{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T16:07:15Z","timestamp":1787069235016,"version":"build-2736575974"},"reference-count":272,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2021,1,20]],"date-time":"2021-01-20T00:00:00Z","timestamp":1611100800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The occurrence of the novel severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), responsible for coronavirus disease 2019 (COVD-19), represents a catastrophic threat to global health. Protruding from the viral surface is a densely glycosylated spike (S) protein, which engages angiotensin-converting enzyme 2 (ACE2) to mediate host cell entry. However, studies have reported viral susceptibility in intra- and extrapulmonary immune and non-immune cells lacking ACE2, suggesting that the S protein may exploit additional receptors for infection. Studies have demonstrated interactions between S protein and innate immune system, including C-lectin type receptors (CLR), toll-like receptors (TLR) and neuropilin-1 (NRP1), and the non-immune receptor glucose regulated protein 78 (GRP78). Recognition of carbohydrate moieties clustered on the surface of the S protein may drive receptor-dependent internalization, accentuate severe immunopathological inflammation, and allow for systemic spread of infection, independent of ACE2. Furthermore, targeting TLRs, CLRs, and other receptors (Ezrin and dipeptidyl peptidase-4) that do not directly engage SARS-CoV-2 S protein, but may contribute to augmented anti-viral immunity and viral clearance, may represent therapeutic targets against COVID-19.<\/jats:p>","DOI":"10.3390\/ijms22030992","type":"journal-article","created":{"date-parts":[[2021,1,20]],"date-time":"2021-01-20T04:10:48Z","timestamp":1611115848000},"page":"992","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":137,"title":["Can SARS-CoV-2 Virus Use Multiple Receptors to Enter Host Cells?"],"prefix":"10.3390","volume":"22","author":[{"given":"Laura Kate","family":"Gadanec","sequence":"first","affiliation":[{"name":"Institute for Health and Sport, Victoria University, Melbourne 3030, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristen Renee","family":"McSweeney","sequence":"additional","affiliation":[{"name":"Institute for Health and Sport, Victoria University, Melbourne 3030, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tawar","family":"Qaradakhi","sequence":"additional","affiliation":[{"name":"Institute for Health and Sport, Victoria University, Melbourne 3030, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8856-9274","authenticated-orcid":false,"given":"Benazir","family":"Ali","sequence":"additional","affiliation":[{"name":"Institute for Health and Sport, Victoria University, Melbourne 3030, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anthony","family":"Zulli","sequence":"additional","affiliation":[{"name":"Institute for Health and Sport, Victoria University, Melbourne 3030, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6788-2771","authenticated-orcid":false,"given":"Vasso","family":"Apostolopoulos","sequence":"additional","affiliation":[{"name":"Institute for Health and Sport, Victoria University, Melbourne 3030, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,1,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1722","DOI":"10.1021\/acscentsci.0c01056","article-title":"Beyond Shielding: The Roles of Glycans in the SARS-CoV-2 Spike Protein","volume":"6","author":"Casalino","year":"2020","journal-title":"ACS Cent. 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