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The copyright holder for this preprint (which was not peer-reviewed) is the . https://doi.org/10.1101/2020.04.14.041459 doi: bioRxiv preprint core proteins as proteoglycans (PGs) and reside inside the cell, at the cell surface, and in the extracellular matrix (ECM) [15] . GAGs facilitate various biological processes, including cellular signaling, pathogenesis, and immunity, and possess diverse therapeutic applications [15] . For example, an FDA approved anticoagulant heparin (HP) is a secretory GAG released from granules of mast cells during infection [15, 16] . Some GAG binding proteins can be identified by amino acid sequences known as Cardin-Weintraub motifs corresponding to 'XBBXBX' and 'XBBBXXBX', where X is a hydropathic residue and B is a basic residue, such as arginine and lysine, responsible for interacting with the sulfate groups present in GAGs [17, 18] . Examination of the SARS-CoV-2 SGP sequence revealed that the GAG-binding motif resides within S1-S2 proteolytic cleavage motif (furin cleavage motif BBXBB) that is not present in SARS-CoV or MERS-CoV SGPs (Fig 1, S2 Fig, S3 Fig) [19] . Additionally, we discovered GAG-binding-like motifs within RBD and S2' proteolytic cleavage site in SARS-CoV-2 SGP (Fig 1, S2 Fig, S3 Fig) .