ABSTRACT A main clinical parameter of COVID-19 pathophysiology is hypoxia. Here we show that hypoxia decreases the attachment of the receptor-binding domain (RBD) and the S1 subunit (S1) of the spike protein of SARS-CoV-2 to epithelial cells. In Vero E6 cells, hypoxia reduces the protein levels of ACE2 and neuropilin-1 (NRP1), which might in part explain the observed reduction of the infection rate. In addition, hypoxia inhibits the binding of the spike to NCI-H460 human lung epithelial cells by decreasing the cell surface levels of heparan sulfate (HS), a known attachment receptor of SARS-CoV-2. This interaction is also reduced by lactoferrin, a glycoprotein that blocks HS moieties on the cell surface. The expression of syndecan-1, an HS-containing proteoglycan expressed in lung, is inhibited by hypoxia on a HIF-1α-dependent manner. Hypoxia or deletion of syndecan-1 results in reduced binding of the RBD to host cells. Our study indicates that hypoxia acts to prevent SARS-CoV-2 infection, suggesting that the hypoxia signalling pathway might offer therapeutic opportunities for the treatment of COVID-19.
【저자키워드】 SARS-CoV-2, ACE2, hypoxia, heparan sulfate, Syndecan-1, 【초록키워드】 COVID-19, Treatment, SARS-COV-2 infection, lung, pathophysiology, RBD, human lung, therapeutic, pathway, VERO E6 cells, NRP1, epithelial cells, glycoprotein, lactoferrin, receptor, infection rate, expression, binding, Interaction, epithelial cell, host cells, reduction, protein level, offer, clinical parameter, block, Prevent, Cell, decrease, the S1 subunit, addition, inhibit, inhibited, reduced, indicate, the spike protein, expressed, the RBD, the receptor-binding domain, reduce, explain, 【제목키워드】 SARS-CoV-2 spike protein, expression, cellular, Cell, reduce, modulating,