9F2I

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

This is a non-PDB format compatible entry.

Summary for 9F2I

• Entry DOI: 10.2210/pdb9f2i/pdb
• Related: 9F2G 9F2H
• Descriptor: Nucleoprotein, 2-amino-1,3-benzothiazol-6-ol, SULFATE ION, ... (5 entities in total)
• Functional Keywords: ctd, sars-cov-2 nucleocapsid, covid-19, riluzole, benzothiazols, viral protein
• Biological source: Severe acute respiratory syndrome coronavirus 2
• Total number of polymer chains: 8
• Total formula weight: 100989.48

Authors

Marquez-Monino, M.A.,Gonzalez, B.,Perez-Canadillas, J.M. (deposition date: 2024-04-23, release date: 2024-11-13, Last modification date: 2024-11-27)

Primary citation

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, 2024

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

Experimental method

X-RAY DIFFRACTION (1.45 Å)