Novel mechanistic insights – A brand new Era for anti-HBV drugs

IF 6 2区 医学 Q1 CHEMISTRY, MEDICINAL European Journal of Medicinal Chemistry Pub Date : 2024-09-13 DOI:10.1016/j.ejmech.2024.116854
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Abstract

Hepatitis B Virus (HBV) remains a critical global health issue, with substantial morbidity and mortality. Current therapies, including interferons and nucleoside analogs, often fail to achieve complete cure or functional eradication. This review explores recent advances in anti-HBV agents, focusing on their innovative mechanisms of action. HBV entry inhibitors target the sodium taurocholate cotransporting polypeptide (NTCP) receptor, impeding viral entry, while nucleus translocation inhibitors disrupt key viral life cycle steps, preventing replication. Capsid assembly modulators inhibit covalently closed circular DNA (cccDNA) formation, aiming to eradicate the persistent viral reservoir. Transcription inhibitors targeting cccDNA and integrated DNA offer significant potential to suppress HBV replication. Immunomodulatory agents are highlighted for their ability to enhance host immune responses, facil-itating better control and possible eradication of HBV. These novel approaches represent significant advancements in HBV therapy, providing new strategies to overcome current treatment limitations. The development of cccDNA reducers is particularly critical, as they directly target the persistent viral reservoir, offering a promising pathway towards achieving a functional cure or complete viral eradication. Continued research in this area is essential to advance the effectiveness of anti-HBV therapies.

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新的机理认识--抗乙肝病毒药物的全新时代
乙型肝炎病毒(HBV)仍然是一个严重的全球健康问题,其发病率和死亡率都很高。目前的疗法,包括干扰素和核苷类似物,往往无法实现完全治愈或功能性根除。本综述探讨了抗 HBV 药物的最新进展,重点关注其创新的作用机制。HBV 进入抑制剂以牛磺胆酸钠共转运多肽(NTCP)受体为靶点,阻碍病毒进入,而细胞核转位抑制剂则破坏病毒生命周期的关键步骤,阻止病毒复制。囊壳组装调节剂可抑制共价闭合环状 DNA(cccDNA)的形成,从而根除持续存在的病毒库。针对cccDNA和整合 DNA 的转录抑制剂在抑制 HBV 复制方面具有巨大潜力。免疫调节药剂因其能够增强宿主免疫反应、促进更好地控制和根除 HBV 而备受关注。这些新方法代表了 HBV 治疗的重大进展,为克服当前治疗的局限性提供了新策略。cccDNA还原剂的开发尤为重要,因为它们直接针对持续存在的病毒库,为实现功能性治愈或彻底根除病毒提供了一条充满希望的途径。要提高抗 HBV 治疗的有效性,就必须在这一领域继续开展研究。
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来源期刊
CiteScore
11.70
自引率
9.00%
发文量
863
审稿时长
29 days
期刊介绍: The European Journal of Medicinal Chemistry is a global journal that publishes studies on all aspects of medicinal chemistry. It provides a medium for publication of original papers and also welcomes critical review papers. A typical paper would report on the organic synthesis, characterization and pharmacological evaluation of compounds. Other topics of interest are drug design, QSAR, molecular modeling, drug-receptor interactions, molecular aspects of drug metabolism, prodrug synthesis and drug targeting. The journal expects manuscripts to present the rational for a study, provide insight into the design of compounds or understanding of mechanism, or clarify the targets.
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Discovery of 1(2H)-phthalazinone and 1(2H)-isoquinolinone derivatives as potent hematopoietic progenitor kinase 1 (HPK1) inhibitors Design, synthesis, and molecular dynamic simulations of some novel benzo[d]thiazoles with anti-virulence activity against Pseudomonas aeruginosa Novel mechanistic insights – A brand new Era for anti-HBV drugs Editorial Board Contents continued
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