| Autor: |
Yamamoto KA; Department of Biochemistry, Institute of Chemistry, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-909, Brazil., Blackburn K; Department of Molecular and Structural Biochemistry, North Carolina State University, Raleigh, NC 27607, USA., Goshe MB; Department of Molecular and Structural Biochemistry, North Carolina State University, Raleigh, NC 27607, USA., Brown DT; Department of Molecular and Structural Biochemistry, North Carolina State University, Raleigh, NC 27607, USA., Migoswski E; Institute of Pediatrics and Puericulture Martagão Gesteira, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-912, Brazil., Campanhon IB; Department of Biochemistry, Institute of Chemistry, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-909, Brazil., Moreira MF; Department of Biochemistry, Institute of Chemistry, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-909, Brazil., Ferreira DF; Department of Molecular and Structural Biochemistry, North Carolina State University, Raleigh, NC 27607, USA.; Department of Virology, Paulo de Góes Microbiology Institute, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-902, Brazil., Soares MR; Department of Biochemistry, Institute of Chemistry, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-909, Brazil. |
| Abstrakt: |
Dengue virus is an important circulating arbovirus in Brazil responsible for high morbidity and mortality worldwide, representing a huge economic and social burden, in addition to affecting public health. In this study, the biological activity, toxicity, and antiviral activity against dengue virus type 2 (DENV-2) of tizoxanide (TIZ) was evaluated in Vero cell culture. TIZ has a broad spectrum of action in inhibiting different pathogens, including bacteria, protozoa, and viruses. Cells were infected for 1 h with DENV-2 and then treated for 24 h with different concentrations of the drug. The quantification of viral production indicated the antiviral activity of TIZ. The protein profiles in infected Vero cells treated and not treated with TIZ were analyzed using the label-free quantitative proteomic approach. TIZ was able to inhibit virus replication mainly intracellularly after DENV-2 penetration and before the complete replication of the viral genome. Additionally, the study of the protein profile of infected not-treated and infected-treated Vero cells showed that TIZ interferes with cellular processes such as intracellular trafficking and vesicle-mediated transport and post-translational modifications when added after infection. Our results also point to the activation of immune response genes that would eventually lead to a decrease of DENV-2 production. TIZ is a promising therapeutic molecule for the treatment of DENV-2 infections. |
