A diarylamine derived from anthranilic acid inhibits ZIKV replication
Autor(a) principal: | |
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Data de Publicação: | 2019 |
Outros Autores: | , , , , , , , , , , , , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da UNESP |
Texto Completo: | http://dx.doi.org/10.1038/s41598-019-54169-z http://hdl.handle.net/11449/197561 |
Resumo: | Zika virus (ZIKV) is a mosquito-transmitted Flavivirus, originally identified in Uganda in 1947 and recently associated with a large outbreak in South America. Despite extensive efforts there are currently no approved antiviral compounds for treatment of ZIKV infection. Here we describe the antiviral activity of diarylamines derived from anthranilic acid (FAMs) against ZIKV. A synthetic FAM (E3) demonstrated anti-ZIKV potential by reducing viral replication up to 86%. We analyzed the possible mechanisms of action of FAM E3 by evaluating the intercalation of this compound into the viral dsRNA and its interaction with the RNA polymerase of bacteriophage SP6. However, FAM E3 did not act by these mechanisms. In silico results predicted that FAM E3 might bind to the ZIKV NS3 helicase suggesting that this protein could be one possible target of this compound. To test this, the thermal stability and the ATPase activity of the ZIKV NS3 helicase domain (NS3(Hel)) were investigated in vitro and we demonstrated that FAM E3 could indeed bind to and stabilize NS3(Hel). |
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A diarylamine derived from anthranilic acid inhibits ZIKV replicationZika virus (ZIKV) is a mosquito-transmitted Flavivirus, originally identified in Uganda in 1947 and recently associated with a large outbreak in South America. Despite extensive efforts there are currently no approved antiviral compounds for treatment of ZIKV infection. Here we describe the antiviral activity of diarylamines derived from anthranilic acid (FAMs) against ZIKV. A synthetic FAM (E3) demonstrated anti-ZIKV potential by reducing viral replication up to 86%. We analyzed the possible mechanisms of action of FAM E3 by evaluating the intercalation of this compound into the viral dsRNA and its interaction with the RNA polymerase of bacteriophage SP6. However, FAM E3 did not act by these mechanisms. In silico results predicted that FAM E3 might bind to the ZIKV NS3 helicase suggesting that this protein could be one possible target of this compound. To test this, the thermal stability and the ATPase activity of the ZIKV NS3 helicase domain (NS3(Hel)) were investigated in vitro and we demonstrated that FAM E3 could indeed bind to and stabilize NS3(Hel).Royal Society -Newton Advanced FellowshipConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Fundação de Amparo à Pesquisa do Estado de Minas Gerais (FAPEMIG)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Wellcome TrustL'Oreal-UNESCO-ABC Para Mulheres na CienciaL'Oreal-UNESCO International Rising Talents ProgramUniv Fed Uberlandia, ICBIM, Inst Biomed Sci, Lab Virol, Uberlandia, MG, BrazilSao Paulo State Univ, IBILCE, Sao Jose Do Rio Preto, SP, BrazilSao Paulo State Univ, IBILCE, Lab Antibiot & Chemotherapeut, Sao Jose Do Rio Preto, SP, BrazilUniv Fed Goias, Fac Farm, LabMol Lab Mol Modeling & Drug Design, BR-74605170 Goiania, Go, BrazilUniv Sao Paulo, Inst Phys Sao Carlos, Sao Carlos, SP, BrazilRutgers State Univ, New Jersey Med Sch, Dept Pharmacol Physiol & Neurosci, Newark, NJ 07103 USARepare Therapeut, 7210 Rue Frederick Banting,Suite 100, Montreal, PQ H4S 2A1, CanadaCollaborat Pharmaceut Inc, 840 Main Campus Dr,Lab 3510, Raleigh, NC 27606 USAUniv Fed Uberlandia, Lab Nanobiotechnol, Uberlandia, MG, BrazilUniv Fed Uberlandia, Integrat Physiol & Salivary Nanobiotechnol Grp, Uberlandia, MG, BrazilUniv Tartu, Inst Technol, Nooruse 1, EE-50411 Tartu, EstoniaUniv Leeds, Sch Mol & Cellular Biol, Fac Biol Sci, Leeds LS2 9JT, W Yorkshire, EnglandUniv Leeds, Astbury Ctr Struct Mol Biol, Leeds LS2 9JT, W Yorkshire, EnglandSao Paulo State Univ, IBILCE, Sao Jose Do Rio Preto, SP, BrazilSao Paulo State Univ, IBILCE, Lab Antibiot & Chemotherapeut, Sao Jose Do Rio Preto, SP, BrazilRoyal Society -Newton Advanced Fellowship: NA 150195CNPq: 445021/2014-4CNPq: 300508/2017-4CNPq: 201710267000063FAPEMIG: APQ-00587-14FAPEMIG: SICONV 793988/2013CAPES: 001CNPq: CNPq-465669/2014-0CNPq: 440610/2016-8CAPES: CNPq-465669/2014-0CAPES: 440610/2016-8FAPEMIG: CNPq-465669/2014-04FAPEMIG: 40610/2016-8Wellcome Trust: 096670Nature Publishing GroupUniversidade Federal de Uberlândia (UFU)Universidade Estadual Paulista (Unesp)Universidade Federal de Goiás (UFG)Universidade de São Paulo (USP)Rutgers State UnivRepare TherapeutCollaborat Pharmaceut IncUniv TartuUniv LeedsSilva, Suely [UNESP]Shimizu, Jacqueline Farinha [UNESP]Oliveira, Debora Moraes deAssis, Leticia Ribeiro de [UNESP]Bittar, Cintia [UNESP]Mottin, MelinaPaula Sousa, Bruna Katiele deMoraes Roso Mesquita, Nathalya Cristina deRegasini, Luis Octavio [UNESP]Rahal, Paula [UNESP]Oliva, GlauciusPerryman, Alexander LukeEkins, SeanAndrade, Carolina HortaGoulart, Luiz RicardoSabino-Silva, RobinsonMerits, AndresHarris, MarkGomes Jardim, Ana Carolina [UNESP]2020-12-11T03:29:36Z2020-12-11T03:29:36Z2019-11-27info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/article12http://dx.doi.org/10.1038/s41598-019-54169-zScientific Reports. London: Nature Publishing Group, v. 9, 12 p., 2019.2045-2322http://hdl.handle.net/11449/19756110.1038/s41598-019-54169-zWOS:00049921050000179910823626712120000-0001-5693-6148Web of Sciencereponame:Repositório Institucional da UNESPinstname:Universidade Estadual Paulista (UNESP)instacron:UNESPengScientific Reportsinfo:eu-repo/semantics/openAccess2021-10-23T10:11:23Zoai:repositorio.unesp.br:11449/197561Repositório InstitucionalPUBhttp://repositorio.unesp.br/oai/requestopendoar:29462021-10-23T10:11:23Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)false |
dc.title.none.fl_str_mv |
A diarylamine derived from anthranilic acid inhibits ZIKV replication |
title |
A diarylamine derived from anthranilic acid inhibits ZIKV replication |
spellingShingle |
A diarylamine derived from anthranilic acid inhibits ZIKV replication Silva, Suely [UNESP] |
title_short |
A diarylamine derived from anthranilic acid inhibits ZIKV replication |
title_full |
A diarylamine derived from anthranilic acid inhibits ZIKV replication |
title_fullStr |
A diarylamine derived from anthranilic acid inhibits ZIKV replication |
title_full_unstemmed |
A diarylamine derived from anthranilic acid inhibits ZIKV replication |
title_sort |
A diarylamine derived from anthranilic acid inhibits ZIKV replication |
author |
Silva, Suely [UNESP] |
author_facet |
Silva, Suely [UNESP] Shimizu, Jacqueline Farinha [UNESP] Oliveira, Debora Moraes de Assis, Leticia Ribeiro de [UNESP] Bittar, Cintia [UNESP] Mottin, Melina Paula Sousa, Bruna Katiele de Moraes Roso Mesquita, Nathalya Cristina de Regasini, Luis Octavio [UNESP] Rahal, Paula [UNESP] Oliva, Glaucius Perryman, Alexander Luke Ekins, Sean Andrade, Carolina Horta Goulart, Luiz Ricardo Sabino-Silva, Robinson Merits, Andres Harris, Mark Gomes Jardim, Ana Carolina [UNESP] |
author_role |
author |
author2 |
Shimizu, Jacqueline Farinha [UNESP] Oliveira, Debora Moraes de Assis, Leticia Ribeiro de [UNESP] Bittar, Cintia [UNESP] Mottin, Melina Paula Sousa, Bruna Katiele de Moraes Roso Mesquita, Nathalya Cristina de Regasini, Luis Octavio [UNESP] Rahal, Paula [UNESP] Oliva, Glaucius Perryman, Alexander Luke Ekins, Sean Andrade, Carolina Horta Goulart, Luiz Ricardo Sabino-Silva, Robinson Merits, Andres Harris, Mark Gomes Jardim, Ana Carolina [UNESP] |
author2_role |
author author author author author author author author author author author author author author author author author author |
dc.contributor.none.fl_str_mv |
Universidade Federal de Uberlândia (UFU) Universidade Estadual Paulista (Unesp) Universidade Federal de Goiás (UFG) Universidade de São Paulo (USP) Rutgers State Univ Repare Therapeut Collaborat Pharmaceut Inc Univ Tartu Univ Leeds |
dc.contributor.author.fl_str_mv |
Silva, Suely [UNESP] Shimizu, Jacqueline Farinha [UNESP] Oliveira, Debora Moraes de Assis, Leticia Ribeiro de [UNESP] Bittar, Cintia [UNESP] Mottin, Melina Paula Sousa, Bruna Katiele de Moraes Roso Mesquita, Nathalya Cristina de Regasini, Luis Octavio [UNESP] Rahal, Paula [UNESP] Oliva, Glaucius Perryman, Alexander Luke Ekins, Sean Andrade, Carolina Horta Goulart, Luiz Ricardo Sabino-Silva, Robinson Merits, Andres Harris, Mark Gomes Jardim, Ana Carolina [UNESP] |
description |
Zika virus (ZIKV) is a mosquito-transmitted Flavivirus, originally identified in Uganda in 1947 and recently associated with a large outbreak in South America. Despite extensive efforts there are currently no approved antiviral compounds for treatment of ZIKV infection. Here we describe the antiviral activity of diarylamines derived from anthranilic acid (FAMs) against ZIKV. A synthetic FAM (E3) demonstrated anti-ZIKV potential by reducing viral replication up to 86%. We analyzed the possible mechanisms of action of FAM E3 by evaluating the intercalation of this compound into the viral dsRNA and its interaction with the RNA polymerase of bacteriophage SP6. However, FAM E3 did not act by these mechanisms. In silico results predicted that FAM E3 might bind to the ZIKV NS3 helicase suggesting that this protein could be one possible target of this compound. To test this, the thermal stability and the ATPase activity of the ZIKV NS3 helicase domain (NS3(Hel)) were investigated in vitro and we demonstrated that FAM E3 could indeed bind to and stabilize NS3(Hel). |
publishDate |
2019 |
dc.date.none.fl_str_mv |
2019-11-27 2020-12-11T03:29:36Z 2020-12-11T03:29:36Z |
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/10.1038/s41598-019-54169-z Scientific Reports. London: Nature Publishing Group, v. 9, 12 p., 2019. 2045-2322 http://hdl.handle.net/11449/197561 10.1038/s41598-019-54169-z WOS:000499210500001 7991082362671212 0000-0001-5693-6148 |
url |
http://dx.doi.org/10.1038/s41598-019-54169-z http://hdl.handle.net/11449/197561 |
identifier_str_mv |
Scientific Reports. London: Nature Publishing Group, v. 9, 12 p., 2019. 2045-2322 10.1038/s41598-019-54169-z WOS:000499210500001 7991082362671212 0000-0001-5693-6148 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
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Scientific Reports |
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info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
12 |
dc.publisher.none.fl_str_mv |
Nature Publishing Group |
publisher.none.fl_str_mv |
Nature Publishing Group |
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Web of Science reponame:Repositório Institucional da UNESP instname:Universidade Estadual Paulista (UNESP) instacron:UNESP |
instname_str |
Universidade Estadual Paulista (UNESP) |
instacron_str |
UNESP |
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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 |
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1799964502924460032 |