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

possess both GAG-binding and furin cleavage motifs at their S1/S2 junction in their SGPs [13] . In the cases of MHV and IBV spike proteins, a single amino acid mutation near the GAG-binding and furin cleavage motifs resulted from a cell culture adaptation, and determines whether a virion binds GAGs or exploits host cell surface protease, but not both [28] . While not within the CoV family, human immunodeficiency virus type 1 (HIV-1) requires HS-binding to achieve optimal furin processing because HS binding allows selective exposure of furin cleavage site [29] . While the idea of repurposing HP as COVID-19 therapeutic sounds appealing, further questions, including in vitro relevance of GAGs as host cell surface receptors, proteolytic processing of SGPs at S1/S2 junction, and their relationship in host cell entry and infectivity, must first be carefully evaluated.