Department of Cardiology, Heart Center, Zhujiang Hospital, Southern Medical University, 235 Industrial Avenue, Guangzhou, 510282, Guangdong, People's Republic of China.
Zhujiang Hospital, Southern Medical University/The Second School of Clinical Medicine, Southern Medical University, No. 6, Chenggui Road, East District, Zhongshan, 528403, Guangdong, People's Republic of China.
Int J Med Sci. 2021 Aug 21;18(15):3533-3543. doi: 10.7150/ijms.62021. eCollection 2021.
Despite the availability of a vaccine against the severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2), humans will have to live with this virus and the after-effects of the coronavirus disease 2019 (COVID-19) infection for a long time. Cholesterol plays an important role in the infection and prognosis of SARS-CoV-2, and the study of its mechanism is of great significance not only for the treatment of COVID-19 but also for research on generic antiviral drugs. Cholesterol promotes the development of atherosclerosis by activating NLR family pyrin domain containing 3 (NLRP3), and the resulting inflammatory environment indirectly contributes to COVID-19 infection and subsequent deterioration. In studies, membrane cholesterol increased the number of viral entry sites on the host cell membrane and the number of angiotensin-converting enzyme 2 (ACE2) receptors in the membrane fusion site. Previous studies have shown that the fusion protein of the virus interacts with cholesterol, and the spike protein of SARS-CoV-2 also requires cholesterol to enter the host cells. Cholesterol in blood interacts with the spike protein to promote the entry of spike cells, wherein the scavenger receptor class B type 1 (SR-B1) plays an important role. Because of the cardiovascular protective effects of lipid-lowering therapy and the additional anti-inflammatory effects of lipid-lowering drugs, it is currently recommended to continue lipid-lowering therapy for patients with COVID-19, but the safety of extremely low LDL-C is questionable. Cholesterol can indirectly increase the susceptibility of patients to SARS-CoV-2 and increase the risk of death from COVID-19, which are mediated by NLRP3 and atherosclerotic plaques, respectively. Cholesterol present in the host cell membrane, virus, and blood may also directly participate in the virus cell entry process, but the specific mechanism still needs further study. Patients with COVID-19 are recommended to continue lipid-lowering therapy.
尽管有针对严重急性呼吸综合征冠状病毒 2（SARS-CoV-2）的疫苗，但人类将不得不长期与这种病毒以及 2019 年冠状病毒病（COVID-19）感染的后遗症共存。胆固醇在 SARS-CoV-2 的感染和预后中起着重要作用，研究其机制不仅对 COVID-19 的治疗具有重要意义，而且对通用抗病毒药物的研究也具有重要意义。胆固醇通过激活 NOD、LRR 和富含pyrin 结构域 3（NLRP3）促进动脉粥样硬化的发展，由此产生的炎症环境间接导致 COVID-19 感染和随后的恶化。在研究中，膜胆固醇增加了宿主细胞膜上病毒进入位点的数量和膜融合位点上血管紧张素转换酶 2（ACE2）受体的数量。先前的研究表明，病毒的融合蛋白与胆固醇相互作用，SARS-CoV-2 的刺突蛋白也需要胆固醇进入宿主细胞。血液中的胆固醇与刺突蛋白相互作用，促进刺突细胞进入，其中清道夫受体 B 类 1（SR-B1）发挥重要作用。由于降脂治疗具有心血管保护作用，降脂药物具有额外的抗炎作用，目前建议 COVID-19 患者继续降脂治疗，但 LDL-C 极低的安全性值得怀疑。胆固醇可以通过 NLRP3 和动脉粥样硬化斑块分别间接增加患者对 SARS-CoV-2 的易感性并增加 COVID-19 死亡的风险。宿主细胞膜、病毒和血液中的胆固醇也可能直接参与病毒细胞进入过程，但具体机制仍需进一步研究。建议 COVID-19 患者继续降脂治疗。
