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-Structure paper
タイトル | Remdesivir overcomes the S861 roadblock in SARS-CoV-2 polymerase elongation complex. |
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ジャーナル・号・ページ | Cell Rep, Vol. 37, Issue 4, Page 109882, Year 2021 |
掲載日 | 2021年10月26日 |
![]() | Jiqin Wu / Haofeng Wang / Qiaojie Liu / Rui Li / Yan Gao / Xiang Fang / Yao Zhong / Meihua Wang / Quan Wang / Zihe Rao / Peng Gong / ![]() |
PubMed 要旨 | 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- ...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. |
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手法 | EM (単粒子) |
解像度 | 3.0 Å |
構造データ | EMDB-30852, PDB-7dte: |
化合物 | ![]() ChemComp-ZN: |
由来 |
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![]() | VIRAL PROTEIN/RNA / COVID-19 / SARS-CoV-2 / Virus / RdRp / nsp12 / nsp7 / nsp8 / RTC / cryo-EM / Viral protein / RNA polymerase / drug target / antiviral / VIRAL PROTEIN-RNA complex |