• Comparative host-coronavirus protein interaction networks reveal pan-viral disease mechanisms

      Gordon, David E; Hiatt, Joseph; Bouhaddou, Mehdi; Rezelj, Veronica V; Ulferts, Svenja; Braberg, Hannes; Jureka, Alexander S; Obernier, Kirsten; Guo, Jeffrey Z; Batra, Jyoti; et al. (American Association for the Advancement of Science, 2020-12-04)
      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 protein-protein 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 SARS-CoV-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.