7D4F

Structure of COVID-19 RNA-dependent RNA polymerase bound to suramin

7D4F の概要

• エントリーDOI: 10.2210/pdb7d4f/pdb
• EMDBエントリー: 30572
• 分子名称: Non-structural protein 8, Non-structural protein 7, RNA-directed RNA polymerase, ... (5 entities in total)
• 機能のキーワード: covid-19, rna polymerase, suramin binding, viral protein
• 由来する生物種: Severe acute respiratory syndrome coronavirus 2 (2019-nCoV); 詳細
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 162815.84

構造登録者

Li, Z.,Yin, W.,Zhou, Z.,Yu, X.,Xu, H. (登録日: 2020-09-23, 公開日: 2020-11-11, 最終更新日: 2025-07-02)

主引用文献

Yin, W.,Luan, X.,Li, Z.,Zhou, Z.,Wang, Q.,Gao, M.,Wang, X.,Zhou, F.,Shi, J.,You, E.,Liu, M.,Wang, Q.,Jiang, Y.,Jiang, H.,Xiao, G.,Zhang, L.,Yu, X.,Zhang, S.,Eric Xu, H.
Structural basis for inhibition of the SARS-CoV-2 RNA polymerase by suramin.
Nat.Struct.Mol.Biol., 28:319-325, 2021

PubMed Abstract: The COVID-19 pandemic caused by nonstop infections of SARS-CoV-2 has continued to ravage many countries worldwide. Here we report that suramin, a 100-year-old drug, is a potent inhibitor of the SARS-CoV-2 RNA-dependent RNA polymerase (RdRp) and acts by blocking the binding of RNA to the enzyme. In biochemical assays, suramin and its derivatives are at least 20-fold more potent than remdesivir, the currently approved nucleotide drug for treatment of COVID-19. The 2.6 Å cryo-electron microscopy structure of the viral RdRp bound to suramin reveals two binding sites. One site directly blocks the binding of the RNA template strand and the other site clashes with the RNA primer strand near the RdRp catalytic site, thus inhibiting RdRp activity. Suramin blocks viral replication in Vero E6 cells, although the reasons underlying this effect are likely various. Our results provide a structural mechanism for a nonnucleotide inhibitor of the SARS-CoV-2 RdRp.

PubMed: 33674802
DOI: 10.1038/s41594-021-00570-0

実験手法

ELECTRON MICROSCOPY (2.57 Å)