Tizoxanide Antiviral Activity on Dengue Virus Replication
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 t...
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2023-03-01
|
| Series: | Viruses |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1999-4915/15/3/696 |
| _version_ | 1797608656763617280 |
|---|---|
| author | Kristie A. Yamamoto Kevin Blackburn Michael B. Goshe Dennis T. Brown Edimilson Migoswski Isabele B. Campanhon Monica F. Moreira Davis F. Ferreira Marcia R. Soares |
| author_facet | Kristie A. Yamamoto Kevin Blackburn Michael B. Goshe Dennis T. Brown Edimilson Migoswski Isabele B. Campanhon Monica F. Moreira Davis F. Ferreira Marcia R. Soares |
| author_sort | Kristie A. Yamamoto |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-11T05:47:37Z |
| format | Article |
| id | doaj.art-ee4e077169a44e79be8a5671f5cf84ee |
| institution | Directory Open Access Journal |
| issn | 1999-4915 |
| language | English |
| last_indexed | 2024-03-11T05:47:37Z |
| publishDate | 2023-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Viruses |
| spelling | doaj.art-ee4e077169a44e79be8a5671f5cf84ee2023-11-17T14:23:04ZengMDPI AGViruses1999-49152023-03-0115369610.3390/v15030696Tizoxanide Antiviral Activity on Dengue Virus ReplicationKristie A. Yamamoto0Kevin Blackburn1Michael B. Goshe2Dennis T. Brown3Edimilson Migoswski4Isabele B. Campanhon5Monica F. Moreira6Davis F. Ferreira7Marcia R. Soares8Department of Biochemistry, Institute of Chemistry, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-909, BrazilDepartment of Molecular and Structural Biochemistry, North Carolina State University, Raleigh, NC 27607, USADepartment of Molecular and Structural Biochemistry, North Carolina State University, Raleigh, NC 27607, USADepartment of Molecular and Structural Biochemistry, North Carolina State University, Raleigh, NC 27607, USAInstitute of Pediatrics and Puericulture Martagão Gesteira, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-912, BrazilDepartment of Biochemistry, Institute of Chemistry, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-909, BrazilDepartment of Biochemistry, Institute of Chemistry, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-909, BrazilDepartment of Molecular and Structural Biochemistry, North Carolina State University, Raleigh, NC 27607, USADepartment of Biochemistry, Institute of Chemistry, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-909, BrazilDengue 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.https://www.mdpi.com/1999-4915/15/3/696antiviraltizoxanidedengue virusvirucidal activity |
| spellingShingle | Kristie A. Yamamoto Kevin Blackburn Michael B. Goshe Dennis T. Brown Edimilson Migoswski Isabele B. Campanhon Monica F. Moreira Davis F. Ferreira Marcia R. Soares Tizoxanide Antiviral Activity on Dengue Virus Replication Viruses antiviral tizoxanide dengue virus virucidal activity |
| title | Tizoxanide Antiviral Activity on Dengue Virus Replication |
| title_full | Tizoxanide Antiviral Activity on Dengue Virus Replication |
| title_fullStr | Tizoxanide Antiviral Activity on Dengue Virus Replication |
| title_full_unstemmed | Tizoxanide Antiviral Activity on Dengue Virus Replication |
| title_short | Tizoxanide Antiviral Activity on Dengue Virus Replication |
| title_sort | tizoxanide antiviral activity on dengue virus replication |
| topic | antiviral tizoxanide dengue virus virucidal activity |
| url | https://www.mdpi.com/1999-4915/15/3/696 |
| work_keys_str_mv | AT kristieayamamoto tizoxanideantiviralactivityondenguevirusreplication AT kevinblackburn tizoxanideantiviralactivityondenguevirusreplication AT michaelbgoshe tizoxanideantiviralactivityondenguevirusreplication AT dennistbrown tizoxanideantiviralactivityondenguevirusreplication AT edimilsonmigoswski tizoxanideantiviralactivityondenguevirusreplication AT isabelebcampanhon tizoxanideantiviralactivityondenguevirusreplication AT monicafmoreira tizoxanideantiviralactivityondenguevirusreplication AT davisfferreira tizoxanideantiviralactivityondenguevirusreplication AT marciarsoares tizoxanideantiviralactivityondenguevirusreplication |