Contribution of Syndecans to the Cellular Entry of SARS-CoV-2
| Autor: | László Szilák, Tamás Letoha, Annamária Letoha, Anett Hudák |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
viruses
Angiotensin-Converting Enzyme Inhibitors spike protein Syndecan 1 Amiloride chemistry.chemical_compound 0302 clinical medicine Biology (General) Receptor Internalization skin and connective tissue diseases Spectroscopy cellular entry media_common 0303 health sciences General Medicine Heparan sulfate Transmembrane protein 3. Good health Computer Science Applications Cell biology Chemistry Ectodomain 030220 oncology & carcinogenesis Spike Glycoprotein Coronavirus Angiotensin-Converting Enzyme 2 QH301-705.5 Cell Survival media_common.quotation_subject coronaviruses Protein domain Biology Article Catalysis Cell Line Inorganic Chemistry 03 medical and health sciences Protein Domains Epithelial Sodium Channel Blockers Humans Physical and Theoretical Chemistry QD1-999 Molecular Biology 030304 developmental biology SARS-CoV-2 Organic Chemistry fungi COVID-19 Virus Internalization syndecans respiratory tract diseases body regions Membrane protein chemistry Syndecan-4 Peptides Receptors Coronavirus |
| Zdroj: | International Journal of Molecular Sciences Volume 22 Issue 10 International Journal of Molecular Sciences, Vol 22, Iss 5336, p 5336 (2021) |
| ISSN: | 1422-0067 |
| DOI: | 10.3390/ijms22105336 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|