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 Acyl-coenzyme 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.

自2019年冠状病毒病爆发以来，高效的抗病毒药物发现一直是全球公共卫生关注的紧迫问题。近年来，大量体外和体内研究表明，25-羟基胆固醇（25HC）是一种由胆固醇催化的活性氧甾醇- 25-羟化酶，具有广谱抗病毒活性，高效低毒。25HC 限制病毒内化并使用多种机制干扰病毒蛋白的成熟。首先，25HC 通过抑制甾醇调节元件结合蛋白 2、刺激肝脏 X 受体和激活酰基辅酶 A：胆固醇酰基转移酶来减少细胞膜中的脂筏和胆固醇。其次，25HC 通过限制氧固醇结合蛋白或 Niemann-pick 蛋白 C1 的功能来损害内体途径，导致病毒无法释放核酸。第三，25HC 通过抑制甾醇调节元件结合蛋白通路和糖基化来干扰病毒蛋白的异戊二烯化，方法是增加聚糖对内切糖苷酶的敏感性。本文回顾了以往关于 25HC 抗病毒活性的研究，以充分了解其在先天免疫中的作用以及它如何有助于开发急需的广谱抗病毒药物。