{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,4]],"date-time":"2026-07-04T01:48:22Z","timestamp":1783129702537,"version":"3.54.6"},"reference-count":28,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,7,28]],"date-time":"2025-07-28T00:00:00Z","timestamp":1753660800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"},{"start":{"date-parts":[[2025,7,28]],"date-time":"2025-07-28T00:00:00Z","timestamp":1753660800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"}],"funder":[{"name":"the grants from the National Natural Science Foundation of China","award":["No. 32200134"],"award-info":[{"award-number":["No. 32200134"]}]},{"name":"the State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases","award":["No. 2024KF00005"],"award-info":[{"award-number":["No. 2024KF00005"]}]},{"name":"grant from the Hubei natural science foundation","award":["No. ZRMS2023001990"],"award-info":[{"award-number":["No. ZRMS2023001990"]}]},{"name":"the Wuhan Science and Technology Bureau","award":["No. 2023020201010211"],"award-info":[{"award-number":["No. 2023020201010211"]}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Virol J"],"DOI":"10.1186\/s12985-025-02881-w","type":"journal-article","created":{"date-parts":[[2025,7,28]],"date-time":"2025-07-28T02:18:05Z","timestamp":1753669085000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Pilaralisib inhibits the replication of enteroviruses by targeting the PI3K\/AKT signaling pathway"],"prefix":"10.1186","volume":"22","author":[{"given":"Jie","family":"Zhou","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanping","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guangyan","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingzhe","family":"Yan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhengnan","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lin","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingwen","family":"Kuang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenyuan","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chaolin","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fuli","family":"Ren","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qingyu","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,7,28]]},"reference":[{"issue":"1","key":"2881_CR1","doi-asserted-by":"publisher","first-page":"91","DOI":"10.1111\/j.1574-6976.2002.tb00601.x","volume":"26","author":"PC McMinn","year":"2002","unstructured":"McMinn PC. An overview of the evolution of enterovirus 71 and its clinical and public health significance. FEMS Microbiol Rev. 2002;26(1):91\u2013107.","journal-title":"FEMS Microbiol Rev"},{"issue":"7","key":"2881_CR2","doi-asserted-by":"publisher","first-page":"2706","DOI":"10.7150\/thno.93883","volume":"14","author":"RH Lai","year":"2024","unstructured":"Lai RH, Chow YH, Lin YW, Chung NH, Nien SW, Juang JL. Hyperglycemia facilitates EV71 replication: insights into miR-206-mediated regulation of G3BP2 promoting EV71 IRES activity. Theranostics. 2024;14(7):2706\u201318.","journal-title":"Theranostics"},{"key":"2881_CR3","doi-asserted-by":"publisher","first-page":"1162209","DOI":"10.3389\/fpubh.2023.1162209","volume":"11","author":"J Wang","year":"2023","unstructured":"Wang J, Zhang S. Epidemiological characteristics and trends of hand-foot-mouth disease in shanghai, China from 2011 to 2021. Front Public Health. 2023;11:1162209.","journal-title":"Front Public Health"},{"issue":"3","key":"2881_CR4","doi-asserted-by":"publisher","first-page":"e1001975","DOI":"10.1371\/journal.pmed.1001975","volume":"13","author":"JT Wu","year":"2016","unstructured":"Wu JT, Jit M, Zheng Y, Leung K, Xing W, Yang J, et al. Routine pediatric enterovirus 71 vaccination in china: a Cost-Effectiveness analysis. PLoS Med. 2016;13(3):e1001975.","journal-title":"PLoS Med"},{"issue":"1","key":"2881_CR5","doi-asserted-by":"publisher","first-page":"e1011967","DOI":"10.1371\/journal.ppat.1011967","volume":"20","author":"T Fan","year":"2024","unstructured":"Fan T, Liu B, Yao H, Chen X, Yang H, Guo S, et al. Cathelicidin peptide analogues inhibit EV71 infection through blocking viral entry and uncoating. PLoS Pathog. 2024;20(1):e1011967.","journal-title":"PLoS Pathog"},{"key":"2881_CR6","doi-asserted-by":"publisher","first-page":"105498","DOI":"10.1016\/j.antiviral.2022.105498","volume":"209","author":"Q Yang","year":"2023","unstructured":"Yang Q, Wu C, Zhu G, Ren F, Lin B, Huang R, et al. ML390 inhibits enterovirus 71 replication by targeting de Novo pyrimidine biosynthesis pathway. Antiviral Res. 2023;209:105498.","journal-title":"Antiviral Res"},{"issue":"1","key":"2881_CR7","doi-asserted-by":"publisher","first-page":"4176","DOI":"10.1038\/s41467-024-48504-w","volume":"15","author":"X Gao","year":"2024","unstructured":"Gao X, Wang B, Zhu K, Wang L, Qin B, Shang K, et al. The EV71 2A protease occupies the central cleft of SETD3 and disrupts SETD3-actin interaction. Nat Commun. 2024;15(1):4176.","journal-title":"Nat Commun"},{"issue":"21","key":"2881_CR8","doi-asserted-by":"publisher","first-page":"11514","DOI":"10.1093\/nar\/gky840","volume":"46","author":"Z Li","year":"2018","unstructured":"Li Z, Ning S, Su X, Liu X, Wang H, Liu Y, et al. Enterovirus 71 antagonizes the Inhibition of the host intrinsic antiviral factor A3G. Nucleic Acids Res. 2018;46(21):11514\u201327.","journal-title":"Nucleic Acids Res"},{"issue":"1","key":"2881_CR9","doi-asserted-by":"publisher","first-page":"4775","DOI":"10.1038\/s41467-020-18594-3","volume":"11","author":"J Davila-Calderon","year":"2020","unstructured":"Davila-Calderon J, Patwardhan NN, Chiu LY, Sugarman A, Cai Z, Penutmutchu SR, et al. IRES-targeting small molecule inhibits enterovirus 71 replication via allosteric stabilization of a ternary complex. Nat Commun. 2020;11(1):4775.","journal-title":"Nat Commun"},{"issue":"7","key":"2881_CR10","doi-asserted-by":"publisher","first-page":"1597","DOI":"10.1080\/15548627.2024.2330105","volume":"20","author":"H Liu","year":"2024","unstructured":"Liu H, Xue Q, Yang F, Cao W, Liu P, Liu X, et al. Foot-and-mouth disease virus VP1 degrades YTHDF2 through autophagy to regulate IRF3 activity for viral replication. Autophagy. 2024;20(7):1597\u2013615.","journal-title":"Autophagy"},{"issue":"4","key":"2881_CR11","doi-asserted-by":"publisher","first-page":"112389","DOI":"10.1016\/j.celrep.2023.112389","volume":"42","author":"KF Weng","year":"2023","unstructured":"Weng KF, Tee HK, Tseligka ED, Cagno V, Mathez G, Rosset S, et al. Variant enterovirus A71 found in immune-suppressed patient binds to Heparan sulfate and exhibits neurotropism in B-cell-depleted mice. Cell Rep. 2023;42(4):112389.","journal-title":"Cell Rep"},{"issue":"7","key":"2881_CR12","doi-asserted-by":"publisher","first-page":"e1005033","DOI":"10.1371\/journal.ppat.1005033","volume":"11","author":"C Kataoka","year":"2015","unstructured":"Kataoka C, Suzuki T, Kotani O, Iwata-Yoshikawa N, Nagata N, Ami Y, et al. The role of VP1 amino acid residue 145 of enterovirus 71 in viral fitness and pathogenesis in a Cynomolgus monkey model. PLoS Pathog. 2015;11(7):e1005033.","journal-title":"PLoS Pathog"},{"issue":"36","key":"2881_CR13","doi-asserted-by":"publisher","first-page":"14753","DOI":"10.1073\/pnas.1217563110","volume":"110","author":"K Fujii","year":"2013","unstructured":"Fujii K, Nagata N, Sato Y, Ong KC, Wong KT, Yamayoshi S, et al. Transgenic mouse model for the study of enterovirus 71 neuropathogenesis. Proc Natl Acad Sci USA. 2013;110(36):14753\u20138.","journal-title":"Proc Natl Acad Sci USA"},{"key":"2881_CR14","doi-asserted-by":"publisher","first-page":"13150","DOI":"10.1038\/ncomms13150","volume":"7","author":"KX Wu","year":"2016","unstructured":"Wu KX, Phuektes P, Kumar P, Goh GY, Moreau D, Chow VT, et al. Human genome-wide RNAi screen reveals host factors required for enterovirus 71 replication. Nat Commun. 2016;7:13150.","journal-title":"Nat Commun"},{"issue":"9","key":"2881_CR15","doi-asserted-by":"publisher","first-page":"829","DOI":"10.1056\/NEJMoa1303224","volume":"370","author":"R Li","year":"2014","unstructured":"Li R, Liu L, Mo Z, Wang X, Xia J, Liang Z, et al. An inactivated enterovirus 71 vaccine in healthy children. N Engl J Med. 2014;370(9):829\u201337.","journal-title":"N Engl J Med"},{"issue":"1","key":"2881_CR16","doi-asserted-by":"publisher","first-page":"164","DOI":"10.1186\/s12943-024-02072-1","volume":"23","author":"H Li","year":"2024","unstructured":"Li H, Wen X, Ren Y, Fan Z, Zhang J, He G, et al. Targeting PI3K family with small-molecule inhibitors in cancer therapy: current clinical status and future directions. Mol Cancer. 2024;23(1):164.","journal-title":"Mol Cancer"},{"issue":"4","key":"2881_CR17","doi-asserted-by":"publisher","first-page":"931","DOI":"10.1158\/1535-7163.MCT-14-0833","volume":"14","author":"P Foster","year":"2015","unstructured":"Foster P, Yamaguchi K, Hsu PP, Qian F, Du X, Wu J, et al. The selective PI3K inhibitor XL147 (SAR245408) inhibits tumor growth and survival and potentiates the activity of chemotherapeutic agents in preclinical tumor models. Mol Cancer Ther. 2015;14(4):931\u201340.","journal-title":"Mol Cancer Ther"},{"issue":"8","key":"2881_CR18","doi-asserted-by":"publisher","first-page":"627","DOI":"10.1038\/nrd2926","volume":"8","author":"P Liu","year":"2009","unstructured":"Liu P, Cheng H, Roberts TM, Zhao JJ. Targeting the phosphoinositide 3-kinase pathway in cancer. Nat Rev Drug Discov. 2009;8(8):627\u201344.","journal-title":"Nat Rev Drug Discov"},{"issue":"2","key":"2881_CR19","doi-asserted-by":"publisher","first-page":"140","DOI":"10.1038\/nrd4204","volume":"13","author":"DA Fruman","year":"2014","unstructured":"Fruman DA, Rommel C. PI3K and cancer: lessons, challenges and opportunities. Nat Rev Drug Discov. 2014;13(2):140\u201356.","journal-title":"Nat Rev Drug Discov"},{"issue":"1","key":"2881_CR20","doi-asserted-by":"publisher","first-page":"138","DOI":"10.1186\/s12943-023-01827-6","volume":"22","author":"A Glaviano","year":"2023","unstructured":"Glaviano A, Foo ASC, Lam HY, Yap KCH, Jacot W, Jones RH, et al. PI3K\/AKT\/mTOR signaling transduction pathway and targeted therapies in cancer. Mol Cancer. 2023;22(1):138.","journal-title":"Mol Cancer"},{"key":"2881_CR21","doi-asserted-by":"publisher","first-page":"101963","DOI":"10.1016\/j.arr.2023.101963","volume":"88","author":"Y Liu","year":"2023","unstructured":"Liu Y, Liu Q, Zhang Z, Yang Y, Zhou Y, Yan H, et al. The regulatory role of PI3K in ageing-related diseases. Ageing Res Rev. 2023;88:101963.","journal-title":"Ageing Res Rev"},{"key":"2881_CR22","doi-asserted-by":"publisher","first-page":"43","DOI":"10.1016\/j.carbpol.2018.07.067","volume":"200","author":"S Wang","year":"2018","unstructured":"Wang S, Wang W, Hao C, Yunjia Y, Qin L, He M, et al. Antiviral activity against enterovirus 71 of sulfated Rhamnan isolated from the green Alga Monostroma latissimum. Carbohydr Polym. 2018;200:43\u201353.","journal-title":"Carbohydr Polym"},{"key":"2881_CR23","doi-asserted-by":"publisher","first-page":"39","DOI":"10.1016\/j.antiviral.2018.02.002","volume":"153","author":"Q Zhang","year":"2018","unstructured":"Zhang Q, Zhao B, Chen X, Song N, Wu J, Li G, et al. GS-9620 inhibits enterovirus 71 replication mainly through the NF-\u03baB and PI3K-AKT signaling pathways. Antiviral Res. 2018;153:39\u201348.","journal-title":"Antiviral Res"},{"issue":"8","key":"2881_CR24","doi-asserted-by":"publisher","first-page":"2718","DOI":"10.1073\/pnas.1018001108","volume":"109","author":"A Chakrabarty","year":"2012","unstructured":"Chakrabarty A, S\u00e1nchez V, Kuba MG, Rinehart C, Arteaga CL. Feedback upregulation of HER3 (ErbB3) expression and activity attenuates antitumor effect of PI3K inhibitors. Proc Natl Acad Sci USA. 2012;109(8):2718\u201323.","journal-title":"Proc Natl Acad Sci USA"},{"issue":"5","key":"2881_CR25","doi-asserted-by":"publisher","first-page":"791","DOI":"10.1002\/pbc.24301","volume":"60","author":"CP Reynolds","year":"2013","unstructured":"Reynolds CP, Kang MH, Carol H, Lock R, Gorlick R, Kolb EA, et al. Initial testing (stage 1) of the phosphatidylinositol 3\u2019 kinase inhibitor, SAR245408 (XL147) by the pediatric preclinical testing program. Pediatr Blood Cancer. 2013;60(5):791\u20138.","journal-title":"Pediatr Blood Cancer"},{"issue":"10","key":"2881_CR26","doi-asserted-by":"publisher","first-page":"2583","DOI":"10.1038\/s41564-024-01801-y","volume":"9","author":"X Zheng","year":"2024","unstructured":"Zheng X, Zhang Y, Zhang L, Yang T, Zhang F, Wang X, et al. Taurolithocholic acid protects against viral haemorrhagic fever via Inhibition of ferroptosis. Nat Microbiol. 2024;9(10):2583\u201399.","journal-title":"Nat Microbiol"},{"issue":"7","key":"2881_CR27","doi-asserted-by":"publisher","first-page":"2974","DOI":"10.1038\/s44319-024-00164-z","volume":"25","author":"P de Antonellis","year":"2024","unstructured":"de Antonellis P, Ferrucci V, Miceli M, Bibbo F, Asadzadeh F, Gorini F, et al. Targeting ATP2B1 impairs PI3K\/Akt\/FOXO signaling and reduces SARS-COV-2 infection and replication. EMBO Rep. 2024;25(7):2974\u20133007.","journal-title":"EMBO Rep"},{"issue":"8","key":"2881_CR28","doi-asserted-by":"publisher","first-page":"1632","DOI":"10.1038\/s41401-024-01282-z","volume":"45","author":"JF Cai","year":"2024","unstructured":"Cai JF, Zhou JS, Meng ZY, Wu ZQ, Zhao JC, Peng HX, et al. Ripretinib inhibits HIV-1 transcription through modulation of PI3K-AKT-mTOR. Acta Pharmacol Sin. 2024;45(8):1632\u201343.","journal-title":"Acta Pharmacol Sin"}],"container-title":["Virology Journal"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12985-025-02881-w.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s12985-025-02881-w\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12985-025-02881-w.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,9,8]],"date-time":"2025-09-08T03:48:55Z","timestamp":1757303335000},"score":1,"resource":{"primary":{"URL":"https:\/\/virologyj.biomedcentral.com\/articles\/10.1186\/s12985-025-02881-w"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,7,28]]},"references-count":28,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["2881"],"URL":"https:\/\/doi.org\/10.1186\/s12985-025-02881-w","relation":{},"ISSN":["1743-422X"],"issn-type":[{"value":"1743-422X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,7,28]]},"assertion":[{"value":"6 May 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"15 July 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"28 July 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The animal experiments had the approval of the Animal Care and Use Committee of the Wuhan Institute of Virology (WIVA38202103).","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval"}},{"value":"All authors have read and agreed to the final version of the manuscript.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"257"}}