, issueComplete=1, articleOrder=1, issueType=-1, specialIssue=null, createTime=1773371939453, creator=13701087609, updateTime=1773372128807, updator=13701087609, preIssue=null, nextIssue=null, ext={EN=IssueExt(id=1239175780396233704, tenantId=1146029695717560320, journalId=1205117082300743687, issueId=1239174986137661844, language=EN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=), CN=IssueExt(id=1239175780396233705, tenantId=1146029695717560320, journalId=1205117082300743687, issueId=1239174986137661844, language=CN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=)}, issueFiles=null}, startPage=241, endPage=246, ext={EN=ArticleExt(id=1239174990969500130, articleId=1239174990747202011, tenantId=1146029695717560320, journalId=1205117082300743687, language=EN, title=Advancements in targeted therapy for chronic hepatitis B virus infection, columnId=1207314219599499390, journalTitle=Chinese Journal of New Drugs and Clinical Remedies, columnName=Review, runingTitle=null, highlight=null, articleAbstract=

Although some progress had been made in the treatment of chronic hepatitis B virus（HBV）infection,current first-line drugs failed to completely eliminate the covalently closed circular DNA（cccDNA）of HBV so as to completely eliminate HBV. Targeted therapy can specifically bind to the target sites, thereby blocking virus invasion, virus transcription, and protein translation, achieving precise treatment. Therefore, this article summarized and reviewed the targets at different stages of the HBV life cycle from the perspectives of targeting virus entry, targeting cccDNA, targeting core protein, targeting hepatitis B surface antigen（HBsAg）release, and targeting viral transcription, with a view to providing ideas for drug development against HBV infection.

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目前临床治疗慢性乙型肝炎病毒（HBV）感染已取得一定进展，但现有的一线药物尚不能完全清除HBV共价闭合环状DNA从而彻底清除HBV。靶向治疗能特异性地结合靶点部位，从而阻断病毒入侵、病毒转录和蛋白翻译等，实现精准治疗。本文整理总结HBV生命周期不同阶段的靶点，从靶向病毒进入、靶向共价闭合环状DNA、靶向核心蛋白、靶向乙型肝炎表面抗原释放、靶向病毒转录等角度进行综述，以期为抗HBV感染的药物研发提供思路。

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唐静，E-mail:
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王聃，女，医师，硕士，主要从事风湿免疫及感染的治疗研究，E-mail:

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王聃，女，医师，硕士，主要从事风湿免疫及感染的治疗研究，E-mail:

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王聃，女，医师，硕士，主要从事风湿免疫及感染的治疗研究，E-mail:

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Hepatitis B[J].Lancet, 2023, 401（10381）: 1039-1052., articleTitle=Hepatitis B, refAbstract=null), Reference(id=1239213763895808491, tenantId=1146029695717560320, journalId=1205117082300743687, articleId=1239174990747202011, doi=null, pmid=null, pmcid=null, year=2022, volume=603, issue=7903, pageStart=null, pageEnd=null, url=null, language=null, rfNumber=[2], rfOrder=1, authorNames=BRODY H, journalName=Nature, refType=null, unstructuredReference=BRODY H. Hepatitis B[J]. Nature, 2022, 603（7903）: S45., articleTitle=Hepatitis B, refAbstract=null), Reference(id=1239213764004860399, tenantId=1146029695717560320, journalId=1205117082300743687, articleId=1239174990747202011, doi=null, pmid=null, pmcid=null, year=2023, volume=388, issue=1, pageStart=55, pageEnd=69, url=null, language=null, rfNumber=[3], rfOrder=2, authorNames=DUSHEIKO G, AGARWAL K, MAINI MK, journalName=N Engl J Med, refType=null, unstructuredReference=DUSHEIKO G, AGARWAL K, MAINI MK. New approaches to chronic hepatitis B[J]. N Engl J Med, 2023, 388（1）: 55-69., articleTitle=New approaches to chronic hepatitis B, refAbstract=null), Reference(id=1239213764076163571, tenantId=1146029695717560320, journalId=1205117082300743687, articleId=1239174990747202011, doi=null, pmid=null, pmcid=null, year=2023, volume=20, issue=8, pageStart=524, pageEnd=537, url=null, language=null, rfNumber=[4], rfOrder=3, authorNames=HSU YC, HUANG DQ, NGUYEN MH, journalName=Nat Rev Gastroenterol Hepatol, refType=null, unstructuredReference=HSU YC, HUANG DQ, NGUYEN MH. Global burden of hepatitis B virus: current status, missed opportunities and a call for action[J]. Nat Rev Gastroenterol Hepatol, 2023, 20（8）: 524-537., articleTitle=Global burden of hepatitis B virus: current status, missed opportunities and a call for action, refAbstract=null), Reference(id=1239213764172632568, tenantId=1146029695717560320, journalId=1205117082300743687, articleId=1239174990747202011, doi=null, pmid=null, pmcid=null, year=2022, volume=19, issue=11, pageStart=727, pageEnd=745, url=null, language=null, rfNumber=[5], rfOrder=4, authorNames=KRAMVIS A, CHANG KM, DANDRI M, journalName=Nat Rev Gastroenterol Hepatol, refType=null, unstructuredReference=KRAMVIS A, CHANG KM, DANDRI M, et al. A roadmap for serum biomarkers for hepatitis B virus: current status and future outlook[J]. Nat Rev Gastroenterol Hepatol, 2022, 19（11）: 727-745., articleTitle=A roadmap for serum biomarkers for hepatitis B virus: current status and future outlook, refAbstract=null), Reference(id=1239213764264907263, tenantId=1146029695717560320, journalId=1205117082300743687, articleId=1239174990747202011, doi=null, pmid=null, pmcid=null, year=2023, volume=20, issue=4, pageStart=238, pageEnd=253, url=null, language=null, rfNumber=[6], rfOrder=5, authorNames=LIM SG, BAUMERT TF, BONI C, journalName=Nat Rev Gastroenterol Hepatol, refType=null, unstructuredReference=LIM SG, BAUMERT TF, BONI C, et al. The scientific basis of combination therapy for chronic hepatitis B functional cure[J].Nat Rev Gastroenterol Hepatol, 2023, 20（4）: 238-253., articleTitle=The scientific basis of combination therapy for chronic hepatitis B functional cure, refAbstract=null), Reference(id=1239213764361376257, tenantId=1146029695717560320, journalId=1205117082300743687, articleId=1239174990747202011, doi=null, pmid=null, pmcid=null, year=2022, volume=13, issue=1, pageStart=1111, pageEnd=1132, url=null, language=null, rfNumber=[7], rfOrder=6, authorNames=PHILLIPS S, JAGATIA R, CHOKSHI S, journalName=Virulence, refType=null, unstructuredReference=PHILLIPS S, JAGATIA R, CHOKSHI S. Novel therapeutic strategies for chronic hepatitis B[J]. Virulence, 2022, 13（1）:1111-1132., articleTitle=Novel therapeutic strategies for chronic hepatitis B, refAbstract=null), Reference(id=1239213764466233859, tenantId=1146029695717560320, journalId=1205117082300743687, articleId=1239174990747202011, doi=null, pmid=null, pmcid=null, year=2021, volume=8, issue=null, pageStart=435, pageEnd=450, url=null, language=null, rfNumber=[8], rfOrder=7, authorNames=JIANG Y, HAN Q, ZHAO H, journalName=J Hepatocell Carcinoma, refType=null, unstructuredReference=JIANG Y, HAN Q, ZHAO H, et al. The mechanisms of HBV-induced hepatocellular carcinoma[J]. J Hepatocell Carcinoma,2021, 8 : 435-450., articleTitle=The mechanisms of HBV-induced hepatocellular carcinoma, refAbstract=null), Reference(id=1239213764558508547, tenantId=1146029695717560320, journalId=1205117082300743687, articleId=1239174990747202011, doi=null, pmid=null, pmcid=null, year=2021, volume=18, issue=1, pageStart=105, pageEnd=null, url=null, language=null, rfNumber=[9], rfOrder=8, authorNames=XU R, HU P, LI Y, journalName=Virol J, refType=null, unstructuredReference=XU R, HU P, LI Y, et al. Advances in HBV infection and replication systems in vitro[J]. Virol J, 2021, 18（1）: 105., articleTitle=Advances in HBV infection and replication systems in vitro, refAbstract=null), Reference(id=1239213764634006024, tenantId=1146029695717560320, journalId=1205117082300743687, articleId=1239174990747202011, doi=null, pmid=null, pmcid=null, year=2020, volume=22, issue=1, pageStart=213, pageEnd=null, url=null, language=null, rfNumber=[10], rfOrder=9, authorNames=LEE HW, LEE JS, AHN SH, journalName=Int J Mol Sci, refType=null, unstructuredReference=LEE HW, LEE JS, AHN SH. Hepatitis B virus cure: targets and future therapies[J]. Int J Mol Sci, 2020, 22（1）: 213., articleTitle=Hepatitis B virus cure: targets and future therapies, refAbstract=null), Reference(id=1239213764713697800, tenantId=1146029695717560320, journalId=1205117082300743687, articleId=1239174990747202011, doi=null, pmid=null, pmcid=null, year=2021, volume=72, issue=null, pageStart=93, pageEnd=105, url=null, language=null, rfNumber=[11], rfOrder=10, authorNames=NAGGIE S, LOK AS, journalName=Annu Rev Med, refType=null, unstructuredReference=NAGGIE S, LOK AS. New therapeutics for hepatitis B: the road to cure[J]. Annu Rev Med, 2021, 72: 93-105., articleTitle=New therapeutics for hepatitis B: the road to cure, refAbstract=null), Reference(id=1239213764843721227, tenantId=1146029695717560320, journalId=1205117082300743687, articleId=1239174990747202011, doi=null, pmid=null, pmcid=null, year=2023, volume=14, issue=1, pageStart=4663, pageEnd=null, url=null, language=null, rfNumber=[12], rfOrder=11, authorNames=LIU W, YAO Q, SU X, journalName=Nat Commun, refType=null, unstructuredReference=LIU W, YAO Q, SU X, et al. Molecular insights into Spindlin1-HBx interplay and its impact on HBV transcription from cccDNA minichromosome[J]. Nat Commun, 2023, 14（1）: 4663., articleTitle=Molecular insights into Spindlin1-HBx interplay and its impact on HBV transcription from cccDNA minichromosome, refAbstract=null), Reference(id=1239213764961161741, tenantId=1146029695717560320, journalId=1205117082300743687, articleId=1239174990747202011, doi=null, pmid=null, pmcid=null, year=2021, volume=64, issue=9, pageStart=5973, pageEnd=6007, url=null, language=null, rfNumber=[13], rfOrder=12, authorNames=LIU Y, ZHANG L, YAN H, journalName=J Med Chem, refType=null, unstructuredReference=LIU Y, ZHANG L, YAN H, et al. Design of dimeric bile acid derivatives as potent and selective human NTCP inhibitors[J]. J Med Chem, 2021, 64（9）: 5973-6007., articleTitle=Design of dimeric bile acid derivatives as potent and selective human NTCP inhibitors, refAbstract=null), Reference(id=1239213765040853520, tenantId=1146029695717560320, journalId=1205117082300743687, articleId=1239174990747202011, doi=null, pmid=null, pmcid=null, year=2019, volume=70, issue=1, pageStart=null, pageEnd=null, url=null, language=null, rfNumber=[14], rfOrder=13, authorNames=WEDEMEYER H, SCHONEWEIS K, BOGOMOLOV PO, journalName=J Hepatol, refType=null, unstructuredReference=WEDEMEYER H, SCHONEWEIS K, BOGOMOLOV PO, et al. Final results of a multicenter, open-label phase 2 clinical trial（MYR203）to assess safety and efficacy of myrcludex B in combination with PEG-interferon alpha 2a in patients with chronic HBV/HDV co-infection[J]. J Hepatol, 2019, 70（1）: e81., articleTitle=Final results of a multicenter, open-label phase 2 clinical trial（MYR203）to assess safety and efficacy of myrcludex B in combination with PEG-interferon alpha 2a in patients with chronic HBV/HDV co-infection, refAbstract=null), Reference(id=1239213765112156692, tenantId=1146029695717560320, journalId=1205117082300743687, articleId=1239174990747202011, doi=null, pmid=null, pmcid=null, year=null, volume=null, issue=null, pageStart=null, pageEnd=null, url=null, language=null, rfNumber=[15], rfOrder=14, authorNames=Shanghai HEP Pharmaceutical Co., Ltd, journalName=null, refType=null, unstructuredReference=Shanghai HEP Pharmaceutical Co., Ltd. A phase Ⅱ study of hepalatide in subjects with chronic hepatitis B[EB/OL].（2023-12-08）[2024-01-26]. https://classic.clinicaltrials.gov/ct2/show/NCT04426968., articleTitle=A phase Ⅱ study of hepalatide in subjects with chronic hepatitis B, refAbstract=null), Reference(id=1239213765200237078, tenantId=1146029695717560320, journalId=1205117082300743687, articleId=1239174990747202011, doi=null, pmid=null, pmcid=null, year=2020, volume=182, issue=null, pageStart=null, pageEnd=null, url=null, language=null, rfNumber=[16], rfOrder=15, authorNames=TSUKUDA S, WATASHI K, journalName=Antiviral Res, refType=null, unstructuredReference=TSUKUDA S, WATASHI K. HEPATITIS B virus biology and life cycle[J]. Antiviral Res, 2020, 182: 104925., articleTitle=HEPATITIS B virus biology and life cycle, refAbstract=null), Reference(id=1239213765288317465, tenantId=1146029695717560320, journalId=1205117082300743687, articleId=1239174990747202011, doi=null, pmid=null, pmcid=null, year=2023, volume=78, issue=4, pageStart=742, pageEnd=753, url=null, language=null, rfNumber=[17], rfOrder=16, authorNames=WANG L, ZHU Q, ZHANG JD, journalName=J Hepatol, refType=null, unstructuredReference=WANG L, ZHU Q, ZHANG JD, et al. Discovery of a first-in-class orally available HBV cccDNA inhibitor[J]. J Hepatol, 2023, 78（4）: 742-753., articleTitle=Discovery of a first-in-class orally available HBV cccDNA inhibitor, refAbstract=null), Reference(id=1239213765401563677, tenantId=1146029695717560320, journalId=1205117082300743687, articleId=1239174990747202011, doi=null, pmid=null, pmcid=null, year=2018, volume=41, issue=4, pageStart=2169, pageEnd=2176, url=null, language=null, rfNumber=[18], rfOrder=17, authorNames=LUO W, WANG J, XU D, journalName=Int J Mol Med, refType=null, unstructuredReference=LUO W, WANG J, XU D, et al. Engineered zinc-finger transcription factors inhibit the replication and transcription of HBV in vitro and in vivo[J]. Int J Mol Med, 2018, 41（4）: 2169-2176., articleTitle=Engineered zinc-finger transcription factors inhibit the replication and transcription of HBV in vitro and in vivo, refAbstract=null), Reference(id=1239213765485449760, tenantId=1146029695717560320, journalId=1205117082300743687, articleId=1239174990747202011, doi=null, pmid=null, pmcid=null, year=2021, volume=13, issue=7, pageStart=1344, pageEnd=null, url=null, language=null, rfNumber=[19], rfOrder=18, authorNames=SMITH T, SINGH P, CHMIELEWSHI KO, journalName=Viruses, refType=null, unstructuredReference=SMITH T, SINGH P, CHMIELEWSHI KO, et al. Improved specificity and safety of anti-hepatitis B virus TALENs using obligate heterodimeric FokI nuclease domains[J]. Viruses, 2021,13（7）: 1344., articleTitle=Improved specificity and safety of anti-hepatitis B virus TALENs using obligate heterodimeric FokI nuclease domains, refAbstract=null), Reference(id=1239213765594501665, tenantId=1146029695717560320, journalId=1205117082300743687, articleId=1239174990747202011, doi=null, pmid=null, pmcid=null, year=2022, volume=20, issue=1, pageStart=27, pageEnd=null, url=null, language=null, rfNumber=[20], rfOrder=19, authorNames=WANG D, CHEN L, LI C, journalName=J Nanobiotechnology, refType=null, unstructuredReference=WANG D, CHEN L, LI C, et al. CRISPR/Cas9 delivery by NIR-responsive biomimetic nanoparticles for targeted HBV therapy[J].J Nanobiotechnology, 2022, 20（1）: 27., articleTitle=CRISPR/Cas9 delivery by NIR-responsive biomimetic nanoparticles for targeted HBV therapy, refAbstract=null), Reference(id=1239213765795828261, tenantId=1146029695717560320, journalId=1205117082300743687, articleId=1239174990747202011, doi=null, pmid=null, pmcid=null, year=2016, volume=24, issue=4, pageStart=671, pageEnd=677, url=null, language=null, rfNumber=[21], rfOrder=20, authorNames=ELY A, MOYO B, ARBUTHNOT P, journalName=Mol Ther, refType=null, unstructuredReference=ELY A, MOYO B, ARBUTHNOT P. Progress with developing use of gene editing to cure chronic infection with hepatitis B virus[J].Mol Ther, 2016, 24（4）: 671-677., articleTitle=Progress with developing use of gene editing to cure chronic infection with hepatitis B virus, refAbstract=null), Reference(id=1239213765892297258, tenantId=1146029695717560320, journalId=1205117082300743687, articleId=1239174990747202011, doi=null, pmid=null, pmcid=null, year=2016, volume=24, issue=7, pageStart=1258, pageEnd=1266, url=null, language=null, rfNumber=[22], rfOrder=21, authorNames=SEEGER C, SOHN JA, journalName=Mol Ther, refType=null, unstructuredReference=SEEGER C, SOHN JA. Complete spectrum of CRISPR/Cas9-induced mutations on HBV cccDNA[J]. Mol Ther, 2016, 24（7）:1258-1266., articleTitle=Complete spectrum of CRISPR/Cas9-induced mutations on HBV cccDNA, refAbstract=null), Reference(id=1239213765997154861, tenantId=1146029695717560320, journalId=1205117082300743687, articleId=1239174990747202011, doi=null, pmid=null, pmcid=null, year=2019, volume=76, issue=9, pageStart=1779, pageEnd=1794, url=null, language=null, rfNumber=[23], rfOrder=22, authorNames=KOSTYUSHEV D, BREZGIN S, KOSTYUSHEVA A, journalName=Cell Mol Life Sci, refType=null, unstructuredReference=KOSTYUSHEV D, BREZGIN S, KOSTYUSHEVA A, et al.Orthologous CRISPR/Cas9 systems for specific and efficient degradation of covalently closed circular DNA of hepatitis B virus[J]. Cell Mol Life Sci, 2019, 76（9）: 1779-1794., articleTitle=Orthologous CRISPR/Cas9 systems for specific and efficient degradation of covalently closed circular DNA of hepatitis B virus, refAbstract=null), Reference(id=1239213766076846641, tenantId=1146029695717560320, journalId=1205117082300743687, articleId=1239174990747202011, doi=null, pmid=null, pmcid=null, year=2018, volume=12, issue=null, pageStart=242, pageEnd=253, url=null, language=null, rfNumber=[24], rfOrder=23, authorNames=SCHIWON M, EHRKE SE, OSWALD A, journalName=Mol Ther Nucleic Acids, refType=null, unstructuredReference=SCHIWON M, EHRKE SE, OSWALD A, et al. One-vector system for multiplexed CRISPR/Cas9 against hepatitis B virus cccDNA utilizing high-capacity adenoviral vectors[J]. Mol Ther Nucleic Acids, 2018, 12: 242-253., articleTitle=One-vector system for multiplexed CRISPR/Cas9 against hepatitis B virus cccDNA utilizing high-capacity adenoviral vectors, refAbstract=null), Reference(id=1239213767549047351, tenantId=1146029695717560320, journalId=1205117082300743687, articleId=1239174990747202011, doi=null, pmid=null, pmcid=null, year=2019, volume=25, issue=2, pageStart=249, pageEnd=254, url=null, language=null, rfNumber=[25], rfOrder=24, authorNames=CHARLESWORTH CT, DESHPANDE PS, DEVER DP, journalName=Nat Med, refType=null, unstructuredReference=CHARLESWORTH CT, DESHPANDE PS, DEVER DP, et al.Identification of preexisting adaptive immunity to Cas9 proteins in humans[J]. Nat Med, 2019, 25（2）: 249-254., articleTitle=Identification of preexisting adaptive immunity to Cas9 proteins in humans, refAbstract=null), Reference(id=1239213767624544823, tenantId=1146029695717560320, journalId=1205117082300743687, articleId=1239174990747202011, doi=null, pmid=null, pmcid=null, year=2020, volume=28, issue=6, pageStart=1432, pageEnd=1441, url=null, language=null, rfNumber=[26], rfOrder=25, authorNames=LI A, TANNER MR, LEE CM, journalName=Mol Ther, refType=null, unstructuredReference=LI A, TANNER MR, LEE CM, et al. AAV-CRISPR gene editing is negated by pre-existing immunity to Cas9[J]. Mol Ther, 2020,28（6）: 1432-1441., articleTitle=AAV-CRISPR gene editing is negated by pre-existing immunity to Cas9, refAbstract=null), Reference(id=1239213767716819513, tenantId=1146029695717560320, journalId=1205117082300743687, articleId=1239174990747202011, doi=null, pmid=null, pmcid=null, year=2020, volume=11, issue=10, pageStart=1113, pageEnd=null, url=null, language=null, rfNumber=[27], rfOrder=26, authorNames=ATES I, RATHBONE T, STUART C, journalName=Genes (Basel), refType=null, unstructuredReference=ATES I, RATHBONE T, STUART C, et al. Delivery approaches for therapeutic genome editing and challenges[J]. Genes (Basel),2020, 11（10）: 1113., articleTitle=Delivery approaches for therapeutic genome editing and challenges, refAbstract=null), Reference(id=1239213767800705596, tenantId=1146029695717560320, journalId=1205117082300743687, articleId=1239174990747202011, doi=null, pmid=null, pmcid=null, year=2016, volume=16, issue=11, pageStart=2846, pageEnd=2854, url=null, language=null, rfNumber=[28], rfOrder=27, authorNames=MURPHY CM, XU Y, LI F, journalName=Cell Rep, refType=null, unstructuredReference=MURPHY CM, XU Y, LI F, et al. Hepatitis B virus X protein promotes degradation of SMC5/6 to enhance HBV replication[J].Cell Rep, 2016, 16（11）: 2846-2854., articleTitle=Hepatitis B virus X protein promotes degradation of SMC5/6 to enhance HBV replication, refAbstract=null), Reference(id=1239213767884591678, tenantId=1146029695717560320, journalId=1205117082300743687, articleId=1239174990747202011, doi=null, pmid=null, pmcid=null, year=2021, volume=74, issue=3, pageStart=522, pageEnd=534, url=null, language=null, rfNumber=[29], rfOrder=28, authorNames=CHENG ST, HU JL, REN JH, journalName=J Hepatol, refType=null, unstructuredReference=CHENG ST, HU JL, REN JH, et al. Dicoumarol, an NQO1 inhibitor,blocks cccDNA transcription by promoting degradation of HBx[J].J Hepatol, 2021, 74（3）: 522-534., articleTitle=Dicoumarol, an NQO1 inhibitor,blocks cccDNA transcription by promoting degradation of HBx, refAbstract=null), Reference(id=1239213767985254977, tenantId=1146029695717560320, journalId=1205117082300743687, articleId=1239174990747202011, doi=null, pmid=null, pmcid=null, year=2017, volume=91, issue=16, pageStart=e00340, pageEnd=17, url=null, language=null, rfNumber=[30], rfOrder=29, authorNames=LIU N, ZHANG J, YANG X, journalName=J Virol, refType=null, unstructuredReference=LIU N, ZHANG J, YANG X, et al. HDM2 promotes NEDDylation of hepatitis B virus HBx to enhance its stability and function[J]. J Virol, 2017, 91（16）: e00340-17., articleTitle=HDM2 promotes NEDDylation of hepatitis B virus HBx to enhance its stability and function, refAbstract=null), Reference(id=1239213768064946755, tenantId=1146029695717560320, journalId=1205117082300743687, articleId=1239174990747202011, doi=null, pmid=null, pmcid=null, year=2019, volume=69, issue=5, pageStart=1903, pageEnd=1915, url=null, language=null, rfNumber=[31], rfOrder=30, authorNames=SEKIBA K, OTSUKA M, OHNO M, journalName=Hepatology, refType=null, unstructuredReference=SEKIBA K, OTSUKA M, OHNO M, et al. Pevonedistat, a neuronal precursor cell-expressed developmentally down-regulated protein 8-activating enzyme inhibitor, is a potent inhibitor of hepatitis B virus[J]. Hepatology, 2019, 69（5）: 1903-1915., articleTitle=Pevonedistat, a neuronal precursor cell-expressed developmentally down-regulated protein 8-activating enzyme inhibitor, is a potent inhibitor of hepatitis B virus, refAbstract=null), Reference(id=1239213768140444229, tenantId=1146029695717560320, journalId=1205117082300743687, articleId=1239174990747202011, doi=null, pmid=null, pmcid=null, year=2019, volume=7, issue=2, pageStart=297, pageEnd=312, url=null, language=null, rfNumber=[32], rfOrder=31, authorNames=SEKIBA K, OTSUKA M, OHNO M, journalName=Cell Mol Gastroenterol Hepatol, refType=null, unstructuredReference=SEKIBA K, OTSUKA M, OHNO M, et al. Inhibition of HBV transcription from cccDNA with nitazoxanide by targeting the HBx-DDB1 interaction[J]. Cell Mol Gastroenterol Hepatol, 2019, 7（2）:297-312., articleTitle=Inhibition of HBV transcription from cccDNA with nitazoxanide by targeting the HBx-DDB1 interaction, refAbstract=null), Reference(id=1239213768220136008, tenantId=1146029695717560320, journalId=1205117082300743687, articleId=1239174990747202011, doi=null, pmid=null, pmcid=null, year=2019, volume=3, issue=6, pageStart=744, pageEnd=747, url=null, language=null, rfNumber=[33], rfOrder=32, authorNames=ROSSIGNOL JF, BRECHOT C, journalName=Hepatol Commun, refType=null, unstructuredReference=ROSSIGNOL JF, BRECHOT C. A pilot clinical trial of nitazoxanide in the treatment of chronic hepatitis B[J]. Hepatol Commun,2019, 3（6）: 744-747., articleTitle=A pilot clinical trial of nitazoxanide in the treatment of chronic hepatitis B, refAbstract=null), Reference(id=1239213768291439179, tenantId=1146029695717560320, journalId=1205117082300743687, articleId=1239174990747202011, doi=null, pmid=null, pmcid=null, year=2021, volume=191, issue=null, pageStart=null, pageEnd=null, url=null, language=null, rfNumber=[34], rfOrder=33, authorNames=LUO Y, CHENG J, HU Z, journalName=Antiviral Res, refType=null, unstructuredReference=LUO Y, CHENG J, HU Z, et al. Identification of hepatitis B virus core protein residues critical for capsid assembly, pgRNA encapsidation and resistance to capsid assembly modulators[J].Antiviral Res, 2021, 191: 105080., articleTitle=Identification of hepatitis B virus core protein residues critical for capsid assembly, pgRNA encapsidation and resistance to capsid assembly modulators, refAbstract=null), Reference(id=1239213768366936655, tenantId=1146029695717560320, journalId=1205117082300743687, articleId=1239174990747202011, doi=null, pmid=null, pmcid=null, year=2020, volume=182, issue=null, pageStart=null, pageEnd=null, url=null, language=null, rfNumber=[35], rfOrder=34, authorNames=VISWANATHAN U, MANI N, HU Z, journalName=Antiviral Res, refType=null, unstructuredReference=VISWANATHAN U, MANI N, HU Z, et al. Targeting the multifunctional HBV core protein as a potential cure for chronic hepatitis B[J]. Antiviral Res, 2020, 182: 104917., articleTitle=Targeting the multifunctional HBV core protein as a potential cure for chronic hepatitis B, refAbstract=null), Reference(id=1239213768467599955, tenantId=1146029695717560320, journalId=1205117082300743687, articleId=1239174990747202011, doi=null, pmid=null, pmcid=null, year=2019, volume=156, issue=5, pageStart=1392, pageEnd=1403, url=null, language=null, rfNumber=[36], rfOrder=35, authorNames=YUEN MF, GANE EJ, KIM DJ, journalName=Gastroenterology, refType=null, unstructuredReference=YUEN MF, GANE EJ, KIM DJ, et al. Antiviral activity, safety,and pharmacokinetics of capsid assembly modulator NVR3-778 in patients with chronic HBV infection[J]. Gastroenterology, 2019,156（5）: 1392-1403., articleTitle=Antiviral activity, safety,and pharmacokinetics of capsid assembly modulator NVR3-778 in patients with chronic HBV infection, refAbstract=null), Reference(id=1239213768547291733, tenantId=1146029695717560320, journalId=1205117082300743687, articleId=1239174990747202011, doi=null, pmid=null, pmcid=null, year=2020, volume=159, issue=2, pageStart=521, pageEnd=533, url=null, language=null, rfNumber=[37], rfOrder=36, authorNames=ZOULIM F, LENZ O, VANDENBOSSCHE JJ, journalName=Gastroenterology, refType=null, unstructuredReference=ZOULIM F, LENZ O, VANDENBOSSCHE JJ, et al. JNJ-56136379,an HBV capsid assembly modulator, is well-tolerated and has antiviral activity in a phase 1 study of patients with chronic infection[J]. Gastroenterology, 2020, 159（2）: 521-533., articleTitle=JNJ-56136379,an HBV capsid assembly modulator, is well-tolerated and has antiviral activity in a phase 1 study of patients with chronic infection, refAbstract=null), Reference(id=1239213768643760727, tenantId=1146029695717560320, journalId=1205117082300743687, articleId=1239174990747202011, doi=null, pmid=null, pmcid=null, year=2021, volume=6, issue=9, pageStart=723, pageEnd=732, url=null, language=null, rfNumber=[38], rfOrder=37, authorNames=YUEN MF, ZHOU X, GANE E, journalName=Lancet Gastroenterol Hepatol, refType=null, unstructuredReference=YUEN MF, ZHOU X, GANE E, et al. Safety, pharmacokinetics, and antiviral activity of RO7049389, a core protein allosteric modulator,in patients with chronic hepatitis B virus infection: a multicentre,randomised, placebo-controlled, phase 1 trial[J]. Lancet Gastroenterol Hepatol, 2021, 6（9）: 723-732., articleTitle=Safety, pharmacokinetics, and antiviral activity of RO7049389, a core protein allosteric modulator,in patients with chronic hepatitis B virus infection: a multicentre,randomised, placebo-controlled, phase 1 trial, refAbstract=null), Reference(id=1239213768752812631, tenantId=1146029695717560320, journalId=1205117082300743687, articleId=1239174990747202011, doi=null, pmid=null, pmcid=null, year=2019, volume=64, issue=1, pageStart=e01686, pageEnd=19, url=null, language=null, rfNumber=[39], rfOrder=38, authorNames=ZHAO N, JIA B, ZHAO H, journalName=Antimicrob Agents Chemother, refType=null, unstructuredReference=ZHAO N, JIA B, ZHAO H, et al. A first-in-human trial of GLS4,a novel inhibitor of hepatitis B virus capsid assembly, following single- and multiple-ascending-oral-dose studies with or without ritonavir in healthy adult volunteers[J]. Antimicrob Agents Chemother, 2019, 64（1）: e01686-19., articleTitle=A first-in-human trial of GLS4,a novel inhibitor of hepatitis B virus capsid assembly, following single- and multiple-ascending-oral-dose studies with or without ritonavir in healthy adult volunteers, refAbstract=null), Reference(id=1239213768840893019, tenantId=1146029695717560320, journalId=1205117082300743687, articleId=1239174990747202011, doi=null, pmid=null, pmcid=null, year=2022, volume=6, issue=9, pageStart=2731, pageEnd=2744, url=null, language=null, rfNumber=[40], rfOrder=39, authorNames=REN W, WANG X, YANG M, journalName=Blood Adv, refType=null, unstructuredReference=REN W, WANG X, YANG M, et al. Distinct clinical and genetic features of hepatitis B virus-associated follicular lymphoma in Chinese patients[J]. Blood Adv, 2022, 6（9）: 2731-2744., articleTitle=Distinct clinical and genetic features of hepatitis B virus-associated follicular lymphoma in Chinese patients, refAbstract=null), Reference(id=1239213768945750620, tenantId=1146029695717560320, journalId=1205117082300743687, articleId=1239174990747202011, doi=10.1038/s41575-018-0060-3, pmid=null, pmcid=null, year=2018, volume=null, issue=null, pageStart=null, pageEnd=null, url=null, language=null, rfNumber=[41], rfOrder=40, authorNames=ZOULIM F, LEVRERO M, TESTONI B, journalName=Nat Rev Gastroenterol Hepatol, refType=null, unstructuredReference=ZOULIM F, LEVRERO M, TESTONI B. Hepatitis B[J]. Nat Rev Gastroenterol Hepatol, 2018., articleTitle=Hepatitis B, refAbstract=null), Reference(id=1239213769042219614, tenantId=1146029695717560320, journalId=1205117082300743687, articleId=1239174990747202011, doi=null, pmid=null, pmcid=null, year=2022, volume=132, issue=18, pageStart=null, pageEnd=null, url=null, language=null, rfNumber=[42], rfOrder=41, authorNames=GRUDDA T, HWANG HS, TADDESE M, journalName=J Clin Invest, refType=null, unstructuredReference=GRUDDA T, HWANG HS, TADDESE M, et al. Integrated hepatitis B virus DNA maintains surface antigen production during antiviral treatment[J]. J Clin Invest, 2022, 132（18）: e161818., articleTitle=Integrated hepatitis B virus DNA maintains surface antigen production during antiviral treatment, refAbstract=null), Reference(id=1239213769130300000, tenantId=1146029695717560320, journalId=1205117082300743687, articleId=1239174990747202011, doi=null, pmid=null, pmcid=null, year=2021, volume=22, issue=17, pageStart=9366, pageEnd=null, url=null, language=null, rfNumber=[43], rfOrder=42, authorNames=LUBKOWSKA A, PLUTA W, STRONSKA A, journalName=Int J Mol Sci, refType=null, unstructuredReference=LUBKOWSKA A, PLUTA W, STRONSKA A, et al. Role of heat shock proteins（HSP70 and HSP90）in viral infection[J]. Int J Mol Sci, 2021, 22（17）: 9366., articleTitle=Role of heat shock proteins（HSP70 and HSP90）in viral infection, refAbstract=null), Reference(id=1239213769235157603, tenantId=1146029695717560320, journalId=1205117082300743687, articleId=1239174990747202011, doi=null, pmid=null, pmcid=null, year=2019, volume=100, issue=8, pageStart=1241, pageEnd=1252, url=null, language=null, rfNumber=[44], rfOrder=43, authorNames=QIAN L, FAN H, JU Y, journalName=J Gen Virol, refType=null, unstructuredReference=QIAN L, FAN H, JU Y, et al. A peptide-based inhibitor of gp96 suppresses HBsAg expression and HBV replication by upregulation of p53[J]. J Gen Virol, 2019, 100（8）: 1241-1252., articleTitle=A peptide-based inhibitor of gp96 suppresses HBsAg expression and HBV replication by upregulation of p53, refAbstract=null), Reference(id=1239213769331626598, tenantId=1146029695717560320, journalId=1205117082300743687, articleId=1239174990747202011, doi=null, pmid=null, pmcid=null, year=2023, volume=25, issue=6S, pageStart=12, pageEnd=null, url=null, language=null, rfNumber=[45], rfOrder=44, authorNames=DU S, WAN X, WU X, journalName=Cytotherapy, refType=null, unstructuredReference=DU S, WAN X, WU X, et al. Infected hepatocyte clearance and sustained tumor regression by first-in-class HBS-Ag-specific TCR-T（SCG101）therapy for HBV-related HCC[J]. Cytotherapy, 2023,25（6S）: 12., articleTitle=Infected hepatocyte clearance and sustained tumor regression by first-in-class HBS-Ag-specific TCR-T（SCG101）therapy for HBV-related HCC, refAbstract=null), Reference(id=1239213769419706984, tenantId=1146029695717560320, journalId=1205117082300743687, articleId=1239174990747202011, doi=null, pmid=null, pmcid=null, year=2023, volume=79, issue=5, pageStart=1139, pageEnd=1149, url=null, language=null, rfNumber=[46], rfOrder=45, authorNames=GANE E, KIM W, LIM TH, journalName=J Hepatol, refType=null, unstructuredReference=GANE E, KIM W, LIM TH, et al. First-in-human randomized study of RNAi therapeutic RG6346 for chronic hepatitis B virus infection[J]. J Hepatol, 2023, 79（5）: 1139-1149., articleTitle=First-in-human randomized study of RNAi therapeutic RG6346 for chronic hepatitis B virus infection, refAbstract=null), Reference(id=1239213769503593067, tenantId=1146029695717560320, journalId=1205117082300743687, articleId=1239174990747202011, doi=null, pmid=null, pmcid=null, year=2023, volume=92, issue=null, pageStart=null, pageEnd=null, url=null, language=null, rfNumber=[47], rfOrder=46, authorNames=KUMAR S, FRY LE, WANG JH, journalName=Prog Retin Eye Res, refType=null, unstructuredReference=KUMAR S, FRY LE, WANG JH, et al. RNA-targeting strategies as a platform for ocular gene therapy[J]. Prog Retin Eye Res, 2023,92 : 101110., articleTitle=RNA-targeting strategies as a platform for ocular gene therapy, refAbstract=null), Reference(id=1239213769595867759, tenantId=1146029695717560320, journalId=1205117082300743687, articleId=1239174990747202011, doi=null, pmid=null, pmcid=null, year=2022, volume=28, issue=3, pageStart=408, pageEnd=424, url=null, language=null, rfNumber=[48], rfOrder=47, authorNames=HUI RW, MAK LY, SETO WK, journalName=Clin Mol Hepatol, refType=null, unstructuredReference=HUI RW, MAK LY, SETO WK, et al. RNA interference as a novel treatment strategy for chronic hepatitis B infection[J]. Clin Mol Hepatol, 2022, 28（3）: 408-424., articleTitle=RNA interference as a novel treatment strategy for chronic hepatitis B infection, refAbstract=null), Reference(id=1239213769675559537, tenantId=1146029695717560320, journalId=1205117082300743687, articleId=1239174990747202011, doi=null, pmid=null, pmcid=null, year=2022, volume=77, issue=5, pageStart=1287, pageEnd=1298, url=null, language=null, rfNumber=[49], rfOrder=48, authorNames=YUEN MF, LOCARNINI S, LIM TH, journalName=J Hepatol, refType=null, unstructuredReference=YUEN MF, LOCARNINI S, LIM TH, et al. Combination treatments including the small-interfering RNA JNJ-3989 induce rapid and sometimes prolonged viral responses in patients with CHB[J]. J Hepatol, 2022, 77（5）: 1287-1298., articleTitle=Combination treatments including the small-interfering RNA JNJ-3989 induce rapid and sometimes prolonged viral responses in patients with CHB, refAbstract=null), Reference(id=1239213769776222835, tenantId=1146029695717560320, journalId=1205117082300743687, articleId=1239174990747202011, doi=null, pmid=null, pmcid=null, year=2021, volume=75, issue=Suppl 2, pageStart=S738, pageEnd=S739, url=null, language=null, rfNumber=[50], rfOrder=49, authorNames=YUEN RMF, LIM YS, CLOUTIER D, journalName=J Hepatol, refType=null, unstructuredReference=YUEN RMF, LIM YS, CLOUTIER D, et al. Preliminary on-treatment data from a phase 2 study evaluating VIR-2218 in combination with pegylated interferon alfa-2a in participants with chronic hepatitis B infection[J]. J Hepatol, 2021, 75（Suppl 2）:S738-S739., articleTitle=Preliminary on-treatment data from a phase 2 study evaluating VIR-2218 in combination with pegylated interferon alfa-2a in participants with chronic hepatitis B infection, refAbstract=null), Reference(id=1239213769860108918, tenantId=1146029695717560320, journalId=1205117082300743687, articleId=1239174990747202011, doi=null, pmid=null, pmcid=null, year=2022, volume=387, issue=21, pageStart=1957, pageEnd=1968, url=null, language=null, rfNumber=[51], rfOrder=50, authorNames=YUEN MF, LIM SG, PLESNIAK R, journalName=N Engl J Med, refType=null, unstructuredReference=YUEN MF, LIM SG, PLESNIAK R, et al. Efficacy and safety of bepirovirsen in chronic hepatitis B infection[J]. N Engl J Med,2022, 387（21）: 1957-1968., articleTitle=Efficacy and safety of bepirovirsen in chronic hepatitis B infection, refAbstract=null), Reference(id=1239213769943995001, tenantId=1146029695717560320, journalId=1205117082300743687, articleId=1239174990747202011, doi=null, pmid=null, pmcid=null, year=2018, volume=68, issue=3, pageStart=412, pageEnd=420, url=null, language=null, rfNumber=[52], rfOrder=51, authorNames=MUELLER H, WILDUM S, LUANGSAY S, journalName=J Hepatol, refType=null, unstructuredReference=MUELLER H, WILDUM S, LUANGSAY S, et al. A novel orally available small molecule that inhibits hepatitis B virus expression[J]. 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病毒通过钠离子-牛磺胆酸共转运多肽受体进入肝细胞，随后HBV基因组进入宿主细胞核中，通过DNA修复机制形成共价闭合环状DNA（cccDNA）。在调节蛋白的作用下，cccDNA作为转录模版形成前基因组RNA（pgRNA）和信使RNA（mRNA），随后pgRNA被选择性包装到核衣壳里，逆转录产生核心蛋白和聚合酶，同时作为模板逆转录产生新的松弛环状DNA（rcDNA），最后进行病毒包膜组装并分泌病毒颗粒

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靶向治疗在慢性乙型肝炎病毒感染中的研究进展
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王聃 1 , 张乘龙 2 , 唐静 1 , 邓琴 1 , 杨磊 3 , 孙强 4 , 王艳 1
中国新药与临床杂志 | 综述 2024,43(4): 241-246
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中国新药与临床杂志 | 综述 2024, 43(4): 241-246
靶向治疗在慢性乙型肝炎病毒感染中的研究进展
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王聃1 , 张乘龙2, 唐静1 , 邓琴1, 杨磊3, 孙强4, 王艳1
作者信息
  • 1.资阳市第一人民医院 感染科，四川 资阳　641300
  • 2.遂宁市中心医院 急诊科，四川 遂宁　629000
  • 3.简阳市人民医院 药学部，四川 简阳　641400
  • 4.四川省人民医院 药学部，四川 成都　610000

    • 王聃，女，医师，硕士，主要从事风湿免疫及感染的治疗研究，E-mail:

通讯作者:

唐静，E-mail:
Advancements in targeted therapy for chronic hepatitis B virus infection
Dan WANG1 , Cheng-long ZHANG2, Jing TANG1 , Qin DENG1, Lei YANG3, Qiang SUN4, Yan WANG1
Affiliations
  • 1.Department of Infection, First People’s Hospital of Ziyang, Ziyang SICHUAN 641300, China
  • 2.Department of Emergency,Suining Central Hospital, Suining SICHUAN 629000, China
  • 3.Department of Pharmacy, Jianyang People’s Hospital,Jianyang SICHUAN 641400, China
  • 4.Department of Pharmacy, Sichuan Provincial People’s Hospital, Chengdu SICHUAN 610000, China
出版时间: 2024-04-25 doi: 10.14109/j.cnki.xyylc.2024.04.01
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摘要
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目前临床治疗慢性乙型肝炎病毒（HBV）感染已取得一定进展，但现有的一线药物尚不能完全清除HBV共价闭合环状DNA从而彻底清除HBV。靶向治疗能特异性地结合靶点部位，从而阻断病毒入侵、病毒转录和蛋白翻译等，实现精准治疗。本文整理总结HBV生命周期不同阶段的靶点，从靶向病毒进入、靶向共价闭合环状DNA、靶向核心蛋白、靶向乙型肝炎表面抗原释放、靶向病毒转录等角度进行综述，以期为抗HBV感染的药物研发提供思路。

乙型肝炎病毒  /  分子靶向治疗  /  慢性乙型肝炎  /  药物研发

Although some progress had been made in the treatment of chronic hepatitis B virus（HBV）infection,current first-line drugs failed to completely eliminate the covalently closed circular DNA（cccDNA）of HBV so as to completely eliminate HBV. Targeted therapy can specifically bind to the target sites, thereby blocking virus invasion, virus transcription, and protein translation, achieving precise treatment. Therefore, this article summarized and reviewed the targets at different stages of the HBV life cycle from the perspectives of targeting virus entry, targeting cccDNA, targeting core protein, targeting hepatitis B surface antigen（HBsAg）release, and targeting viral transcription, with a view to providing ideas for drug development against HBV infection.

hepatitis B virus  /  molecular targeted therapy  /  chronic hepatitis B  /  drug development
王聃, 张乘龙, 唐静, 邓琴, 杨磊, 孙强, 王艳. 靶向治疗在慢性乙型肝炎病毒感染中的研究进展. 中国新药与临床杂志, 2024 , 43 (4) : 241 -246 . DOI: 10.14109/j.cnki.xyylc.2024.04.01
Dan WANG, Cheng-long ZHANG, Jing TANG, Qin DENG, Lei YANG, Qiang SUN, Yan WANG. Advancements in targeted therapy for chronic hepatitis B virus infection[J]. Chinese Journal of New Drugs and Clinical Remedies, 2024 , 43 (4) : 241 -246 . DOI: 10.14109/j.cnki.xyylc.2024.04.01
正文
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乙型肝炎病毒（hepatitis B virus，HBV）感染是世界范围内导致慢性肝病的主要原因之一，随着病毒在肝脏细胞中的持续复制，从而导致进行性肝纤维化、肝硬化，并显著增加肝癌的发生率[1，2]，有研究发现50%的肝癌患者是由HBV感染进行性造成[3]。据统计，世界上约2.57亿人感染HBV，每年约有100万人死于HBV相关的肝脏疾病或肝癌，其中我国每年约有30万人死于HBV感染所引起的肝脏相关疾病[4]。在过去20年里乙型肝炎（乙肝）疫苗的出现有效降低了HBV感染率，但携带者的数量仍然不可小觑。尽管抗病毒药物，例如干扰素、核苷类药物已被用于HBV感染患者的治疗，但由于HBV共价闭合环状DNA（covalently closed circular DNA, cccDNA）在肝脏细胞中持续存在，抗病毒药物无法将其清除[5]，因此缺乏对慢性HBV感染患者的根治药物。
目前，功能性治愈标准为持久性乙肝表面抗原（HBsAg）< 0.05 IU·mL-1且HBV-DNA低于检测值、有或没有乙肝表面抗体血清学转换，被认为是一个可能实现的目标[6]。然而，现有药物对乙肝e抗原（HBeAg）和HBsAg的清除率很低，往往长期服药治疗也很难达到功能性治愈的目的[7]。而靶向治疗药物能特异性地结合靶点部位，达到精准治疗的目的。本文对HBV生命周期不同阶段的靶点进行整理总结，主要从靶向病毒进入、靶向cccDNA、靶向核心蛋白、靶向HBsAg释放、靶向病毒转录等角度综述针对HBV存在的潜在靶向治疗策略（图1），以期为HBV感染的功能性治愈和完全治愈的药物研发提供思路。
病毒的生命周期
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HBV作为一种嗜肝DNA病毒，主要感染人体肝细胞从而引起肝脏疾病的发生发展[8]。HBV产生的感染性病毒颗粒（Dane颗粒）大小约为42 nm，病毒外壳由HBsAg和从感染细胞中提取的磷脂组成，病毒核心包括核衣壳，以及含有约240个HBV核心蛋白和部分双链HBV基因组[9]。
有研究[10-12]发现，HBV首先附着于细胞表面硫酸乙酰肝素蛋白聚糖，通过特异性结合肝细胞上钠离子-牛磺胆酸共转运多肽（Na+-taurocholate cotransporting polypeptide, NTCP）受体进入细胞后，病毒脱壳，HBV基因组进入宿主细胞核中，通过DNA修复机制，将残缺的双链病毒松弛环状DNA（relaxed circular DNA, rcDNA）进行修复，形成cccDNA。随后，在调节性HBV X蛋白（HBV X protein, HBx）的作用下，cccDNA作为转录模版形成前基因组RNA（pregenomic RNA, pgRNA）和信使RNA（messenger RNA, mRNA）。pgRNA被选择性包装到核衣壳里，逆转录产生核心蛋白和聚合酶，同时作为模板逆转录产生新的rcDNA，在多囊泡体（multivesicular bodies, MVBs）中进行病毒包膜组装，形成并分泌病毒颗粒，也可再循环到细胞核中参与cccDNA的扩增和（或）维持。此外，少数pgRNA逆转录成双链线性DNA（double-stranded linear DNA, dslDNA），整合到宿主DNA中，不具有复制能力，但可以翻译成S蛋白并以亚病毒颗粒（subviral particle, SVP）的形式分泌。
潜在靶向治疗策略
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1　靶向病毒进入
HBV感染依赖于病毒包膜糖蛋白L与宿主入侵受体NTCP之间的分子相互作用，靶向病毒入侵肝细胞可以在病毒生命周期的早期阶段阻止病毒感染，从而在源头上阻止HBV感染。近年来，随着HBV入侵肝细胞的机制以及NTCP蛋白结构的解析越来越清晰，给HBV进入抑制剂的研发带来了新希望。
通过化合物抑制HBV感染的实验，发现熊去氧胆酸聚合而成的二聚胆酸衍生物具有高效抑制NTCP的活性，并证实了胆酸二聚体具有高活性和高持续性抑制NTCP的功能[13]。bulevirtide是一种来源于HBV Pre-S1多肽的大分子药物，临床研究发现其可与NTCP受体特异性结合从而阻断HBV感染进入细胞。在一项多中心Ⅱ期临床试验中，分别给予HBeAg阴性的慢性乙肝患者口服恩替卡韦或皮下注射bulevirtide治疗后，bulevirtide组血清HBsAg水平显著降低，且该组不良事件发生率低[14]。此外，hepalatide同样能与NTCP受体特异性结合从而干扰HBV进入肝细胞。另一项正在进行的Ⅱ期临床试验，分别给予未接受治疗的慢性乙肝患者皮下注射不同剂量hepalatide联合聚乙二醇干扰素24周或者仅皮下注射聚乙二醇干扰素[15]。研究者在2023欧洲肝病学会年会中展示了该Ⅱ期临床试验的部分数据，联合治疗组HBV-DNA水平以hepalatide剂量依赖性的方式降低，并且安全性、耐受性良好。以上结果均提示靶向NTCP受体药物，可有效抑制HBV进入肝细胞，其在慢性乙肝患者的功能性治愈方面具有良好的应用潜力。
2　靶向cccDNA
cccDNA是由病毒释放的rcDNA进入宿主细胞核后在宿主因子和病毒蛋白的双重调控下修复形成，在病毒转录过程中起着关键作用，cccDNA在肝细胞核内的持续存在是HBV不能被治愈的主要原因之一[16，17]。因此，清除或功能性沉默cccDNA是实现HBV功能性治愈和完全治愈的关键策略。
有研究报道基因编辑技术可直接应用于靶向破坏cccDNA。锌指核酸酶、转录激活样效应因子核酸酶以及成簇规律性间隔短回文重复序列（CRISPR）核酸酶等在抑制cccDNA的形成和核内积累方面具有较大潜力[18-21]。多项研究[22-24]均显示CRISPR/Cas9可使Cas9核酸酶靶向cccDNA，在体内、体外实验中均可成功切割并灭活cccDNA。然而，目前将CRISPR/Cas9等基因编辑技术应用于临床实践仍面临一定挑战，例如，体内预先存在的适应性免疫反应、HBV基因组高异质性以及肝细胞递送缺乏特异性等[25-27]。HBx是一种由HBV编码的非结构小调控蛋白，在促进cccDNA转录过程中发挥重要作用[28]。CHENG等[29]发现双香豆素可通过靶向HBx从而抑制cccDNA的转录，为靶向HBx开发抗HBV药物奠定基础。另一方面，HBx复合物降解途径需要泛素样修饰因子NEDD8来激活[30]。SEKIBA等[31]研究发现pevonedistat作为NEDD8激活酶抑制剂，可抑制HBV转录，降低cccDNA和病毒蛋白质表达。此外，硝唑尼特（nitazoxanide）作为噻唑类抗寄生虫药被证明可有效抑制HBx，从而抑制HBV病毒转录、降低蛋白质表达[32]。一项临床研究发现硝唑尼特组89%的患者HBV-DNA水平降低至定量下线，33%的患者HBsAg转阴[33]。由此可见，靶向cccDNA以及cccDNA的形成途径对于治疗HBV感染具有重要作用。
3　靶向HBV核心蛋白（core protein, Cp）
HBV Cp是HBV核衣壳的组成部分，在调节病毒生命周期及宿主免疫反应中扮演重要角色，因此Cp逐渐成为抗HBV治疗的重要靶点之一。核心蛋白变构调节剂（core protein allosteric modulators, CpAMs）作为一种新型抗HBV药物，可与Cp二聚体界面之间的疏水袋结合，以增强二聚体之间的相互作用，从而干扰Cp组装[34]，抑制病毒发生发展。
根据Cp组装产物的结构与代谢，可将CpAMs分为两种类型：Ⅰ类CpAMs，可诱导出异常组装的核衣壳，如杂芳基二氢嘧啶；Ⅱ类CpAMs，可诱导出形态正常、不含病毒核酸的空核衣壳，如苯基丙烯酰胺或氨磺酰基苯甲酰胺[35]。药物NVR3-778和JNJ6379是目前在研的两种代表性Ⅱ类CpAMs，一项Ⅰ期临床试验发现，NVR3-778联合聚乙二醇干扰素治疗组具有抗HBV活性且耐受性良好，相较于单药治疗，两者联合应用可更大程度地降低患者血清中HBV-DNA及HBV-RNA水平[36]。此外，JNJ-6379在慢性乙肝患者中治疗效果显著，能降低患者HBV-DNA及HBV-RNA水平，并且具有良好的耐受性[37]。另一方面，作为Ⅰ类CpAMs的代表分子RO7049389[38]和GLS4[39]，在慢性乙肝患者的临床试验中也表现出了良好的治疗效果和安全性，但遗憾的是停药后病毒出现反弹，pgRNA水平恢复到了基线水平。因此，CpAMs常需与一种或多种药物联合应用，以避免单独应用导致的耐药性。这提示CpAMs有望成为慢性乙肝患者未来治疗方案的一部分，从而在更大程度上治疗HBV感染。
4　靶向HBsAg释放
HBsAg是慢性乙肝患者外周血中最常见的HBV蛋白，其蛋白浓度可高达105 IU·mL-1，在体内的长期刺激可引起T细胞耐受和衰竭[40]。HBV入侵肝细胞后，在宿主细胞中合成HBsAg的mRNA和蛋白质，由HBsAg组成的非感染性亚病毒粒子的数量远远超过成熟病毒粒子的数量[41]。然而，目前抗HBV药物对HBsAg mRNA转录和蛋白质表达影响较小。因此，只有少数接受干扰素α、核酸聚合物或其联合治疗的患者才能勉强清除血清中的HBsAg[42]。
研究发现热休克蛋白（HSPs）在HBV生命周期的多种宿主因素中起着关键作用，能调节病毒DNA复制、病毒蛋白表达和组装[43]。QIAN等[44]设计了一种含有反式转录激活物的蛋白转导域PTD-p37，在体内、体外实验中均能有效抑制HBsAg表达和病毒复制，并且发现PTD-p37对拉米夫定（lamivudine）耐药的HBV株仍具有抗病毒活性。T细胞受体细胞治疗在靶向治疗、个体化治疗中已取得重要进展。有研究报道，一款靶向HBsAg的T细胞受体药物SCG101具有显著的抗病毒活性，患者使用该药后血清HBsAg快速、持续地降低，疾病控制率达到66%[45]。此外，小干扰RNA（small interfering RNA, siRNA）药物ALG-125755、RNA干扰药物RG6346以及单克隆抗体KW-027等靶向HBsAg的药物，均在临床试验中取得了重要进展[46]，这给乙肝患者的功能性治愈以及临床治愈带来了希望。
5　靶向病毒转录
在HBV感染的肝细胞核内，病毒以cccDNA为复制模板进行转录，产生不同长度的病毒mRNA。编码蛋白质的mRNA在HBV感染的发生发展中起着重要作用，因此，抑制病毒转录已成为治疗HBV的有效策略。目前，靶向HBV-mRNA可通过RNA干扰以及反义寡核苷酸等途径实现[47]。
siRNA在特异性靶向治疗中已取得了显著的治疗效果，可通过靶向病毒转录的mRNA，对特定核酸序列进行降解从而阻止蛋白表达[48]。有研究发现siRNA药物JNJ-3989[49]和VIR-2218[50]可降低患者血清中HBsAg水平，并具有良好的耐受性。相较于单独给药，VIR-2218与聚乙二醇干扰素α联合应用可更大程度并且更快速地降低HBsAg水平[50]。此外，YUEN等[51]在临床试验中发现反义寡核苷酸GSK3228836能使9%~10%的慢性乙肝患者血清中HBsAg和HBV-DNA持续降低，提示该药物在乙肝患者的治疗中具有较大治疗作用。一些小分子药物也被用于抑制病毒RNAs。MUELLER等[52]研究发现，RG7834作为新型HBV基因表达小分子抑制剂，可通过特异性降解HBV-mRNA来抑制病毒蛋白表达，从而抑制病毒的发生发展过程。
总结与展望
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近年来，HBV感染的治疗主要依赖于抗病毒药物，如核苷酸类似物和干扰素。然而，传统的治疗方法存在一些局限性，无法完全清除病毒，导致持续感染和病毒复制。因此，靶向干扰病毒的进入、生命周期和复制过程等已成为治疗HBV感染的研究热点，如siRNA药物ALG-125755、RNA干扰药物RG6346以及单克隆抗体KW-027等均在临床研究中取得重要进展。
目前，HBV感染仍严重威胁人们的生命健康，随着HBV感染宿主细胞的机制、生命周期以及相关蛋白结构逐渐被证实，越来越多的靶点药物被开发应用于HBV感染的靶向治疗，这给许多慢性乙肝患者的功能性治愈带来了希望。然而，仍需更多临床研究进一步考察这些药物的安全性和有效性。随着对病毒和宿主细胞相互作用的深入研究，创新药物、靶向药物以及创新联合治疗策略将有望实现HBV感染的功能性治愈，并最终清除病毒，从而降低肝纤维化、肝硬化以及肝癌的发生率，为慢性乙肝患者带来福祉。
基金
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  • 四川省科技厅重点研发项目(2023YFS0110)
文献
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参考文献 引证文献
排序方式：
[1]
JENG WJ, PAPATHEODORIDIS GV, LOK ASF. Hepatitis B[J].Lancet, 2023, 401（10381）: 1039-1052.
[2]
BRODY H. Hepatitis B[J]. Nature, 2022, 603（7903）: S45.
[3]
DUSHEIKO G, AGARWAL K, MAINI MK. New approaches to chronic hepatitis B[J]. N Engl J Med, 2023, 388（1）: 55-69.
[4]
HSU YC, HUANG DQ, NGUYEN MH. Global burden of hepatitis B virus: current status, missed opportunities and a call for action[J]. Nat Rev Gastroenterol Hepatol, 2023, 20（8）: 524-537.
[5]
KRAMVIS A, CHANG KM, DANDRI M, et al. A roadmap for serum biomarkers for hepatitis B virus: current status and future outlook[J]. Nat Rev Gastroenterol Hepatol, 2022, 19（11）: 727-745.
[6]
LIM SG, BAUMERT TF, BONI C, et al. The scientific basis of combination therapy for chronic hepatitis B functional cure[J].Nat Rev Gastroenterol Hepatol, 2023, 20（4）: 238-253.
[7]
PHILLIPS S, JAGATIA R, CHOKSHI S. Novel therapeutic strategies for chronic hepatitis B[J]. Virulence, 2022, 13（1）:1111-1132.
[8]
JIANG Y, HAN Q, ZHAO H, et al. The mechanisms of HBV-induced hepatocellular carcinoma[J]. J Hepatocell Carcinoma,2021, 8 : 435-450.
[9]
XU R, HU P, LI Y, et al. Advances in HBV infection and replication systems in vitro[J]. Virol J, 2021, 18（1）: 105.
[10]
LEE HW, LEE JS, AHN SH. Hepatitis B virus cure: targets and future therapies[J]. Int J Mol Sci, 2020, 22（1）: 213.
[11]
NAGGIE S, LOK AS. New therapeutics for hepatitis B: the road to cure[J]. Annu Rev Med, 2021, 72: 93-105.
[12]
LIU W, YAO Q, SU X, et al. Molecular insights into Spindlin1-HBx interplay and its impact on HBV transcription from cccDNA minichromosome[J]. Nat Commun, 2023, 14（1）: 4663.
[13]
LIU Y, ZHANG L, YAN H, et al. Design of dimeric bile acid derivatives as potent and selective human NTCP inhibitors[J]. J Med Chem, 2021, 64（9）: 5973-6007.
[14]
WEDEMEYER H, SCHONEWEIS K, BOGOMOLOV PO, et al. Final results of a multicenter, open-label phase 2 clinical trial（MYR203）to assess safety and efficacy of myrcludex B in combination with PEG-interferon alpha 2a in patients with chronic HBV/HDV co-infection[J]. J Hepatol, 2019, 70（1）: e81.
[15]
Shanghai HEP Pharmaceutical Co., Ltd. A phase Ⅱ study of hepalatide in subjects with chronic hepatitis B[EB/OL].（2023-12-08）[2024-01-26]. https://classic.clinicaltrials.gov/ct2/show/NCT04426968.
[16]
TSUKUDA S, WATASHI K. HEPATITIS B virus biology and life cycle[J]. Antiviral Res, 2020, 182: 104925.
[17]
WANG L, ZHU Q, ZHANG JD, et al. Discovery of a first-in-class orally available HBV cccDNA inhibitor[J]. J Hepatol, 2023, 78（4）: 742-753.
[18]
LUO W, WANG J, XU D, et al. Engineered zinc-finger transcription factors inhibit the replication and transcription of HBV in vitro and in vivo[J]. Int J Mol Med, 2018, 41（4）: 2169-2176.
[19]
SMITH T, SINGH P, CHMIELEWSHI KO, et al. Improved specificity and safety of anti-hepatitis B virus TALENs using obligate heterodimeric FokI nuclease domains[J]. Viruses, 2021,13（7）: 1344.
[20]
WANG D, CHEN L, LI C, et al. CRISPR/Cas9 delivery by NIR-responsive biomimetic nanoparticles for targeted HBV therapy[J].J Nanobiotechnology, 2022, 20（1）: 27.
[21]
ELY A, MOYO B, ARBUTHNOT P. Progress with developing use of gene editing to cure chronic infection with hepatitis B virus[J].Mol Ther, 2016, 24（4）: 671-677.
[22]
SEEGER C, SOHN JA. Complete spectrum of CRISPR/Cas9-induced mutations on HBV cccDNA[J]. Mol Ther, 2016, 24（7）:1258-1266.
[23]
KOSTYUSHEV D, BREZGIN S, KOSTYUSHEVA A, et al.Orthologous CRISPR/Cas9 systems for specific and efficient degradation of covalently closed circular DNA of hepatitis B virus[J]. Cell Mol Life Sci, 2019, 76（9）: 1779-1794.
[24]
SCHIWON M, EHRKE SE, OSWALD A, et al. One-vector system for multiplexed CRISPR/Cas9 against hepatitis B virus cccDNA utilizing high-capacity adenoviral vectors[J]. Mol Ther Nucleic Acids, 2018, 12: 242-253.
[25]
CHARLESWORTH CT, DESHPANDE PS, DEVER DP, et al.Identification of preexisting adaptive immunity to Cas9 proteins in humans[J]. Nat Med, 2019, 25（2）: 249-254.
[26]
LI A, TANNER MR, LEE CM, et al. AAV-CRISPR gene editing is negated by pre-existing immunity to Cas9[J]. Mol Ther, 2020,28（6）: 1432-1441.
[27]
ATES I, RATHBONE T, STUART C, et al. Delivery approaches for therapeutic genome editing and challenges[J]. Genes (Basel),2020, 11（10）: 1113.
[28]
MURPHY CM, XU Y, LI F, et al. Hepatitis B virus X protein promotes degradation of SMC5/6 to enhance HBV replication[J].Cell Rep, 2016, 16（11）: 2846-2854.
[29]
CHENG ST, HU JL, REN JH, et al. Dicoumarol, an NQO1 inhibitor,blocks cccDNA transcription by promoting degradation of HBx[J].J Hepatol, 2021, 74（3）: 522-534.
[30]
LIU N, ZHANG J, YANG X, et al. HDM2 promotes NEDDylation of hepatitis B virus HBx to enhance its stability and function[J]. J Virol, 2017, 91（16）: e00340-17.
[31]
SEKIBA K, OTSUKA M, OHNO M, et al. Pevonedistat, a neuronal precursor cell-expressed developmentally down-regulated protein 8-activating enzyme inhibitor, is a potent inhibitor of hepatitis B virus[J]. Hepatology, 2019, 69（5）: 1903-1915.
[32]
SEKIBA K, OTSUKA M, OHNO M, et al. Inhibition of HBV transcription from cccDNA with nitazoxanide by targeting the HBx-DDB1 interaction[J]. Cell Mol Gastroenterol Hepatol, 2019, 7（2）:297-312.
[33]
ROSSIGNOL JF, BRECHOT C. A pilot clinical trial of nitazoxanide in the treatment of chronic hepatitis B[J]. Hepatol Commun,2019, 3（6）: 744-747.
[34]
LUO Y, CHENG J, HU Z, et al. Identification of hepatitis B virus core protein residues critical for capsid assembly, pgRNA encapsidation and resistance to capsid assembly modulators[J].Antiviral Res, 2021, 191: 105080.
[35]
VISWANATHAN U, MANI N, HU Z, et al. Targeting the multifunctional HBV core protein as a potential cure for chronic hepatitis B[J]. Antiviral Res, 2020, 182: 104917.
[36]
YUEN MF, GANE EJ, KIM DJ, et al. Antiviral activity, safety,and pharmacokinetics of capsid assembly modulator NVR3-778 in patients with chronic HBV infection[J]. Gastroenterology, 2019,156（5）: 1392-1403.
[37]
ZOULIM F, LENZ O, VANDENBOSSCHE JJ, et al. JNJ-56136379,an HBV capsid assembly modulator, is well-tolerated and has antiviral activity in a phase 1 study of patients with chronic infection[J]. Gastroenterology, 2020, 159（2）: 521-533.
[38]
YUEN MF, ZHOU X, GANE E, et al. Safety, pharmacokinetics, and antiviral activity of RO7049389, a core protein allosteric modulator,in patients with chronic hepatitis B virus infection: a multicentre,randomised, placebo-controlled, phase 1 trial[J]. Lancet Gastroenterol Hepatol, 2021, 6（9）: 723-732.
[39]
ZHAO N, JIA B, ZHAO H, et al. A first-in-human trial of GLS4,a novel inhibitor of hepatitis B virus capsid assembly, following single- and multiple-ascending-oral-dose studies with or without ritonavir in healthy adult volunteers[J]. Antimicrob Agents Chemother, 2019, 64（1）: e01686-19.
[40]
REN W, WANG X, YANG M, et al. Distinct clinical and genetic features of hepatitis B virus-associated follicular lymphoma in Chinese patients[J]. Blood Adv, 2022, 6（9）: 2731-2744.
[41]
ZOULIM F, LEVRERO M, TESTONI B. Hepatitis B[J]. Nat Rev Gastroenterol Hepatol, 2018.
[42]
GRUDDA T, HWANG HS, TADDESE M, et al. Integrated hepatitis B virus DNA maintains surface antigen production during antiviral treatment[J]. J Clin Invest, 2022, 132（18）: e161818.
[43]
LUBKOWSKA A, PLUTA W, STRONSKA A, et al. Role of heat shock proteins（HSP70 and HSP90）in viral infection[J]. Int J Mol Sci, 2021, 22（17）: 9366.
[44]
QIAN L, FAN H, JU Y, et al. A peptide-based inhibitor of gp96 suppresses HBsAg expression and HBV replication by upregulation of p53[J]. J Gen Virol, 2019, 100（8）: 1241-1252.
[45]
DU S, WAN X, WU X, et al. Infected hepatocyte clearance and sustained tumor regression by first-in-class HBS-Ag-specific TCR-T（SCG101）therapy for HBV-related HCC[J]. Cytotherapy, 2023,25（6S）: 12.
[46]
GANE E, KIM W, LIM TH, et al. First-in-human randomized study of RNAi therapeutic RG6346 for chronic hepatitis B virus infection[J]. J Hepatol, 2023, 79（5）: 1139-1149.
[47]
KUMAR S, FRY LE, WANG JH, et al. RNA-targeting strategies as a platform for ocular gene therapy[J]. Prog Retin Eye Res, 2023,92 : 101110.
[48]
HUI RW, MAK LY, SETO WK, et al. RNA interference as a novel treatment strategy for chronic hepatitis B infection[J]. Clin Mol Hepatol, 2022, 28（3）: 408-424.
[49]
YUEN MF, LOCARNINI S, LIM TH, et al. Combination treatments including the small-interfering RNA JNJ-3989 induce rapid and sometimes prolonged viral responses in patients with CHB[J]. J Hepatol, 2022, 77（5）: 1287-1298.
[50]
YUEN RMF, LIM YS, CLOUTIER D, et al. Preliminary on-treatment data from a phase 2 study evaluating VIR-2218 in combination with pegylated interferon alfa-2a in participants with chronic hepatitis B infection[J]. J Hepatol, 2021, 75（Suppl 2）:S738-S739.
[51]
YUEN MF, LIM SG, PLESNIAK R, et al. Efficacy and safety of bepirovirsen in chronic hepatitis B infection[J]. N Engl J Med,2022, 387（21）: 1957-1968.
[52]
MUELLER H, WILDUM S, LUANGSAY S, et al. A novel orally available small molecule that inhibits hepatitis B virus expression[J]. J Hepatol, 2018, 68（3）: 412-420.
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doi: 10.14109/j.cnki.xyylc.2024.04.01
  • 接收时间：2023-09-19
  • 首发时间：2026-03-13
  • 出版时间：2024-04-25
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  • 收稿日期：2023-09-19
  • 录用日期：2024-02-02
基金
四川省科技厅重点研发项目(2023YFS0110)
作者信息
    1.资阳市第一人民医院 感染科，四川 资阳　641300
    2.遂宁市中心医院 急诊科，四川 遂宁　629000
    3.简阳市人民医院 药学部，四川 简阳　641400
    4.四川省人民医院 药学部，四川 成都　610000

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species		 占总种数比例
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鹅膏菌科Amanitaceae 2 11 5.26 鹅膏菌属 Amanita 10 4.78
小菇科 Mycenaceae 2 12 5.74 丝盖伞属 Inocybe 5 2.39
多孔菌科 Polyporaceae 8 14 6.70 蜡蘑属 Laccaria 5 2.39
红菇科 Russulaceae 3 23 11.00 小皮伞属 Marasmius 6 2.87
小菇属 Mycena 11 5.26
光柄菇属 Pluteus 5 2.39
红菇属 Russula 17 8.13
栓菌属 Trametes 5 2.39
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