Heparan Sulfate-Mimicking Glycopolymers Bind SARS-CoV-2 Spike Protein in a Length- and Sulfation Pattern-Dependent Manner.

ABSTRACT: Heparan sulfate-mimicking glycopolymers, composed of glucosamine (GlcN)-glucuronic acid (GlcA) repeating units, bind to the receptor-binding subunit (S1) and spike glycoprotein (S) domains of the SARS-CoV-2 spike protein in a length- and sulfation pattern-dependent fashion. A glycopolymer composed of 12 repeating GlcNS6S-GlcA units exhibits a much higher affinity to the S1 protein (IC₅₀ = 13 ± 1.1 nM) compared with the receptor-binding domain (RBD). This glycopolymer does not interfere in angiotensin-converting enzyme 2 binding of the RBD. Although this compound binds strongly to the S1/membrane-fusion subunit (S2) junction (K_D = 29.7 ± 4.18 nM), it does not shield the S1/S2 site from cleavage by furin-a behavior contrary to natural heparin. This glycopolymer l

SUBMITTER: Abdulsalam H 

PROVIDER: S-EPMC10577887 | biostudies-literature | 2023 Oct

REPOSITORIES: biostudies-literature