9BLF

SARS-CoV-2 core polymerase complex inhibited by araCTP

9BLF の概要

• エントリーDOI: 10.2210/pdb9blf/pdb
• 関連するPDBエントリー: 9PYW 9PYZ 9PZ0
• EMDBエントリー: 44654
• 分子名称: RNA-directed RNA polymerase nsp12, Non-structural protein 8, Non-structural protein 7, ... (8 entities in total)
• 機能のキーワード: sars-cov-2, rdrp, polymerase, aractp, viral protein, viral protein-rna-inhibitor complex, viral protein/rna/inhibitor
• 由来する生物種: Severe acute respiratory syndrome coronavirus 2; 詳細
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 186914.20

構造登録者

Anderson, T.K.,Xiao, Z.,Kirchdeorfer, R.N. (登録日: 2024-04-30, 公開日: 2025-05-14, 最終更新日: 2026-05-27)

主引用文献

Xiao, Z.,Das, A.,Jain, A.,Anderson, T.K.,Cameron, C.E.,Arnold, J.J.,Dulin, D.,Kirchdoerfer, R.N.
Incorporation of arabinose-CTP and arabinose-UTP inhibits viral polymerases by inducing long pauses.
J.Biol.Chem., 302:111027-111027, 2026

PubMed Abstract: Key to supporting human health in the face of evolving viruses is the development of novel antiviral drug scaffolds with the potential for broad inhibition of viral families. Nucleoside analogs are a key class of drugs that have demonstrated potential for the inhibition of several viral species. Here, we evaluate arabinose nucleotides (ara-NTP) as inhibitors of the severe acute respiratory syndrome coronavirus 2 and poliovirus polymerases using biochemistry, biophysics, and structural biology. Ara-NTPs compete poorly with their natural counterparts for incorporation into RNA by viral polymerases. However, upon incorporation, ara-NMPs induce long polymerase pausing during both severe acute respiratory syndrome coronavirus 2 and poliovirus polymerase RNA elongation. Our studies suggest that following ara-NMP incorporation, additional nucleotide incorporation is inhibited at the catalytic step.

PubMed: 41380964
DOI: 10.1016/j.jbc.2025.111027

実験手法

ELECTRON MICROSCOPY (3.31 Å)