Promising natural compounds against flavivirus proteases: Citrus flavonoids hesperetin and hesperidin
Autor(a) principal: | |
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Data de Publicação: | 2021 |
Outros Autores: | , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da UNESP |
Texto Completo: | http://dx.doi.org/10.3390/plants10102183 http://hdl.handle.net/11449/222641 |
Resumo: | Ubiquitous in citrus plants, Hesperidin and Hesperetin flavanones possess several biological functions, including antiviral activity. Arbovirus infections pose an ever-increasing threat to global healthcare systems. Among the severe arboviral infections currently known are those caused by members of the Flavivirus genus, for example, Dengue Virus—DENV, Yellow Fever Virus— YFV, and West Nile Virus—WNV. In this study, we characterize the inhibitory effect of Hesperidin and Hesperetin against DENV2, YFV, and WNV NS2B/NS3 proteases. We report the noncompetitive inhibition of the NS2B/NS3pro by the two bioflavonoids with half maximal inhibitory concentration (IC50) values < 5 µM for HST and <70 µM for HSD. The determined dissociation constants (KD) of both flavonoids is significantly below the threshold value of 30 µM. Our findings demonstrate that a new generation of anti-flavivirus drugs could be developed based on selective optimization of both molecules. |
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Promising natural compounds against flavivirus proteases: Citrus flavonoids hesperetin and hesperidinFlavivirusHesperetinHesperidinNoncompetitive inhibitorsNS2B/NS3proUbiquitous in citrus plants, Hesperidin and Hesperetin flavanones possess several biological functions, including antiviral activity. Arbovirus infections pose an ever-increasing threat to global healthcare systems. Among the severe arboviral infections currently known are those caused by members of the Flavivirus genus, for example, Dengue Virus—DENV, Yellow Fever Virus— YFV, and West Nile Virus—WNV. In this study, we characterize the inhibitory effect of Hesperidin and Hesperetin against DENV2, YFV, and WNV NS2B/NS3 proteases. We report the noncompetitive inhibition of the NS2B/NS3pro by the two bioflavonoids with half maximal inhibitory concentration (IC50) values < 5 µM for HST and <70 µM for HSD. The determined dissociation constants (KD) of both flavonoids is significantly below the threshold value of 30 µM. Our findings demonstrate that a new generation of anti-flavivirus drugs could be developed based on selective optimization of both molecules.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Fundação de Apoio ao Desenvolvimento do Ensino, Ciência e Tecnologia do Estado de Mato Grosso do SulConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Institute of Biological Information Processing (IBI-7 Structural Biochemistry) Forschungszentrum JülichInstitut für Physikalische Biologie Heinrich-Heine-Universität Düsseldorf, UniversitätsstraßeIntegrated Sciences Center Federal University of TocantinsInstitute of Physics Federal University of Mato Grosso do SulJuStruct: Jülich Centre for Structural Biology Forchungszentrum JülichMultiuser Center for Biomolecular Innovation Departament of Physics Universidade Estadual Paulista (UNESP)Multiuser Center for Biomolecular Innovation Departament of Physics Universidade Estadual Paulista (UNESP)FAPESP: 2016/12904-0FAPESP: 2018/07572-3FAPESP: 2018/12659-0FAPESP: 2019/05614-3Fundação de Apoio ao Desenvolvimento do Ensino, Ciência e Tecnologia do Estado de Mato Grosso do Sul: 23/200.307/2014CNPq: 307338/2014-2CNPq: 401270/2014-9CNPq: 435913/2016-6Forschungszentrum JülichHeinrich-Heine-Universität DüsseldorfFederal University of TocantinsFederal University of Mato Grosso do SulForchungszentrum JülichUniversidade Estadual Paulista (UNESP)Eberle, Raphael J.Olivier, Danilo S.Amaral, Marcos S.Willbold, DieterArni, Raghuvir K. [UNESP]Coronado, Monika A.2022-04-28T19:45:55Z2022-04-28T19:45:55Z2021-10-01info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articlehttp://dx.doi.org/10.3390/plants10102183Plants, v. 10, n. 10, 2021.2223-7747http://hdl.handle.net/11449/22264110.3390/plants101021832-s2.0-85117057314Scopusreponame:Repositório Institucional da UNESPinstname:Universidade Estadual Paulista (UNESP)instacron:UNESPengPlantsinfo:eu-repo/semantics/openAccess2022-04-28T19:45:55Zoai:repositorio.unesp.br:11449/222641Repositório InstitucionalPUBhttp://repositorio.unesp.br/oai/requestopendoar:29462022-04-28T19:45:55Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)false |
dc.title.none.fl_str_mv |
Promising natural compounds against flavivirus proteases: Citrus flavonoids hesperetin and hesperidin |
title |
Promising natural compounds against flavivirus proteases: Citrus flavonoids hesperetin and hesperidin |
spellingShingle |
Promising natural compounds against flavivirus proteases: Citrus flavonoids hesperetin and hesperidin Eberle, Raphael J. Flavivirus Hesperetin Hesperidin Noncompetitive inhibitors NS2B/NS3pro |
title_short |
Promising natural compounds against flavivirus proteases: Citrus flavonoids hesperetin and hesperidin |
title_full |
Promising natural compounds against flavivirus proteases: Citrus flavonoids hesperetin and hesperidin |
title_fullStr |
Promising natural compounds against flavivirus proteases: Citrus flavonoids hesperetin and hesperidin |
title_full_unstemmed |
Promising natural compounds against flavivirus proteases: Citrus flavonoids hesperetin and hesperidin |
title_sort |
Promising natural compounds against flavivirus proteases: Citrus flavonoids hesperetin and hesperidin |
author |
Eberle, Raphael J. |
author_facet |
Eberle, Raphael J. Olivier, Danilo S. Amaral, Marcos S. Willbold, Dieter Arni, Raghuvir K. [UNESP] Coronado, Monika A. |
author_role |
author |
author2 |
Olivier, Danilo S. Amaral, Marcos S. Willbold, Dieter Arni, Raghuvir K. [UNESP] Coronado, Monika A. |
author2_role |
author author author author author |
dc.contributor.none.fl_str_mv |
Forschungszentrum Jülich Heinrich-Heine-Universität Düsseldorf Federal University of Tocantins Federal University of Mato Grosso do Sul Forchungszentrum Jülich Universidade Estadual Paulista (UNESP) |
dc.contributor.author.fl_str_mv |
Eberle, Raphael J. Olivier, Danilo S. Amaral, Marcos S. Willbold, Dieter Arni, Raghuvir K. [UNESP] Coronado, Monika A. |
dc.subject.por.fl_str_mv |
Flavivirus Hesperetin Hesperidin Noncompetitive inhibitors NS2B/NS3pro |
topic |
Flavivirus Hesperetin Hesperidin Noncompetitive inhibitors NS2B/NS3pro |
description |
Ubiquitous in citrus plants, Hesperidin and Hesperetin flavanones possess several biological functions, including antiviral activity. Arbovirus infections pose an ever-increasing threat to global healthcare systems. Among the severe arboviral infections currently known are those caused by members of the Flavivirus genus, for example, Dengue Virus—DENV, Yellow Fever Virus— YFV, and West Nile Virus—WNV. In this study, we characterize the inhibitory effect of Hesperidin and Hesperetin against DENV2, YFV, and WNV NS2B/NS3 proteases. We report the noncompetitive inhibition of the NS2B/NS3pro by the two bioflavonoids with half maximal inhibitory concentration (IC50) values < 5 µM for HST and <70 µM for HSD. The determined dissociation constants (KD) of both flavonoids is significantly below the threshold value of 30 µM. Our findings demonstrate that a new generation of anti-flavivirus drugs could be developed based on selective optimization of both molecules. |
publishDate |
2021 |
dc.date.none.fl_str_mv |
2021-10-01 2022-04-28T19:45:55Z 2022-04-28T19:45:55Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://dx.doi.org/10.3390/plants10102183 Plants, v. 10, n. 10, 2021. 2223-7747 http://hdl.handle.net/11449/222641 10.3390/plants10102183 2-s2.0-85117057314 |
url |
http://dx.doi.org/10.3390/plants10102183 http://hdl.handle.net/11449/222641 |
identifier_str_mv |
Plants, v. 10, n. 10, 2021. 2223-7747 10.3390/plants10102183 2-s2.0-85117057314 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
Plants |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.source.none.fl_str_mv |
Scopus reponame:Repositório Institucional da UNESP instname:Universidade Estadual Paulista (UNESP) instacron:UNESP |
instname_str |
Universidade Estadual Paulista (UNESP) |
instacron_str |
UNESP |
institution |
UNESP |
reponame_str |
Repositório Institucional da UNESP |
collection |
Repositório Institucional da UNESP |
repository.name.fl_str_mv |
Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP) |
repository.mail.fl_str_mv |
|
_version_ |
1803047230902370304 |