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, A. J.; Muehlberger, E.; van Die, I.; Kwan, J.; Tantisira, K.; Emili, A.; Cummings, R. D.

doi:10.1101/2020.07.29.227462

bioRxiv · 10.1101/2020.07.29.227462

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, A. J.·Muehlberger, E.·van Die, I.·Kwan, J.·Tantisira, K.·Emili, A.·Cummings, R. D.

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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.

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Gao, C., Zeng, J., Jia, N., Stavenhagen, K., Matsumoto, Y., Zhang, H., Li, J., Hume, A. J., Muehlberger, E., van Die, I., Kwan, J., Tantisira, K., Emili, A., Cummings, R. D.. 2020-07-30. SARS-CoV-2 Spike Protein Interacts with Multiple Innate Immune Receptors. https://doi.org/10.1101/2020.07.29.227462

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