9f2h
From Proteopedia
Crystal structure of SARS-CoV-2 N-protein C-terminal domain in complex with riluzole
Structural highlights
FunctionNCAP_SARS2 Packages the positive strand viral genome RNA into a helical ribonucleocapsid (RNP) and plays a fundamental role during virion assembly through its interactions with the viral genome and membrane protein M. Plays an important role in enhancing the efficiency of subgenomic viral RNA transcription as well as viral replication. Publication Abstract from PubMedNucleoproteins (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. The ALS drug riluzole binds to the C-terminal domain of SARS-CoV-2 nucleocapsid protein and has antiviral activity.,Marquez-Monino MA, Santiveri CM, de Leon P, Camero S, Campos-Olivas R, Jimenez MA, Saiz M, Gonzalez B, Perez-Canadillas JM Structure. 2024 Nov 8:S0969-2126(24)00460-X. doi: 10.1016/j.str.2024.10.025. PMID:39541975[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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