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Through single-molecule F\u00f6rster resonance energy transfer imaging of individual S trimers, we demonstrate that SA binding to the NTD allosterically shifts the S conformational equilibrium, favoring enhanced exposure of the ACE2-binding site. Antibodies that target the NTD block SA binding, which contributes to their mechanism of neutralization. These findings inform on mechanisms of S activation at the cell surface.<\/jats:p>","DOI":"10.1126\/sciadv.adk4920","type":"journal-article","created":{"date-parts":[[2024,7,17]],"date-time":"2024-07-17T18:00:47Z","timestamp":1721239247000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":23,"title":["Single-molecule imaging reveals allosteric stimulation of SARS-CoV-2 spike receptor binding domain by host sialic acid"],"prefix":"10.1126","volume":"10","author":[{"given":"Marco A.","family":"D\u00edaz-Salinas","sequence":"first","affiliation":[{"name":"Department of Microbiology and Physiological Systems, University of Massachusetts Chan Medical School, Worcester, MA 01605, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2827-6263","authenticated-orcid":true,"given":"Aastha","family":"Jain","sequence":"additional","affiliation":[{"name":"Department of Microbiology and 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