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

Previous reports showed that various CoV bind GAGs through their SGPs to invade host cells [13] . In the current study, we utilized SPR to measure the binding kinetics and interaction affinity of monomeric and trimeric SARS-CoV-2, monomeric SARS-CoV and MERS-CoV with SGP-HP using a sensor chip with immobilized HP. Sensorgrams of CoV SGP-HP interactions are shown in Fig 2. The sensorgrams were fit globally to obtain association rate constant (ka), dissociation rate constant (kd) and equilibrium dissociation constant (KD) ( Table 1) using the BiaEvaluation software and assuming a 1:1 Langmuir model. SARS-CoV-2 and MERS CoV SGP exhibited a markedly low dissociation rate constant (kd ~ 10 -7 1/s) suggesting excellent binding strength. The HP binding properties of monomeric SARS-CoV-2 SGP was comparable to that of the trimeric form (KD of monomer and trimer were 40 pM and 73 pM, respectively). In comparison, previously known HP binding SARS-CoV SGP showed nearly 10-fold lower affinity, 500 nM.