Riboflavin, a Potent Neuroprotective Vitamin: Focus on Flavivirus and Alphavirus Proteases

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dc.contributor.authorEberle, Raphael J.
dc.contributor.authorOlivier, Danilo S.
dc.contributor.authorAmaral, Marcos S.
dc.contributor.authorPacca, Carolina C.
dc.contributor.authorNogueira, Mauricio L.
dc.contributor.authorArni, Raghuvir K. [UNESP]
dc.contributor.authorWillbold, Dieter
dc.contributor.authorCoronado, Monika A.
dc.contributor.institutionForschungszentrum Jülich GmbH
dc.contributor.institutionUniversitätsstraße
dc.contributor.institutionFederal University of Tocantins
dc.contributor.institutionFederal University of Mato Grosso do Sul
dc.contributor.institutionFACERES Medical School
dc.contributor.institutionFaculdade de Medicina de São José do Rio Preto-FAMERP
dc.contributor.institutionUniversity of Texas Medical Branch
dc.contributor.institutionUniversidade Estadual Paulista (UNESP)
dc.contributor.institutionForchungszentrum Jülich
dc.date.accessioned2023-03-01T20:53:37Z
dc.date.available2023-03-01T20:53:37Z
dc.date.issued2022-07-01
dc.description.abstractSeveral neurotropic viruses are members of the flavivirus and alphavirus families. Infections caused by these viruses may cause long-term neurological sequelae in humans. The continuous emergence of infections caused by viruses around the world, such as the chikungunya virus (CHIKV) (Alphavirus genus), the zika virus (ZIKV) and the yellow fever virus (YFV) (both of the Flavivirus genus), warrants the development of new strategies to combat them. Our study demonstrates the inhibitory potential of the water-soluble vitamin riboflavin against NS2B/NS3pro of ZIKV and YFV and nsP2pro of CHIKV. Riboflavin presents a competitive inhibition mode with IC50 values in the medium µM range of 79.4 ± 5.0 µM for ZIKV NS2B/NS3pro and 45.7 ± 2.9 µM for YFV NS2B/NS3pro. Against CHIKV nsP2pro, the vitamin showed a very strong effect (93 ± 5.7 nM). The determined dissociation constants (KD) are significantly below the threshold value of 30 µM. The ligand binding increases the thermal stability between 4 °C and 8 °C. Unexpectedly, riboflavin showed inhibiting activity against another viral protein; the molecule was also able to inhibit the viral entry of CHIKV. Molecular dynamics simulations indicated great stability of riboflavin in the protease active site, which validates the repurposing of riboflavin as a promising molecule in drug development against the viruses presented here.en
dc.description.affiliationInstitute of Biological Information Processing (IBI-7 Structural Biochemistry) Forschungszentrum Jülich GmbH
dc.description.affiliationInstitut für Physikalische Biologie Heinrich-Heine-Universität Düsseldorf Universitätsstraße
dc.description.affiliationCenter of Integrated Sciences Campus Cimba Federal University of Tocantins, TO
dc.description.affiliationInstitute of Physics Federal University of Mato Grosso do Sul, MS
dc.description.affiliationInstituto Superior de Educação Ceres FACERES Medical School, SP
dc.description.affiliationLaboratório de Pesquisas em Virologia Departamento de Doenças Dermatológicas Infecciosas e Parasitárias Faculdade de Medicina de São José do Rio Preto-FAMERP, SP
dc.description.affiliationDepartment of Pathology University of Texas Medical Branch
dc.description.affiliationMultiuser Center for Biomolecular Innovation Department of Physics IBILCE São Paulo State University, SP
dc.description.affiliationJuStruct: Jülich Centre for Structural Biology Forchungszentrum Jülich
dc.description.affiliationUnespMultiuser Center for Biomolecular Innovation Department of Physics IBILCE São Paulo State University, SP
dc.description.sponsorshipConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
dc.description.sponsorshipFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
dc.description.sponsorshipDeutsche Forschungsgemeinschaft
dc.description.sponsorshipIdFAPESP: 2020/08615-8
dc.description.sponsorshipIdDeutsche Forschungsgemeinschaft: 267205415
dc.description.sponsorshipIdDeutsche Forschungsgemeinschaft: SFB 1208
dc.identifierhttp://dx.doi.org/10.3390/microorganisms10071331
dc.identifier.citationMicroorganisms, v. 10, n. 7, 2022.
dc.identifier.doi10.3390/microorganisms10071331
dc.identifier.issn2076-2607
dc.identifier.scopus2-s2.0-85133142521
dc.identifier.urihttp://hdl.handle.net/11449/241251
dc.language.isoeng
dc.relation.ispartofMicroorganisms
dc.sourceScopus
dc.subjectalphavirus
dc.subjectcompetitive inhibitor
dc.subjectflavivirus
dc.subjectNS2B/NS3pro
dc.subjectnsP2pro
dc.subjectriboflavin
dc.titleRiboflavin, a Potent Neuroprotective Vitamin: Focus on Flavivirus and Alphavirus Proteasesen
dc.typeArtigo

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