dc.contributor.author | Prieto Fernández, Endika | |
dc.contributor.author | Egia Mendikute, Leire | |
dc.contributor.author | Vila Vecilla, Laura | |
dc.contributor.author | Bosch, Alexandre | |
dc.contributor.author | Barreira Manrique, Adrián | |
dc.contributor.author | Lee, So Young | |
dc.contributor.author | García del Río, Ana | |
dc.contributor.author | Antoñana Vildosola, Asier | |
dc.contributor.author | Jiménez Lasheras, Borja | |
dc.contributor.author | Moreno Cugnon, Leire | |
dc.contributor.author | Jiménez Barbero, Jesús | |
dc.contributor.author | Berra Ramírez, Miren Edurne | |
dc.contributor.author | Ereño Orbea, June | |
dc.contributor.author | Palazón, Asís | |
dc.date.accessioned | 2021-06-10T08:46:41Z | |
dc.date.available | 2021-06-10T08:46:41Z | |
dc.date.issued | 2021-06-06 | |
dc.identifier.citation | Emerging Microbes And Infections 10(1) : 1065-1076 (2021) | es_ES |
dc.identifier.issn | 2222-1751 | |
dc.identifier.uri | http://hdl.handle.net/10810/51825 | |
dc.description.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-1αdependent 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. | es_ES |
dc.description.sponsorship | This research was supported by the SPRI I+D COVID-19 fund (Basque Government, bG-COVID-19), the European Research Council (ERC) (grant numbers: ERC-2018-StG 804236-NEXTGEN-IO to A.P and ERC-2017-AdG 788143-RECGLYCANMR to J.J-B.), the Severo Ochoa Excellence Accreditation from MCIU (SEV-2016-0644) and the FERO Foundation. Personal fellowships: E.P. (Juan de la Cierva-Formación, FJC2018-035449-I), L.V. (Juan de la Cierva-Formación, FJCI-2017-34099), A.B. (AECC Bizkaia Scientific Foundation, PRDVZ19003BOSC), A.G. (Programa Bikaintek from the Basque Government, 48-AF-W1-2019-00012), A.A (La Caixa Inphinit, LCF/BQ/DR20/11790022), B.J. (Basque Government, PRE_2019_1_0320), L.M. (Juan de la Cierva-Formación, FJC2019-039983-I), E.B. (MINECO, BFU2016-76872-R; Excellence Networks, SAF2017-90794-REDT) and A.P. (Ramón y Cajal, RYC2018-024183-I; Proyectos I+D+I, PID2019-107956RA-I00; and Ikerbasque Research Associate). | es_ES |
dc.language.iso | eng | es_ES |
dc.publisher | Taylor & Francis | es_ES |
dc.relation | info:eu-repo/grantAgreement/EC/H2020/804236 | es_ES |
dc.relation | info:eu-repo/grantAgreement/EC/H2020/788143 | es_ES |
dc.relation | info:eu-repo/grantAgreement/MICINN/SEV-2016-0644 | es_ES |
dc.relation | info:eu-repo/grantAgreement/MICINN/FJC2018-035449-I | es_ES |
dc.relation | info:eu-repo/grantAgreement/MICINN/FJCI-2017-34099 | es_ES |
dc.relation | info:eu-repo/grantAgreement/MICINN/FJC2019-039983-I | es_ES |
dc.relation | info:eu-repo/grantAgreement/MINECO/BFU2016-76872-R | es_ES |
dc.relation | info:eu-repo/grantAgreement/MICINN/SAF2017-90794-REDT | es_ES |
dc.relation | info:eu-repo/grantAgreement/MICINN/RYC2018-024183-I | es_ES |
dc.relation | info:eu-repo/grantAgreement/MICINN/PID2019-107956RA-I00 | es_ES |
dc.rights | info:eu-repo/semantics/openAccess | es_ES |
dc.rights.uri | http://creativecommons.org/licenses/by/3.0/es/ | * |
dc.subject | SARS-CoV-2 | es_ES |
dc.subject | hypoxia | es_ES |
dc.subject | ACE2 | es_ES |
dc.subject | heparan sulfate | es_ES |
dc.subject | syndecan-1 | es_ES |
dc.title | Hypoxia Reduces Cell Attachment of SARS-CoV-2 Spike Protein by Modulating the Expression of ACE2, Neuropilin-1, Syndecan-1 and Cellular Heparan Sulfate | es_ES |
dc.type | info:eu-repo/semantics/article | es_ES |
dc.rights.holder | This is an open access article distributed under the terms of the Creative Commons license (CC BY) | es_ES |
dc.rights.holder | Atribución 3.0 España | * |
dc.relation.publisherversion | https://www.tandfonline.com/doi/full/10.1080/22221751.2021.1932607 | es_ES |
dc.identifier.doi | 10.1080/22221751.2021.1932607 | |
dc.contributor.funder | European Commission | |
dc.departamentoes | Química orgánica II | es_ES |
dc.departamentoeu | Kimika organikoa II | es_ES |