8X1H

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

Summary for 8X1H

• Entry DOI: 10.2210/pdb8x1h/pdb
• Descriptor: Nucleoprotein, GLYCEROL (3 entities in total)
• Functional Keywords: nucleocapsid, sars-cov-2, coronavirus, rna binding protein
• Biological source: Severe acute respiratory syndrome coronavirus 2
• Total number of polymer chains: 4
• Total formula weight: 58757.58

Authors

Kumari, S.,Gupta, G.D. (deposition date: 2023-11-07, release date: 2023-11-22, Last modification date: 2025-01-29)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (2 Å)