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Spike glycosylation is critical for ACE2 binding and subsequent viral fusion and entry. Here, we studied lectins for their ability to bind to SARS-CoV-2 Spike glycoprotein and SARS-CoV-2 virions by employing an array of 95 lectins, for 68 of which we predicted glycan-binding specificities using publically available glycan array data and MotifFinder software. We identified lectins with diverse glycan binding specificities that bound with high intensities to recombinant Spike and cultured SARS-CoV-2 virus \u2013 AAL, ABL, ACL, AMA, ASA, BANLEC, BC2L-A, RCA 120, CALSEPA, GAL3, GS-II, PALa, CA, HHA, PHA-L, PA-IIL, MNA-M, STL, LSL-N, GRFT, PSA, RS-FUC, PHA-E, CPA, LENTIL, RCA 60, GNA, ORYSATA, LcH A, PHA-P, PTL-2, MAA, Con A, TL, NPA, and SBA. Analyzing the glycan-binding specificities of these lectins, we predict that the Spike glycoprotein is modified with high mannose\/hybrid N-glycans with terminal mannose residues, \u03b11-6 core fucosylated N-glycans with terminal GlcNAc residues, and complex glycans with Lewis A, Lewis B, Lewis X, Lewis Y, and Blood group H structures on type-1 or type-2 extension sequences. The SARS-CoV-2-specific lectins identified in our study may be assessed for their antiviral potential in future studies.<\/jats:p>","DOI":"10.1038\/s41598-025-01903-5","type":"journal-article","created":{"date-parts":[[2025,7,1]],"date-time":"2025-07-01T18:28:44Z","timestamp":1751394524000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Identification of SARS-CoV-2-binding lectins on a commercial lectin array"],"prefix":"10.1038","volume":"15","author":[{"family":"Neetu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shimona","family":"Ahlawat","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rathina","family":"Delipan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rajesh P.","family":"Ringe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alka","family":"Rao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T. 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Cell 181, 271-280.e278. https:\/\/doi.org\/10.1016\/j.cell.2020.02.052 (2020).","journal-title":"Cell"},{"key":"1903_CR3","doi-asserted-by":"publisher","first-page":"221","DOI":"10.1038\/s41586-020-2179-y","volume":"581","author":"J Shang","year":"2020","unstructured":"Shang, J. et al. Structural basis of receptor recognition by SARS-CoV-2. Nature 581, 221\u2013224. https:\/\/doi.org\/10.1038\/s41586-020-2179-y (2020).","journal-title":"Nature"},{"key":"1903_CR4","doi-asserted-by":"publisher","first-page":"270","DOI":"10.1038\/s41586-020-2012-7","volume":"579","author":"P Zhou","year":"2020","unstructured":"Zhou, P. et al. A pneumonia outbreak associated with a new coronavirus of probable bat origin. Nature 579, 270\u2013273. https:\/\/doi.org\/10.1038\/s41586-020-2012-7 (2020).","journal-title":"Nature"},{"key":"1903_CR5","doi-asserted-by":"publisher","first-page":"1260","DOI":"10.1126\/science.abb2507","volume":"367","author":"D Wrapp","year":"2020","unstructured":"Wrapp, D. et al. Cryo-EM structure of the 2019-nCoV spike in the prefusion conformation. Science 367, 1260\u20131263. https:\/\/doi.org\/10.1126\/science.abb2507 (2020).","journal-title":"Science"},{"key":"1903_CR6","doi-asserted-by":"publisher","first-page":"343","DOI":"10.1038\/s41422-020-0305-x","volume":"30","author":"S Xia","year":"2020","unstructured":"Xia, S. et al. Inhibition of SARS-CoV-2 (previously 2019-nCoV) infection by a highly potent pan-coronavirus fusion inhibitor targeting its spike protein that harbors a high capacity to mediate membrane fusion. Cell. Res. 30, 343\u2013355. https:\/\/doi.org\/10.1038\/s41422-020-0305-x (2020).","journal-title":"Cell. Res."},{"key":"1903_CR7","doi-asserted-by":"publisher","first-page":"281","DOI":"10.1016\/j.cell.2020.02.058","volume":"181","author":"AC Walls","year":"2020","unstructured":"Walls, A. C. et al. Structure, Function, and Antigenicity of the SARS-CoV-2 Spike Glycoprotein. 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