{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T14:47:26Z","timestamp":1786978046473,"version":"build-2736575974"},"reference-count":41,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2025,2,8]],"date-time":"2025-02-08T00:00:00Z","timestamp":1738972800000},"content-version":"vor","delay-in-days":7,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal of Medical Virology"],"published-print":{"date-parts":[[2025,2]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Influenza A virus (IAV) remains a major global public health threat, especially with the emergence of antiviral resistance, highlighting the urgent need for novel therapeutics. Alkaloids are known for their antiviral properties, and chemical synthesis has become a key strategy in developing new alkaloid compounds. In this study, we synthesized a series of novel alkaloids using the Ugi reaction and assessed their antiviral potential and mechanisms. Through screening and validation, Zj6\u201011 was identified as a promising compound that effectively inhibits IAV infection in vitro. Molecular docking and binding affinity assays showed that Zj6\u201011 binds with high affinity to IAV nucleoprotein (NP) and inhibits its interaction with nucleic acids. Further, in vitro nuclear translocation assays confirmed that Zj6\u201011 suppresses NP nuclear import. Mechanistically, Zj6\u201011 significantly inhibits IAV\u2010induced apoptosis and mitigates mitochondrial membrane potential dysfunction. Zj6\u201011 also inhibits cytochrome c release, reduces the expression of cleaved Caspase\u20109 and Caspase\u20103, and suppresses IAV\u2010induced apoptosis\u2010inducing factor (Aif) expression, suppressing IAV\u2010induced mitochondrial apoptosis. More importantly, Zj6\u201011 plays a crucial role in protecting mice from IAV infection and reducing IAV pathogenicity. Our study provides mechanistic insights into Zj6\u201011's control of IAV infection in vitro and in vivo, offering new perspectives for antiviral therapy development.<\/jats:p>","DOI":"10.1002\/jmv.70230","type":"journal-article","created":{"date-parts":[[2025,2,11]],"date-time":"2025-02-11T00:49:13Z","timestamp":1739234953000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Identification of a Novel Alkaloid Zj6\u201011 as a Potent Inhibitor of Influenza Virus Infection via Repression of Virus\u2010Induced Mitochondria\u2010Dependent Apoptosis"],"prefix":"10.1002","volume":"97","author":[{"given":"Hanbai","family":"Liang","sequence":"first","affiliation":[{"name":"Department of Immunology, International Cancer Center, College of Pharmacy, Shenzhen University Medical School Shenzhen University Shenzhen China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Immunology, International Cancer Center, College of Pharmacy, Shenzhen University Medical School Shenzhen University Shenzhen China"},{"name":"Guangdong Key Laboratory for Biomedical Measurements and Ultrasound Imaging, National Regional Key Technology Engineering Laboratory for Medical Ultrasound, School of Biomedical Engineering Shenzhen University Medical School Shenzhen China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenhao","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Immunology, International Cancer Center, College of Pharmacy, Shenzhen University Medical School Shenzhen University Shenzhen China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaomei","family":"Xiao","sequence":"additional","affiliation":[{"name":"Department of Immunology, International Cancer Center, College of Pharmacy, Shenzhen University Medical School Shenzhen University Shenzhen China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiwen","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Immunology, International Cancer Center, College of Pharmacy, Shenzhen University Medical School Shenzhen University Shenzhen China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bin","family":"Tan","sequence":"additional","affiliation":[{"name":"Shenzhen Grubbs Institute and Department of Chemistry Southern University of Science and Technology Shenzhen China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian","family":"Zhang","sequence":"additional","affiliation":[{"name":"Shenzhen Grubbs Institute and Department of Chemistry Southern University of Science and Technology Shenzhen China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xun","family":"Song","sequence":"additional","affiliation":[{"name":"College of Pharmacy Shenzhen Technology University Shenzhen China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhengdan","family":"He","sequence":"additional","affiliation":[{"name":"College of Pharmacy Shenzhen Technology University Shenzhen China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6735-0836","authenticated-orcid":false,"given":"Liang","family":"Ye","sequence":"additional","affiliation":[{"name":"Department of Immunology, International Cancer Center, College of Pharmacy, Shenzhen University Medical School Shenzhen University Shenzhen China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,2,8]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(17)33293-2"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/s12276-021-00603-0"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(22)00982-5"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.antiviral.2020.104780"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharmthera.2020.107512"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/ciz911"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1811345115"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.3201\/eid2511.190757"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.archoralbio.2019.04.017"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jep.2024.118613"},{"issue":"1","key":"e_1_2_9_12_1","first-page":"6","article-title":"International Journal of Ayurvedic Medicine. 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