High resolution photocatalytic mapping of SARS-CoV-2 Spike protein-host cell membrane interactions

Datta, S.; Tavares, A. H.; Reyes-Robles, T.; Ryu, K. A.; Khan, N.; Bechtel, T. J.; Bertoch, J. M.; White, C. H.; Hazuda, D. J.; Vora, K. A.; Hett, E. C.; Fadeyi, O. O.; Oslund, R. C.; Saeed, M.; Emili, A.

doi:10.1101/2022.09.02.506438

bioRxiv · 10.1101/2022.09.02.506438

High resolution photocatalytic mapping of SARS-CoV-2 Spike protein-host cell membrane interactions

Datta, S.·Tavares, A. H.·Reyes-Robles, T.·Ryu, K. A.·Khan, N.·Bechtel, T. J.·Bertoch, J. M.·White, C. H.·Hazuda, D. J.·Vora, K. A.·Hett, E. C.·Fadeyi, O. O.·Oslund, R. C.·Saeed, M.·Emili, A.

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Abstract

Identifying protein environments at the virus-host cell interface can improve our understanding of viral entry and pathogenesis. SARS-CoV-2, the virus behind the ongoing COVID-19 pandemic, uses the cell surface ACE2 protein as a major receptor, but the contribution of other cellular proteins in the entry process is unknown. To probe the microenvironment of SARS-CoV-2 Spike-ACE2 protein interactomes on human cells, we developed a photocatalyst-based viral-host protein microenvironment mapping platform (ViraMap) employing iridium photocatalysts conjugated to Spike for visible-light driven proximity labelling on host cells. Application of ViraMap on ACE2-expressing cells captured ACE2, the established co-receptor NRP1, as well as other proteins implicated in host cell entry and immunomodulation. We further investigated these enriched proteins via loss-of-function and over-expression in pseudotype and authentic infection models and observed that the Ig receptor PTGFRN and tyrosine kinase ligand EFNB1 can serve as SARS-CoV-2 entry factors. Our results highlight additional host targets that participate infection and showcase ViraMap for interrogating virus-host cell surface interactomes.

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Datta, S., Tavares, A. H., Reyes-Robles, T., Ryu, K. A., Khan, N., Bechtel, T. J., Bertoch, J. M., White, C. H., Hazuda, D. J., Vora, K. A., Hett, E. C., Fadeyi, O. O., Oslund, R. C., Saeed, M., Emili, A.. 2022-09-03. High resolution photocatalytic mapping of SARS-CoV-2 Spike protein-host cell membrane interactions. https://doi.org/10.1101/2022.09.02.506438

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