Dependence of SARS-CoV-2 infection on cholesterol-rich lipid raft and endosomal acidification

• Published in: Computational and structural biotechnology journal Vol. 19; pp. 1933 - 1943
• Main Authors: Li, Xiaowei, Zhu, Wenhua, Fan, Meiyang, Zhang, Jing, Peng, Yizhao, Huang, Fumeng, Wang, Nan, He, Langchong, Zhang, Lei, Holmdahl, Rikard, Meng, Liesu, Lu, Shemin
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.01.2021; Research Network of Computational and Structural Biotechnology; Elsevier
• Subjects: Cholesterol; Endocytosis; Endosomal acidification; Lipid rafts; Medicin och hälsovetenskap; SARS-CoV-2; Endosomal acidification; SARS-CoV-2; Endocytosis; Lipid rafts; Cholesterol
• ISSN: 2001-0370; 2001-0370
• DOI: 10.1016/j.csbj.2021.04.001

[Display omitted] Coronavirus disease 2019 is a kind of viral pneumonia caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, the mechanism whereby SARS-CoV-2 invades host cells remains poorly understood. Here we used SARS-CoV-2 pseudoviruses to infect human angiotensin-converting enzyme 2 (ACE2) expressing HEK293T cells and evaluated virus infection. We confirmed that SARS-CoV-2 entry was dependent on ACE2 and sensitive to pH of endosome/lysosome in HEK293T cells. The infection of SARS-CoV-2 pseudoviruses is independent of dynamin, clathrin, caveolin and endophilin A2, as well as macropinocytosis. Instead, we found that the infection of SARS-CoV-2 pseudoviruses was cholesterol-rich lipid raft dependent. Cholesterol depletion of cell membranes with methyl-β-cyclodextrin resulted in reduction of pseudovirus infection. The infection of SARS-CoV-2 pseudoviruses resumed with cholesterol supplementation. Together, cholesterol-rich lipid rafts, and endosomal acidification, are key steps of SARS-CoV-2 required for infection of host cells. Therefore, our finding expands the understanding of SARS-CoV-2 entry mechanism and provides a new anti-SARS-CoV-2 strategy.