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The present study reports the effects of the natural flavonoid quercetin (QUER) on the infection of A549 and Vero cells with Jun\u00edn virus (JUNV), agent of the Argentine HF. By infectivity assays, a very effective dose-dependent reduction of JUNV multiplication was shown by cell pretreatment at 2\u20136 h prior to the infection at non-cytotoxic concentrations, with 50% effective concentration values in the range of 6.1\u20137.5 \u00b5g\/mL. QUER was also active by post-infection treatment but with minor efficacy. Mechanistic studies indicated that QUER mainly affected the early steps of virus adsorption and internalization in the multiplication cycle of JUNV. Treatment with QUER blocked the phosphorylation of Akt without changes in the total protein expression, detected by Western blot, and the consequent perturbation of the PI3K\/Akt pathway was also associated with the fluorescence redistribution from membrane to cytoplasm of TfR1, the cell receptor recognized by JUNV. Then, it appears that the cellular antiviral state, induced by QUER treatment, leads to the prevention of JUNV entry into the cell.<\/jats:p>","DOI":"10.3390\/v15081741","type":"journal-article","created":{"date-parts":[[2023,8,15]],"date-time":"2023-08-15T11:06:16Z","timestamp":1692097576000},"page":"1741","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Effects of the Natural Flavonoid Quercetin on Arenavirus Jun\u00edn Infection"],"prefix":"10.3390","volume":"15","author":[{"given":"Aaron Ezequiel","family":"Alvarez De Lauro","sequence":"first","affiliation":[{"name":"Laboratory of Antiviral Strategies, Biochemistry Department, School of Sciences, University of Buenos Aires, IQUIBICEN, University of Buenos Aires\/Consejo Nacional de Investigaciones Cient\u00edficas y T\u00e9cnicas, Buenos Aires 1428, Argentina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Miguel Angel","family":"Pelaez","sequence":"additional","affiliation":[{"name":"Laboratory of Antiviral Strategies, Biochemistry Department, School of Sciences, University of Buenos Aires, IQUIBICEN, University of Buenos Aires\/Consejo Nacional de Investigaciones Cient\u00edficas y T\u00e9cnicas, Buenos Aires 1428, Argentina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Agostina Bel\u00e9n","family":"Marquez","sequence":"additional","affiliation":[{"name":"Laboratory of Antiviral Strategies, Biochemistry Department, School of Sciences, University of Buenos Aires, IQUIBICEN, University of Buenos Aires\/Consejo Nacional de Investigaciones Cient\u00edficas y T\u00e9cnicas, Buenos Aires 1428, Argentina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mariel Selene","family":"Wagner","sequence":"additional","affiliation":[{"name":"Laboratory of Antiviral Strategies, Biochemistry Department, School of Sciences, University of Buenos Aires, IQUIBICEN, University of Buenos Aires\/Consejo Nacional de Investigaciones Cient\u00edficas y T\u00e9cnicas, Buenos Aires 1428, Argentina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luis Alberto","family":"Scolaro","sequence":"additional","affiliation":[{"name":"Laboratory of Antiviral Strategies, Biochemistry Department, School of Sciences, University of Buenos Aires, IQUIBICEN, University of Buenos Aires\/Consejo Nacional de Investigaciones Cient\u00edficas y T\u00e9cnicas, Buenos Aires 1428, Argentina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6431-7176","authenticated-orcid":false,"given":"Cybele Carina","family":"Garc\u00eda","sequence":"additional","affiliation":[{"name":"Laboratory of Antiviral Strategies, Biochemistry Department, School of Sciences, University of Buenos Aires, IQUIBICEN, University of Buenos Aires\/Consejo Nacional de Investigaciones Cient\u00edficas y T\u00e9cnicas, Buenos Aires 1428, Argentina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elsa Beatriz","family":"Damonte","sequence":"additional","affiliation":[{"name":"Laboratory of Antiviral Strategies, Biochemistry Department, School of Sciences, University of Buenos Aires, IQUIBICEN, University of Buenos Aires\/Consejo Nacional de Investigaciones Cient\u00edficas y T\u00e9cnicas, Buenos Aires 1428, Argentina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2356-6624","authenticated-orcid":false,"given":"Claudia Soledad","family":"Sep\u00falveda","sequence":"additional","affiliation":[{"name":"Laboratory of Antiviral Strategies, Biochemistry Department, School of Sciences, University of Buenos Aires, IQUIBICEN, University of Buenos Aires\/Consejo Nacional de Investigaciones Cient\u00edficas y T\u00e9cnicas, Buenos Aires 1428, Argentina"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,8,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1569","DOI":"10.3390\/v4091569","article-title":"Host Cell Factors as Antiviral Targets in Arenavirus Infection","volume":"4","author":"Linero","year":"2012","journal-title":"Viruses"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2219350","DOI":"10.1080\/22221751.2023.2219350","article-title":"Circulation of Lassa Virus across the Endemic Edo-Ondo Axis, Nigeria, with Cross-Species Transmission between Multimammate Mice","volume":"12","author":"Adesina","year":"2023","journal-title":"Emerg. 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