Promising Natural Compounds against Flavivirus Proteases: Citrus Flavonoids Hesperetin and Hesperidin

Autor(es)

Eberle, Raphael J. ^{[1, 2]} ; Olivier, Danilo S. ^[3] ; Amaral, Marcos S. ^[4] ; Willbold, Dieter ^{[1, 5, 2]} ; Arni, Raghuvir K. ^[6] ; Coronado, Monika A. ^[2]

Afiliação do(s) autor(es)

^[1] Heinrich Heine Univ Dusseldorf, Inst Phys Biol, Univ Str, D-40225 Dusseldorf - Germany

^[2] Forschungszentrum Julich, Inst Biol Informat Proc IBI 7 Struct Biochem, D-52428 Julich - Germany

^[3] Fed Univ Tocantins, Integrated Sci Ctr, BR-77824838 Araguaina - Brazil

^[4] Univ Fed Mato Grosso do Sul, Inst Phys, BR-79070900 Campo Grande, MS - Brazil

^[5] Forchungszentrum Julich, JuStruct Julich Ctr Struct Biol, D-52428 Julich - Germany

^[6] Univ Estadual Paulista UNESP, Multiuser Ctr Biomol Innovat, Dept Phys, BR-15054000 Sao Jose Do Rio Preto - Brazil

• Tipo de documento: Artigo Científico
• Fonte: PLANTS-BASEL; v. 10, n. 10 OCT 2021.
• Citações Web of Science: 0

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/NS3(pro) by the two bioflavonoids with half maximal inhibitory concentration (IC50) values < 5 mu M for HST and < 70 mu M for HSD. The determined dissociation constants (K-D) of both flavonoids is significantly below the threshold value of 30 mu M. Our findings demonstrate that a new generation of anti-flavivirus drugs could be developed based on selective optimization of both molecules.</p> (AU)

• Processo FAPESP: 18/07572-3 - Explorando a protease nsP2 dos vírus Chikungunya e Mayaro: estruturas e inibição.
• Beneficiário: Raphael Josef Eberle
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado
• Processo FAPESP: 19/05614-3 - Identificação de moléculas bioativas que inibem a atividades dos vírus Chikungunya e Mayaro
• Beneficiário: Raphael Josef Eberle
• Modalidade de apoio: Bolsas no Exterior - Estágio de Pesquisa - Pós-Doutorado
• Processo FAPESP: 18/12659-0 - Mecanismos e Interações Moleculares de Moléculas Bioativas com a Protease NS3 do Zika Vírus - De novo drug design -
• Beneficiário: Monika Aparecida Coronado
• Modalidade de apoio: Bolsas no Exterior - Estágio de Pesquisa - Pós-Doutorado
• Processo FAPESP: 16/12904-0 - Mecanismos e Interações Moleculares de Moléculas Bioativas com a Protease NS3 do Zika Vírus.
• Beneficiário: Monika Aparecida Coronado
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado