7DTE

SARS-CoV-2 RdRP catalytic complex with T33-1 RNA

Summary for 7DTE

• Entry DOI: 10.2210/pdb7dte/pdb
• EMDB information: 30852
• Descriptor: RNA-directed RNA polymerase, Non-structural protein 8, Non-structural protein 7, ... (6 entities in total)
• Functional Keywords: covid-19, sars-cov-2, virus, rdrp, nsp12, nsp7, nsp8, rtc, cryo-em, viral protein, rna polymerase, drug target, antiviral, viral protein-rna complex, viral protein/rna
• Biological source: Severe acute respiratory syndrome coronavirus 2 (2019-nCoV); More
• Total number of polymer chains: 6
• Total formula weight: 191174.31

Authors

Wang, Q.,Gong, P. (deposition date: 2021-01-04, release date: 2021-10-20, Last modification date: 2024-06-05)

Primary citation

Wu, J.,Wang, H.,Liu, Q.,Li, R.,Gao, Y.,Fang, X.,Zhong, Y.,Wang, M.,Wang, Q.,Rao, Z.,Gong, P.
Remdesivir overcomes the S861 roadblock in SARS-CoV-2 polymerase elongation complex.
Cell Rep, 37:109882-109882, 2021

PubMed Abstract: Remdesivir (RDV), a nucleotide analog with broad-spectrum features, has exhibited effectiveness in COVID-19 treatment. However, the precise working mechanism of RDV when targeting the viral RNA-dependent RNA polymerase (RdRP) has not been fully elucidated. Here, we solve a 3.0-Å structure of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RdRP elongation complex (EC) and assess RDV intervention in polymerase elongation phase. Although RDV could induce an "i+3" delayed termination in meta-stable complexes, only pausing and subsequent elongation are observed in the EC. A comparative investigation using an enterovirus RdRP further confirms similar delayed intervention and demonstrates that steric hindrance of the RDV-characteristic 1'-cyano at the -4 position is responsible for the "i+3" intervention, although two representative Flaviviridae RdRPs do not exhibit similar behavior. A comparison of representative viral RdRP catalytic complex structures indicates that the product RNA backbone encounters highly conserved structural elements, highlighting the broad-spectrum intervention potential of 1'-modified nucleotide analogs in anti-RNA virus drug development.

PubMed: 34653416
DOI: 10.1016/j.celrep.2021.109882

Experimental method

ELECTRON MICROSCOPY (3 Å)