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This is largely due to the lack of universal drug targets across diverse viral families and high variability among viral proteins. In this study, we evaluated 57 synthetic carbohydrate receptors (SCRs) for antiviral activity in cellulo using pseudotyped virus particles (PVPs) from six high-risk viruses across three families: Paramyxoviridae, Filoviridae, and Coronaviridae. Four SCRs inhibited all tested PVPs, and their efficacy was confirmed against live viruses including SARS-CoV-2, MERS-CoV, EBOV, MARV, NiV, and HeV. Notably,\n            <jats:bold>SCR005<\/jats:bold>\n            and\n            <jats:bold>SCR007<\/jats:bold>\n            , which exhibited minimal toxicity, significantly reduced SARS-CoV-2 infection in a severe animal model with a single dose. Mechanistic studies suggested that SCRs bind viral envelope N-glycans, blocking viral attachment and\/or fusion. These results identify conserved viral N-glycans as promising BSA targets and establish SCRs as candidate prophylactic agents against enveloped viruses with pandemic potential.\n          <\/jats:p>","DOI":"10.1126\/sciadv.ady3554","type":"journal-article","created":{"date-parts":[[2025,8,27]],"date-time":"2025-08-27T17:59:06Z","timestamp":1756317546000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":3,"title":["Broad-spectrum synthetic carbohydrate receptors (SCRs) inhibit viral entry across multiple virus families"],"prefix":"10.1126","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9688-2375","authenticated-orcid":true,"given":"Shahrzad","family":"Ezzatpour","sequence":"first","affiliation":[{"name":"Department of Microbiology and Immunology, Cornell University College of Veterinary Medicine, Ithaca, NY 14853, USA."},{"name":"Department of Microbiology, College of Agriculture and Life Sciences, Cornell University, Ithaca, NY."}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6498-7487","authenticated-orcid":true,"given":"Khushabu","family":"Thakur","sequence":"additional","affiliation":[{"name":"Advanced Science Research Center at The Graduate Center of the City University of New York 85 St Nicholas Terrace, New York, NY 10031 USA."},{"name":"Department of Chemistry and Biochemistry, Hunter College, 695 Park Ave., New York, NY 10065 USA."}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-4089-8456","authenticated-orcid":true,"given":"Kenneth","family":"Erzoah Ndede","sequence":"additional","affiliation":[{"name":"Advanced Science Research Center at The Graduate Center of the City University of New York 85 St Nicholas Terrace, New York, NY 10031 USA."},{"name":"Graduate program in Chemistry, Graduate Center of the City University of New York, 365 5th Ave., New York, NY 10016 (USA)."}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8874-6648","authenticated-orcid":true,"given":"David W.","family":"Buchholz","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Cornell University College of Veterinary Medicine, Ithaca, NY 14853, USA."}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9537-5037","authenticated-orcid":true,"given":"Annette","family":"Choi","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Cornell University College of Veterinary Medicine, Ithaca, NY 14853, USA."}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8538-5445","authenticated-orcid":true,"given":"Brian","family":"Imbiakha","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Cornell University College of Veterinary Medicine, Ithaca, NY 14853, USA."}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-9679-4285","authenticated-orcid":true,"given":"Jordan","family":"Carter","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Cornell University College of Veterinary Medicine, Ithaca, NY 14853, USA."}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6386-0716","authenticated-orcid":true,"given":"David","family":"Onofrei","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Biochemistry, San Diego State University, San Diego, CA 92182 USA."}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3060-2913","authenticated-orcid":true,"given":"Brett","family":"Eaton","sequence":"additional","affiliation":[{"name":"National Institute of Allergy and Infectious Diseases Integrated Research Facility, Ft. 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