| Texto completo | |
| Autor(es): Mostrar menos - |
Coimbra, Lais D.
;
Shimizu, Jacqueline F.
;
Nagai, Alice
;
Borin, Alexandre
;
Fontoura, Marina A.
;
Concha, Juan O.
;
Leme, Luiza
;
do Carmo, Ketleen Lucas
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de Oliveira, Leonardo C.
;
Soprano, Adriana S.
;
Felipe, Jaqueline S.
;
Silva, Amanda B.
;
Forato, Julia
;
Scachetti, Gabriel C.
;
Crump, Colin M.
;
Sacchetto, Livia
;
Nogueira, Mauricio L.
;
Bezerra, Eduardo H. S.
;
Guimaraes, Samuel L.
;
Cordeiro, Artur T.
;
Proenca-Modena, Jose Luiz
;
Dasilva, Luis L. P.
;
Boratto, Paulo V. M.
;
Hanchuk, Talita D. Melo
;
Marques, Rafael Elias
Número total de Autores: 25
|
| Tipo de documento: | Artigo Científico |
| Fonte: | Antiviral Research; v. 238, p. 12-pg., 2025-04-24. |
| Resumo | |
Oropouche virus (OROV) has caused a new outbreak, with thousands of cases of febrile disease in South and Central America, including regions where the virus was not detected before. Oropouche fever is a neglected mosquito-borne disease that still lacks options for antiviral treatment. We developed a high-throughput screening phenotypic assay using human hepatocyte-derived HuH-7.0 cells to screen over 7700 compounds against OROV infection. We identified 13 hit compounds that were protective against OROV-induced cytopathic effect in cell culture, of which 3 were confirmed: lysergol, amiloride hydrochloride, and pyridostatin TFA, with EC50 values below 2 mu M. Orthogonal assays indicate that both lysergol and pyridostatin present antiviral activity against OROV in HuH-7.0 and T24 cell lines, but lysergol is far more potent, causing up to a 100,000-fold reduction in viral load in the low micromolar range. Mechanistic studies indicate that the antiviral effect of lysergol affects early stages of viral replication, and that lysergol is also active against a recently isolated OROV strain. In conclusion, our phenotypical screening campaign led to the identification of a first-in-class compound with potent antiviral activity against the emerging OROV in cell culture. We conclude that high-throughput screening assays can be implemented in response to the emergence of arboviruses and accelerate the discovery of candidate treatments. (AU) | |
| Processo FAPESP: | 22/01379-2 - O papel da microbiota intestinal na suscetibilidade à infecção experimental pelo vírus da encefalite de saint louis |
| Beneficiário: | Jaqueline de Souza Felipe |
| Modalidade de apoio: | Bolsas no Brasil - Doutorado |
| Processo FAPESP: | 21/05519-0 - Entendendo o papel do recrutamento e ativação de neutrófilos em doenças arbovirais |
| Beneficiário: | Rafael Elias Marques Pereira Silva |
| Modalidade de apoio: | Auxílio à Pesquisa - Regular |
| Processo FAPESP: | 22/02278-5 - Seleção de compostos através de reposicionamento de fármacos e caracterização da atividade antiviral contra oropouche orthobunyavirus |
| Beneficiário: | Alexandre Borin Pereira |
| Modalidade de apoio: | Bolsas no Brasil - Doutorado |
| Processo FAPESP: | 19/02418-9 - Mecanismos moleculares envolvidos na montagem do Vírus Oropouche |
| Beneficiário: | Luis Lamberti Pinto da Silva |
| Modalidade de apoio: | Auxílio à Pesquisa - Regular |
| Processo FAPESP: | 23/16611-0 - Estudo da migração de células imunes inatas em um modelo de zebrafish infectado com Orthobunyavirus oropoucheense |
| Beneficiário: | Alexandre Borin Pereira |
| Modalidade de apoio: | Bolsas no Exterior - Estágio de Pesquisa - Doutorado |
| Processo FAPESP: | 23/10771-6 - Estudo funcional da glicosilação tipo N da proteína E na infecção do vírus da encefalite de St. Louis |
| Beneficiário: | Luiza Leme |
| Modalidade de apoio: | Bolsas no Brasil - Doutorado |