Searching for drug leads targeted to the hydrophobic cleft of dengue virus capsid protein

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MetadadosDescriçãoIdioma
Autor(es): dc.contributorMilitary Institute of Engineering (IME)-
Autor(es): dc.contributorUniversidade Federal do Rio de Janeiro (UFRJ)-
Autor(es): dc.contributorUniversidade Estadual Paulista (UNESP)-
Autor(es): dc.contributorFederal University of the State of Rio de Janeiro (UNIRIO)-
Autor(es): dc.creatorOrtlieb, Liliane O.-
Autor(es): dc.creatorCaruso, Ícaro P.-
Autor(es): dc.creatorMebus-Antunes, Nathane C.-
Autor(es): dc.creatorDa Poian, Andrea T.-
Autor(es): dc.creatorPetronilho, Elaine da C.-
Autor(es): dc.creatorFigueroa-Villar, José Daniel-
Autor(es): dc.creatorNascimento, Claudia J.-
Autor(es): dc.creatorAlmeida, Fabio C. L.-
Data de aceite: dc.date.accessioned2025-08-21T19:08:59Z-
Data de disponibilização: dc.date.available2025-08-21T19:08:59Z-
Data de envio: dc.date.issued2022-04-29-
Data de envio: dc.date.issued2022-04-29-
Data de envio: dc.date.issued2021-12-31-
Fonte completa do material: dc.identifierhttp://dx.doi.org/10.1080/14756366.2021.2004591-
Fonte completa do material: dc.identifierhttp://hdl.handle.net/11449/230055-
Fonte: dc.identifier.urihttp://educapes.capes.gov.br/handle/11449/230055-
Descrição: dc.descriptionWe synthesised and screened 18 aromatic derivatives of guanylhydrazones and oximes aromatic for their capacity to bind to dengue virus capsid protein (DENVC). The intended therapeutic target was the hydrophobic cleft of DENVC, which is a region responsible for its anchoring in lipid droplets in the infected cells. The inhibition of this process completely suppresses virus infectivity. Using NMR, we describe five compounds able to bind to the α1-α2 interface in the hydrophobic cleft. Saturation transfer difference experiments showed that the aromatic protons of the ligands are important for the interaction with DENVC. Fluorescence binding isotherms indicated that the selected compounds bind at micromolar affinities, possibly leading to binding-induced conformational changes. NMR-derived docking calculations of ligands showed that they position similarly in the hydrophobic cleft. Cytotoxicity experiments and calculations of in silico drug properties suggest that these compounds may be promising candidates in the search for antivirals targeting DENVC.-
Descrição: dc.descriptionDepartment of Chemistry Military Institute of Engineering (IME)-
Descrição: dc.descriptionInstitute of Medical Biochemistry Leopoldo de Meis (IBqM) and National Center for Structural Biology and Bioimaging (CENABIO) Federal University of Rio de Janeiro (UFRJ)-
Descrição: dc.descriptionMultiuser Center for Biomolecular Innovation (CMIB) and Department of Physics Institute of Biosciences Letters and Exact Sciences (IBILCE) São Paulo State University (UNESP)-
Descrição: dc.descriptionInstitute of Medical Biochemistry Leopoldo de Meis (IBqM) Federal University of Rio de Janeiro (UFRJ)-
Descrição: dc.descriptionDepartment of Natural Sciences Institute of Biosciences Federal University of the State of Rio de Janeiro (UNIRIO)-
Descrição: dc.descriptionMultiuser Center for Biomolecular Innovation (CMIB) and Department of Physics Institute of Biosciences Letters and Exact Sciences (IBILCE) São Paulo State University (UNESP)-
Formato: dc.format287-298-
Idioma: dc.languageen-
Relação: dc.relationJournal of Enzyme Inhibition and Medicinal Chemistry-
???dc.source???: dc.sourceScopus-
Palavras-chave: dc.subjectDengue virus-
Palavras-chave: dc.subjectDENVC-
Palavras-chave: dc.subjectdrug-ligand interaction-
Palavras-chave: dc.subjectfluorescence-
Palavras-chave: dc.subjectNMR-
Título: dc.titleSearching for drug leads targeted to the hydrophobic cleft of dengue virus capsid protein-
Tipo de arquivo: dc.typelivro digital-
Aparece nas coleções:Repositório Institucional - Unesp

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