9PYW

SARS-CoV-2 nsp7, nsp8 and nsp12 bound to a primer-template pair with incorporated ara-UMP

9PYW の概要

• エントリーDOI: 10.2210/pdb9pyw/pdb
• 関連するPDBエントリー: 9BLF 9PYZ 9PZ0
• EMDBエントリー: 72038
• 分子名称: RNA-directed RNA polymerase nsp12, Non-structural protein 8, Non-structural protein 7, ... (7 entities in total)
• 機能のキーワード: rna-dependent rna polymerase (rdrp), viral rna synthesis, arabinose utp, nsp7, nsp8, nsp12, viral protein
• 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: 185381.87

構造登録者

Xiao, Z.,Kirchdeorfer, R.N. (登録日: 2025-08-08, 公開日: 2025-09-17)

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.
The 2'-endo conformation of arabinose-CTP and arabinose-UTP inhibit viral polymerases by inducing long pauses.
Biorxiv, 2025

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 SARS-CoV-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 in both SARS-CoV-2 and poliovirus polymerase RNA elongation. Our studies suggest that subsequent nucleotide incorporation is inhibited at the catalytic step due to the 2'-endo sugar pucker of the incorporated ara-NMP.

PubMed: 40909592
DOI: 10.1101/2025.08.26.672356

実験手法

ELECTRON MICROSCOPY (3.1 Å)