A SARS-CoV-2 BioID-based virus-host membrane protein interactome and virus peptide compendium: new proteomics resources for COVID-19 research

St-Germain, J. R.; Astori, A.; Samavarchi-Tehrani, P.; Abdouni, H.; Macwan, V.; Kim, D.-K.; Knapp, J. J.; Roth, F. P.; Gingras, A.-C.; Raught, B.

doi:10.1101/2020.08.28.269175

bioRxiv · 10.1101/2020.08.28.269175

A SARS-CoV-2 BioID-based virus-host membrane protein interactome and virus peptide compendium: new proteomics resources for COVID-19 research

St-Germain, J. R.·Astori, A.·Samavarchi-Tehrani, P.·Abdouni, H.·Macwan, V.·Kim, D.-K.·Knapp, J. J.·Roth, F. P.·Gingras, A.-C.·Raught, B.

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Abstract

Key steps of viral replication take place at host cell membranes, but the detection of membrane-associated protein-protein interactions using standard affinity-based approaches (e.g. immunoprecipitation coupled with mass spectrometry, IP-MS) is challenging. To learn more about SARS-CoV-2 - host protein interactions that take place at membranes, we utilized a complementary technique, proximity-dependent biotin labeling (BioID). This approach uncovered a virus-host topology network comprising 3566 proximity interactions amongst 1010 host proteins, highlighting extensive virus protein crosstalk with: (i) host protein folding and modification machinery; (ii) membrane-bound vesicles and organelles, and; (iii) lipid trafficking pathways and ER-organelle membrane contact sites. The design and implementation of sensitive mass spectrometric approaches for the analysis of complex biological samples is also important for both clinical and basic research proteomics focused on the study of COVID-19. To this end, we conducted a mass spectrometry-based characterization of the SARS-CoV-2 virion and infected cell lysates, identifying 189 unique high-confidence virus tryptic peptides derived from 17 different virus proteins, to create a high quality resource for use in targeted proteomics approaches. Together, these datasets comprise a valuable resource for MS-based SARS-CoV-2 research, and identify novel virus-host protein interactions that could be targeted in COVID-19 therapeutics.

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St-Germain, J. R., Astori, A., Samavarchi-Tehrani, P., Abdouni, H., Macwan, V., Kim, D.-K., Knapp, J. J., Roth, F. P., Gingras, A.-C., Raught, B.. 2020-08-28. A SARS-CoV-2 BioID-based virus-host membrane protein interactome and virus peptide compendium: new proteomics resources for COVID-19 research. https://doi.org/10.1101/2020.08.28.269175

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