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However, the precise pathogenic mechanisms of EV\u2010A71 remain unclear, and specific drugs targeting it have yet to be successfully developed. To explore the mechanisms underlying EV\u2010A71 pathogenesis and to identify potential therapeutic opportunities, we performed a comprehensive proteogenomic characterization of muscle tissues from BALB\/c mice infected with EV\u2010A71, integrating transcriptomic, proteomic, and phosphoproteomic analyses. Our results showed that phagosome, complement, and coagulation cascade pathway\u2010related molecules were activated, and the expression of cell growth\u2010related molecules was downregulated. Concurrently, a rapid activation of the neutrophil extracellular trap pathway was observed at the protein level. Additionally, we mapped the global phosphorylation profiles to dysregulated kinases, predicting 32 drugs corresponding to 27 kinases. We found that kinase inhibitors have antiviral activity in vitro; vandetanib, nintedanib, dasatinib, avitinib, and nilotinib can inhibit virus replication in mice to some extent. Overall, this study provides a multi\u2010omics resource for elucidating EV\u2010A71\u2010induced alterations in target tissues and for linking omics\u2010based target discovery with drug screening and functional validation, providing new insights into both pathogenesis and therapeutic exploration.<\/jats:p>","DOI":"10.1002\/mco2.70668","type":"journal-article","created":{"date-parts":[[2026,4,3]],"date-time":"2026-04-03T06:50:21Z","timestamp":1775199021000},"source":"Crossref","is-referenced-by-count":0,"title":["Systematic Proteomic Characterization of EV\u2010A71\u2010Infected Mice Identifies Dynamic Molecular Changes and Therapeutic Targets"],"prefix":"10.1002","volume":"7","author":[{"given":"Wanjun","family":"Peng","sequence":"first","affiliation":[{"name":"NHC Key Laboratory of Human Disease Comparative Medicine Beijing Key Laboratory for Animal Models of Emerging and Remerging Infectious Diseases Institute of Laboratory Animal Science Chinese Academy of Medical Sciences and 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