直接作用抗病毒药物和针对宿主靶点药物的研发用于乙型肝炎病毒感染的治疗。
Development of Direct-acting Antiviral and Host-targeting Agents for Treatment of Hepatitis B Virus Infection.
机构信息
Liver Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland, 20892.
Liver Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland, 20892.
出版信息
Gastroenterology. 2019 Jan;156(2):311-324. doi: 10.1053/j.gastro.2018.07.057. Epub 2018 Sep 19.
Abstract
Hepatitis B virus (HBV) infection affects approximately 300 million people worldwide. Although antiviral therapies have improved the long-term outcomes, patients often require life-long treatment and there is no cure for HBV infection. New technologies can help us learn more about the pathogenesis of HBV infection and develop therapeutic agents to reduce its burden. We review recent advances in development of direct-acting antiviral and host-targeting agents, some of which have entered clinical trials. We also discuss strategies for unbiased high-throughput screens to identify compounds that inhibit HBV and for repurposing existing drugs.
摘要
乙型肝炎病毒 (HBV) 感染影响全球约 3 亿人。尽管抗病毒疗法改善了长期预后，但患者通常需要终身治疗，而且目前尚无治愈乙型肝炎病毒感染的方法。新技术可以帮助我们更多地了解乙型肝炎病毒感染的发病机制，并开发治疗药物以减轻其负担。我们综述了直接作用抗病毒药物和宿主靶向药物的最新进展，其中一些已进入临床试验。我们还讨论了用于无偏高通量筛选以鉴定抑制乙型肝炎病毒的化合物和重新利用现有药物的策略。
相似文献
1
Development of Direct-acting Antiviral and Host-targeting Agents for Treatment of Hepatitis B Virus Infection.
Gastroenterology. 2019 Jan;156(2):311-324. doi: 10.1053/j.gastro.2018.07.057. Epub 2018 Sep 19.
2
Targets and future direct-acting antiviral approaches to achieve hepatitis B virus cure.
Lancet Gastroenterol Hepatol. 2019 Nov;4(11):883-892. doi: 10.1016/S2468-1253(19)30190-6.
3
The Heteroaryldihydropyrimidine Bay 38-7690 Induces Hepatitis B Virus Core Protein Aggregates Associated with Promyelocytic Leukemia Nuclear Bodies in Infected Cells.
mSphere. 2018 Apr 18;3(2). doi: 10.1128/mSphereDirect.00131-18. Print 2018 Apr 25.
4
Targeting the multifunctional HBV core protein as a potential cure for chronic hepatitis B.
Antiviral Res. 2020 Oct;182:104917. doi: 10.1016/j.antiviral.2020.104917. Epub 2020 Aug 17.
5
Getting to HBV cure: The promising paths forward.
Hepatology. 2022 Jul;76(1):233-250. doi: 10.1002/hep.32314. Epub 2022 Feb 16.
6
Antiviral Properties and Mechanism of Action Studies of the Hepatitis B Virus Capsid Assembly Modulator JNJ-56136379.
Antimicrob Agents Chemother. 2020 Apr 21;64(5). doi: 10.1128/AAC.02439-19.
7
Review article: novel therapies for hepatitis B virus cure - advances and perspectives.
Aliment Pharmacol Ther. 2016 Aug;44(3):213-22. doi: 10.1111/apt.13694. Epub 2016 Jun 15.
8
Novel Antivirals in Clinical Development for Chronic Hepatitis B Infection.
Viruses. 2021 Jun 18;13(6):1169. doi: 10.3390/v13061169.
9
Measurement of Antiviral Effect and Innate Immune Response During Treatment of Primary Woodchuck Hepatocytes.
Methods Mol Biol. 2017;1540:277-294. doi: 10.1007/978-1-4939-6700-1_24.
10
Toward a Functional Cure for Hepatitis B.
Gut Liver. 2024 Jul 15;18(4):593-601. doi: 10.5009/gnl240023. Epub 2024 Mar 27.
引用本文的文献
1
Screening of different species reveals cat hepatocytes support HBV infection.
PLoS Pathog. 2025 Aug 4;21(8):e1013390. doi: 10.1371/journal.ppat.1013390. eCollection 2025 Aug.
2
Interferon Lambda: The Next Frontier in Antiviral Therapy?
Pharmaceuticals (Basel). 2025 May 24;18(6):785. doi: 10.3390/ph18060785.
3
Sphingomyelin phosphodiesterase 3 as a novel host factor inhibiting hepatitis B virus transcription.
Virol Sin. 2025 Apr;40(2):292-295. doi: 10.1016/j.virs.2025.02.004. Epub 2025 Feb 27.
4
AAV-based vectors for human diseases modeling in laboratory animals.
Front Med (Lausanne). 2025 Feb 12;11:1499605. doi: 10.3389/fmed.2024.1499605. eCollection 2024.
5
Advances and Challenges in Antiviral Development for Respiratory Viruses.
Pathogens. 2024 Dec 31;14(1):20. doi: 10.3390/pathogens14010020.
6
Chronic Hepatitis B Genotype C Mouse Model with Persistent Covalently Closed Circular DNA.
Viruses. 2024 Dec 7;16(12):1890. doi: 10.3390/v16121890.
7
Hepatitis B virus hijacks MRE11-RAD50-NBS1 complex to form its minichromosome.
PLoS Pathog. 2025 Jan 3;21(1):e1012824. doi: 10.1371/journal.ppat.1012824. eCollection 2025 Jan.
8
Dysfunction and regulatory interplay of T and B cells in chronic hepatitis B: immunotherapy and emerging antiviral strategies.
Front Cell Infect Microbiol. 2024 Dec 9;14:1488527. doi: 10.3389/fcimb.2024.1488527. eCollection 2024.
9
Clinical characteristics of coronavirus disease 2019 patients with hepatitis B virus super-infection.
Rev Inst Med Trop Sao Paulo. 2024 Dec 16;66:e74. doi: 10.1590/S1678-9946202466074. eCollection 2024.
10
SARS-CoV-2 nsp13 suppresses hepatitis B virus replication by targeting cccDNA transcription.
J Virol. 2024 Nov 19;98(11):e0104224. doi: 10.1128/jvi.01042-24. Epub 2024 Oct 7.
本文引用的文献
1
Flap endonuclease 1 is involved in cccDNA formation in the hepatitis B virus.
PLoS Pathog. 2018 Jun 21;14(6):e1007124. doi: 10.1371/journal.ppat.1007124. eCollection 2018 Jun.
2
CRISPR-Cas9 genome editing induces a p53-mediated DNA damage response.
Nat Med. 2018 Jul;24(7):927-930. doi: 10.1038/s41591-018-0049-z. Epub 2018 Jun 11.
3
Liver-Targeted Anti-HBV Single-Stranded Oligonucleotides with Locked Nucleic Acid Potently Reduce HBV Gene Expression In Vivo.
Mol Ther Nucleic Acids. 2018 Jun 1;11:441-454. doi: 10.1016/j.omtn.2018.02.005. Epub 2018 Feb 23.
4
CRISPR off-target analysis in genetically engineered rats and mice.
Nat Methods. 2018 Jul;15(7):512-514. doi: 10.1038/s41592-018-0011-5. Epub 2018 May 21.
5
Review article: the prevention of hepatitis B-related hepatocellular carcinoma.
Aliment Pharmacol Ther. 2018 Jul;48(1):5-14. doi: 10.1111/apt.14683. Epub 2018 May 3.
6
Chronic Hepatitis B Infection: A Review.
JAMA. 2018 May 1;319(17):1802-1813. doi: 10.1001/jama.2018.3795.
7
A novel SMAC mimetic APG-1387 exhibits dual antitumor effect on HBV-positive hepatocellular carcinoma with high expression of cIAP2 by inducing apoptosis and enhancing innate anti-tumor immunity.
Biochem Pharmacol. 2018 Aug;154:127-135. doi: 10.1016/j.bcp.2018.04.020. Epub 2018 Apr 18.
8
SIRT3 restricts hepatitis B virus transcription and replication through epigenetic regulation of covalently closed circular DNA involving suppressor of variegation 3-9 homolog 1 and SET domain containing 1A histone methyltransferases.
Hepatology. 2018 Oct;68(4):1260-1276. doi: 10.1002/hep.29912. Epub 2018 Jul 25.
9
Global prevalence, treatment, and prevention of hepatitis B virus infection in 2016: a modelling study.
Lancet Gastroenterol Hepatol. 2018 Jun;3(6):383-403. doi: 10.1016/S2468-1253(18)30056-6. Epub 2018 Mar 27.
10
Epigenetic regulation of HIV-1 latency: focus on polycomb group (PcG) proteins.
Clin Epigenetics. 2018 Feb 5;10:14. doi: 10.1186/s13148-018-0441-z. eCollection 2018.
Zotero 插件