A glycosaminoglycan microarray identifies the binding of SARS‐CoV‐2 spike protein to chondroitin sulfate E

Heparan sulfate (HS), a sulfated glycosaminoglycan (GAG), was reported to be a necessary host attachment factor that promotes SARS‐CoV‐2 infection. In this study, we developed GAG microarrays based on fluorescence detection for high‐sensitivity screening of the GAG‐binding specificity of proteins and applied it for the analysis of SARS‐CoV‐2 spike (S) protein. Among the 20 distinct GAGs, the S protein bound not only to heparin (HEP)/HS but also to chondroitin sulfate E (CSE) in a concentration‐dependent manner. We then analyzed the specificity of each subunit of the S protein. While the S1 subunit showed exclusive binding to HEP, the S2 subunit also bound to CSE and HEP/HS. CSE might act as an alternative attachment factor for HS in SARS‐CoV‐2 infection.