Schmidt Nathalie M, Wing Peter A C, McKeating Jane A, Maini Mala K
Division of Infection & Immunity, Institute of Immunity & Transplantation, University College London, London, UK.
Nuffield Department of Medicine, Oxford University, Oxford, UK.
Oxf Open Immunol. 2020;1(1):iqaa001. doi: 10.1093/oxfimm/iqaa001. Epub 2020 Jun 18.
Infection with severe acute respiratory syndrom coronavirus 2 (SARS-CoV-2) is more likely to lead to poor outcomes in the elderly and those with cardiovascular disease, obesity or metabolic syndrome. Here, we consider mechanisms by which dyslipidaemia and the use of cholesterol-modifying drugs could influence the virus-host relationship. Cholesterol is essential for the assembly, replication and infectivity of enveloped virus particles; we highlight several cholesterol-modifying drugs with the potential to alter the SARS-CoV-2 life cycle that could be tested in and models. Although cholesterol is an essential component of immune cell membranes, excess levels can dysregulate protective immunity and promote exaggerated pulmonary and systemic inflammatory responses. Statins block the production of multiple sterols, oxysterols and isoprenoids, resulting in a pleiotropic range of context-dependent effects on virus infectivity, immunity and inflammation. We highlight antiviral, immunomodulatory and anti-inflammatory effects of cholesterol-modifying drugs that merit further consideration in the management of SARS-CoV-2 infection.
感染严重急性呼吸综合征冠状病毒2（SARS-CoV-2）在老年人以及患有心血管疾病、肥胖症或代谢综合征的人群中更有可能导致不良后果。在此，我们探讨血脂异常和使用胆固醇调节药物可能影响病毒与宿主关系的机制。胆固醇对于包膜病毒颗粒的组装、复制和感染性至关重要；我们重点介绍了几种有可能改变SARS-CoV-2生命周期的胆固醇调节药物，这些药物可在[具体模型1]和[具体模型2]模型中进行测试。尽管胆固醇是免疫细胞膜的重要组成部分，但过量的胆固醇会破坏保护性免疫并促进过度的肺部和全身炎症反应。他汀类药物可阻断多种固醇、氧化固醇和类异戊二烯的产生，从而对病毒感染性、免疫和炎症产生一系列取决于具体情况的多效性影响。我们强调了胆固醇调节药物的抗病毒、免疫调节和抗炎作用，这些作用在SARS-CoV-2感染的管理中值得进一步考虑。
