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In this study, we evaluated the in vitro activity of 19 FDA\u2010approved drugs against a clinical isolate of SFTSV using cell\u2010based assays, and immunofluorescence analysis. Simeprevir, Novobiocin, and Levofloxacin hydrochloride demonstrated significant antiviral activity (EC50: 0.009774, 25.12, and 46.30\u2009\u03bcM, respectively) with minimal cytotoxicity. Immunofluorescence analysis revealed a dose\u2010dependent reduction in SFTSV nucleoprotein expression, correlating with decreased viral replication. The remaining 16 drugs exhibited low antiviral efficacy or high cytotoxicity. Although these three small\u2010molecule drugs show promise for SFTSV treatment, further in vivo studies are necessary to confirm their safety and optimize their structures. Our findings highlight the potential of drug repurposing as a strategy for developing effective therapies against emerging viral infections.<\/jats:p>","DOI":"10.1002\/jmv.70655","type":"journal-article","created":{"date-parts":[[2025,10,21]],"date-time":"2025-10-21T15:44:19Z","timestamp":1761061459000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Drug Repurposing: In Vitro Evaluation of Simeprevir as a Novel Antiviral Drug Against Severe Fever With Thrombocytopenia Syndrome Virus"],"prefix":"10.1002","volume":"97","author":[{"given":"Qian","family":"Chen","sequence":"first","affiliation":[{"name":"School of Public Health Hangzhou Medical College Hangzhou Zhejiang China"},{"name":"Zhejiang Key Laboratory of Public Health Detection and Pathogenesis Research, Department of Microbiology Zhejiang Provincial Center for Disease Control and Prevention Hangzhou 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