RT Journal Article
SR Electronic
T1 Hypoxia reduces cell attachment of SARS-CoV-2 spike protein by modulating the expression of ACE2 and heparan sulfate
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2021.01.09.426021
DO 10.1101/2021.01.09.426021
A1 Endika Prieto-Fernández
A1 Leire Egia-Mendikute
A1 Laura Vila-Vecilla
A1 So Young Lee
A1 Alexandre Bosch
A1 Adrián Barreira-Manrique
A1 Ana García-del Río
A1 Asier Antoñana-Vildosola
A1 Borja Jimenez-Lasheras
A1 Asis Palazon
YR 2021
UL http://biorxiv.org/content/early/2021/01/11/2021.01.09.426021.abstract
AB 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 to epithelial cells. In Vero E6 cells, hypoxia reduces the protein levels of ACE2, which might in part explain the observed reduction of the infection rate. However, hypoxia also inhibits the binding of the spike to human lung epithelial cells lacking ACE2 expression, indicating that hypoxia modulates the expression of additional binding partners of SARS-CoV-2. We show that hypoxia also decreases the total cell surface levels of heparan sulfate, a known attachment receptor of SARS-CoV-2, by reducing the expression of syndecan-1 and syndecan3, the main proteoglycans containing heparan sulfate. Our study indicates that hypoxia acts to prevent SARS-CoV-2 infection, suggesting that the hypoxia signaling pathway might offer therapeutic opportunities for the treatment of Covid-19.Competing Interest StatementThe authors have declared no competing interest.