Viral Proteome – Host Proteome Interactions

A SARS-CoV-2-Human Protein-Protein Interaction Map Reveals Drug Targets and Potential Drug Repurposing

  • NSP 2 – binds EIF4E2, FKBP15, GIGYF2, POR, WASHC4, RAP1GDS1, and SLC27A2
  • PL Proteinase / NSP 3 –
  • NSP 4 – binds TIM complex proteins (TIMM10, TIMM10b, TIMM29, TIMM9), NUP210, IDE, ALG11, and DNAJC11 . Has 4 transmembrane spanning segments.
  • 3 CL Proteinase / NSP 5 – binds HDAC2 or version C145A binds TRMT1 and GPX1
  • NSP 6 -binds SIGMAR1, ATP13A3, ATP5MG, ATP6AP1 . Has 6 transmembrane spanning segments.
  • NSP 7 – binds Rab signaling proteins
  • NSP 8 – binds exosome, 7SK SNRP, Signal Recognition Particle, Mitochondrial Ribosome, and other proteins
  • NSP 9 – binds Nuclear pore (), Fibrillin
  • NSP 10 -binds AP2 Clathrin
  • NSP 11 – binds TBCA
  • Spike protein – binds protein palmitoylation proteins ( GCLGA7, ZDHHC5)
  • Orf 3a and 3b – Forms homotetrameric potassium sensitive ion channels (viroporin) and may modulate virus release. Up-regulates expression of fibrinogen subunits FGA, FGB and FGG in host lung epithelial cells. Induces apoptosis in cell culture. Downregulates the type 1 interferon receptor by inducing serine phosphorylation within the IFN alpha-receptor subunit 1 (IFNAR1) degradation motif and increasing IFNAR1 ubiquitination Involved in escort independent budding. binds HOPS complex, and STOML2
  • Envelope protein Central role in viral morphogenesis and assembly. Interacts with membrane protein Behaves like a viroporin. Promotes apoptosis
  • Membrane protein – Central role in viral morphogenesis and assembly. Interacts with envelope proteins. binds solute carrier family proteins, and ER morphology proteins.
  • Orf 6 Disrupts interferon signaling by preventing nuclear import of proteins. Disrupts cell nuclear import complex formation by tethering karyopherin alpha 2 and karyopherin beta 1 to the membrane. Retention of import factors at the ER/Golgi membrane leads to a loss of transport into the nucleus. Thereby prevents STAT1 nuclear translocation in response to interferon signaling, thus blocking the expression of interferon stimulated genes (ISGs) that display multiple antiviral activities. binds nuclear pore proteins
  • Orf 7a Disrupts tetherin antiviral activity
  • Orf 7b Interacts with MAVS and UNC93B1
  • Orf 8 Inhibition of MHC Class I presentation. Binds ER protein quality control proteins
  • Orf 9b (Alternative Orf in N gene) Disrupts RiG like receptor based innate immunity. binds MARK kinases
  • Orf 9c – binds Electron transport proteins and GPI anchor biosynthesis enzymes.
  • Nucleocapsid – binds stress granules and RNA processing proteins
  • Orf 10 – ? if expressed . binds CUL2 complex
  • Orf 14