| Texto completo | |
| Autor(es): |
Fernandes, Rafaela Sachetto
[1]
;
de Godoy, Andre Schutzer
[1]
;
Santos, Igor Andrade
[2]
;
Noske, Gabriela Dias
[1]
;
de Oliveira, Ketllyn Irene Zagato
[1]
;
Gawriljuk, Victor Oliveira
[1]
;
Jardim, Ana Carolina Gomes
[2]
;
Oliva, Glaucius
[1]
Número total de Autores: 8
|
| Afiliação do(s) autor(es): | [1] Univ Sao Paulo, Phys Inst Sao Carlos, Ave Joao Dagnone 1100, BR-13563120 Sao Carlos - Brazil
[2] Univ Fed Uberlandia, Inst Biomed Sci, Ave Amazonas 1700, Bloco 4C Sala 216, BR-38405317 Uberlandia, MG - Brazil
Número total de Afiliações: 2
|
| Tipo de documento: | Artigo Científico |
| Fonte: | VIRUS RESEARCH; v. 299, JUL 2 2021. |
| Citações Web of Science: | 0 |
| Resumo | |
The 2015/16 Zika virus (ZIKV) epidemic led to almost 1 million confirmed cases in 84 countries and was associated to the development of congenital microcephaly and Guillain-Barre ` syndrome. More recently, a ZIKV African lineage was identified in Brazil raising concerns about a future outbreak. The long-term consequences of viral infection emphasizes the need for the development of effective anti-ZIKV drugs. In this study, we developed and characterized a ZIKV replicon cell line for the screening of viral replication inhibitors. The replicon system was developed by engineering the IRES-Neo cassette into the 3' UTR terminus of the ZIKV Rluc DNA construct. After in vitro transcription, replicon RNA was used to transfect BHK-21 cells, that were selected with G418, thus generating the BHK-21-RepZIKV\_IRES-Neo cell line. Through this replicon-based cell system, we identified two molecules with potent anti-ZIKV activities, an imidazonaphthyridine and a riminophenazine, both from the MMV/DNDi Pandemic Response Box library of 400 drug-like compounds. The imidazonaphthyridine, known as RO8191, showed remarkable selectivity against ZIKV, while the riminophenazine, the antibiotic Clofazimine, could act as a non-nucleoside analog inhibitor of viral RNA-dependent RNA polymerase (RdRp), as evidenced both in vitro and in silico. The data showed herein supports the use of replicon-based assays in high-throughput screening format as a biosafe and reliable tool for antiviral drug discovery. (AU) | |
| Processo FAPESP: | 18/05130-3 - Construção e caracterização de um sistema replicon sub-genômico do ZIKV para a descoberta de agentes antivirais. |
| Beneficiário: | Rafaela Sachetto Fernandes |
| Modalidade de apoio: | Bolsas no Brasil - Pós-Doutorado |
| Processo FAPESP: | 16/19712-9 - Caracterização estrutural das proteínas do vírus Zika e busca por agentes antivirais |
| Beneficiário: | Andre Schutzer de Godoy |
| Modalidade de apoio: | Bolsas no Brasil - Pós-Doutorado |
| Processo FAPESP: | 13/07600-3 - CIBFar - Centro de Inovação em Biodiversidade e Fármacos |
| Beneficiário: | Glaucius Oliva |
| Modalidade de apoio: | Auxílio à Pesquisa - Centros de Pesquisa, Inovação e Difusão - CEPIDs |