中文English
ISSN 1001-5256 (Print)
ISSN 2097-3497 (Online)
CN 22-1108/R

留言板

尊敬的读者、作者、审稿人, 关于本刊的投稿、审稿、编辑和出版的任何问题, 您可以本页添加留言。我们将尽快给您答复。谢谢您的支持!

姓名
邮箱
手机号码
标题
留言内容
验证码

抗HBV药物的研究进展

蔡梦芝 秦刚

引用本文:
Citation:

抗HBV药物的研究进展

DOI: 10.3969/j.issn.1001-5256.2019.10.037
基金项目: 

江苏省重点病种规范化诊疗项目(BE2015655); 南通市市级临床医学中心项目(HS2016002); 

详细信息
  • 中图分类号: R512.62

Research advances in anti-hepatitis B virus drugs

Research funding: 

 

  • 摘要: HBV感染严重危害全球公众健康,全球约有20亿人感染过HBV。HBV感染可导致慢性肝炎、肝硬化、肝衰竭甚至肝癌。目前,我国已批准可用于慢性乙型肝炎治疗的药物有核苷(酸)类似物和干扰素两大类。长期应用核苷类似物安全性和耐受性良好,且可以有效抑制病毒复制并降低肝脏相关并发症的发生风险,但疗程长且不确定,存在耐药风险及停药后易复发等问题。干扰素类药物副作用较大,且血清学转换及治愈率有限。因此,研发针对HBV不同靶点的新型抗病毒药物对于治疗慢性乙型肝炎至关重要。主要归纳了针对不同靶点的抗HBV药物的研究进展,旨在为临床及相关科研工作提供参考。

     

  • [1] SETO WK,LO YR,PAWLOTSKY JM,et al. Chronic hepatitis B virus infection[J]. Lancet,2018,392(10161):2313-2324.
    [2] SORIANO V,YOUNG B,REAU N. Report from the international conference on viral hepatitis-2017[J]. AIDS Rev,2018,20(1):58-70.
    [3] HOU JL,WANG GQ,WANG FS,et al. Guideline of prevention and treatment for chronic hepatitis B(2015 update)[J]. J Clin Transl Hepatol,2017,5(4):297-318.
    [4] LI Y,ZHAN J,WANG ZF. Prognostic factors for patients with hepatitis B virus-related acute-on-chronic liver failure[J].J Clin Hepatol,2017,33(3):497-501.(in Chinese)李蓥,詹婧,王中峰. HBV相关慢加急性肝衰竭患者预后危险因素分析[J].临床肝胆病杂志,2017,33(3):497-501.
    [5] WANG XL,SHAO JG,ZHU YC,et al. Epidemiological analysis of acute-on-chronic liver failure in Nantong,Jiangsu Province,2005-2014[J]. Chin J Infect Dis,2016,34(9):530-535.(in Chinese)汪徐林,邵建国,朱永昌,等.江苏省南通地区2005年至2014年慢加急性肝功能衰竭流行病学调查分析[J].中华传染病杂志,2016,34(9):530-535.
    [6] YAN H,ZHONG G,XU G,et al. Sodium taurocholate cotransporting polypeptide is a functional receptor for human hepatitis B and D virus[J]. Elife,2012,1:e00049.
    [7] GEHRING A,PROTZER U. Targeting innate and adaptive immune responses to cure chronic HBV infection[J]. Gastroenterology,2019,156(2):325-337.
    [8] LIU H. The curative effect of two drugs in the treatment of HBe Ag positive chronic hepatitis B and the forecast factors analysis of the serological conversion[J]. J Clin Exp Med,2017,16(9):883-886.(in Chinese)刘海.两种药物治疗HBe Ag阳性慢性乙型肝炎的疗效及血清学转换预测因素分析[J].临床和实验医学杂志,2017,16(9):883-886.
    [9] SLIJEPCEVIC D,KAUFMAN C,WICHERS CG,et al. Impaired uptake of conjugated bile acids and hepatitis b virus pres1-binding in na(+)-taurocholate cotransporting polypeptide knockout mice[J]. Hepatology,2015,62(1):207-219.
    [10] 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]. J Hepatol,2016,65(3):483-489.
    [11] BOGOMOLOV P,ALEXANDROV A,VORONKOVA N,et al.Treatment of chronic hepatitis D with the entry inhibitor myrcludex B:First results of a phase Ib/IIa study[J]. J Hepatol,2016,65(3):490-498.
    [12] LAI CL,AHN SH,LEE KS,et al. Phase IIb multicentred randomised trial of besifovir(LB80380)versus entecavir in Asian patients with chronic hepatitis B[J]. Gut,2014,63(6):996-1004.
    [13] LIANG TJ,BLOCK TM,MCMAHON BJ,et al. Present and future therapies of hepatitis B:From discovery to cure[J]. Hepatology,2015,62(6):1893-1908.
    [14] ZHANG PH,LIU F,GUO F,et al. Characterization of novel hepadnaviral RNA species accumulated in hepatoma cells treated with viral DNA polymerase inhibitors[J]. Antiviral Res,2016,131:40-48.
    [15] SCHLUEP T,LICKLITER J,HAMILTON J,et al. Safety,tolerability,and pharmacokinetics of ARC-520 injection,an RNA interference-based therapeutic for the treatment of chronic hepatitis B virus infection,in healthy volunteers[J]. Clin Pharmacol Drug Dev,2017,6(4):350-362.
    [16] YE X,TATENO C,THI EP,et al. Hepatitis B virus therapeutic agent ARB-1740 has inhibitory effect on hepatitis Delta virus in a new dually-infected humanized mouse model[J]. ACS Infect Dis,2019,5(5):738-749.
    [17] THI EP,DHILLON AP,ARDZINSKI A,et al. ARB-1740,a RNA interference therapeutic for chronic hepatitis B infection[J]. ACS Infect Dis,2019,5(5):725-737.
    [18] SHIH YM,SUN CP,CHOU HH,et al. Combinatorial RNA interference therapy prevents selection of pre-existing HBV variants in human liver chimeric mice[J]. Sci Rep,2015,5:15259.
    [19] TANG LD,ZHAO Q,WU S,et al. The current status and future directions of hepatitis B antiviral drug discovery[J]. Expert Opin Drug Discov,2017,12(1):5-15.
    [20] HU J,FLORES D,TOFT D,et al. Requirement of heat shock protein 90 for human hepatitis B virus reverse transcriptase function[J]. J Virol,2004,78(23):13122-13131.
    [21] REN QY,LIU XC,YAN GH,et al. 3-((R)-4-(((R)-6-(2-Bromo-4-fluorophenyl)-5-(ethoxycarbonyl)-2-(thiazol-2-yl)-3,6-dihydropyrimidin-4-yl)methyl)morpholin-2-yl)propanoic acid(HEC72702),a novel hepatitis B virus capsid inhibitor based on clinical candidate GLS4[J]. J Med Chem,2018,61(3):1355-1374.
    [22] REN QY,LIU XC,LUO ZH,et al. Discovery of hepatitis B virus capsid assembly inhibitors leading to a heteroaryldihydropyrimidine based clinical candidate(GLS4)[J]. Bioorg Med Chem,2017,25(3):1042-1056.
    [23] WU G,LIU B,ZHANG Y,et al. Preclinical characterization of GLS4,an inhibitor of hepatitis B virus core particle assembly[J]. Antimicrob Agents Chemother,2013,57(11):5344-5354.
    [24] BAZINET M,PANTEA V,CEBOTARESCU V,et al. Safety and efficacy of REP 2139 and pegylated interferon alfa-2a for treatment-naive patients with chronic hepatitis B virus and hepatitis D virus co-infection(REP 301 and REP 301-LTF):A non-randomised,open-label,phase 2 trial[J]. Lancet Gastroenterol Hepatol,2017,2(12):877-889.
    [25] AL-MAHTAB M,BAZINET M,VAILLANT A. Safety and efficacy of nucleic acid polymers in monotherapy and combined with immunotherapy in treatment-naive bangladeshi patients with HBe Ag+chronic hepatitis B infection[J]. PLo S One,2016,11(6):e0156667.
    [26] BAZINET M,PANTEA V,PLACINTA G,et al. THU-154-update on safety and efficacy in the REP 401 protocol:REP 2139-Mg or REP 2165-Mg used in combination with tenofovir disoproxil fumarate and pegylated Interferon alpha-2a in treatment nave caucasian patients with chronic HBe Ag negative HBV[J]. J Hepatol,2017,66(1):s256-s257.
    [27] EMERY JS,FELD JJ. Treatment of hepatitis B virus with combination therapy now and in the future[J]. Best Pract Res Clin Gastroenterol,2017,31(3):347-355.
    [28] LOMONOSOVA E,DAW J,GARIMALLAPRABHAKARAN AK,et al. Efficacy and cytotoxicity in cell culture of novel alphahydroxytropolone inhibitors of hepatitis B virus ribonuclease H[J]. Antiviral Res,2017,144:164-172.
    [29] LIAW YF. Natural history of chronic hepatitis B virus infection and long-term outcome under treatment[J]. Liver Int,2009,29(Suppl 1):100-107.
    [30] AGUILAR JC,LOBAINA Y,MUZIO V,et al. Development of a nasal vaccine for chronic hepatitis B infection that uses the ability of hepatitis B core antigen to stimulate a strong Th1 response against hepatitis B surface antigen[J]. Immunol Cell Biol,2004,82(5):539-546.
    [31] ROTH Y,CHAPNIK JS,COLE P. Feasibility of aerosol vaccination in humans[J]. Ann Otol Rhinol Laryngol,2003,112(3):264-270.
    [32] NEUTRA MR,PRINGAULT E,KRAEHENBUHL JP. Antigen sampling across epithelial barriers and induction of mucosal immune responses[J]. Annu Rev Immunol,1996,14:275-300.
    [33] WU SS,TANG YY,CHEN XH,et al. Immune response elicited in HBV-transgenic mice by cytoplasmic transduction peptide-HBcAg18-27-Tapasin adjuvanted with CpG ODN[J].Chin J Clin Pharmacol Ther,2018,23(3):271-276.(in Chinese)吴姗姗,唐余燕,陈小华,等. CTP-HBcAg18-27-Tapasin联合佐剂CpG ODN免疫转基因小鼠的免疫应答研究[J].中国临床药理学与治疗学,2018,23(3):271-276.
    [34] BETANCOURT AA,DELGADO CA,ESTEVEZ ZC,et al. Phase I clinical trial in healthy adults of a nasal vaccine candidate containing recombinant hepatitis B surface and core antigens[J]. Int J Infect Dis,2007,11(5):394-401.
    [35] AL-MAHTAB M,AKBAR SM,AGUILAR JC,et al. Therapeutic potential of a combined hepatitis B virus surface and core antigen vaccine in patients with chronic hepatitis B[J]. Hepatol Int,2013,7(4):981-989.
    [36] PAULSEN D,WEBER O,RUEBSAMEN-SCHAEFF H,et al.AIC649 induces a bi-phasic treatment response in the woodchuck model of chronic hepatitis B[J]. PLo S One,2015,10(12):e0144383.
    [37] MARTIN P,DUBOIS C,JACQUIER E,et al. TG1050,an immunotherapeutic to treat chronic hepatitis B,induces robust T cells and exerts an antiviral effect in HBV-persistent mice[J]. Gut,2015,64(12):1961-1971.
    [38] LI N,FENG L,HAN HQ,et al. A novel Smac mimetic APG-1387 demonstrates potent antitumor activity in nasopharyngeal carcinoma cells by inducing apoptosis[J]. Cancer Lett,2016,381(1):14-22.
    [39] FATTAHI S,KARIMI ALIVIJE M,BABAMAHMOODI F,et al.Cytochrome P450 genes(CYP2E1 and CYP1A1)variants and susceptibility to chronic hepatitis B virus infection[J]. Indian J Clin Biochem,2018,33(4):467-472.
    [40] TREPANIER DJ,URE DR,FOSTER RT. Development,characterization, and pharmacokinetic evaluation of a CRV431loaded self-microemulsifying drug delivery system[J]. J Pharm Pharm Sci,2018,21(1s):335s-348s.
    [41] TREPANIER DJ,URE DR,FOSTER RT. In vitro phase i metabolism of CRV431,a novel oral drug candidate for chronic hepatitis B[J]. Pharmaceutics,2017,9(4):51.
    [42] LUCIFORA J,XIA Y,REISINGER F,et al. Specific and nonhepatotoxic degradation of nuclear hepatitis B virus cccDNA[J]. Science,2014,343(6176):1221-1228.
    [43] SHIN YW,CHO DH,SONG GW,et al. A new ELISA to overcome the pitfalls in quantification of recombinant human monoclonal Anti-HBs,GC1102,by commercial immunoassays[J]. Biol Proced Online,2018,20:18.
  • 加载中
计量
  • 文章访问数:  1465
  • HTML全文浏览量:  63
  • PDF下载量:  423
  • 被引次数: 0
出版历程
  • 收稿日期:  2019-05-31
  • 出版日期:  2019-10-20
  • 分享
  • 用微信扫码二维码

    分享至好友和朋友圈

目录

    /

    返回文章
    返回