{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T13:39:20Z","timestamp":1791639560045,"version":"4.3.4"},"reference-count":66,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2023,3,7]],"date-time":"2023-03-07T00:00:00Z","timestamp":1678147200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100008521","name":"National Science Foundation","doi-asserted-by":"publisher","award":["DBI-1126244"],"award-info":[{"award-number":["DBI-1126244"]}],"id":[{"id":"10.13039\/100008521","id-type":"DOI","asserted-by":"publisher"}]},{"name":"North Carolina Agricultural Research Service","award":["DBI-1126244"],"award-info":[{"award-number":["DBI-1126244"]}]},{"name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico (CNPq)","award":["DBI-1126244"],"award-info":[{"award-number":["DBI-1126244"]}]},{"name":"Coordena\u00e7\u00e3o de Aperfei\u00e7oamento de Pessoal de N\u00edvel Superior (CAPES)","award":["DBI-1126244"],"award-info":[{"award-number":["DBI-1126244"]}]},{"name":"Funda\u00e7\u00e3o Carlos Chagas Filho de Amparo \u00e0 Pesquisa do Estado do Rio de Janeiro (FAPERJ)","award":["DBI-1126244"],"award-info":[{"award-number":["DBI-1126244"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>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.<\/jats:p>","DOI":"10.3390\/v15030696","type":"journal-article","created":{"date-parts":[[2023,3,8]],"date-time":"2023-03-08T03:29:05Z","timestamp":1678246145000},"page":"696","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Tizoxanide Antiviral Activity on Dengue Virus Replication"],"prefix":"10.3390","volume":"15","author":[{"given":"Kristie A.","family":"Yamamoto","sequence":"first","affiliation":[{"name":"Department of Biochemistry, Institute of Chemistry, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-909, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin","family":"Blackburn","sequence":"additional","affiliation":[{"name":"Department of Molecular and Structural Biochemistry, North Carolina State University, Raleigh, NC 27607, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael B.","family":"Goshe","sequence":"additional","affiliation":[{"name":"Department of Molecular and Structural Biochemistry, North Carolina State University, Raleigh, NC 27607, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dennis T.","family":"Brown","sequence":"additional","affiliation":[{"name":"Department of Molecular and Structural Biochemistry, North Carolina State University, Raleigh, NC 27607, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edimilson","family":"Migoswski","sequence":"additional","affiliation":[{"name":"Institute of Pediatrics and Puericulture Martag\u00e3o Gesteira, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-912, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabele B.","family":"Campanhon","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Institute of Chemistry, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-909, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3720-415X","authenticated-orcid":false,"given":"Monica F.","family":"Moreira","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Institute of Chemistry, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-909, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Davis F.","family":"Ferreira","sequence":"additional","affiliation":[{"name":"Department of Molecular and Structural Biochemistry, North Carolina State University, Raleigh, NC 27607, USA"},{"name":"Department of Virology, Paulo de G\u00f3es Microbiology Institute, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-902, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9272-9488","authenticated-orcid":false,"given":"Marcia R.","family":"Soares","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Institute of Chemistry, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-909, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,3,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"168","DOI":"10.1016\/j.coviro.2012.02.011","article-title":"Degrees of maturity: The complex structure and biology of flaviviruses","volume":"2","author":"Pierson","year":"2012","journal-title":"Curr. 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