Chloroquine and Sulfadoxine Derivatives Inhibit ZIKV Replication in Cervical Cells

Detalhes bibliográficos
Autor(a) principal: Souza, Audrien Alves Andrade de
Data de Publicação: 2020
Outros Autores: Torres, Lauana Ribas, Capobianco, Lyana Rodrigues Pinto Lima, Paula, Vanessa Salete de, Cascabulho, Cynthia Machado, Salomão, Kelly, Bonecini-Almeida, Maria da Gloria, Ferreira, Maria de Lourdes Garcia, Boechat, Nubia, Pinheiro, Luiz Carlos da Silva, Souza, Elen Mello de
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Institucional da FIOCRUZ (ARCA)
Texto Completo: https://www.arca.fiocruz.br/handle/icict/45939
Resumo: Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Virologia Molecular. Rio de Janeiro, RJ, Brasil.
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spelling Souza, Audrien Alves Andrade deTorres, Lauana RibasCapobianco, Lyana Rodrigues Pinto LimaPaula, Vanessa Salete deCascabulho, Cynthia MachadoSalomão, KellyBonecini-Almeida, Maria da GloriaFerreira, Maria de Lourdes GarciaBoechat, NubiaPinheiro, Luiz Carlos da SilvaSouza, Elen Mello de2021-02-02T20:46:49Z2021-02-02T20:46:49Z2020SOUZA, Audrien Alves Andrade et al. Chloroquine and Sulfadoxine Derivatives Inhibit ZIKV Replication in Cervical Cells. Viruses, v. 13, n. 36, p. 1-15, Dec. 2020.1999-4915https://www.arca.fiocruz.br/handle/icict/4593910.3390/v13010036engMDPIChloroquine and Sulfadoxine Derivatives Inhibit ZIKV Replication in Cervical Cellsinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleFundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Virologia Molecular. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Virologia Molecular. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Virologia Molecular. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Virologia Molecular. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Inovações em Terapias, Ensino e Bioprodutos. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Laboratório de Imunologia e Imunogenética em Doenças Infecciosas. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto de Tecnologia em Fármacos Farmanguinhos. Laboratório de Síntese de Fármacos. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto de Tecnologia em Fármacos Farmanguinhos. Laboratório de Síntese de Fármacos. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto de Tecnologia em Fármacos Farmanguinhos. Laboratório de Síntese de Fármacos. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Virologia Molecular. Rio de Janeiro, RJ, Brasil.Despite the severe morbidity caused by Zika fever, its specific treatment is still a challenge for public health. Several research groups have investigated the drug repurposing of chloroquine. However, the highly toxic side effect induced by chloroquine paves the way for the improvement of this drug for use in Zika fever clinics. Our aim is to evaluate the anti-Zika virus (ZIKV) effect of hybrid compounds derived from chloroquine and sulfadoxine antimalarial drugs. The antiviral activity of hybrid compounds (C-Sd1 to C-Sd7) was assessed in an in-vitro model of human cervical and Vero cell lines infected with a Brazilian (BR) ZIKV strain. First, we evaluated the cytotoxic effect on cultures treated with up to 200 µM of C-Sds and observed CC50 values that ranged from 112.0 ± 1.8 to >200 µM in cervical cells and 43.2 ± 0.4 to 143.0 ± 1.3 µM in Vero cells. Then, the cultures were ZIKV-infected and treated with up to 25 µM of C-Sds for 48 h. The treatment of cervical cells with C-Sds at 12 µM induced a reduction of 79.8% ± 4.2% to 90.7% ± 1.5% of ZIKV-envelope glycoprotein expression in infected cells as compared to 36.8% ± 2.9% of infection in vehicle control. The viral load was also investigated and revealed a reduction of 2- to 3-logs of ZIKV genome copies/mL in culture supernatants compared to 6.7 ± 0.7 × 108 copies/mL in vehicle control. The dose-response curve by plaque-forming reduction (PFR) in cervical cells revealed a potent dose-dependent activity of C-Sds in inhibiting ZIKV replication, with PFR above 50% and 90% at 6 and 12 µM, respectively, while 25 µM inhibited 100% of viral progeny. The treatment of Vero cells at 12 µM led to 100% PFR, confirming the C-Sds activity in another cell type. Regarding effective concentration in cervical cells, the EC50 values ranged from 3.2 ± 0.1 to 5.0 ± 0.2 µM, and the EC90 values ranged from 7.2 ± 0.1 to 11.6 ± 0.1 µM, with selectivity index above 40 for most C-Sds, showing a good therapeutic window. Here, our aim is to investigate the anti-ZIKV activity of new hybrid compounds that show highly potent efficacy as inhibitors of ZIKV in-vitro infection. However, further studies will be needed to investigate whether these new chemical structures can lead to the improvement of chloroquine antiviral activity.Zika virusAntiviral effectChloroquineHuman cervical cellsHybrid compoundsSulfadoxineinfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da FIOCRUZ (ARCA)instname:Fundação Oswaldo Cruz (FIOCRUZ)instacron:FIOCRUZLICENSElicense.txtlicense.txttext/plain; charset=utf-83099https://www.arca.fiocruz.br/bitstream/icict/45939/1/license.txt586c046dcfeef936e32f0323bb9a47c0MD51ORIGINALChloroquine_Maria_Bonecini-Almeida_etal_INI_2020.pdfChloroquine_Maria_Bonecini-Almeida_etal_INI_2020.pdfapplication/pdf4566203https://www.arca.fiocruz.br/bitstream/icict/45939/2/Chloroquine_Maria_Bonecini-Almeida_etal_INI_2020.pdfcc91ac8d5fb8df1d3af59d30777499e7MD52TEXTChloroquine_Maria_Bonecini-Almeida_etal_INI_2020.pdf.txtChloroquine_Maria_Bonecini-Almeida_etal_INI_2020.pdf.txtExtracted 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dc.title.pt_BR.fl_str_mv Chloroquine and Sulfadoxine Derivatives Inhibit ZIKV Replication in Cervical Cells
title Chloroquine and Sulfadoxine Derivatives Inhibit ZIKV Replication in Cervical Cells
spellingShingle Chloroquine and Sulfadoxine Derivatives Inhibit ZIKV Replication in Cervical Cells
Souza, Audrien Alves Andrade de
Zika virus
Antiviral effect
Chloroquine
Human cervical cells
Hybrid compounds
Sulfadoxine
title_short Chloroquine and Sulfadoxine Derivatives Inhibit ZIKV Replication in Cervical Cells
title_full Chloroquine and Sulfadoxine Derivatives Inhibit ZIKV Replication in Cervical Cells
title_fullStr Chloroquine and Sulfadoxine Derivatives Inhibit ZIKV Replication in Cervical Cells
title_full_unstemmed Chloroquine and Sulfadoxine Derivatives Inhibit ZIKV Replication in Cervical Cells
title_sort Chloroquine and Sulfadoxine Derivatives Inhibit ZIKV Replication in Cervical Cells
author Souza, Audrien Alves Andrade de
author_facet Souza, Audrien Alves Andrade de
Torres, Lauana Ribas
Capobianco, Lyana Rodrigues Pinto Lima
Paula, Vanessa Salete de
Cascabulho, Cynthia Machado
Salomão, Kelly
Bonecini-Almeida, Maria da Gloria
Ferreira, Maria de Lourdes Garcia
Boechat, Nubia
Pinheiro, Luiz Carlos da Silva
Souza, Elen Mello de
author_role author
author2 Torres, Lauana Ribas
Capobianco, Lyana Rodrigues Pinto Lima
Paula, Vanessa Salete de
Cascabulho, Cynthia Machado
Salomão, Kelly
Bonecini-Almeida, Maria da Gloria
Ferreira, Maria de Lourdes Garcia
Boechat, Nubia
Pinheiro, Luiz Carlos da Silva
Souza, Elen Mello de
author2_role author
author
author
author
author
author
author
author
author
author
dc.contributor.author.fl_str_mv Souza, Audrien Alves Andrade de
Torres, Lauana Ribas
Capobianco, Lyana Rodrigues Pinto Lima
Paula, Vanessa Salete de
Cascabulho, Cynthia Machado
Salomão, Kelly
Bonecini-Almeida, Maria da Gloria
Ferreira, Maria de Lourdes Garcia
Boechat, Nubia
Pinheiro, Luiz Carlos da Silva
Souza, Elen Mello de
dc.subject.en.pt_BR.fl_str_mv Zika virus
Antiviral effect
Chloroquine
Human cervical cells
Hybrid compounds
Sulfadoxine
topic Zika virus
Antiviral effect
Chloroquine
Human cervical cells
Hybrid compounds
Sulfadoxine
description Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Virologia Molecular. Rio de Janeiro, RJ, Brasil.
publishDate 2020
dc.date.issued.fl_str_mv 2020
dc.date.accessioned.fl_str_mv 2021-02-02T20:46:49Z
dc.date.available.fl_str_mv 2021-02-02T20:46:49Z
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.citation.fl_str_mv SOUZA, Audrien Alves Andrade et al. Chloroquine and Sulfadoxine Derivatives Inhibit ZIKV Replication in Cervical Cells. Viruses, v. 13, n. 36, p. 1-15, Dec. 2020.
dc.identifier.uri.fl_str_mv https://www.arca.fiocruz.br/handle/icict/45939
dc.identifier.issn.pt_BR.fl_str_mv 1999-4915
dc.identifier.doi.none.fl_str_mv 10.3390/v13010036
identifier_str_mv SOUZA, Audrien Alves Andrade et al. Chloroquine and Sulfadoxine Derivatives Inhibit ZIKV Replication in Cervical Cells. Viruses, v. 13, n. 36, p. 1-15, Dec. 2020.
1999-4915
10.3390/v13010036
url https://www.arca.fiocruz.br/handle/icict/45939
dc.language.iso.fl_str_mv eng
language eng
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv MDPI
publisher.none.fl_str_mv MDPI
dc.source.none.fl_str_mv reponame:Repositório Institucional da FIOCRUZ (ARCA)
instname:Fundação Oswaldo Cruz (FIOCRUZ)
instacron:FIOCRUZ
instname_str Fundação Oswaldo Cruz (FIOCRUZ)
instacron_str FIOCRUZ
institution FIOCRUZ
reponame_str Repositório Institucional da FIOCRUZ (ARCA)
collection Repositório Institucional da FIOCRUZ (ARCA)
bitstream.url.fl_str_mv https://www.arca.fiocruz.br/bitstream/icict/45939/1/license.txt
https://www.arca.fiocruz.br/bitstream/icict/45939/2/Chloroquine_Maria_Bonecini-Almeida_etal_INI_2020.pdf
https://www.arca.fiocruz.br/bitstream/icict/45939/3/Chloroquine_Maria_Bonecini-Almeida_etal_INI_2020.pdf.txt
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