Abstract
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.
Competing Interest Statement
The authors have declared no competing interest.
Footnotes
Email Addresses: Chao Gao cgao3{at}bidmc.harvard.edu, Junwei Zeng jzeng1{at}bidmc.harvard.edu, Nan Jia njia{at}bidmc.harvard.edu, Kathrin Stavenhagen kstavenh{at}bidmc.harvard.edu, Yasuyuki Matsumoto ymatsumo{at}bidmc.harvard.edu, Hua Zhang Hua.Zhang{at}nyulangone.org, Jiang Li rejia{at}channing.harvard.edu, Adam J. Hume hume{at}bu.edu, Elke Mühlberger muehlber{at}bu.edu, Irma van Die irma.van.die{at}gmail.com, Julian Kwan jhkwan{at}bu.edu, Kelan Tantisira kelan.tantisira{at}channing.harvard.edu, Andrew Emili aemili{at}bu.edu