Human coronaviruses are typically associated with mild upper respiratory illness. However, SARS-CoV-2 belongs to the Betacoronavirus genus, which also includes SARS-CoV (79% genetic similarity), and Middle East respiratory syndrome coronavirus (MERS-CoV) (about 50% similarity), and has the potential to infect both the upper and lower respiratory tracts leading to a severe and fatal respiratory syndrome in humans. Evasion of IFN-mediated antiviral signaling is a common defense strategy that pathogenic viruses use to replicate and propagate in their host. In this study, we show that SARS-CoV-2 is able to efficiently block STAT1 and STAT2 nuclear translocation in order to impair transcriptional induction of IFN-stimulated genes (ISGs). The viral accessory protein Orf6 exerts this anti-IFN activity. SARS-CoV-2 Orf6 localizes at the nuclear pore complex (NPC) and directly interacts with Nup98-Rae1 via its C-terminal domain to impair docking of cargo-receptor (karyopherin/importin) complex and disrupt nuclear import. All these events describes how the virus hijacks the Nup98-Rae1 complex to overcome the antiviral action of IFN. Here you can see the crystal structure of the C-terminal tail of SARS-CoV-2 Orf6 (ribbon model) complex with human nucleoporin pair Rae1-Nup98 (sphere model) (PDB code: 7VPH)
#molecularart ... #immolecular ... #SARS-CoV-2 ... #IFN ... #orf6 ... #hijacking ... #interferon ... #nuclearcomplex ... #xray
SARS-CoV-2 Orf6 in complex with nucleoporin rendered with @proteinimaging and depicted with @corelphotopaint.
#molecularart ... #immolecular ... #SARS-CoV-2 ... #IFN ... #orf6 ... #hijacking ... #interferon ... #nuclearcomplex ... #xray
SARS-CoV-2 Orf6 in complex with nucleoporin rendered with @proteinimaging and depicted with @corelphotopaint.
