Zika virus NS2B/NS3 proteinase: A new target for an old drug - Suramin a lead compound for NS2B/NS3 proteinase inhibition

Autor(es)

Coronado, Monika Aparecida ^[1] ; Eberle, Raphael Josef ^[1] ; Bleffert, Nicole ^{[2, 3]} ; Feuerstein, Sophie ^{[2, 3]} ; Olivier, Danilo Silva ^[1] ; de Moraes, Fabio Rogerio ^[1] ; Willbold, Dieter ^{[2, 3]} ; Arni, Raghuvir Krishnaswamy ^[1]

Afiliação do(s) autor(es)

^[1] Univ Estadual Paulista, UNESP, Dept Phys, Multiuser Ctr Biomol Innovat, BR-15054000 Sao Jose Do Rio Preto, SP - Brazil

^[2] Forschungszentrum Julich, Inst Complex Syst Struct Biochem ICS 6, Julich - Germany

^[3] Heinrich Heine Univ Dusseldorf, Inst Phys Biol, Univ Str, Dusseldorf - Germany

• Tipo de documento: Artigo Científico
• Fonte: Antiviral Research; v. 160, p. 118-125, DEC 2018.
• Citações Web of Science: 6

Resumo

Zika virus infection is the focus of much research due to the medical and social repercussions. Due the role of the viral NS2B/NS3 proteinase in maturation of the viral proteins, it had become an attractive antiviral target. Numerous investigations on viral epidemiology, structure and function analysis, vaccines, and therapeutic drugs have been conducted around the world. At present, no approved vaccine or even drugs have been reported. Thus, there is an urgent need to develop therapeutic agents to cure this epidemic disease. In the present study, we identified the polyanion suramin, an approved antiparasitic drug with antiviral properties, as a potential inhibitor of Zika virus complex NS2B/NS3 proteinase with IC50 of 47 mu M. Using fluorescence spectroscopy results we could determine a k(d) value of 28 mu M and had shown that the ligand does not affect the thermal stability of the protein. STD NMR spectroscopy experiments and molecular docking followed by molecular dynamics simulation identified the binding epitopes of the molecule and shows the mode of interaction, respectively. The computational analysis showed that suramin block the Ser135 residue and interact with the catalytically histidine residue. (AU)

• Processo FAPESP: 16/08104-8 - Aspectos funcionais e estruturais de duas proteínas de ligação de DNA codificadas pela Corynebacterium pseudotuberculosis
• Beneficiário: Raphael Josef Eberle
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado
• Processo FAPESP: 15/13765-0 - ESTUDOS ESTRUTURAIS E CARACTERIZAÇÃO DE PROTEÍNAS POR CRISTALOGRAFIA DE RAIOS-X E RESSONÂNCIA MAGNETICA NUCLEAR. Investigações estruturais e biofísicas dos mecanismos moleculares de proteínas funcionais
• Beneficiário: Raghuvir Krishnaswamy Arni
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 15/18868-2 - Aquisição de equipamento multiusuário para biologia molecular e estrutural
• Beneficiário: Raghuvir Krishnaswamy Arni
• Modalidade de apoio: Auxílio à Pesquisa - Programa Equipamentos Multiusuários
• Processo FAPESP: 09/53989-4 - EMU: aquisição de espectrômetro de ressonância magnética nuclear para estudos de biomoléculas
• Beneficiário: Raghuvir Krishnaswamy Arni
• Modalidade de apoio: Auxílio à Pesquisa - Programa Equipamentos Multiusuários
• 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