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Structure of the SARS-CoV nsp12 polymerase bound to nsp7 and nsp8 co-factors.

Robert N KirchdoerferAndrew B Ward
Published in: Nature communications (2019)
Recent history is punctuated by the emergence of highly pathogenic coronaviruses such as SARS- and MERS-CoV into human circulation. Upon infecting host cells, coronaviruses assemble a multi-subunit RNA-synthesis complex of viral non-structural proteins (nsp) responsible for the replication and transcription of the viral genome. Here, we present the 3.1 Å resolution structure of the SARS-CoV nsp12 polymerase bound to its essential co-factors, nsp7 and nsp8, using single particle cryo-electron microscopy. nsp12 possesses an architecture common to all viral polymerases as well as a large N-terminal extension containing a kinase-like fold and is bound by two nsp8 co-factors. This structure illuminates the assembly of the coronavirus core RNA-synthesis machinery, provides key insights into nsp12 polymerase catalysis and fidelity and acts as a template for the design of novel antiviral therapeutics.
Keyphrases
  • sars cov
  • respiratory syndrome coronavirus
  • endothelial cells
  • induced apoptosis
  • transcription factor
  • mass spectrometry
  • structural basis
  • coronavirus disease
  • tyrosine kinase