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

Science. 2020 Dec 4;370(6521):eabe9403. doi: 10.1126/science.abe9403. Epub 2020 Oct 15.

Abstract

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.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • COVID-19 / metabolism*
  • Conserved Sequence
  • Coronavirus Nucleocapsid Proteins / genetics
  • Coronavirus Nucleocapsid Proteins / metabolism*
  • Cryoelectron Microscopy
  • Host Microbial Interactions*
  • Humans
  • Mitochondrial Membrane Transport Proteins / genetics
  • Mitochondrial Membrane Transport Proteins / metabolism*
  • Phosphoproteins / genetics
  • Phosphoproteins / metabolism
  • Protein Conformation
  • Protein Interaction Maps*
  • SARS Virus / metabolism*
  • SARS-CoV-2 / metabolism*
  • Severe Acute Respiratory Syndrome / metabolism*

Substances

  • Coronavirus Nucleocapsid Proteins
  • Mitochondrial Membrane Transport Proteins
  • Phosphoproteins
  • TOMM70 protein, human
  • nucleocapsid phosphoprotein, SARS-CoV-2

Grant support