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.
【저자키워드】 SARS virus, Cryoelectron microscopy, 【초록키워드】 coronavirus, Nsp12, SARS-CoV, Transcription, Cryo-electron microscopy, antiviral drug, Replication, non-structural protein, antiviral therapeutics, RNA polymerase, viral genome, host cells, complex, severe respiratory disease, extension, polymerase, N-terminal, highly pathogenic, infecting, recent, cryo-EM structure, responsible, provide, SARS- and MERS-CoV, human circulation, pathogenic human coronavirus, 【제목키워드】 Structure, Nsp12, SARS-CoV, polymerase,