Amphiphilic Heparinoids as Potent Antiviral Agents against SARS-CoV-2.

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  • Additional Information
    • Source:
      Publisher: American Chemical Society Country of Publication: United States NLM ID: 9716531 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1520-4804 (Electronic) Linking ISSN: 00222623 NLM ISO Abbreviation: J Med Chem Subsets: MEDLINE
    • Publication Information:
      Publication: Washington Dc : American Chemical Society
      Original Publication: [Easton, Pa.] : American Chemical Society, [c1963-
    • Subject Terms:
      Antiviral Agents*/pharmacology ; Antiviral Agents*/chemistry ; Antiviral Agents*/chemical synthesis ; SARS-CoV-2*/drug effects; Humans ; Oligosaccharides/pharmacology ; Oligosaccharides/chemical synthesis ; Oligosaccharides/chemistry ; COVID-19 Drug Treatment ; Animals ; Vero Cells ; Chlorocebus aethiops ; Structure-Activity Relationship ; COVID-19/virology ; Glucuronidase ; Saponins
    • Abstract:
      Herein, we report the synthesis and biological evaluation of a novel series of heparinoid amphiphiles as inhibitors of heparanase and SARS-CoV-2. By employing a tailor-made synthetic strategy, a library of highly sulfated homo-oligosaccharides bearing d-glucose or a C5-epimer (i.e., l-idose or l-iduronic acid) conjugated with various lipophilic groups was synthesized and investigated for antiviral activity. Sulfated higher oligosaccharides of d-glucose or l-idose with lipophilic aglycones displayed potent anti-SARS-CoV-2 and antiheparanse activity, similar to or better than pixatimod (PG545), and were more potent than their isosteric l-iduronic acid congeners. Lipophilic groups such as cholestanol and C 18 -aliphatic substitution are more advantageous than functional group appended lipophilic moieties. These findings confirm that fine-tuning of higher oligosaccharides, degree of sulfation, and lipophilic groups can yield compounds with potent anti-SARS-CoV-2 activity.
    • Accession Number:
      0 (Antiviral Agents)
      EC 3.2.1.- (heparanase)
      0 (Oligosaccharides)
      0 (PG 545)
      EC 3.2.1.31 (Glucuronidase)
      0 (Saponins)
    • Publication Date:
      Date Created: 20240712 Date Completed: 20240725 Latest Revision: 20240729
    • Publication Date:
      20240730
    • Accession Number:
      10.1021/acs.jmedchem.4c00487
    • Accession Number:
      38995734