College of Animal Science and Technology, Guangxi University, Nanning, China.
Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Shanghai, China.
Front Immunol. 2022 Apr 21;13:791267. doi: 10.3389/fimmu.2022.791267. eCollection 2022.
Host cholesterol metabolism remodeling is significantly associated with the spread of human pathogenic coronaviruses, suggesting virus-host relationships could be affected by cholesterol-modifying drugs. Cholesterol has an important role in coronavirus entry, membrane fusion, and pathological syncytia formation, therefore cholesterol metabolic mechanisms may be promising drug targets for coronavirus infections. Moreover, cholesterol and its metabolizing enzymes or corresponding natural products exert antiviral effects which are closely associated with individual viral steps during coronavirus replication. Furthermore, the coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 infections are associated with clinically significant low cholesterol levels, suggesting cholesterol could function as a potential marker for monitoring viral infection status. Therefore, weaponizing cholesterol dysregulation against viral infection could be an effective antiviral strategy. In this review, we comprehensively review the literature to clarify how coronaviruses exploit host cholesterol metabolism to accommodate viral replication requirements and interfere with host immune responses. We also focus on targeting cholesterol homeostasis to interfere with critical steps during coronavirus infection.
宿主胆固醇代谢重编程与人类致病性冠状病毒的传播密切相关,这表明病毒-宿主关系可能受到胆固醇修饰药物的影响。胆固醇在冠状病毒进入、膜融合和病理性合胞体形成中起着重要作用,因此胆固醇代谢机制可能是冠状病毒感染的有前途的药物靶点。此外,胆固醇及其代谢酶或相应的天然产物具有抗病毒作用,这些作用与冠状病毒复制过程中单个病毒步骤密切相关。此外,由严重急性呼吸系统综合征冠状病毒 2 感染引起的 2019 年冠状病毒病(COVID-19)与临床意义上的低胆固醇水平相关,表明胆固醇可能作为监测病毒感染状态的潜在标志物。因此,针对病毒感染调节胆固醇失调可能是一种有效的抗病毒策略。在这篇综述中,我们全面回顾了文献,以阐明冠状病毒如何利用宿主胆固醇代谢来适应病毒复制的要求并干扰宿主免疫反应。我们还重点关注靶向胆固醇动态平衡以干扰冠状病毒感染过程中的关键步骤。