PropertyValue
?:abstract
  • The COVID-19 pandemic caused by SARS-CoV-2 is in immediate need of an effective antidote. Although the Spike glycoprotein (SgP) of SARS-CoV-2 has been shown to bind to heparins, the structural features of this interaction, the role of a plausible heparan sulfate proteoglycan (HSPG) receptor, and the antagonism of this pathway through small molecules remain unaddressed. Using an in vitro cellular assay, we demonstrate HSPGs modified by the 3-O-sulfotransferase isoform-3, but not isoform-5, preferentially increased SgP-mediated cell-to-cell fusion in comparison to control, unmodified, wild-type HSPGs. Computational studies support preferential recognition of the receptor-binding domain of SgP by 3-O-sulfated HS sequences. Competition with either fondaparinux, a 3-O-sulfated HS-binding oligopeptide, or a synthetic, non-sugar small molecule, blocked SgP-mediated cell-to-cell fusion. Finally, the synthetic, sulfated molecule inhibited fusion of GFP-tagged pseudo SARS-CoV-2 with human 293T cells with sub-micromolar potency. Overall, overexpression of 3-O-sulfated HSPGs contribute to fusion of SARS-CoV-2, which could be effectively antagonized by a synthetic, small molecule.
is ?:annotates of
?:creator
?:doi
?:doi
  • 10.1101/2020.10.08.331751
?:journal
  • bioRxiv
?:license
  • cc-by-nc-nd
?:pdf_json_files
  • document_parses/pdf_json/a74396d30933b3200d39c24b07328fa1b9f4aae3.json; document_parses/pdf_json/8c96333b80abfb7dc08478b37720e45b523787f9.json
?:pmc_json_files
  • document_parses/pmc_json/PMC7553162.xml.json
?:pmcid
?:pmid
?:pmid
  • 33052337.0
?:publication_isRelatedTo_Disease
is ?:relation_isRelatedTo_publication of
?:sha_id
?:source
  • BioRxiv; Medline; PMC; WHO
?:title
  • Preferential recognition and antagonism of SARS-CoV-2 spike glycoprotein binding to 3-O-sulfated heparan sulfate
?:type
?:year
  • 2020-10-08

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