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

After discovering the high binding affinity between HP and SARS-CoV-2 SGP, we next found that the degree and position of sulfation within HP was important for its successful binding to monomeric SARS-CoV-2 SGP (Figs 3 and 4) . The low IC50 of these GAGs suggest that the FDA approved anticoagulant HP, or its nonanticoagulant derivatives, might have therapeutic potential against SARS-CoV-2 infection as competitive inhibitors. The location of proposed GAG-binding sites is also of interest. Unlike SARS-CoV and MERS-CoV SGPs, SARS-CoV-2 SGP has a novel insert in the amino acid sequence (681-686 (PRRARS)) that fully follows GAG-binding Cardin-Weintraub motif (XBBXBX) and a furin-cleavage motif (BBXBB) at the S1/S2 junction (Fig 1) . This site was also shown to be a preferred GAG-binding motif by our unbiased docking study (Fig 5) . Proteolytic cleavage at S1/S2 is not required for successful viral-host cellular membrane fusion in SARS-CoV author/funder. All rights reserved. No reuse allowed without permission.