We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Discovery and structural characterization of chicoric acid as a SARS-CoV-2 nucleocapsid protein ligand and RNA binding disruptor.
- Authors
Mercaldi, Gustavo Fernando; Bezerra, Eduardo Henrique Salviano; Batista, Fernanda Aparecida Heleno; Tonoli, Celisa Caldana Costa; Soprano, Adriana Santos; Shimizu, Jacqueline Farinha; Nagai, Alice; da Silva, Jaqueline Cristina; Filho, Helder Veras Ribeiro; do Nascimento Faria, Jéssica; da Cunha, Marcos Guilherme; Zeri, Ana Carolina Mattos; Nascimento, Andrey Fabricio Ziem; Proenca-Modena, José Luiz; Bajgelman, Marcio Chaim; Rocco, Silvana Aparecida; Lopes-de-Oliveira, Paulo Sérgio; Cordeiro, Artur Torres; Bruder, Marjorie; Marques, Rafael Elias
- Abstract
The nucleocapsid (N) protein plays critical roles in coronavirus genome transcription and packaging, representing a key target for the development of novel antivirals, and for which structural information on ligand binding is scarce. We used a novel fluorescence polarization assay to identify small molecules that disrupt the binding of the N protein to a target RNA derived from the SARS-CoV-2 genome packaging signal. Several phenolic compounds, including L-chicoric acid (CA), were identified as high-affinity N-protein ligands. The binding of CA to the N protein was confirmed by isothermal titration calorimetry, 1H-STD and 15N-HSQC NMR, and by the crystal structure of CA bound to the N protein C-terminal domain (CTD), further revealing a new modulatory site in the SARS-CoV-2 N protein. Moreover, CA reduced SARS-CoV-2 replication in cell cultures. These data thus open venues for the development of new antivirals targeting the N protein, an essential and yet underexplored coronavirus target.
- Subjects
RNA-binding proteins; SARS-CoV-2; C-terminal binding proteins; ISOTHERMAL titration calorimetry; SMALL molecules; LIGAND binding (Biochemistry)
- Publication
Scientific Reports, 2022, Vol 12, Issue 1, p1
- ISSN
2045-2322
- Publication type
Article
- DOI
10.1038/s41598-022-22576-4