| Texto completo | |
| Autor(es): Mostrar menos - |
de Sousa, Francielle Tramontini Gomes
;
Biering, Scott B.
;
Patel, Trishna S.
;
Blanc, Sophie F.
;
Camelini, Carla M.
;
Venzke, Dalila
;
Nunes, Ricardo J.
;
Romano, Camila M.
;
Beatty, P. Robert
;
Sabino, Ester C.
;
Harris, Eva
Número total de Autores: 11
|
| Tipo de documento: | Artigo Científico |
| Fonte: | Antiviral Research; v. 203, p. 9-pg., 2022-05-18. |
| Resumo | |
Despite substantial morbidity and mortality, no therapeutic agents exist for treatment of dengue or Zika, and the currently available dengue vaccine is only recommended for dengue virus (DENV)-immune individuals. Thus, development of therapeutic and/or preventive drugs is urgently needed. DENV and Zika virus (ZIKV) nonstructural protein 1 (NS1) can directly trigger endothelial barrier dysfunction and induce inflammatory re-sponses, contributing to vascular leak in vivo. Here we evaluated the efficacy of the (1-6,1-3)-beta-D-glucan isolated from Agaricus subrufescens fruiting bodies (FR) and its sulfated derivative (FR-S) against DENV-2 and ZIKV infection and NS1-mediated pathogenesis. FR-S, but not FR, significantly inhibited DENV-2 and ZIKV replication in human monocytic cells (EC50 = 36.5 and 188.7 mu g/mL, respectively) when added simultaneously with viral infection. No inhibitory effect was observed when FR or FR-S were added post-infection, suggesting inhibition of viral entry as a mechanism of action. In an in vitro model of endothelial permeability using human pulmonary microvascular endothelial cells (HPMECs), FR and FR-S (0.12 mu g/mL) inhibited DENV-2 NS1-and ZIKV NS1-induced hyperpermeability by 50% and 100%, respectively, as measured by Trans-Endothelial Electrical Resistance. Treatment with 0.25 mu g/mL of FR and FR-S inhibited DENV-2 NS1 binding to HPMECs. Further, FR-S significantly reduced intradermal hyperpermeability induced by DENV-2 NS1 in C57BL/6 mice and protected against DENV-induced morbidity and mortality in a murine model of dengue vascular leak syndrome. Thus, we demonstrate efficacy of FR-S against DENV and ZIKV infection and NS1-induced endothelial permeability in vitro and in vivo. These findings encourage further exploration of FR-S and other glycan candidates for flavivirus treatment alone or in combination with compounds with different mechanisms of action. (AU) | |
| Processo FAPESP: | 13/01690-0 - Implantação de um modelo in vitro de avaliação da permeabilidade vascular para estudos da patogênese da dengue hemorrágica e triagem de compostos com potencial terapêutico |
| Beneficiário: | Ester Cerdeira Sabino |
| Modalidade de apoio: | Auxílio à Pesquisa - Regular |
| Processo FAPESP: | 13/01702-9 - Avaliação da permeabilidade endotelial para estudos da patogênese da dengue e triagem de compostos com potencial terapêutico |
| Beneficiário: | Francielle Tramontini Gomes de Sousa |
| Modalidade de apoio: | Bolsas no Brasil - Pós-Doutorado |
| Processo FAPESP: | 17/16627-3 - Avaliação dos efeitos das quimiocinas CXCL1 e CXCL10 e do potencial terapêutico de uma glucomanana sulfatada do Agaricus brasiliensis (MI-S) na dengue grave através de modelos in vitro e in vivo de extravasamento plasmático |
| Beneficiário: | Francielle Tramontini Gomes de Sousa |
| Modalidade de apoio: | Bolsas no Exterior - Estágio de Pesquisa - Pós-Doutorado |