{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T19:33:52Z","timestamp":1791920032865,"version":"4.3.4"},"reference-count":50,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2021,10,14]],"date-time":"2021-10-14T00:00:00Z","timestamp":1634169600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Plants"],"abstract":"<jats:p>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\u2014DENV, Yellow Fever Virus\u2014YFV, and West Nile Virus\u2014WNV. 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 &lt;5 \u00b5M for HST and &lt;70 \u00b5M for HSD. The determined dissociation constants (KD) of both flavonoids is significantly below the threshold value of 30 \u00b5M. Our findings demonstrate that a new generation of anti-flavivirus drugs could be developed based on selective optimization of both molecules.<\/jats:p>","DOI":"10.3390\/plants10102183","type":"journal-article","created":{"date-parts":[[2021,10,14]],"date-time":"2021-10-14T23:02:16Z","timestamp":1634252536000},"page":"2183","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Promising Natural Compounds against Flavivirus Proteases: Citrus Flavonoids Hesperetin and Hesperidin"],"prefix":"10.3390","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8763-3884","authenticated-orcid":false,"given":"Raphael J.","family":"Eberle","sequence":"first","affiliation":[{"name":"Institute of Biological Information Processing (IBI-7: Structural Biochemistry), Forschungszentrum J\u00fclich, 52428 J\u00fclich, Germany"},{"name":"Institut f\u00fcr Physikalische Biologie, Heinrich-Heine-Universit\u00e4t D\u00fcsseldorf, Universit\u00e4tsstra\u00dfe, 40225 D\u00fcsseldorf, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1269-3783","authenticated-orcid":false,"given":"Danilo S.","family":"Olivier","sequence":"additional","affiliation":[{"name":"Integrated Sciences Center, Federal University of Tocantins, Aragua\u00edna 77824-838, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8101-6933","authenticated-orcid":false,"given":"Marcos S.","family":"Amaral","sequence":"additional","affiliation":[{"name":"Institute of Physics, Federal University of Mato Grosso do Sul, Campo Grande 79070-900, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0065-7366","authenticated-orcid":false,"given":"Dieter","family":"Willbold","sequence":"additional","affiliation":[{"name":"Institute of Biological Information Processing (IBI-7: Structural Biochemistry), Forschungszentrum J\u00fclich, 52428 J\u00fclich, Germany"},{"name":"Institut f\u00fcr Physikalische Biologie, Heinrich-Heine-Universit\u00e4t D\u00fcsseldorf, Universit\u00e4tsstra\u00dfe, 40225 D\u00fcsseldorf, Germany"},{"name":"JuStruct: J\u00fclich Centre for Structural Biology, Forchungszentrum J\u00fclich, 52428 J\u00fclich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2460-1145","authenticated-orcid":false,"given":"Raghuvir K.","family":"Arni","sequence":"additional","affiliation":[{"name":"Multiuser Center for Biomolecular Innovation, Departament of Physics, Universidade Estadual Paulista (UNESP), S\u00e3o Jose do Rio Preto 15054-000, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6518-6497","authenticated-orcid":false,"given":"Monika A.","family":"Coronado","sequence":"additional","affiliation":[{"name":"Institute of Biological Information Processing (IBI-7: Structural Biochemistry), Forschungszentrum J\u00fclich, 52428 J\u00fclich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,10,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"111596","DOI":"10.1016\/j.biopha.2021.111596","article-title":"Antiviral activities of flavonoids","volume":"140","author":"Badshah","year":"2021","journal-title":"Biomed. 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