SARS-CoV-2 may use the cell's internal cholesterol mechanisms to enhance infection, suggests an article published in Nature Metabolism. This finding may help explain why individuals with both COVID-19 and a metabolic disorder such as diabetes or cardiovascular disease have elevated rates of morbidity and mortality, and it hints at new targets for potential therapeutic intervention.
During SARS-CoV-2 infection, the spike protein on the virus binds a host-cell receptor called angiotensin-converting enzyme 2 (ACE2). In this cell culture study, Hui Zhong and colleagues highlight the role of another receptor, called HDL scavenger receptor B type 1 (SR-B1), which is expressed in several tissues, including human lung cells. This receptor usually binds high-density lipoprotein (HDL, also known as ‘good cholesterol’). However, in this study, the viral spike protein bound cholesterol, and expression of SR-B1 and the presence of HDL together helped the virus bind and enter ACE2-expressing cells.
The virus seems to hijack the cell’s cholesterol-uptake machinery to facilitate entry into host cells, but when the authors blocked this pathway with a monoclonal antibody or a specific pharmacological antagonist of SR-B1, the HDL-mediated enhancement of viral infection was absent. The authors conclude that the study highlights a potential molecular connection between COVID-19 and cholesterol, and they suggest that drugs targeting SR-B1 may help limit SARS-CoV-2 infection.
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