Hesperetin targets the hydrophobic pocket of the nucleoprotein/phosphoprotein binding site of human respiratory syncytial virus

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MetadadosDescriçãoIdioma
Autor(es): dc.contributorUniversidade Estadual Paulista (Unesp)-
Autor(es): dc.contributorUniversidade Estadual de Campinas (UNICAMP)-
Autor(es): dc.contributorUniversidade Federal do Rio de Janeiro (UFRJ)-
Autor(es): dc.creatorSá, Jéssica M. [UNESP]-
Autor(es): dc.creatorPiloto, João V. [UNESP]-
Autor(es): dc.creatorCilli, Eduardo M. [UNESP]-
Autor(es): dc.creatorTasic, Ljubica-
Autor(es): dc.creatorFossey, Marcelo A. [UNESP]-
Autor(es): dc.creatorAlmeida, Fábio C. L.-
Autor(es): dc.creatorSouza, Fátima P. [UNESP]-
Autor(es): dc.creatorCaruso, Ícaro P. [UNESP]-
Data de aceite: dc.date.accessioned2022-02-22T00:47:53Z-
Data de disponibilização: dc.date.available2022-02-22T00:47:53Z-
Data de envio: dc.date.issued2021-06-25-
Data de envio: dc.date.issued2021-06-25-
Data de envio: dc.date.issued2019-12-31-
Fonte completa do material: dc.identifierhttp://dx.doi.org/10.1080/07391102.2020.1835717-
Fonte completa do material: dc.identifierhttp://hdl.handle.net/11449/206697-
Fonte: dc.identifier.urihttp://educapes.capes.gov.br/handle/11449/206697-
Descrição: dc.descriptionThe 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.-
Descrição: dc.descriptionMultiuser Center for Biomolecular Innovation (CMIB) Instituto de Biociências Letras e Ciências Exatas UNESP-
Descrição: dc.descriptionDepartment of Physics Instituto de Biociências Letras e Ciências Exatas UNESP-
Descrição: dc.descriptionDepartment of Biochemistry and Organic Chemistry Instituto de Química UNESP-
Descrição: dc.descriptionOrganic Chemistry Department Instituto de Química UNICAMP-
Descrição: dc.descriptionNational 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-
Descrição: dc.descriptionMultiuser Center for Biomolecular Innovation (CMIB) Instituto de Biociências Letras e Ciências Exatas UNESP-
Descrição: dc.descriptionDepartment of Physics Instituto de Biociências Letras e Ciências Exatas UNESP-
Descrição: dc.descriptionDepartment of Biochemistry and Organic Chemistry Instituto de Química UNESP-
Idioma: dc.languageen-
Relação: dc.relationJournal of Biomolecular Structure and Dynamics-
???dc.source???: dc.sourceScopus-
Palavras-chave: dc.subjectfluorescence anisotropy-
Palavras-chave: dc.subjectHesperetin-
Palavras-chave: dc.subjecthRSV nucleoprotein-
Palavras-chave: dc.subjectmolecular docking-
Palavras-chave: dc.subjectmolecular dynamics-
Palavras-chave: dc.subjectSTD-NMR-
Título: dc.titleHesperetin targets the hydrophobic pocket of the nucleoprotein/phosphoprotein binding site of human respiratory syncytial virus-
Tipo de arquivo: dc.typelivro digital-
Aparece nas coleções:Repositório Institucional - Unesp

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