Binding of the SARS-CoV-2 Spike Protein to Glycans

The 2019 novel coronavirus (SARS-CoV-2) is the seventh human coronavirus. The pandemic of this virus has caused a high number of deaths in the world. In order to more efficiently combat this pandemic, it is necessary to develop a better understanding of how the virus infects host cells. Infection normally starts with the initial attachment of the virus to cell-surface glycans like heparan sulfate (HS) proteoglycans and sialic acid-containing oligosaccharides. In this study, we used glycan microarray technology to study the binding of the SARS-CoV-2 spike protein (S protein) to HS and sialic acid. Our results indicated that the S protein can bind to HS in a sulfation-dependent manner and the length of HS appears not to be a critical factor for the binding. No binding with sialic acid residues was detected. In addition, we applied sequence alignment and molecular docking to analyze and explain the observed binding results. Our results suggested that HS may stabilize the open conformation of the S protein to promote the subsequent binding of the S protein to the virus entry receptor ACE2. Overall, this work supports the potential importance of HS in SARS-CoV-2 infection and in the development of antiviral agents.