{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T07:50:19Z","timestamp":1782892219044,"version":"3.54.5"},"reference-count":124,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2021,5,19]],"date-time":"2021-05-19T00:00:00Z","timestamp":1621382400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100010661","name":"Horizon 2020 Framework Programme","doi-asserted-by":"publisher","award":["863214"],"award-info":[{"award-number":["863214"]}],"id":[{"id":"10.13039\/100010661","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010661","name":"Horizon 2020 Framework Programme","doi-asserted-by":"publisher","award":["807015"],"award-info":[{"award-number":["807015"]}],"id":[{"id":"10.13039\/100010661","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100015269","name":"Magyarorsz\u00e1g Korm\u00e1nya","doi-asserted-by":"publisher","award":["GINOP-2.1.2-8-1-4-16-2017-00234"],"award-info":[{"award-number":["GINOP-2.1.2-8-1-4-16-2017-00234"]}],"id":[{"id":"10.13039\/501100015269","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012550","name":"Nemzeti Kutat\u00e1si, Fejleszt\u00e9si \u00e9s Innovaci\u00f3s Alap","doi-asserted-by":"publisher","award":["EUREKA_16-1-2017-0018"],"award-info":[{"award-number":["EUREKA_16-1-2017-0018"]}],"id":[{"id":"10.13039\/501100012550","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012550","name":"Nemzeti Kutat\u00e1si, Fejleszt\u00e9si \u00e9s Innovaci\u00f3s Alap","doi-asserted-by":"publisher","award":["2017-2.3.6-T\u00c9T-CN-2018-00023"],"award-info":[{"award-number":["2017-2.3.6-T\u00c9T-CN-2018-00023"]}],"id":[{"id":"10.13039\/501100012550","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>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\u2019s 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.<\/jats:p>","DOI":"10.3390\/ijms22105336","type":"journal-article","created":{"date-parts":[[2021,5,19]],"date-time":"2021-05-19T12:58:07Z","timestamp":1621429087000},"page":"5336","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":52,"title":["Contribution of Syndecans to the Cellular Entry of SARS-CoV-2"],"prefix":"10.3390","volume":"22","author":[{"given":"Anett","family":"Hud\u00e1k","sequence":"first","affiliation":[{"name":"Pharmacoidea Ltd., H-6726 Szeged, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annam\u00e1ria","family":"Letoha","sequence":"additional","affiliation":[{"name":"Department of Medicine, Albert Szent-Gy\u00f6rgyi Clinical Center, Faculty of Medicine, University of Szeged, H-6725 Szeged, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L\u00e1szl\u00f3","family":"Szil\u00e1k","sequence":"additional","affiliation":[{"name":"Pharmacoidea Ltd., H-6726 Szeged, Hungary"},{"name":"Szilak Laboratories, Bioinformatics and Molecule-Design, H-6723 Szeged, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6035-4009","authenticated-orcid":false,"given":"Tam\u00e1s","family":"Letoha","sequence":"additional","affiliation":[{"name":"Pharmacoidea Ltd., H-6726 Szeged, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,5,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"100124","DOI":"10.1016\/j.onehlt.2020.100124","article-title":"From SARS to COVID-19: A previously unknown SARS- related coronavirus (SARS-CoV-2) of pandemic potential infecting humans\u2014Call for a One Health approach","volume":"9","author":"Jarhult","year":"2020","journal-title":"One Health"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"549","DOI":"10.1093\/clinchem\/hvaa029","article-title":"Molecular Diagnosis of a Novel Coronavirus (2019-nCoV) Causing an Outbreak of Pneumonia","volume":"66","author":"Chu","year":"2020","journal-title":"Clin. 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