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.
This work is licensed under a Creative Commons Attribution 4.0 International (CC BY 4.0) license, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. To view a copy of this license, visit https://creativecommons.org/licenses/by/4.0/. This license does not apply to figures/photos/artwork or other content included in the article that is credited to a third party; obtain authorization from the rights holder before using such material.
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