ArticleInternational journal of molecular sciences2021
Contribution of Syndecans to the Cellular Entry of SARS-CoV-2.
Article in International journal of molecular sciences, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
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Who cites it
43 citing papers in PubMed, 58 citations in OpenAlex.
- Review
- Insight to Neglected Biomarkers in COVID-19: A Comprehensive Narrative Review".Biomarker insights · 2026Review
- UHRF1 restricts HCoV-229E infection through epigenetic silencing of the viral receptor APN.Nature communications · 2025Article
- Review
- MixOmics Integration of Biological Datasets Identifies Highly Correlated Variables of COVID-19 Severity.International journal of molecular sciences · 2025Article
- Endocytic Pathways Unveil the Role of Syndecans in the Seeding and Spreading of Pathological Protein Aggregates: Insights into Neurodegenerative Disorders.International journal of molecular sciences · 2025Review
- Leveraging Artificial Intelligence and Gene Expression Analysis to Identify Some Potential Bovine Coronavirus (BCoV) Receptors and Host Cell Enzymes Potentially Involved in the Viral Replication and Tissue Tropism.International journal of molecular sciences · 2025Article
- Article
- Impact of a Functional Dairy Powder and Its Primary Component on the Growth of Pathogenic and Probiotic Gut Bacteria and Human Coronavirus 229E.International journal of molecular sciences · 2024Article
- Kinetic Landscape of Single Virus-like Particles Highlights the Efficacy of SARS-CoV-2 Internalization.Viruses · 2024Article
- Mutual Inhibition of Antithrombin III and SARS-CoV-2 Cellular Attachment to Syndecans: Implications for COVID-19 Treatment and Vaccination.International journal of molecular sciences · 2024Article
- SARS-CoV-2-associated lymphopenia: possible mechanisms and the role of CD147.Cell communication and signaling : CCS · 2024Review
- Proteome profiling of home-sampled dried blood spots reveals proteins of SARS-CoV-2 infections.Communications medicine · 2024Article
- SARS-CoV-2 Lurking and Lingering in the Depths of Lungs.American journal of respiratory and critical care medicine · 2024Article
- SARS-CoV-2 Viral Replication Persists in the Human Lung for Several Weeks after Symptom Onset.American journal of respiratory and critical care medicine · 2024Article
- High-resolution single-cell transcriptomic survey of cardiomyocytes from patients with hypertrophic cardiomyopathy.Cell proliferation · 2024Article
- Article
- Exploring the Syndecan-Mediated Cellular Internalization of the SARS-CoV-2 Omicron Variant.International journal of molecular sciences · 2023Article
- Apolipoprotein E and viral infection: Risks and Mechanisms.Molecular therapy. Nucleic acids · 2023Review
- Syndecan-4 is the key proteoglycan involved in mediating sepsis-associated lung injury.Heliyon · 2023Article
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a novel emerging pathogen causing an unprecedented pandemic in 21st century medicine. Due to the significant health and economic burden of the current SARS-CoV-2 outbreak, there is a huge unmet medical need for novel interventions effectively blocking SARS-CoV-2 infection. Unknown details of SARS-CoV-2 cellular biology hamper the development of potent and highly specific SARS-CoV-2 therapeutics. Angiotensin-converting enzyme-2 (ACE2) has been reported to be the primary receptor for SARS-CoV-2 cellular entry. However, emerging scientific evidence suggests the involvement of additional membrane proteins, such as heparan sulfate proteoglycans, in SARS-CoV-2 internalization. Here, we report that syndecans, the evolutionarily conserved family of transmembrane proteoglycans, facilitate the cellular entry of SARS-CoV-2. Among syndecans, the lung abundant syndecan-4 was the most efficient in mediating SARS-CoV-2 uptake. The S1 subunit of the SARS-CoV-2 spike protein plays a dominant role in the virus's interactions with syndecans. Besides the polyanionic heparan sulfate chains, other parts of the syndecan ectodomain, such as the cell-binding domain, also contribute to the interaction with SARS-CoV-2. During virus internalization, syndecans colocalize with ACE2, suggesting a jointly shared internalization pathway. Both ACE2 and syndecan inhibitors exhibited significant efficacy in reducing the cellular entry of SARS-CoV-2, thus supporting the complex nature of internalization. Data obtained on syndecan specific in vitro assays present syndecans as novel cellular targets of SARS-CoV-2 and offer molecularly precise yet simple strategies to overcome the complex nature of SARS-CoV-2 infection.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.