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SARS-CoV-2 Nucleocapsid (N) protein binds a subset of human CHKs with high affinity, inhibiting their chemoattractant properties. Here, we report that both N\u2019s RNA-binding and dimerization domains participate individually in CHK binding. CHKs typically possess independent sites for binding glycosaminoglycans\u00a0(GAG) and their receptor proteins. We show that the interaction with the N protein occurs through the CHK GAG-binding site, pointing the way to developing compounds that block this interaction for potential anti-coronavirus therapeutics.<\/jats:p>","DOI":"10.1186\/s12985-025-02658-1","type":"journal-article","created":{"date-parts":[[2025,3,17]],"date-time":"2025-03-17T11:47:24Z","timestamp":1742212044000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Chemokines simultaneously bind SARS-CoV-2 nucleocapsid protein RNA-binding and dimerization domains"],"prefix":"10.1186","volume":"22","author":[{"given":"Alberto Domingo","family":"L\u00f3pez-Mu\u00f1oz","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jonathan W.","family":"Yewdell","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2025,3,17]]},"reference":[{"issue":"1","key":"2658_CR1","doi-asserted-by":"publisher","first-page":"36","DOI":"10.1038\/nri980","volume":"3","author":"A Alcami","year":"2003","unstructured":"Alcami A. 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