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dc.contributor.authorEberle, Raphael J. [UNESP]
dc.contributor.authorOlivier, Danilo S.
dc.contributor.authorPacca, Carolina C. [UNESP]
dc.contributor.authorAvilla, Clarita M.S. [UNESP]
dc.contributor.authorNogueira, Mauricio L.
dc.contributor.authorAmaral, Marcos S.
dc.contributor.authorWillbold, Dieter
dc.contributor.authorArni, Raghuvir K. [UNESP]
dc.contributor.authorCoronado, Monika A. [UNESP]
dc.date.accessioned2021-06-25T10:55:22Z
dc.date.available2021-06-25T10:55:22Z
dc.date.issued2021-03-01
dc.identifierhttp://dx.doi.org/10.1371/journal.pone.0246319
dc.identifier.citationPLoS ONE, v. 16, n. 3 March, 2021.
dc.identifier.issn1932-6203
dc.identifier.urihttp://hdl.handle.net/11449/207450
dc.description.abstractThe potential outcome of flavivirus and alphavirus co-infections is worrisome due to the development of severe diseases. Hundreds of millions of people worldwide live under the risk of infections caused by viruses like chikungunya virus (CHIKV, genus Alphavirus), dengue virus (DENV, genus Flavivirus), and zika virus (ZIKV, genus Flavivirus). So far, neither any drug exists against the infection by a single virus, nor against co-infection. The results described in our study demonstrate the inhibitory potential of two flavonoids derived from citrus plants: Hesperetin (HST) against NS2B/NS3pro of ZIKV and nsP2pro of CHIKV and, Hesperidin (HSD) against nsP2pro of CHIKV. The flavonoids are noncompetitive inhibitors and the determined IC50 values are in low µM range for HST against ZIKV NS2B/NS3pro (12.6 ± 1.3 µM) and against CHIKV nsP2pro (2.5 ± 0.4 µM). The IC50 for HSD against CHIKV nsP2pro was 7.1 ± 1.1 µM. The calculated ligand efficiencies for HST were > 0.3, which reflect its potential to be used as a lead compound. Docking and molecular dynamics simulations display the effect of HST and HSD on the protease 3D models of CHIKV and ZIKV. Conformational changes after ligand binding and their effect on the substrate-binding pocket of the proteases were investigated. Additionally, MTT assays demonstrated a very low cytotoxicity of both the molecules. Based on our results, we assume that HST comprise a chemical structure that serves as a starting point molecule to develop a potent inhibitor to combat CHIKV and ZIKV co-infections by inhibiting the virus proteases.en
dc.description.sponsorshipNational Institute of Biological Resources
dc.language.isoeng
dc.relation.ispartofPLoS ONE
dc.sourceScopus
dc.titleIn vitro study of Hesperetin and Hesperidin as inhibitors of zika and chikungunya virus proteasesen
dc.typeArtigo
dc.contributor.institutionUniversidade Estadual Paulista (Unesp)
dc.contributor.institutionForschungszentrum Jülich
dc.contributor.institutionFederal University of Tocantins
dc.contributor.institutionFACERES Medical School
dc.contributor.institutionFaculdade de Medicina de São José do Rio Preto-FAMERP
dc.contributor.institutionFederal University of Mato Grosso do Sul
dc.contributor.institutionHeinrich-Heine-Universität Düsseldorf
dc.contributor.institutionForchungszentrum Jülich
dc.description.affiliationMultiuser Center for Biomolecular Innovation Departament of Physics Instituto de Biociências Letras e Ciências Exatas (Ibilce) Universidade Estadual Paulista (UNESP)
dc.description.affiliationInstitute of Biological Information Processing (IBI-7: Structural Biochemistry) Forschungszentrum Jülich
dc.description.affiliationFederal University of Tocantins
dc.description.affiliationInstituto de Biociências Letras e Ciências Exatas (Ibilce) Universidade Estadual Paulista (UNESP)
dc.description.affiliationFACERES Medical School
dc.description.affiliationFaculdade de Medicina de São José do Rio Preto-FAMERP
dc.description.affiliationInstitute of Physics Federal University of Mato Grosso do Sul
dc.description.affiliationInstitut für Physikalische Biologie Heinrich-Heine-Universität Düsseldorf
dc.description.affiliationJuStruct: Jülich Centre for Structural Biology Forchungszentrum Jülich
dc.description.affiliationUnespMultiuser Center for Biomolecular Innovation Departament of Physics Instituto de Biociências Letras e Ciências Exatas (Ibilce) Universidade Estadual Paulista (UNESP)
dc.description.affiliationUnespInstituto de Biociências Letras e Ciências Exatas (Ibilce) Universidade Estadual Paulista (UNESP)
dc.identifier.doi10.1371/journal.pone.0246319
dc.identifier.scopus2-s2.0-85102490831
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