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

Based on our findings, we propose a model on how GAGs may facilitate host cell entry of SARS-CoV-2 (Fig 6) . First, virions land on the epithelial surface in the airway by binding to HS through their SGPs (Fig 6A) . Host cell surface proteoglycans utilize their long HS chains to securely wrap around the trimeric SGP ( Fig 6A) . During this step, heavily sulfated HS chains span inter-domain channel containing GAG-binding site 2 on each monomer in the trimeric SGP and binds site 1 within the RBD in an open conformation (Fig 5) . Host cell surface and extracellular proteases, such as furin and transmembrane serine protease 2 (TMPRSS2), may process site 2 (S1/S2 junction) and/or 3 (S2') and GAG chains come off from site 2 upon cleavage (Fig 6B) . HS and ACE2 binding to more readily accessible RBD containing site 1 may drive conformational change of SGP and activate viral-cellular membrane fusion [30] . Finally, SGP on the endocytosed author/funder. All rights reserved. No reuse allowed without permission.