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Several investigational therapeutic agents and vaccine candidates are being developed. However, no approved drug against EV\u2010A71 infection is available, and no proven drug target has been identified. Since host kinases are key regulators of multiple signaling pathways in response to viral infections, here we screened a kinase inhibitor library and identified potent inhibitors against EV\u2010A71 infection. Among the hits, GSK269962A, a Rho Associated Coiled\u2010Coil Containing Protein Kinase (Rock) inhibitor with potent antiviral activity, was selected for further analysis. We found that this Rock inhibitor not only efficiently suppressed the replication of EV\u2010A71 in RD cells, but also in human intestinal organoids, in a dose\u2010dependent manner. Interestingly, small interfering RNA depletion of Rock1, but not Rock2, significantly restricted viral replication in RD cells, indicating that Rock1 is a novel host dependency factor for EV\u2010A71 replication and can serve as a target for the development of anti\u2010EV\u2010A71 therapeutics.<\/jats:p>","DOI":"10.1002\/jmv.27975","type":"journal-article","created":{"date-parts":[[2022,7,6]],"date-time":"2022-07-06T06:09:58Z","timestamp":1657087798000},"page":"5415-5424","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Rock1 is a novel host dependency factor of human enterovirus A71: Implication as a drug target"],"prefix":"10.1002","volume":"94","author":[{"given":"Xiaoyu","family":"Zhao","sequence":"first","affiliation":[{"name":"State Key Laboratory of Genetic Engineering, Shanghai Institute of Infectious Disease and Biosecurity, School of Life Sciences Fudan University  Shanghai China"},{"name":"Department of 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