The rapid development of vaccines to combat severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections has been critical to reduce the severity of COVID-19. However, the continuous emergence of new SARS-CoV-2 subtypes highlights the need to develop additional approaches that oppose viral infections. Targeting host factors that support virus entry, replication, and propagation provide opportunities to lower SARS-CoV-2 infection rates and improve COVID-19 outcome. This includes cellular cholesterol, which is critical for viral spike proteins to capture the host machinery for SARS-CoV-2 cell entry. Once endocytosed, exit of SARS-CoV-2 from the late endosomal/lysosomal compartment occurs in a cholesterol-sensitive manner. In addition, effective release of new viral particles also requires cholesterol. Hence, cholesterol-lowering statins, proprotein convertase subtilisin/kexin type 9 antibodies, and ezetimibe have revealed potential to protect against COVID-19. In addition, pharmacological inhibition of cholesterol exiting late endosomes/lysosomes identified drug candidates, including antifungals, to block SARS-CoV-2 infection. This review describes the multiple roles of cholesterol at the cell surface and endolysosomes for SARS-CoV-2 entry and the potential of drugs targeting cholesterol homeostasis to reduce SARS-CoV-2 infectivity and COVID-19 disease severity.

中文翻译：

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进入细胞期间宿主/病毒界面的胆固醇和 COVID-19 治疗机会。

对抗严重急性呼吸综合征冠状病毒 2 (SARS-CoV-2) 感染的疫苗的快速开发对于降低 COVID-19 的严重程度至关重要。然而，新的 SARS-CoV-2 亚型的不断出现凸显了开发其他对抗病毒感染方法的必要性。针对支持病毒进入、复制和传播的宿主因素提供了降低 SARS-CoV-2 感染率和改善 COVID-19 结果的机会。其中包括细胞胆固醇，这对于病毒刺突蛋白捕获宿主机制以进入 SARS-CoV-2 细胞至关重要。一旦被内吞，SARS-CoV-2就会以胆固醇敏感的方式从晚期内体/溶酶体区室中退出。此外，新病毒颗粒的有效释放也需要胆固醇。因此，降胆固醇他汀类药物、前蛋白转化酶枯草杆菌蛋白酶/kexin 9 型抗体和依折麦布已显示出预防 COVID-19 的潜力。此外，对离开晚期内体/溶酶体的胆固醇的药理抑制确定了候选药物，包括抗真菌药物，以阻止 SARS-CoV-2 感染。本综述描述了胆固醇在细胞表面和内溶酶体对 SARS-CoV-2 进入的多重作用，以及针对胆固醇稳态的药物降低 SARS-CoV-2 感染性和 COVID-19 疾病严重程度的潜力。