Zika virus NS2B/NS3 proteinase: A new target for an old drug - Suramin a lead compound for NS2B/NS3 proteinase inhibition-
Autor(a) principal: | |
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Data de Publicação: | 2018 |
Outros Autores: | , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da UNESP |
Texto Completo: | http://dx.doi.org/10.1016/j.antiviral.2018.10.019 http://hdl.handle.net/11449/188299 |
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 IC 50 of 47 μM. Using fluorescence spectroscopy results we could determine a k d value of 28 μM 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. |
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Zika virus NS2B/NS3 proteinase: A new target for an old drug - Suramin a lead compound for NS2B/NS3 proteinase inhibition-InhibitorLead compoundNS2B/NS3 proteinaseSuraminZika virusZika 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 IC 50 of 47 μM. Using fluorescence spectroscopy results we could determine a k d value of 28 μM 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.Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Universidade Estadual PaulistaMultiuser Center for Biomolecular Innovation Department of Physics Universidade Estadual Paulista (UNESP)Institute of Complex System Structural Biochemistry (ICS-6) Forchungszentrum JülichInstitut für Physikalische Biologie Heinrich-Heine-Universität DüsseldorfCentro Multiusuário de Inovação Biomolecular Departamento de Física Instituto de Biociências Letras e Ciências Exatas (Ibilce) Universidade Estadual Paulista (UNESP), Rua Cristóvão Colombo 2265Multiuser Center for Biomolecular Innovation Department of Physics Universidade Estadual Paulista (UNESP)Centro Multiusuário de Inovação Biomolecular Departamento de Física Instituto de Biociências Letras e Ciências Exatas (Ibilce) Universidade Estadual Paulista (UNESP), Rua Cristóvão Colombo 2265FAPESP: 2009/53989-4FAPESP: 2015/13765-0FAPESP: 2015/18868-2FAPESP: 2016/08104-8FAPESP: 2016/12904-0CNPq: 307338/2014-2CNPq: 401270/2014-9CNPq: 435913/2016-6Universidade Estadual Paulista (Unesp)Forchungszentrum JülichHeinrich-Heine-Universität DüsseldorfCoronado, Monika Aparecida [UNESP]Eberle, Raphael Josef [UNESP]Bleffert, NicoleFeuerstein, SophieOlivier, Danilo Silva [UNESP]de Moraes, Fabio Rogerio [UNESP]Willbold, DieterArni, Raghuvir Krishnaswamy [UNESP]2019-10-06T16:03:37Z2019-10-06T16:03:37Z2018-12-01info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/article118-125http://dx.doi.org/10.1016/j.antiviral.2018.10.019Antiviral Research, v. 160, p. 118-125.1872-90960166-3542http://hdl.handle.net/11449/18829910.1016/j.antiviral.2018.10.0192-s2.0-8505573570091625089789458870000-0003-2460-1145Scopusreponame:Repositório Institucional da UNESPinstname:Universidade Estadual Paulista (UNESP)instacron:UNESPengAntiviral Researchinfo:eu-repo/semantics/openAccess2021-10-23T09:20:08Zoai:repositorio.unesp.br:11449/188299Repositório InstitucionalPUBhttp://repositorio.unesp.br/oai/requestopendoar:29462024-05-23T11:51:10.558590Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)false |
dc.title.none.fl_str_mv |
Zika virus NS2B/NS3 proteinase: A new target for an old drug - Suramin a lead compound for NS2B/NS3 proteinase inhibition- |
title |
Zika virus NS2B/NS3 proteinase: A new target for an old drug - Suramin a lead compound for NS2B/NS3 proteinase inhibition- |
spellingShingle |
Zika virus NS2B/NS3 proteinase: A new target for an old drug - Suramin a lead compound for NS2B/NS3 proteinase inhibition- Coronado, Monika Aparecida [UNESP] Inhibitor Lead compound NS2B/NS3 proteinase Suramin Zika virus |
title_short |
Zika virus NS2B/NS3 proteinase: A new target for an old drug - Suramin a lead compound for NS2B/NS3 proteinase inhibition- |
title_full |
Zika virus NS2B/NS3 proteinase: A new target for an old drug - Suramin a lead compound for NS2B/NS3 proteinase inhibition- |
title_fullStr |
Zika virus NS2B/NS3 proteinase: A new target for an old drug - Suramin a lead compound for NS2B/NS3 proteinase inhibition- |
title_full_unstemmed |
Zika virus NS2B/NS3 proteinase: A new target for an old drug - Suramin a lead compound for NS2B/NS3 proteinase inhibition- |
title_sort |
Zika virus NS2B/NS3 proteinase: A new target for an old drug - Suramin a lead compound for NS2B/NS3 proteinase inhibition- |
author |
Coronado, Monika Aparecida [UNESP] |
author_facet |
Coronado, Monika Aparecida [UNESP] Eberle, Raphael Josef [UNESP] Bleffert, Nicole Feuerstein, Sophie Olivier, Danilo Silva [UNESP] de Moraes, Fabio Rogerio [UNESP] Willbold, Dieter Arni, Raghuvir Krishnaswamy [UNESP] |
author_role |
author |
author2 |
Eberle, Raphael Josef [UNESP] Bleffert, Nicole Feuerstein, Sophie Olivier, Danilo Silva [UNESP] de Moraes, Fabio Rogerio [UNESP] Willbold, Dieter Arni, Raghuvir Krishnaswamy [UNESP] |
author2_role |
author author author author author author author |
dc.contributor.none.fl_str_mv |
Universidade Estadual Paulista (Unesp) Forchungszentrum Jülich Heinrich-Heine-Universität Düsseldorf |
dc.contributor.author.fl_str_mv |
Coronado, Monika Aparecida [UNESP] Eberle, Raphael Josef [UNESP] Bleffert, Nicole Feuerstein, Sophie Olivier, Danilo Silva [UNESP] de Moraes, Fabio Rogerio [UNESP] Willbold, Dieter Arni, Raghuvir Krishnaswamy [UNESP] |
dc.subject.por.fl_str_mv |
Inhibitor Lead compound NS2B/NS3 proteinase Suramin Zika virus |
topic |
Inhibitor Lead compound NS2B/NS3 proteinase Suramin Zika virus |
description |
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 IC 50 of 47 μM. Using fluorescence spectroscopy results we could determine a k d value of 28 μM 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. |
publishDate |
2018 |
dc.date.none.fl_str_mv |
2018-12-01 2019-10-06T16:03:37Z 2019-10-06T16:03:37Z |
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/10.1016/j.antiviral.2018.10.019 Antiviral Research, v. 160, p. 118-125. 1872-9096 0166-3542 http://hdl.handle.net/11449/188299 10.1016/j.antiviral.2018.10.019 2-s2.0-85055735700 9162508978945887 0000-0003-2460-1145 |
url |
http://dx.doi.org/10.1016/j.antiviral.2018.10.019 http://hdl.handle.net/11449/188299 |
identifier_str_mv |
Antiviral Research, v. 160, p. 118-125. 1872-9096 0166-3542 10.1016/j.antiviral.2018.10.019 2-s2.0-85055735700 9162508978945887 0000-0003-2460-1145 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
Antiviral Research |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
118-125 |
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_ |
1803045894793199616 |