7NT4

X-ray structure of SCoV2-PLpro in complex with small molecule inhibitor

7NT4 の概要

• エントリーDOI: 10.2210/pdb7nt4/pdb
• 分子名称: Non-structural protein 3, PROFLAVIN, 1,2-ETHANEDIOL, ... (6 entities in total)
• 機能のキーワード: drug repurposing, scov2-plpro inhibitor, hydrolase
• 由来する生物種: Severe acute respiratory syndrome coronavirus 2 (2019-nCoV, SARS-CoV-2)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 74162.75

構造登録者

Napolitano, V.,Mourao, A.,Bostock, M.,Matsuda, A.,Czarna, A.,Popowicz, G.M. (登録日: 2021-03-09, 公開日: 2022-02-02, 最終更新日: 2024-11-06)

主引用文献

Napolitano, V.,Dabrowska, A.,Schorpp, K.,Mourao, A.,Barreto-Duran, E.,Benedyk, M.,Botwina, P.,Brandner, S.,Bostock, M.,Chykunova, Y.,Czarna, A.,Dubin, G.,Frohlich, T.,Holscher, M.,Jedrysik, M.,Matsuda, A.,Owczarek, K.,Pachota, M.,Plettenburg, O.,Potempa, J.,Rothenaigner, I.,Schlauderer, F.,Slysz, K.,Szczepanski, A.,Greve-Isdahl Mohn, K.,Blomberg, B.,Sattler, M.,Hadian, K.,Popowicz, G.M.,Pyrc, K.
Acriflavine, a clinically approved drug, inhibits SARS-CoV-2 and other betacoronaviruses.
Cell Chem Biol, 29:774-, 2022

PubMed Abstract: The COVID-19 pandemic caused by SARS-CoV-2 has been socially and economically devastating. Despite an unprecedented research effort and available vaccines, effective therapeutics are still missing to limit severe disease and mortality. Using high-throughput screening, we identify acriflavine (ACF) as a potent papain-like protease (PL) inhibitor. NMR titrations and a co-crystal structure confirm that acriflavine blocks the PL catalytic pocket in an unexpected binding mode. We show that the drug inhibits viral replication at nanomolar concentration in cellular models, in vivo in mice and ex vivo in human airway epithelia, with broad range activity against SARS-CoV-2 and other betacoronaviruses. Considering that acriflavine is an inexpensive drug approved in some countries, it may be immediately tested in clinical trials and play an important role during the current pandemic and future outbreaks.

PubMed: 35021060
DOI: 10.1016/j.chembiol.2021.11.006

実験手法

X-RAY DIFFRACTION (2.68 Å)