ArticleEmerging microbes & infections2021
Hypoxia reduces cell attachment of SARS-CoV-2 spike protein by modulating the expression of ACE2, neuropilin-1, syndecan-1 and cellular heparan sulfate.
Article in Emerging microbes & infections, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 38 citations in OpenAlex.
- A nomogram for predicting ARDS progression and need for invasive ventilation in COVID-19 patients using plasma hyaluronic acid and clinical scores.Frontiers in cellular and infection microbiology · 2026Article
- Hypoxia: a critical pathophysiological driver in respiratory inflammatory diseases.Military Medical Research · 2026Review
- Hypoxia signaling in cancer: HIF-1α stimulated by COVID-19 can lead to cancer progression and chemo-resistance in oral squamous cell carcinoma (OSCC).Discover oncology · 2025Review
- Lactoferrin Binds through Its N-Terminus to the Receptor-Binding Domain of the SARS-CoV-2 Spike Protein.Pharmaceuticals (Basel, Switzerland) · 2024Article
- LINC01002 functions as a ceRNA to regulate FRMD8 by sponging miR-4324 for the development of COVID-19.Virology journal · 2024Article
- Immunomodulatory effect of bovine lactoferrin during SARS-CoV-2 infection.Frontiers in immunology · 2024Article
- The potential of lactoferrin as antiviral and immune-modulating agent in viral infectious diseases.Frontiers in immunology · 2024Review
- The Serum ACE2, CTSL, AngII, and TNFα Levels after COVID-19 and mRNA Vaccines: The Molecular Basis.Biomedicines · 2023Article
- Exploring the Syndecan-Mediated Cellular Internalization of the SARS-CoV-2 Omicron Variant.International journal of molecular sciences · 2023Article
- The role of asymmetric dimethylarginine (ADMA) in COVID-19: association with respiratory failure and predictive role for outcome.Scientific reports · 2023Article
- Molecular mimicry of the receptor-binding domain of the SARS-CoV-2 spike protein: from the interaction of spike-specific antibodies with transferrin and lactoferrin to the antiviral effects of human recombinant lactoferrin.Biometals : an international journal on the role of metal ions in biology, biochemistry, and medicine · 2023Article
- Blood pH Analysis in Combination with Molecular Medical Tools in Relation to COVID-19 Symptoms.Biomedicines · 2023Article
- Hypoxia-Inducible Factor 1α and Its Role in Lung Injury: Adaptive or Maladaptive.Inflammation · 2023Review
- Time to Kill and Time to Heal: The Multifaceted Role of Lactoferrin and Lactoferricin in Host Defense.Pharmaceutics · 2023Review
- Impaired VEGF-A-Mediated Neurovascular Crosstalk Induced by SARS-CoV-2 Spike Protein: A Potential Hypothesis Explaining Long COVID-19 Symptoms and COVID-19 Vaccine Side Effects?Microorganisms · 2022Review
- COVID-19, vaccines and deficiency of ACEEuropean journal of internal medicine · 2022Review
- The spike of SARS-CoV-2 promotes metabolic rewiring in hepatocytes.Communications biology · 2022Article
- Hypoxia signaling in human health and diseases: implications and prospects for therapeutics.Signal transduction and targeted therapy · 2022Review
- Syndecan-4 Is a Key Facilitator of the SARS-CoV-2 Delta Variant's Superior Transmission.International journal of molecular sciences · 2022Article
- The impact of COVID-19 on populations living at high altitude: Role of hypoxia-inducible factors (HIFs) signaling pathway in SARS-CoV-2 infection and replication.Frontiers in physiology · 2022Article
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Authors and funding
14 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
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.
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