8C19

SARS-CoV-2 NSP3 macrodomain in complex with 1-methyl-4-[5-(morpholin-4-ylcarbonyl)-2-furyl]-1H-pyrrolo[2,3-b]pyridine

8C19 の概要

• エントリーDOI: 10.2210/pdb8c19/pdb
• 分子名称: Non-structural protein 3, 1,2-ETHANEDIOL, [5-(1-methylpyrrolo[2,3-b]pyridin-4-yl)furan-2-yl]-morpholin-4-yl-methanone, ... (4 entities in total)
• 機能のキーワード: macrodomain, adp-ribose, sars-cov-2, viral protein
• 由来する生物種: Severe acute respiratory syndrome coronavirus 2
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 36979.21

構造登録者

Schuller, M.,Ahel, I. (登録日: 2022-12-20, 公開日: 2023-03-08, 最終更新日: 2024-06-19)

主引用文献

Schuller, M.,Zarganes-Tzitzikas, T.,Bennett, J.,De Cesco, S.,Fearon, D.,von Delft, F.,Fedorov, O.,Brennan, P.E.,Ahel, I.
Discovery and Development Strategies for SARS-CoV-2 NSP3 Macrodomain Inhibitors.
Pathogens, 12:-, 2023

PubMed Abstract: The worldwide public health and socioeconomic consequences caused by the COVID-19 pandemic highlight the importance of increasing preparedness for viral disease outbreaks by providing rapid disease prevention and treatment strategies. The NSP3 macrodomain of coronaviruses including SARS-CoV-2 is among the viral protein repertoire that was identified as a potential target for the development of antiviral agents, due to its critical role in viral replication and consequent pathogenicity in the host. By combining virtual and biophysical screening efforts, we discovered several experimental small molecules and FDA-approved drugs as inhibitors of the NSP3 macrodomain. Analogue characterisation of the hit matter and crystallographic studies confirming binding modes, including that of the antibiotic compound aztreonam, to the active site of the macrodomain provide valuable structure-activity relationship information that support current approaches and open up new avenues for NSP3 macrodomain inhibitor development.

PubMed: 36839595
DOI: 10.3390/pathogens12020324

実験手法

X-RAY DIFFRACTION (1.95 Å)