Hesperetin targets the hydrophobic pocket of the nucleoprotein/phosphoprotein binding site of human respiratory syncytial virus
| Autor: | Fátima Pereira de Souza, Eduardo Maffud Cilli, Fabio C. L. Almeida, Ljubica Tasic, Jessica M. Sa, Marcelo Andrés Fossey, João V Piloto, Ícaro Putinhon Caruso |
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| Přispěvatelé: | Universidade Estadual Paulista (Unesp), Universidade Estadual de Campinas (UNICAMP), Universidade Federal do Rio de Janeiro (UFRJ) |
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
030303 biophysics
Plasma protein binding fluorescence anisotropy 03 medical and health sciences Structural Biology Transcription (biology) Hesperetin Humans Binding site Child Molecular Biology hRSV nucleoprotein Polymerase 0303 health sciences Binding Sites STD-NMR biology Chemistry Hesperidin General Medicine molecular docking Phosphoprotein binding Phosphoproteins Molecular biology molecular dynamics Nucleoprotein Molecular Docking Simulation Nucleoproteins Epitope mapping Respiratory Syncytial Virus Human Phosphoprotein biology.protein Protein Binding |
| Zdroj: | Scopus Repositório Institucional da UNESP Universidade Estadual Paulista (UNESP) instacron:UNESP |
| Popis: | Made available in DSpace on 2021-06-25T10:36:42Z (GMT). No. of bitstreams: 0 Previous issue date: 2020-01-01 The human Respiratory Syncytial Virus (hRSV) is one of the most common causes of acute respiratory diseases such as bronchiolitis and pneumonia in children worldwide. Among the viral proteins, the nucleoprotein (N) stands out for forming the nucleocapsid (NC) that functions as a template for replication and transcription by the viral polymerase complex. The NC/polymerase recognition is mediated by the phosphoprotein (P), which establishes an interaction of its C-terminal residues with a hydrophobic pocket in the N-terminal domain of N (N-NTD). The present study consists of biophysical characterization of N-NTD and investigation of flavonoids binding to this domain using experimental and computational approaches. Saturation transfer difference (STD)-NMR measurements showed that among the investigated flavonoids, only hesperetin (Hst) bound to N-NTD. The binding epitope mapping of Hst suggested that its fused aromatic ring is buried in the protein binding site. STD-NMR and fluorescence anisotropy experiments showed that Hst competes with P protein C-terminal dipeptides for the hRSV nucleoprotein/phosphoprotein (N/P) interaction site in N-NTD, indicating that Hst binds to the hydrophobic pocket in this domain. Computational simulations of molecular docking and dynamics corroborated with experimental results, presenting that Hst established a stable interaction with the N/P binding site. The outcomes presented herein shed light on literature reports that described a significant antireplicative activity of Hst against hRSV, revealing molecular details that can provide the development of a new strategy against this virus. Multiuser Center for Biomolecular Innovation (CMIB) Instituto de Biociências Letras e Ciências Exatas UNESP Department of Physics Instituto de Biociências Letras e Ciências Exatas UNESP Department of Biochemistry and Organic Chemistry Instituto de Química UNESP Organic Chemistry Department Instituto de Química UNICAMP National Center for Nuclear Magnetic Resonance of Macromolecules Instituto de Bioquímica Médica Leopoldo de Meis (IBqM) e Centro Nacional de Biologia Estrutural e Bioimagem (CENABIO) UFRJ Multiuser Center for Biomolecular Innovation (CMIB) Instituto de Biociências Letras e Ciências Exatas UNESP Department of Physics Instituto de Biociências Letras e Ciências Exatas UNESP Department of Biochemistry and Organic Chemistry Instituto de Química UNESP |
| Databáze: | OpenAIRE |
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