{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T04:25:22Z","timestamp":1791433522413,"version":"4.3.3"},"reference-count":36,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,3,19]],"date-time":"2026-03-19T00:00:00Z","timestamp":1773878400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell. Infect. Microbiol."],"abstract":"<jats:p>\n                    Viruses pose a significant threat to global public health, yet therapeutic options remain limited. Zotatifin, a synthetic rocaglate targeting eukaryotic initiation factor 4A (eIF4A), inhibits viral protein synthesis and potentially triggers interferon responses; however, its broad-spectrum antiviral potential remains unclear. We evaluated zotatifin\u2019s cytotoxicity using MTT assays and assessed its antiviral activity through plaque-forming assays, Western blot analysis, immunofluorescence, and flow cytometry across multiple cell lines and virus strains. Zotatifin demonstrated superior tolerability compared to rocaglamide A and CR-1-31-B. The compound exhibited potent, dose-dependent inhibition of Mayaro virus, achieving a &amp;gt;4-log\n                    <jats:sub>10<\/jats:sub>\n                    reduction in viral titers at 50 nM across all cell lines or virus strains tested. Zotatifin also effectively inhibited multiple arboviruses (Chikungunya, Una, and Zika viruses), influenza A virus, vesicular stomatitis virus, and vaccinia virus. Mechanistically, Zotatifin down-regulated viral protein synthesis for all viruses tested, and RT-qPCR analysis revealed activation of the type I interferon pathway in treated cells. Collectively, these results demonstrate that zotatifin exhibits broad-spectrum antiviral activity against five virus families, through different molecular mechanisms, supporting its potential therapeutic use as a pan-antiviral drug in humans.\n                  <\/jats:p>","DOI":"10.3389\/fcimb.2026.1752166","type":"journal-article","created":{"date-parts":[[2026,3,19]],"date-time":"2026-03-19T06:48:06Z","timestamp":1773902886000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Broad-spectrum antiviral activity of the synthetic rocaglate zotatifin against Mayaro virus and other viruses"],"prefix":"10.3389","volume":"16","author":[{"given":"Patricia","family":"Vald\u00e9s-Torres","sequence":"first","affiliation":[{"name":"Grupo de Biolog\u00eda Celular y Molecular de Arbovirus, Departamento de Investigaci\u00f3n en Virolog\u00eda y Biotecnolog\u00eda, Instituto Conmemorativo Gorgas de Estudios de la 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