Molecular Factors and Pathways of Hepatotoxicity Associated with HIV/SARS-CoV-2 Protease Inhibitors.
Molecular Factors and Pathways of Hepatotoxicity Associated with HIV/SARS-CoV-2 Protease Inhibitors.
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DOI：
10.3390/ijms24097938
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发表时间：
2023-04-27
影响因子：
5.6
通讯作者：
Ji, Cheng
中科院分区：
文献类型：
--
作者：
Ji, Cheng
关键词：
抗病毒蛋白酶抑制剂是一种拟肽分子，可阻断病毒蛋白酶的活性催化中心，从而阻止病毒多蛋白前体裂解成熟。它们仍然是一类关键的抗病毒药物，既可以用作其他类抗病毒药物的增强剂，也可以用作治疗人类免疫缺陷病毒（HIV）和严重急性呼吸综合征冠状病毒2 （SARS-CoV-2）感染的当前治疗方案的主要组成部分。然而，持续/终身使用该药物或与其他药物联合使用通常会导致严重的肝脏副作用，如脂质异常、胰岛素抵抗和肝毒性。潜在的致病机制尚不完全清楚，正在继续调查中。本文综述了与er -高尔基转运相关的转运蛋白、载脂蛋白B、细胞色素P450同工酶、胰岛素受体底物1、Akt/PKB信号转导、脂肪生成因子、udp -葡萄糖醛基转移酶、孕烷X受体、肝细胞核因子4α、活性氧、炎症因子、脱靶蛋白酶和小GTPase Rab蛋白等蛋白酶抑制剂诱导肝毒性的一般和特定分子机制。细胞器应激和肝损伤。还讨论了抗病毒药物引起的肝脏副作用的潜在药物/治疗解决方案。
Antiviral protease inhibitors are peptidomimetic molecules that block the active catalytic center of viral proteases and, thereby, prevent the cleavage of viral polyprotein precursors into maturation. They continue to be a key class of antiviral drugs that can be used either as boosters for other classes of antivirals or as major components of current regimens in therapies for the treatment of infections with human immunodeficiency virus (HIV) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, sustained/lifelong treatment with the drugs or drugs combined with other substance(s) often leads to severe hepatic side effects such as lipid abnormalities, insulin resistance, and hepatotoxicity. The underlying pathogenic mechanisms are not fully known and are under continuous investigation. This review focuses on the general as well as specific molecular mechanisms of the protease inhibitor-induced hepatotoxicity involving transporter proteins, apolipoprotein B, cytochrome P450 isozymes, insulin-receptor substrate 1, Akt/PKB signaling, lipogenic factors, UDP-glucuronosyltransferase, pregnane X receptor, hepatocyte nuclear factor 4α, reactive oxygen species, inflammatory cytokines, off-target proteases, and small GTPase Rab proteins related to ER-Golgi trafficking, organelle stress, and liver injury. Potential pharmaceutical/therapeutic solutions to antiviral drug-induced hepatic side effects are also discussed.
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DOI：
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发表时间：
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期刊：
World journal of virology
影响因子：
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作者：
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通讯作者：
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影响因子：
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