{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T02:45:22Z","timestamp":1772160322374,"version":"3.50.1"},"reference-count":32,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2024,12,22]],"date-time":"2024-12-22T00:00:00Z","timestamp":1734825600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001843","name":"Science and Engineering Research Board","doi-asserted-by":"publisher","award":["EMR\/2017\/001490"],"award-info":[{"award-number":["EMR\/2017\/001490"]}],"id":[{"id":"10.13039\/501100001843","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001407","name":"Department of Biotechnology, Ministry of Science and Technology, India","doi-asserted-by":"publisher","award":["BT\/PR15984\/MED\/31\/325\/2015"],"award-info":[{"award-number":["BT\/PR15984\/MED\/31\/325\/2015"]}],"id":[{"id":"10.13039\/501100001407","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001411","name":"Indian Council of Medical Research","doi-asserted-by":"publisher","award":["EMDR\/SG\/9\/20232364"],"award-info":[{"award-number":["EMDR\/SG\/9\/20232364"]}],"id":[{"id":"10.13039\/501100001411","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["febs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FEBS Journal"],"published-print":{"date-parts":[[2025,2]]},"abstract":"<jats:p>Japanese encephalitis virus (JEV) is the leading causative agent of viral encephalitis in India and contributes to a significant disease burden in South Asian countries. However, no antiviral treatment is available against JEV\u2010induced encephalitis, highlighting the urgent need for novel therapeutic approaches. Repurposing or repositioning drugs was found to be more economical and practical in the current drug development scenario. The present study aimed to develop a host\u2010directed strategy through a computational drug repurposing approach. As part of the strategy, we first\u00a0generated a dynamic signature of differentially expressed JEV infection\u2010associated proteins in mice brains through a semiquantitative proteomics approach. With the help of the Connectivity Map (CMap) analysis, we narrowed down the lists of drugs with a high negative CMap score (\u221270 or lower). Based on the CMap score, we chose the top three compounds (Tipifarnib, Ly303511 and MDL11939) with CMap scores of \u221291.83, \u221288.18 and \u221291.15, respectively. The antiviral potential of these three compounds was further compared in both JEV\u2010infected mouse neuroblastoma cells and C57BL\/6 mice. Oral administration of Ly303511 and MDL11939, alone or in combination, showed improved outcomes (e.g. delayed death, increased survival, and less viral load than Tipifarnib alone or combined). The JEV\u2010infected mice survived upon drug treatment, effectively reducing viral load and reversing the antiviral signature. Our results highlight Ly303511 and MDL11939 as promising host\u2010targeted inhibitors of JEV infection and pathogenesis. Moreover, our results favor the combination of Ly303511 and MDL11939 therapy to improve clinical symptoms and reduce JEV\u2010induced damage, thus warranting inclusion in clinical studies.<\/jats:p>","DOI":"10.1111\/febs.17370","type":"journal-article","created":{"date-parts":[[2024,12,23]],"date-time":"2024-12-23T01:00:57Z","timestamp":1734915657000},"page":"864-880","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Integrated proteomics and connectivity map\u2010based analysis reveal compounds with a potential antiviral effect against Japanese encephalitis virus infection in a mouse model"],"prefix":"10.1111","volume":"292","author":[{"given":"Rohit","family":"Soni","sequence":"first","affiliation":[{"name":"Laboratory of Virology Regional Centre for Biotechnology  Faridabad 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