On the Selectivity of Heparan Sulfate Recognition by SARS-CoV-2 Spike Glycoprotein.

ABSTRACT: SARS-CoV-2 infects human cells through its surface spike glycoprotein (SgP), which relies on host cell surface heparan sulfate (HS) proteoglycans that facilitate interaction with the ACE2 receptor. Targeting this process could lead to inhibitors of early steps in viral entry. Screening a microarray of 24 HS oligosaccharides against recombinant S1 and receptor-binding domain (RBD) proteins led to identification of only eight sequences as potent antagonists; results that were supported by detailed dual-filter computational studies. Competitive studies using the HS microarray suggested almost equivalent importance of IdoA2S-GlcNS6S and GlcNS3S structures, which were supported by affinity studies. Exhaustive virtual screening on a library of >93 000 sequences led to a novel pharmacophore with

SUBMITTER: Chittum JE 

PROVIDER: S-EPMC8525342 | biostudies-literature | 2021 Nov

REPOSITORIES: biostudies-literature