{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T16:58:43Z","timestamp":1785430723103,"version":"3.56.0"},"reference-count":51,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2026,7,23]],"date-time":"2026-07-23T00:00:00Z","timestamp":1784764800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82372238"],"award-info":[{"award-number":["82372238"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"award":["82372238"],"award-info":[{"award-number":["82372238"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005230","name":"Natural Science Foundation of Chongqing, China","doi-asserted-by":"publisher","award":["CSTB2023NSCQ-MSX0482"],"award-info":[{"award-number":["CSTB2023NSCQ-MSX0482"]}],"id":[{"id":"10.13039\/501100005230","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Venture & Innovation Program for Chongqing Overseas Returnees","award":["cx2023050"],"award-info":[{"award-number":["cx2023050"]}]},{"DOI":"10.13039\/501100012226","name":"Fundamental Research Funds for the Central Universities","doi-asserted-by":"crossref","award":["2023CDJKYJH063"],"award-info":[{"award-number":["2023CDJKYJH063"]}],"id":[{"id":"10.13039\/501100012226","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Int. J. Mol. Sci.","IJMS"],"abstract":"<jats:p>Enterovirus A71 (EV-A71) is a major causative agent of hand, foot, and mouth disease, yet no specific antiviral therapy has been approved. This study systematically evaluated the efficacy and mechanisms of alkaloids against EV-A71 infection by integrating meta-analysis, network pharmacology, and molecular docking. Nine animal studies were included. Meta-analysis suggested that alkaloid intervention significantly improved survival (OR = 30.62, 95% CI: 10.44\u201389.82), reduced clinical severity, attenuated body weight loss, and decreased viral loads in infected tissues. Subgroup analyses preliminarily suggested that quinolizidine alkaloids and high-dose regimens (&gt;5 mg\/kg) may be associated with preclinical intervention effects. Network pharmacology predicted 155 shared targets between seven active alkaloids and EV-A71-related genes, with MAPK1, MAPK3, JUN, AURKB, and MAPK8 recognized as core targets through computational screening. Functional enrichment analysis suggested significant involvement of the MAPK, TNF, and IL-17 signaling pathways. Molecular docking provided computational support for stable binding affinities between active alkaloids and core targets (\u22126.7 to \u22129.3 kcal\/mol). Collectively, these findings suggest that alkaloids exert anti-EV-A71 effects through both direct antiviral activity and host-directed regulatory mechanisms, supporting their potential as candidates for the development of novel anti-EV-A71 therapeutics.<\/jats:p>","DOI":"10.3390\/ijms27156571","type":"journal-article","created":{"date-parts":[[2026,7,23]],"date-time":"2026-07-23T17:13:17Z","timestamp":1784826797000},"page":"6571","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Efficacy and Mechanisms of Alkaloids Against Enterovirus A71: A Systematic Review and Meta-Analysis of Preclinical Evidence Integrated with Network Pharmacology and Molecular Docking"],"prefix":"10.3390","volume":"27","author":[{"given":"Wenzhan","family":"Xie","sequence":"first","affiliation":[{"name":"Center of Smart Laboratory and Molecular Medicine, School of Medicine, Chongqing University, Chongqing 400044, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linxi","family":"Lv","sequence":"additional","affiliation":[{"name":"Center of Smart Laboratory and Molecular Medicine, School of Medicine, Chongqing University, Chongqing 400044, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-2108-9765","authenticated-orcid":false,"given":"Tian","family":"Wang","sequence":"additional","affiliation":[{"name":"College of Chemistry and Chemical Engineering, Southwest University, Chongqing 400715, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jialong","family":"Wei","sequence":"additional","affiliation":[{"name":"Center of Smart Laboratory and Molecular Medicine, School of Medicine, Chongqing University, Chongqing 400044, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanshan","family":"Gui","sequence":"additional","affiliation":[{"name":"Center of Smart Laboratory and Molecular Medicine, School of Medicine, Chongqing University, Chongqing 400044, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Gu","sequence":"additional","affiliation":[{"name":"Center of Smart Laboratory and Molecular Medicine, School of Medicine, Chongqing University, Chongqing 400044, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Feng","sequence":"additional","affiliation":[{"name":"Center of Smart Laboratory and Molecular Medicine, School of Medicine, Chongqing University, Chongqing 400044, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1016\/0168-1702(95)00087-9","article-title":"Complete nucleotide sequence of enterovirus 71 is distinct from poliovirus","volume":"39","author":"Brown","year":"1995","journal-title":"Virus Res."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1146\/annurev.ge.27.120193.002033","article-title":"Genetics of poliovirus","volume":"27","author":"Wimmer","year":"1993","journal-title":"Annu. 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