Systematic transcriptomic analysis enables targeted drug repurposing for neurotropic flavivirus infections

Systematic transcriptomic analysis enables targeted drug repurposing for neurotropic flavivirus infections | Authorea try { document.documentElement.classList.add('js'); } catch (e) { } var _gaq = _gaq || []; _gaq.push(['_setAccount', 'G-8VDV14Y67G']); _gaq.push(['_trackPageview']); (function() { var ga = document.createElement('script'); ga.type = 'text/javascript'; ga.async = true; ga.src = ('https:' == document.location.protocol ? 'https://ssl' : 'http://www') + '.google-analytics.com/ga.js'; var s = document.getElementsByTagName('script')[0]; s.parentNode.insertBefore(ga, s); })(); Skip to main content Preprints Collections Wiley Open Research IET Open Research Ecological Society of Japan All Collections About About Authorea FAQs Contact Us Quick Search anywhere Search for preprint articles, keywords, etc. Search Search ADVANCED SEARCH SCROLL This is a preprint and has not been peer reviewed. Data may be preliminary. 2 December 2025 V1 Latest version Share on Systematic transcriptomic analysis enables targeted drug repurposing for neurotropic flavivirus infections Authors : Poderoso T , Freije-Zazo M , Esteban A , Mingo-Casas P , Jiménez de Oya N , Miguel A Martín-Acebes , and Ana-Belén Blázquez 0000-0002-0847-0977 [email protected] Authors Info & Affiliations https://doi.org/10.22541/au.176465355.51617557/v1 187 views 132 downloads Contents Abstract Supplementary Material Information & Authors Metrics & Citations View Options References Figures Tables Media Share Abstract Emerging infectious diseases, and particularly mosquito-borne orthoflaviviruses such as West Nile virus (WNV) and Usutu virus (USUV), pose significant global health challenges due to their capacity for quick spread, severe neurological outcomes and lack of approved antiviral therapies. Drug repurposing offers a rapid and cost-effective strategy to accelerate therapeutic availability during outbreaks and global health emergencies. In this study, we applied transcriptomic and bioinformatic analyses to characterize host–pathogen interactions and identify molecular pathways relevant to WNV and USUV infection. This approach enabled the prioritization of approved therapeutic candidates to assess their potential antiviral activity. From the resulting data, two compounds were selected for experimental validation, paroxetine and clozapine. Among them, paroxetine, a widely used antidepressant, showed a better antiviral profile than clozapine, making it a promising candidate that deserves further consideration. Our findings highlight the value of integrating transcriptomic profiling with rational drug repurposing to expedite the identification of potential antivirals, thereby enhancing preparedness for emerging viral threats. Supplementary Material File (figure legends.docx) Download 15.38 KB File (poderoso et al.docx) Download 115.60 KB Information & Authors Information Version history V1 Version 1 02 December 2025 Copyright This work is licensed under a Non Exclusive No Reuse License. Keywords antiviral agents flavirus rational drug design virus classification Authors Affiliations Poderoso T Instituto Nacional de Investigacion y Tecnologia Agraria y Alimentaria View all articles by this author Freije-Zazo M Instituto Nacional de Investigacion y Tecnologia Agraria y Alimentaria View all articles by this author Esteban A Instituto Nacional de Investigacion y Tecnologia Agraria y Alimentaria View all articles by this author Mingo-Casas P Instituto Nacional de Investigacion y Tecnologia Agraria y Alimentaria View all articles by this author Jiménez de Oya N Instituto Nacional de Investigacion y Tecnologia Agraria y Alimentaria View all articles by this author Miguel A Martín-Acebes Instituto Nacional de Investigacion y Tecnologia Agraria y Alimentaria View all articles by this author Ana-Belén Blázquez 0000-0002-0847-0977 [email protected] Instituto Nacional de Investigacion y Tecnologia Agraria y Alimentaria View all articles by this author Metrics & Citations Metrics Article Usage 187 views 132 downloads .FvxKWukQNSOunydq8rnd { width: 100px; } Citations Download citation Poderoso T, Freije-Zazo M, Esteban A, et al. Systematic transcriptomic analysis enables targeted drug repurposing for neurotropic flavivirus infections. Authorea . 02 December 2025. DOI: https://doi.org/10.22541/au.176465355.51617557/v1 If you have the appropriate software installed, you can download article citation data to the citation manager of your choice. Simply select your manager software from the list below and click Download. For more information or tips please see 'Downloading to a citation manager' in the Help menu . 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