期刊
CELL
卷 182, 期 6, 页码 1560-+出版社
CELL PRESS
DOI: 10.1016/j.cell.2020.07.033
关键词
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资金
- NIH National Institute of General Medical Sciences [P41 GM103310]
- NYSTAR
- Simons Foundation [SF349247]
- NIH Common Fund Transformative High Resolution Cryo-Electron Microscopy Program [U24 GM129539]
- NY State Assembly Majority
- Pels Family Center for Biochemistry and Structural Biology (The Rockefeller University)
- NIH [P41 GM109824, P41 GM103314, R35 GM130234, R35 GM118130, R01 GM114450]
SARS-CoV-2 is the causative agent of the 2019-2020 pandemic. The SARS-CoV-2 genome is replicated and transcribed by the RNA-dependent RNA polymerase holoenzyme (subunits nsp7/nsp82/nsp12) along with a cast of accessory factors. One of these factors is the nsp13 helicase. Both the holo-RdRp and nsp13 are essential for viral replication and are targets for treating the disease COVID-19. Here we present cryoelectron microscopic structures of the SARS-CoV-2 holo-RdRp with an RNA template product in complex with two molecules of the nsp13 helicase. The Nidovirales order-specific N-terminal domains of each nsp13 interact with the N-terminal extension of each copy of nsp8. One nsp13 also contacts the nsp12 thumb. The structure places the nucleic acid-binding ATPase domains of the helicase directly in front of the replicating-transcribing holo-RdRp, constraining models for nsp13 function. We also observe ADP-Mg2+ bound in the nsp12 N-terminal nidovirus RdRp-associated nucleotidyltransferase domain, detailing a new pocket for anti-viral therapy development.
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