The Culprit Behind HBV-Infected Hepatocytes: NTCP.

IF 4.7 2区医学 Q1 CHEMISTRY, MEDICINAL

Drug Design, Development and Therapy Pub Date : 2024-10-28 eCollection Date: 2024-01-01 DOI:10.2147/DDDT.S480151

Shenghao Li, Liyuan Hao, Jiali Deng, Junli Zhang, Fei Yu, Fanghang Ye, Na Li, Xiaoyu Hu

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引用次数: 0

Abstract

Hepatitis B virus (HBV) is a globally prevalent human DNA virus responsible for over 250 million cases of chronic liver infections, leading to conditions such as liver inflammation, cirrhosis and hepatocellular carcinoma (HCC). Sodium taurocholate co-transporting polypeptide (NTCP) is a transmembrane protein highly expressed in human hepatocytes and functions as a bile acid (BA) transporter. NTCP has been identified as the receptor that HBV and its satellite virus, hepatitis delta virus (HDV), use to enter hepatocytes. HBV entry into hepatocytes is tightly regulated by various signaling pathways, and NTCP plays an important role as the initial stage of HBV infection. NTCP acts as an initiation signal, causing metabolic changes in hepatocytes and facilitating the entry of HBV into hepatocytes. Thus, a comprehensive understanding of NTCP's role is crucial. In this review, we will examine the regulatory mechanisms governing HBV pre-S1 binding to liver membrane NTCP, the role of NTCP in HBV internalization, and the transcriptional and translational regulation of NTCP expression. Additionally, we will discuss clinical drugs targeting NTCP, including combination therapies involving NTCP inhibitors, and consider the safety of NTCP as a therapeutic target.

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HBV 感染肝细胞背后的罪魁祸首：NTCP。

乙型肝炎病毒（HBV）是一种全球流行的人类 DNA 病毒，造成超过 2.5 亿例慢性肝脏感染病例，导致肝脏炎症、肝硬化和肝细胞癌（HCC）等病症。牛磺胆酸钠共转运多肽（NTCP）是一种在人类肝细胞中高度表达的跨膜蛋白，具有胆汁酸（BA）转运体的功能。NTCP 已被确定为 HBV 及其卫星病毒--乙型肝炎病毒（HDV）进入肝细胞的受体。HBV 进入肝细胞受到各种信号通路的严格调控，而 NTCP 在 HBV 感染的初始阶段发挥着重要作用。NTCP 作为启动信号，可引起肝细胞的代谢变化，促进 HBV 进入肝细胞。因此，全面了解 NTCP 的作用至关重要。在这篇综述中，我们将探讨 HBV pre-S1 与肝膜 NTCP 结合的调控机制、NTCP 在 HBV 内化中的作用以及 NTCP 表达的转录和翻译调控。此外，我们还将讨论针对 NTCP 的临床药物，包括涉及 NTCP 抑制剂的联合疗法，并考虑 NTCP 作为治疗靶点的安全性。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Drug Design, Development and Therapy CHEMISTRY, MEDICINAL-PHARMACOLOGY & PHARMACY

CiteScore

9.00

自引率

0.00%

发文量

382

审稿时长

>12 weeks

期刊介绍： Drug Design, Development and Therapy is an international, peer-reviewed, open access journal that spans the spectrum of drug design, discovery and development through to clinical applications. The journal is characterized by the rapid reporting of high-quality original research, reviews, expert opinions, commentary and clinical studies in all therapeutic areas. Specific topics covered by the journal include: Drug target identification and validation Phenotypic screening and target deconvolution Biochemical analyses of drug targets and their pathways New methods or relevant applications in molecular/drug design and computer-aided drug discovery* Design, synthesis, and biological evaluation of novel biologically active compounds (including diagnostics or chemical probes) Structural or molecular biological studies elucidating molecular recognition processes Fragment-based drug discovery Pharmaceutical/red biotechnology Isolation, structural characterization, (bio)synthesis, bioengineering and pharmacological evaluation of natural products** Distribution, pharmacokinetics and metabolic transformations of drugs or biologically active compounds in drug development Drug delivery and formulation (design and characterization of dosage forms, release mechanisms and in vivo testing) Preclinical development studies Translational animal models Mechanisms of action and signalling pathways Toxicology Gene therapy, cell therapy and immunotherapy Personalized medicine and pharmacogenomics Clinical drug evaluation Patient safety and sustained use of medicines.