Glycosaminoglycan binding motif at S1/S2 proteolytic cleavage site on spike glycoprotein may facilitate novel coronavirus (SARS-CoV-2) host cell entry

So Young Kim; Weihua Jin; Amika Sood; David W. Montgomery; Oliver C. Grant; Mark M. Fuster; Li Fu; Jonathan S. Dordick; Robert J. Woods; Fuming Zhang; Robert J. Linhardt

Using a modified version of Autodock Vina tuned for use with carbohydrates (Vina-Carb) [20, 21] , we performed blind docking on the trimeric SARS-CoV-2 SGP model to discover objectively the preferred binding GAG-binding sites on the SGP protein surface. The SGP contains three putative GAG-binding motifs with the following sequences: 453-459 (YRLFRKS), 681-686 (PRRARS), and 810-816 (SKPSKRS), which we define as sites 1, 2, and 3, respectively (Fig 1, S2 Fig, S3 Fig) . An HS hexasaccharide fragment (GlcA(2S)-GlcNS(6S)) binds site 2 in each monomer chain in the trimeric SGP ( Fig 5C, S3 Fig) . The docking results also indicates that HS may bind to site 1 when the apex of the S1 monomer is in an open conformation, as this allows basic residues to be more accessible to ligand binding. The site 1 residues are less accessible for GAG binding when the domain is in a closed conformation (Fig 5D) . The electrostatic potential surface representation of the trimeric SGP confirms that the GAG-binding poses generally prefer regions of positive charge, as expected, and illustrates that basic residues within site 3 are not exposed for binding to HS on any of the chains (Fig 5A) . Finally, our blind docking analysis reveals that a longer HS polymer may span an inter-domain channel that contains site 2.