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

Nat Commun. 2019 May 28;10(1):2342. doi: 10.1038/s41467-019-10280-3.

Abstract

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.

Publication types

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

MeSH terms

  • Coenzymes / ultrastructure*
  • Cryoelectron Microscopy
  • DNA-Directed RNA Polymerases / ultrastructure*
  • Genome, Viral
  • Severe acute respiratory syndrome-related coronavirus / metabolism
  • Severe acute respiratory syndrome-related coronavirus / ultrastructure*
  • Viral Nonstructural Proteins / ultrastructure*

Substances

  • Coenzymes
  • Viral Nonstructural Proteins
  • DNA-Directed RNA Polymerases