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Minist?rio da Sa?de. Secretaria de Vigil?ncia em Sa?de. Instituto Evandro Chagas. Ananindeua, PA, Brasil / Universidade Federal do Par?. Instituto de Ci?ncias Biol?gicas. Bel?m, PA, Brazil. Minist?rio da Sa?de. Secretaria de Vigil?ncia em Sa?de. Instituto Evandro Chagas. Ananindeua, PA, Brasil. Universidade de S?o Paulo. Departamento de Patologia. Faculdade de Medicina. S?o Paulo, SP, Brazil. Funda??o Oncocentro de S?o Paulo. S?o Paulo, SP, Brazil. Faculdade de Medicina de S?o Jos? Do Rio Preto. S?o Paulo, SP, Brazil. Minist?rio da Sa?de. Secretaria de Vigil?ncia em Sa?de. Instituto Evandro Chagas. Ananindeua, PA, Brasil. Universidade Federal do Par?. Instituto de Ci?ncias Biol?gicas. Bel?m, PA, Brazil. Minist?rio da Sa?de. Secretaria de Vigil?ncia em Sa?de. Instituto Evandro Chagas. Ananindeua, PA, Brasil. Universidade Federal Do Cear?. Drug Research and Development Center. Laboratory of Pharmacogenetics. Fortaleza, CE, Brazil. Universidade Federal do Par?. Instituto de Ci?ncias Biol?gicas. Bel?m, PA, Brazil. Minist?rio da Sa?de. Secretaria de Vigil?ncia em Sa?de. Instituto Evandro Chagas. Ananindeua, PA, Brasil. Universidade Federal do Par?. Instituto de Ci?ncias Biol?gicas. Bel?m, PA, Brazil. Minist?rio da Sa?de. Secretaria de Vigil?ncia em Sa?de. Instituto Evandro Chagas. Ananindeua, PA, Brasil. Dengue virus causes dengue hemorrhagic fever (DHF) and has been associated to fatal cases worldwide. The liver is one of the most important target tissues in severe cases, due to its intense viral replication and metabolic role. microRNAs role during infection is crucial to understand the regulatory mechanisms of DENV infection and can help in diagnostic and anti-viral therapies development. We sequenced the miRNome of six fatal cases and compared to five controls, to characterize the human microRNAs expression profile in the liver tissue during DHF. Eight microRNAs were differentially expressed, including miR-126-5p, a regulatory molecule of endothelial cells, miR-122-5p, a liver specific homeostasis regulator, and miR-146a-5p, an interferon-regulator. Enrichment analysis with predicted target genes of microRNAs revealed regulatory pathways of apoptosis, involving MAPK, RAS, CDK and FAS. Immune response pathways were related to NF- kB, CC and CX families, IL and TLR. This is the first description of the human microRNA and isomicroRNA profile in liver tissues from DHF cases. The results demonstrated the association of miR-126-5p, miR-122-5p and miR-146a-5p with DHF liver pathogenesis, involving endothelial repair and vascular permeability regulation, control of homeostasis and expression of inflammatory cytokines.

Universidade Federal do Rio de Janeiro. Instituto de Microbiologia Paulo de Goes, Centro de Ci?ncias da Sa?de. Rio de Janeiro, RJ, Brazil. Universidade Federal do Rio de Janeiro. Instituto de Microbiologia Paulo de Goes, Centro de Ci?ncias da Sa?de. Rio de Janeiro, RJ, Brazil. Universidade Federal do Rio de Janeiro. Instituto de Biologia. Rio de Janeiro, RJ, Brazil. Universidade Federal do Rio de Janeiro. Instituto de Microbiologia Paulo de Goes, Centro de Ci?ncias da Sa?de. Rio de Janeiro, RJ, Brazil. Universidade Federal do Rio de Janeiro. Instituto de Bioqu?mica M?dica Leopoldo de Meis. Centro de Ci?ncias da Sa?de. Rio de Janeiro, RJ, Brazil / Minist?rio da Sa?de. Secretaria de Vigil?ncia em Sa?de. Instituto Evandro Chagas. Ananindeua, PA, Brasil / Universidade do Estado do Par?. Departamento de Morfologia e Ci?ncias Fisiol?gicas. Centro de Ci?ncias Biol?gicas e da Sa?de. Bel?m, PA, Brazil. Universidade Federal do Rio de Janeiro. N?cleo Multidisciplinar de Pesquisas. Polo Avan?ado de Xer?m. Duque de Caxias, RJ, Brazil. Universidade Federal do Rio de Janeiro. Instituto de Microbiologia Paulo de Goes, Centro de Ci?ncias da Sa?de. Rio de Janeiro, RJ, Brazil. Universidade Federal do Rio de Janeiro. N?cleo Multidisciplinar de Pesquisas. Polo Avan?ado de Xer?m. Duque de Caxias, RJ, Brazil. Universidade Federal do Rio de Janeiro. Instituto de Biologia. Rio de Janeiro, RJ, Brazil. Universidade Federal do Rio de Janeiro. Instituto de Bioqu?mica M?dica Leopoldo de Meis. Centro de Ci?ncias da Sa?de. Rio de Janeiro, RJ, Brazil. Universidade Federal do Rio de Janeiro. Instituto de Microbiologia Paulo de Goes, Centro de Ci?ncias da Sa?de. Rio de Janeiro, RJ, Brazil. Universidade Federal do Rio de Janeiro. Instituto de Bioqu?mica M?dica Leopoldo de Meis. Centro de Ci?ncias da Sa?de. Rio de Janeiro, RJ, Brazil Universidade Federal do Rio de Janeiro. Instituto de Bioqu?mica M?dica Leopoldo de Meis. Centro de Ci?ncias da Sa?de. Rio de Janeiro, RJ, Brazil Universidade Federal do Rio de Janeiro. Instituto de Microbiologia Paulo de Goes, Centro de Ci?ncias da Sa?de. Rio de Janeiro, RJ, Brazil. The global situation of diseases transmitted by arthropod-borne viruses such as Dengue (DENV), Yellow Fever (YFV), Chikungunya (CHIKV) and Zika (ZIKV) viruses is alarming and treatment of human infection by these arboviruses faces several challenges. The discovery of broad-spectrum antiviral molecules, able to inactivate different groups of viruses, is an interesting approach. The viral envelope is a common structure among arboviruses, being a potential target for antivirals. Porphyrins are amphipathic molecules able to interact with membranes and absorb light, being widely used in photodynamic therapy. Previously, we showed that heme, Co-protoporphyrin IX (CoPPIX) and Sn-protoporphyrin IX (SnPPIX) directly inactivate DENV and YFV infectious particles. Here we demonstrate that the antiviral activity of these porphyrins can be broadened to CHIKV, ZIKV, Mayaro virus, Sindbis virus and Vesicular Stomatitis virus. Porphyrin treatment causes viral envelope protein loss, affecting viral morphology, adsorption and entry into target cells. Also, light-stimulation enhanced the SnPPIX activity against all tested arboviruses. In summary, CoPPIX and SnPPIX were shown to be efficient broad-spectrum compounds to inactivate medically and veterinary important viruses.

The Zika virus (ZIKV) is an arthropod-borne virus that belongs to the Flaviviridae family. The ZIKV infection is usually asymptomatic or is associated with mild clinical manifestations; however, increased numbers of cases of microcephaly and birth defects have been recently reported. To date, neither a vaccine nor an antiviral treatment has become available to control ZIKV replication. Among the natural compounds recognized for their medical properties, flavonoids, which can be found in fruits and vegetables, have been found to possess biological activity against a variety of viruses. Here, we demonstrate that the citrus flavanone naringenin (NAR) prevented ZIKV infection in human A549 cells in a concentration-dependent and ZIKV-lineage independent manner. NAR antiviral activity was also observed when primary human monocyte-derived dendritic cells were infected by ZIKV. NAR displayed its antiviral activity when the cells were treated after infection, suggesting that NAR acts on the viral replication or assembly of viral particles. Moreover, a molecular docking analysis suggests a potential interaction between NAR and the protease domain of the NS2B-NS3 protein of ZIKV which could explain the anti-ZIKV activity of NAR. Finally, the results support the potential of NAR as a suitable candidate molecule for developing anti-ZIKV treatments.