RT Journal Article
SR Electronic
T1 Hypoxia reduces cell attachment of SARS-CoV-2 spike protein by modulating the expression of ACE2, neuropilin-1, syndecan-1 and cellular 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 Alexandre Bosch
A1 Adrián Barreira-Manrique
A1 So Young Lee
A1 Ana García-del Río
A1 Asier Antoñana-Vildosola
A1 Borja Jiménez-Lasheras
A1 Leire Moreno-Cugnon
A1 Jesús Jiménez-Barbero
A1 Edurne Berra
A1 June Ereño-Orbea
A1 Asis Palazon
YR 2021
UL http://biorxiv.org/content/early/2021/05/17/2021.01.09.426021.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 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 signaling pathway might offer therapeutic opportunities for the treatment of COVID-19.Competing Interest StatementThe authors have declared no competing interest.