Inhibition of Brazilian ZIKV strain replication in primary human placental chorionic cells and cervical cells treated with nitazoxanide
Braz. j. infect. dis
;
24(6): 505-516, Nov.-Dec. 2020. tab, graf
Artigo
em Inglês
| LILACS
| ID: biblio-1153491
ABSTRACT
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.
Texto completo:
DisponíveL
Índice:
LILACS (Américas)
Assunto principal:
Zika virus
/
Infecção por Zika virus
Tipo de estudo:
Estudo prognóstico
Limite:
Animais
/
Feminino
/
Humanos
/
Gravidez
País/Região como assunto:
América do Sul
/
Brasil
Idioma:
Inglês
Revista:
Braz. j. infect. dis
Assunto da revista:
Doenças Transmissíveis
Ano de publicação:
2020
Tipo de documento:
Artigo
/
Documento de projeto
País de afiliação:
Brasil
Instituição/País de afiliação:
FIOCRUZ/BR
/
FIOCRUZ+BR
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