SARS-CoV-2 Spike Protein Interacts with Multiple Innate Immune Receptors


Gao C, Zeng J, Jia N, Stavenhagen K, Matsumoto Y, Zhang H, Li J, Hume AJ, Mühlberger E, van Die I, et al. SARS-CoV-2 Spike Protein Interacts with Multiple Innate Immune Receptors. bioRxiv. 2020.

Date Published:

2020 Jul 30


The spike (S) glycoprotein in the envelope of SARS-CoV-2 is densely glycosylated but the functions of its glycosylation are unknown. Here we demonstrate that S is recognized in a glycan-dependent manner by multiple innate immune receptors including the mannose receptor MR/CD206, DC-SIGN/CD209, L-SIGN/CD209L, and MGL/CLEC10A/CD301. Single-cell RNA sequencing analyses indicate that such receptors are highly expressed in innate immune cells in tissues susceptible to SARS-CoV-2 infection. Binding of the above receptors to S is characterized by affinities in the picomolar range and consistent with S glycosylation analysis demonstrating a variety of N- and O-glycans as receptor ligands. These results indicate multiple routes for SARS-CoV-2 to interact with human cells and suggest alternative strategies for therapeutic intervention.