Gene

Coronavirus

Cell biology

Linguistics

Philosophy

Biology

RNA polymerase II

Virology

Transcription (linguistics)

Promoter

Coronavirus disease 2019 (COVID-19)

Genetics

Infectious disease (medical specialty)

Polymerase

Protein subunit

Medicine

Disease

RNA polymerase

Gene expression

Pathology

Nature Communications

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.

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