The COVID-19 pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a grave threat to public health and the global economy. SARS-CoV-2 is closely related to the more lethal but less transmissible coronaviruses SARS-CoV-1 and Middle East respiratory syndrome coronavirus (MERS-CoV). Here, we have carried out comparative viral-human proteinprotein interaction and viral protein localization analyses for all three viruses. Subsequent functional genetic screening identified host factors that functionally impinge on coronavirus proliferation, including Tom70, a mitochondrial chaperone protein that interacts with both SARS-CoV-1 and SARSCoV- 2 ORF9b, an interaction we structurally characterized using cryo-electron microscopy. Combining genetically validated host factors with both COVID-19 patient genetic data and medical billing records identified molecular mechanisms and potential drug treatments that merit further molecular and clinical study.


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Gordon, D., Hiatt, J., Bouhaddou, M., Rezelj, V., Ulferts, S., Braberg, H., Jureka, A., Obernier, K., Guo, J., Batra, J., Kaake, R., Weckstein, A., Owens, T., Gupta, M., Pourmal, S., Titus, E., Cakir, M., Soucheray, M., McGregor, M., Cakir, Z., Jang, G., O'Meara, M., Tummino, T., Zhang, Z., Foussard, H., Rojc, A., Zhou, Y., Kuchenov, D., Hüttenhain, R., Xu, J., Eckhardt, M., Swaney, D., Fabius, J., Ummadi, M., Tutuncuoglu, B., Rathore, U., Modak, M., Haas, P., Haas, K., Williams, D., Hastie, C., Elliott, M., Brown, F., Burness, K., Reid, E., Baillie, C., Raggett, S., Toth, R., Alessi, D., Davies, P., García-Sastre, A., Rassen, J., Grosse, R., Rosenberg, O., Verba, K., Basler, C., Vignuzzi, M., Peden, A., Beltrao, P. & Krogan, N. 2020, 'Comparative host-coronavirus protein interaction networks reveal pan-viral disease mechanisms', Science, 370(6521), article no: eabe9403. https://doi.org/10.1126/science.abe9403

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Last updated: 01 April 2023
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