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

The original SARS-CoV and numerous pathogens exploit host cell surface GAGs during the initial step of host cell entry [12] [13] [14] . Based on our discovery of GAG-binding and GAGbinding-like motifs at site 1 (within the RBD, Y453-S459), site 2 (at the proteolytic cleavage site at S1/S2 junction, P681-S686), and site 3 (at the S2' proteolytic cleavage site, S810-S816), we hypothesized that SARS-CoV-2 may also interact with host cell surface GAGs through its SGPs to invade host cell (Fig 1, S2 Fig, S3 Fig) . The predominant GAG in normal human lung is HS followed by CS [22] and it is noteworthy that lung tissue is rich in mast cells and has been a source of commercial HP [23] . Using unbiased docking, we found that TriS HS hexasaccharide 5D ). Docking results indicated that the HS hexasaccharides could span an inter-domain channel that includes site 2, suggesting a mechanism for the binding of a longer HS sequence ( Fig 5C) .