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

• Published in: Nature communications Vol. 10; no. 1; pp. 2342 - 9
• Main Authors: Kirchdoerfer, Robert N., Ward, Andrew B.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 28.05.2019; Nature Publishing Group; Nature Portfolio
• Subjects: 101/28; 631/326/596/2078; 631/45/535/1258/1259; 82/83; Catalysis; Coenzymes - ultrastructure; Coronaviridae; Coronaviruses; COVID-19; Cryoelectron Microscopy; DNA-Directed RNA Polymerases - ultrastructure; Drug development; Electron microscopy; Genome, Viral; Genomes; Humanities and Social Sciences; Kinases; multidisciplinary; Respiratory diseases; Ribonucleic acid; RNA; RNA polymerase; Science; Science (multidisciplinary); Severe acute respiratory syndrome; Severe acute respiratory syndrome-related coronavirus - metabolism; Severe acute respiratory syndrome-related coronavirus - ultrastructure; Structural proteins; Transcription; Viral Nonstructural Proteins - ultrastructure
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-019-10280-3

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. The pathogenic human coronaviruses SARS- and MERS-CoV can cause severe respiratory disease. Here the authors present the 3.1Å cryo-EM structure of the SARS-CoV RNA polymerase nsp12 bound to its essential co-factors nsp7 and nsp8, which is of interest for antiviral drug development.