9F2I

Crystal structure of SARS-CoV-2 N-protein C-terminal domain in complex with 2-amino-1,3-benzothiazol-6-ol

これはPDB形式変換不可エントリーです。

9F2I の概要

• エントリーDOI: 10.2210/pdb9f2i/pdb
• 関連するPDBエントリー: 9F2G 9F2H
• 分子名称: Nucleoprotein, 2-amino-1,3-benzothiazol-6-ol, SULFATE ION, ... (5 entities in total)
• 機能のキーワード: ctd, sars-cov-2 nucleocapsid, covid-19, riluzole, benzothiazols, 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: 8
• 化学式量合計: 100989.48

構造登録者

Marquez-Monino, M.A.,Gonzalez, B.,Perez-Canadillas, J.M. (登録日: 2024-04-23, 公開日: 2024-11-13, 最終更新日: 2025-01-15)

主引用文献

Marquez-Monino, M.A.,Santiveri, C.M.,de Leon, P.,Camero, S.,Campos-Olivas, R.,Jimenez, M.A.,Saiz, M.,Gonzalez, B.,Perez-Canadillas, J.M.
The ALS drug riluzole binds to the C-terminal domain of SARS-CoV-2 nucleocapsid protein and has antiviral activity.
Structure, 33:39-, 2025

PubMed Abstract: Nucleoproteins (N) play an essential role in virus assembly and are less prone to mutation than other viral structural proteins, making them attractive targets for drug discovery. Using an NMR fragment-based drug discovery approach, we identified the 1,3-benzothiazol-2-amine (BZT) group as a scaffold to develop potential antivirals for SARS-CoV-2 nucleocapsid (N) protein. A thorough characterization of BZT derivatives using NMR, X-ray crystallography, antiviral activity assays, and intrinsic fluorescence measurements revealed their binding in the C-terminal domain (CTD) domain of the N protein, to residues Arg 259, Trp 330, and Lys 338, coinciding with the nucleotide binding site. Our most effective compound exhibits a slightly better affinity than GTP and the ALS drug riluzole, also identified during the screening, and displays notable viral inhibition activity. A virtual screening of 218 BZT-based compounds revealed a potential extended binding site that could be exploited for the future development of new SARS-CoV-2 antivirals.

PubMed: 39541975
DOI: 10.1016/j.str.2024.10.025

実験手法

X-RAY DIFFRACTION (1.45 Å)