4.7 Article

Studies in the antiviral molecular mechanisms of 25-hydroxycholesterol: Disturbing cholesterol homeostasis and post-translational modification of proteins

期刊

EUROPEAN JOURNAL OF PHARMACOLOGY
卷 926, 期 -, 页码 -

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ELSEVIER
DOI: 10.1016/j.ejphar.2022.175033

关键词

25-Hydroxycholesterol; Antiviral mechanism; Cholesterol; Post-translational modification; Lipid raft

资金

  1. Joint Funds of Natural Science Foun-dation of Zhejiang Province [LQY20F050001]

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Efficient antiviral drug discovery is a pressing issue in global public health. Recent studies have shown that 25-hydroxycholesterol (25HC) has broad-spectrum antiviral activity with high efficiency and low toxicity. It restricts viral internalization and disturbs the maturity of viral proteins through multiple mechanisms. Understanding the role of 25HC in innate immunity may contribute to the development of urgently needed broad-spectrum antiviral drugs.
Efficient antiviral drug discovery has been a pressing issue of global public health concern since the outbreak of coronavirus disease 2019. In recent years, numerous in vitro and in vivo studies have shown that 25-hydroxycholesterol (25HC), a reactive oxysterol catalyzed by cholesterol-25-hydroxylase, exerts broad-spectrum antiviral activity with high efficiency and low toxicity. 25HC restricts viral internalization and disturbs the maturity of viral proteins using multiple mechanisms. First, 25HC reduces lipid rafts and cholesterol in the cytomembrane by inhibiting sterol-regulatory element binding proteins-2, stimulating liver X receptor, and activating Acylcoenzyme A: cholesterol acyl-transferase. Second, 25HC impairs endosomal pathways by restricting the function of oxysterol-binding protein or Niemann-pick protein C1, causing the virus to fail to release nucleic acid. Third, 25HC disturbs the prenylation of viral proteins by suppressing the sterol-regulatory element binding protein pathway and glycosylation by increasing the sensitivity of glycans to endoglycosidase. This paper reviews previous studies on the antiviral activity of 25HC in order to fully understand its role in innate immunity and how it may contribute to the development of urgently needed broad-spectrum antiviral drugs.

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