Download MendeleyThe ALS drug riluzole binds to the C-terminal domain of SARS-CoV-2 nucleocapsid protein and has antiviral activity.
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.(2025) Structure 33: 39
- PubMed: 39541975
- DOI: https://doi.org/10.1016/j.str.2024.10.025
- Primary Citation of Related Structures:
9F2G, 9F2H, 9F2I - 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.
Organizational Affiliation:
Institute of Physical-Chemistry "Blas Cabrera", CSIC, C/ Serrano 119, 28006 Madrid, Spain.
