EMD-30275

Single-particle
2.93 Å
EMD-30275 Deposition: 07/05/2020
Map released: 03/06/2020
Last modified: 13/11/2024
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links

EMD-30275

COVID-19 RNA-dependent RNA polymerase pre-translocated catalytic complex

EMD-30275

Single-particle
2.93 Å
EMD-30275 Deposition: 07/05/2020
Map released: 03/06/2020
Last modified: 13/11/2024
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links
Sample Organism: Severe acute respiratory syndrome coronavirus 2, Foot-and-mouth disease virus
Sample: COVID-19 RNA-dependent RNA polymerase pre-translocated catalytic complex
Fitted models: 7c2k (Avg. Q-score: 0.581)

Deposition Authors: Wang Q, Gao Y, Ji W , Mu A, Rao Z
Structural Basis for RNA Replication by the SARS-CoV-2 Polymerase.
PUBMED: 32526208
DOI: doi:10.1016/j.cell.2020.05.034
ISSN: 1097-4172
Abstract:
Nucleotide analog inhibitors, including broad-spectrum remdesivir and favipiravir, have shown promise in in vitro assays and some clinical studies for COVID-19 treatment, this despite an incomplete mechanistic understanding of the viral RNA-dependent RNA polymerase nsp12 drug interactions. Here, we examine the molecular basis of SARS-CoV-2 RNA replication by determining the cryo-EM structures of the stalled pre- and post- translocated polymerase complexes. Compared with the apo complex, the structures show notable structural rearrangements happening to nsp12 and its co-factors nsp7 and nsp8 to accommodate the nucleic acid, whereas there are highly conserved residues in nsp12, positioning the template and primer for an in-line attack on the incoming nucleotide. Furthermore, we investigate the inhibition mechanism of the triphosphate metabolite of remdesivir through structural and kinetic analyses. A transition model from the nsp7-nsp8 hexadecameric primase complex to the nsp12-nsp7-nsp8 polymerase complex is also proposed to provide clues for the understanding of the coronavirus transcription and replication machinery.