8X1H

Crystal structure of N-terminal domain of Nucleocapsid protein of SARS-CoV-2

8X1H の概要

• エントリーDOI: 10.2210/pdb8x1h/pdb
• 分子名称: Nucleoprotein, GLYCEROL (3 entities in total)
• 機能のキーワード: nucleocapsid, sars-cov-2, coronavirus, rna binding protein
• 由来する生物種: Severe acute respiratory syndrome coronavirus 2
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 58757.58

構造登録者

Kumari, S.,Gupta, G.D. (登録日: 2023-11-07, 公開日: 2023-11-22, 最終更新日: 2025-01-29)

主引用文献

Kumari, S.,Mistry, H.,Bihani, S.C.,Mukherjee, S.P.,Gupta, G.D.
Unveiling potential inhibitors targeting the nucleocapsid protein of SARS-CoV-2: Structural insights into their binding sites.
Int.J.Biol.Macromol., 273:133167-133167, 2024

PubMed Abstract: The Nucleocapsid (N) protein of SARS-CoV-2 plays a crucial role in viral replication and pathogenesis, making it an attractive target for developing antiviral therapeutics. In this study, we used differential scanning fluorimetry to establish a high-throughput screening method for identifying high-affinity ligands of N-terminal domain of the N protein (N-NTD). We screened an FDA-approved drug library of 1813 compounds and identified 102 compounds interacting with N-NTD. The screened compounds were further investigated for their ability to inhibit the nucleic-acid binding activity of the N protein using electrophoretic mobility-shift assays. We have identified three inhibitors, Ceftazidime, Sennoside A, and Tannic acid, that disrupt the N protein's interaction with RNA probe. Ceftazidime and Sennoside A exhibited nano-molar range binding affinities with N protein, determined through surface plasmon resonance. The binding sites of Ceftazidime and Sennoside A were investigated using [H, N]-heteronuclear single quantum coherence (HSQC) NMR spectroscopy. Ceftazidime and Sennoside A bind to the putative RNA binding site of the N protein, thus providing insights into the inhibitory mechanism of these compounds. These findings will contribute to the development of novel antiviral agents targeting the N protein of SARS-CoV-2.

PubMed: 38885868
DOI: 10.1016/j.ijbiomac.2024.133167

実験手法

X-RAY DIFFRACTION (2 Å)