Inhibition of Brazilian ZIKV strain replication in primary human placental chorionic cells and cervical cells treated with nitazoxanide
Autor(a) principal: | |
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Data de Publicação: | 2020 |
Outros Autores: | , , , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Brazilian Journal of Infectious Diseases |
Texto Completo: | http://old.scielo.br/scielo.php?script=sci_arttext&pid=S1413-86702020000600505 |
Resumo: | ABSTRACT Zika virus (ZIKV) infection during pregnancy is associated with a congenital syndrome. Although the virus can be detected in human placental tissue and sexual transmission has been verified, it is not clear how the virus reaches the fetus. Despite the emerging severity caused by ZIKV infection, no specific prophylactic and/or therapeutic treatment is available. The aim of the present study was to evaluate the effectiveness antiviral of nitazoxanide (NTZ) in two important congenital transmission targets: (i) a primary culture of human placental chorionic cells, and (ii) human cervical epithelial cells (C33-A) infected with Brazilian ZIKV strain. Initially, NTZ activity was screened in ZIKV infected Vero cells under different treatment regimens with non-toxic drug concentrations for 48 h. Antiviral effect was found only when the treatment was carried out after the viral inoculum. A strong effect against the dengue virus serotype 2 (DENV-2) was also observed suggesting the possibility of treating other Flaviviruses. Additionally, it was shown that the treatment did not reduce the production of infectious viruses in insect cells (C6/36) infected with ZIKV, indicating that the activity of this drug is also related to host factors. Importantly, we demonstrated that NTZ treatment in chorionic and cervical cells caused a reduction of infected cells in a dose-dependent manner and decreased viral loads in up to 2 logs. Pre-clinical in vitro testing evidenced excellent therapeutic response of infected chorionic and cervical cells and point to future NTZ activity investigation in ZIKV congenital transmission models with the perspective of possible repurposing of NTZ to treat Zika fever, especially in pregnant women. |
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Brazilian Journal of Infectious Diseases |
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Inhibition of Brazilian ZIKV strain replication in primary human placental chorionic cells and cervical cells treated with nitazoxanideZIKVAntiviral effectNitazoxanideRepurposingPrimary culturePlacentaABSTRACT Zika virus (ZIKV) infection during pregnancy is associated with a congenital syndrome. Although the virus can be detected in human placental tissue and sexual transmission has been verified, it is not clear how the virus reaches the fetus. Despite the emerging severity caused by ZIKV infection, no specific prophylactic and/or therapeutic treatment is available. The aim of the present study was to evaluate the effectiveness antiviral of nitazoxanide (NTZ) in two important congenital transmission targets: (i) a primary culture of human placental chorionic cells, and (ii) human cervical epithelial cells (C33-A) infected with Brazilian ZIKV strain. Initially, NTZ activity was screened in ZIKV infected Vero cells under different treatment regimens with non-toxic drug concentrations for 48 h. Antiviral effect was found only when the treatment was carried out after the viral inoculum. A strong effect against the dengue virus serotype 2 (DENV-2) was also observed suggesting the possibility of treating other Flaviviruses. Additionally, it was shown that the treatment did not reduce the production of infectious viruses in insect cells (C6/36) infected with ZIKV, indicating that the activity of this drug is also related to host factors. Importantly, we demonstrated that NTZ treatment in chorionic and cervical cells caused a reduction of infected cells in a dose-dependent manner and decreased viral loads in up to 2 logs. Pre-clinical in vitro testing evidenced excellent therapeutic response of infected chorionic and cervical cells and point to future NTZ activity investigation in ZIKV congenital transmission models with the perspective of possible repurposing of NTZ to treat Zika fever, especially in pregnant women.Brazilian Society of Infectious Diseases2020-12-01info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersiontext/htmlhttp://old.scielo.br/scielo.php?script=sci_arttext&pid=S1413-86702020000600505Brazilian Journal of Infectious Diseases v.24 n.6 2020reponame:Brazilian Journal of Infectious Diseasesinstname:Brazilian Society of Infectious Diseases (BSID)instacron:BSID10.1016/j.bjid.2020.09.001info:eu-repo/semantics/openAccessSouza,Audrien A.A. deTorres,Lauana R.Lima,Lyana R.P.Paula,Vanessa deBarros,José J.Bonecini-Almeida,Maria da GloriaWaghabi,Mariana CaldasGardel,Marcelo A.Meuser-Batista,MarceloSouza,Elen M. deeng2021-01-13T00:00:00Zoai:scielo:S1413-86702020000600505Revistahttps://www.bjid.org.br/https://old.scielo.br/oai/scielo-oai.phpbjid@bjid.org.br||lgoldani@ufrgs.br1678-43911413-8670opendoar:2021-01-13T00:00Brazilian Journal of Infectious Diseases - Brazilian Society of Infectious Diseases (BSID)false |
dc.title.none.fl_str_mv |
Inhibition of Brazilian ZIKV strain replication in primary human placental chorionic cells and cervical cells treated with nitazoxanide |
title |
Inhibition of Brazilian ZIKV strain replication in primary human placental chorionic cells and cervical cells treated with nitazoxanide |
spellingShingle |
Inhibition of Brazilian ZIKV strain replication in primary human placental chorionic cells and cervical cells treated with nitazoxanide Souza,Audrien A.A. de ZIKV Antiviral effect Nitazoxanide Repurposing Primary culture Placenta |
title_short |
Inhibition of Brazilian ZIKV strain replication in primary human placental chorionic cells and cervical cells treated with nitazoxanide |
title_full |
Inhibition of Brazilian ZIKV strain replication in primary human placental chorionic cells and cervical cells treated with nitazoxanide |
title_fullStr |
Inhibition of Brazilian ZIKV strain replication in primary human placental chorionic cells and cervical cells treated with nitazoxanide |
title_full_unstemmed |
Inhibition of Brazilian ZIKV strain replication in primary human placental chorionic cells and cervical cells treated with nitazoxanide |
title_sort |
Inhibition of Brazilian ZIKV strain replication in primary human placental chorionic cells and cervical cells treated with nitazoxanide |
author |
Souza,Audrien A.A. de |
author_facet |
Souza,Audrien A.A. de Torres,Lauana R. Lima,Lyana R.P. Paula,Vanessa de Barros,José J. Bonecini-Almeida,Maria da Gloria Waghabi,Mariana Caldas Gardel,Marcelo A. Meuser-Batista,Marcelo Souza,Elen M. de |
author_role |
author |
author2 |
Torres,Lauana R. Lima,Lyana R.P. Paula,Vanessa de Barros,José J. Bonecini-Almeida,Maria da Gloria Waghabi,Mariana Caldas Gardel,Marcelo A. Meuser-Batista,Marcelo Souza,Elen M. de |
author2_role |
author author author author author author author author author |
dc.contributor.author.fl_str_mv |
Souza,Audrien A.A. de Torres,Lauana R. Lima,Lyana R.P. Paula,Vanessa de Barros,José J. Bonecini-Almeida,Maria da Gloria Waghabi,Mariana Caldas Gardel,Marcelo A. Meuser-Batista,Marcelo Souza,Elen M. de |
dc.subject.por.fl_str_mv |
ZIKV Antiviral effect Nitazoxanide Repurposing Primary culture Placenta |
topic |
ZIKV Antiviral effect Nitazoxanide Repurposing Primary culture Placenta |
description |
ABSTRACT Zika virus (ZIKV) infection during pregnancy is associated with a congenital syndrome. Although the virus can be detected in human placental tissue and sexual transmission has been verified, it is not clear how the virus reaches the fetus. Despite the emerging severity caused by ZIKV infection, no specific prophylactic and/or therapeutic treatment is available. The aim of the present study was to evaluate the effectiveness antiviral of nitazoxanide (NTZ) in two important congenital transmission targets: (i) a primary culture of human placental chorionic cells, and (ii) human cervical epithelial cells (C33-A) infected with Brazilian ZIKV strain. Initially, NTZ activity was screened in ZIKV infected Vero cells under different treatment regimens with non-toxic drug concentrations for 48 h. Antiviral effect was found only when the treatment was carried out after the viral inoculum. A strong effect against the dengue virus serotype 2 (DENV-2) was also observed suggesting the possibility of treating other Flaviviruses. Additionally, it was shown that the treatment did not reduce the production of infectious viruses in insect cells (C6/36) infected with ZIKV, indicating that the activity of this drug is also related to host factors. Importantly, we demonstrated that NTZ treatment in chorionic and cervical cells caused a reduction of infected cells in a dose-dependent manner and decreased viral loads in up to 2 logs. Pre-clinical in vitro testing evidenced excellent therapeutic response of infected chorionic and cervical cells and point to future NTZ activity investigation in ZIKV congenital transmission models with the perspective of possible repurposing of NTZ to treat Zika fever, especially in pregnant women. |
publishDate |
2020 |
dc.date.none.fl_str_mv |
2020-12-01 |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://old.scielo.br/scielo.php?script=sci_arttext&pid=S1413-86702020000600505 |
url |
http://old.scielo.br/scielo.php?script=sci_arttext&pid=S1413-86702020000600505 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
10.1016/j.bjid.2020.09.001 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
text/html |
dc.publisher.none.fl_str_mv |
Brazilian Society of Infectious Diseases |
publisher.none.fl_str_mv |
Brazilian Society of Infectious Diseases |
dc.source.none.fl_str_mv |
Brazilian Journal of Infectious Diseases v.24 n.6 2020 reponame:Brazilian Journal of Infectious Diseases instname:Brazilian Society of Infectious Diseases (BSID) instacron:BSID |
instname_str |
Brazilian Society of Infectious Diseases (BSID) |
instacron_str |
BSID |
institution |
BSID |
reponame_str |
Brazilian Journal of Infectious Diseases |
collection |
Brazilian Journal of Infectious Diseases |
repository.name.fl_str_mv |
Brazilian Journal of Infectious Diseases - Brazilian Society of Infectious Diseases (BSID) |
repository.mail.fl_str_mv |
bjid@bjid.org.br||lgoldani@ufrgs.br |
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1754209245122789376 |