ArticleInternational journal of molecular sciences2022
Syndecan-4 Is a Key Facilitator of the SARS-CoV-2 Delta Variant's Superior Transmission.
Article in International journal of molecular sciences, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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The trial behind it
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Who cites it
11 citing papers in PubMed, 14 citations in OpenAlex.
- Article
- 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
- In Silico Exploration of CD200 as a Therapeutic Target for COVID-19.Microorganisms · 2024Article
- Special Issue "Molecular and Genetic Aspects of SARS-CoV-2 Infection and COVID-19 Disease".International journal of molecular sciences · 2024Article
- Exploring the Syndecan-Mediated Cellular Internalization of the SARS-CoV-2 Omicron Variant.International journal of molecular sciences · 2023Article
- Syndecan-4 Mediates the Cellular Entry of Adeno-Associated Virus 9.International journal of molecular sciences · 2023Article
- Article
- Article
- Heparan Sulfate and Sialic Acid in Viral Attachment: Two Sides of the Same Coin?International journal of molecular sciences · 2022Review
- Biodistribution and Cellular Internalization of Inactivated SARS-CoV-2 in Wild-Type Mice.International journal of molecular sciences · 2022Article
- The SARS-CoV-2 Entry Inhibition Mechanisms of Serine Protease Inhibitors, OM-85, Heparin and Soluble HS Might Be Linked to HS Attachment Sites.Molecules (Basel, Switzerland) · 2022Review
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Emerging SARS-CoV-2 variants pose threats to vaccination campaigns against COVID-19. Being more transmissible than the original virus, the SARS-CoV-2 B.1.617 lineage, named the Delta variant, swept through the world in 2021. The mutations in the Delta's spike protein shift the protein towards a net positive electrostatic potential. To understand the key molecular drivers of the Delta infection, we investigate the cellular uptake of the Delta spike protein and Delta spike-bearing SARS-CoV-2 pseudoviruses. Specific in vitro modification of ACE2 and syndecan expression enabled us to demonstrate that syndecan-4, the syndecan isoform abundant in the lung, enhances the transmission of the Delta variant by attaching its mutated spike glycoprotein and facilitating its cellular entry. Compared to the wild-type spike, the Delta one shows a higher affinity towards heparan sulfate proteoglycans than towards ACE2. In addition to attachment to the polyanionic heparan sulfate chains, the Delta spike's molecular interactions with syndecan-4 also involve syndecan-4's cell-binding domain that mediates cell-to-cell adhesion. Regardless of the complexity of these interactions, exogenously added heparin blocks Delta's cellular entry as efficiently as syndecan-4 knockdown. Therefore, a profound understanding of the molecular mechanisms underlying Delta infections enables the development of molecularly targeted yet simple strategies to reduce the Delta variant's spread.
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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.