Synthesis of multivalent sialyllactose-conjugated PAMAM dendrimers: Binding to SARS-CoV-2 spike protein and influenza hemagglutinin

Authors:

Peng He a b, Ke Xia a b, Yuefan Song a b, Ritesh Tandon c, Rudra Channappanavar d, Fuming Zhang b e, Robert J. Linhardt a b e

Affiliation:

Department of Chemistry and Chemical Biology, Rensselaer Polytechnic Institute, Troy, NY 12180, USA

Center for Biotechnology and Interdisciplinary Studies, Rensselaer Polytechnic Institute, Troy, NY 12180, USA

Center for Immunology and Microbial Research, Department of Cell Biology, Medicine and BioMolecular Sciences, University of Mississippi Medical Center, Jackson, MS, USA

Department of Veterinary Pathobiology, Oklahoma Center for Respiratory and Infectious Diseases (OCRID), Oklahoma State University, Stillwater, OK, USA

Department of Chemical and Biological Engineering, Rensselaer Polytechnic Institute, Troy, NY 12180, USA

Description:

Severe acute respiratory syndrome-related coronavirus-2 (SARS-CoV-2) and influenza viruses have spread around the world at an unprecedented rate. Despite multiple vaccines, new variants of SARS-CoV-2 and influenza have caused a remarkable level of pathogenesis. The development of effective antiviral drugs to treat SARS-CoV-2 and influenza remains a high priority. Inhibiting viral cell surface attachment represents an early and efficient means to block virus infection. Sialyl glycoconjugates, on the surface of human cell membranes, play an important role as host cell receptors for influenza A virus and 9-O-acetyl-sialylated glycoconjugates are receptors for MERS, HKU1 and bovine coronaviruses. We designed and synthesized multivalent 6′-sialyllactose-counjugated polyamidoamine dendrimers through click chemistry at room temperature concisely. These dendrimer derivatives have good solubility and stability in aqueous solutions. SPR, a real-time analysis quantitative method for of biomolecular interactions, was used to study the binding affinities of our dendrimer derivatives by utilizing only 200 micrograms of each dendrimer. Three SARS-CoV-2 S-protein receptor binding domain (wild type and two Omicron mutants) bound to multivalent 9-O-acetyl-6′-sialyllactose-counjugated and 6′-sialyllactose-counjugated dendrimers bound to a single H3N2 influenza A virus's HA protein (A/Hong Kong/1/1968), the SPR study results suggest their potential anti-viral activities.

Publications:

  • He, Peng, et al.; Synthesis of multivalent sialyllactose-conjugated PAMAM dendrimers: Binding to SARS-CoV-2 spike protein and influenza hemagglutinin; International Journal of Biological Macromolecules, 2023
  • Tags:

    Click chemistry
    SARS-CoV-2
    Sialyl glycoconjugate

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