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  3. Broad-spectrum synthetic carbohydrate receptors (SCRs) inhibit viral entry across multiple virus families

Broad-spectrum synthetic carbohydrate receptors (SCRs) inhibit viral entry across multiple virus families

  • Sci Adv. 2025 Aug 29;11(35):eady3554. doi: 10.1126/sciadv.ady3554.
Shahrzad Ezzatpour 1 2,  Khushabu Thakur 3 4,  Kenneth Erzoah Ndede 3 5,  David W Buchholz 1,  Annette Choi 1,  Brian Imbiakha 1,  Jordan Carter 1,  David Onofrei 6,  Brett Eaton 7,  Elena Postnikova 7,  Michael Murphy 7,  Beicer C Tapia 4 8,  Diana Bello 4 5,  Siddharth Pasari 9,  Anthony Russo 9,  Matthew Babayev 10,  Gregory P Holland 6,  Michael R Holbrook 7,  Sara L Caddy 11,  Steven J Moran 11,  Seyed Mohammad Davachi 12,  Isaac Abrrey Monreal 1,  Julie Sahler 1,  Victoria Ortega 1,  Jose M Miranda 13,  Gary R Whittaker 1,  Mason C Jager 14,  Seema K Bhagwat 15,  Pradeep Chopra 15,  Geert Jan-Boons 15 16 17,  Mateusz Marianski 4 5 8,  Adam B Braunschweig 3 4 5 8,  Hector C Aguilar 1 18
Affiliations

Affiliations

  • 1 Department of Microbiology and Immunology, Cornell University College of Veterinary Medicine, Ithaca, NY 14853, USA.
  • 2 Department of Microbiology, College of Agriculture and Life Sciences, Cornell University, Ithaca, NY.
  • 3 Advanced Science Research Center at The Graduate Center of the City University of New York 85 St Nicholas Terrace, New York, NY 10031 USA.
  • 4 Department of Chemistry and Biochemistry, Hunter College, 695 Park Ave., New York, NY 10065 USA.
  • 5 Graduate program in Chemistry, Graduate Center of the City University of New York, 365 5th Ave., New York, NY 10016 (USA).
  • 6 Department of Chemistry and Biochemistry, San Diego State University, San Diego, CA 92182 USA.
  • 7 National Institute of Allergy and Infectious Diseases Integrated Research Facility, Ft. Detrick, Frederick, MD 21702 USA.
  • 8 Graduate program in Biochemistry, Graduate Center of the City University of New York, 365 5th Ave., New York, NY 10016 (USA).
  • 9 Hunter High School, 71 East 94th Street, New York, NY 10128, USA.
  • 10 Sophie Davis Biomedical Education Program at the CUNY School of Medicine, 160 Convent Ave., New York, NY 10031 USA.
  • 11 Baker Institute for Animal Health, Cornell University, Ithaca, NY 14850, USA.
  • 12 Department of Biology and Chemistry, Texas A&M International University, Laredo, TX 78041, United States.
  • 13 Department of Analytical Chemistry, Nutrition and Food Science, School of Veterinary Sciences, Universidade de Santiago de Compostela, Pabellon 4, Planta Baja, 27002 Lugo, Spain.
  • 14 Department of Population Medicine and Diagnostic Sciences, Cornell University College of Veterinary Medicine, Ithaca, NY 14853, USA.
  • 15 Complex Carbohydrate Research Center, University of Georgia, 315 Riverbend Rd., Athens, GA 30602, USA.
  • 16 Department of Chemistry, University of Georgia, Athens, GA 30602, USA.
  • 17 Chemical Biology & Drug Discovery, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, 3584 CG Utrecht, Netherlands.
  • 18 Department of Microbiology, Immunology, and Molecular Genetics, David Geffen School of Medicine, Division of Life Sciences, College of Letters and Science, University of California, Los Angeles, CA 90095, USA.
PMID: 40864723 DOI: 10.1126/sciadv.ady3554
Abstract

Viral pandemics continue to threaten global health and economic stability. Despite medical advances, the absence of broad-spectrum antivirals (BSAs) prevents rapid responses to emerging viral threats. 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, SCR005 and SCR007, 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.

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