{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,20]],"date-time":"2026-05-20T03:41:01Z","timestamp":1779248461664,"version":"3.51.4"},"reference-count":30,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2023,3,9]],"date-time":"2023-03-09T00:00:00Z","timestamp":1678320000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Animal Disease Management Technology Development Program","award":["118097-2"],"award-info":[{"award-number":["118097-2"]}]},{"name":"Animal Disease Management Technology Development Program","award":["KGM5242322"],"award-info":[{"award-number":["KGM5242322"]}]},{"name":"Ministry of Agriculture, Food and Rural Affairs (MAFRA) and the KRIBB Research Initiative Program","award":["118097-2"],"award-info":[{"award-number":["118097-2"]}]},{"name":"Ministry of Agriculture, Food and Rural Affairs (MAFRA) and the KRIBB Research Initiative Program","award":["KGM5242322"],"award-info":[{"award-number":["KGM5242322"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["CIMB"],"abstract":"<jats:p>Although vaccines and antiviral drugs are available, influenza viruses continue to pose a significant threat to vulnerable populations globally. With the emergence of drug-resistant strains, there is a growing need for novel antiviral therapeutic approaches. We found that 18-hydroxyferruginol (1) and 18-oxoferruginol (2) isolated from Torreya nucifera exhibited strong anti-influenza activity, with 50% inhibitory concentration values of 13.6 and 18.3 \u03bcM against H1N1, 12.8 and 10.8 \u03bcM against H9N2, and 29.2 \u03bcM (only compound 2) against H3N2 in the post-treatment assay, respectively. During the viral replication stages, the two compounds demonstrated stronger inhibition of viral RNA and protein in the late stages (12\u201318 h) than in the early stages (3\u20136 h). Moreover, both compounds inhibited PI3K-Akt signaling, which participates in viral replication during the later stages of infection. The ERK signaling pathway is also related to viral replication and was substantially inhibited by the two compounds. In particular, the inhibition of PI3K-Akt signaling by these compounds inhibited viral replication by sabotaging influenza ribonucleoprotein nucleus-to-cytoplasm export. These data indicate that compounds 1 and 2 could potentially reduce viral RNA and viral protein levels by inhibiting the PI3K-Akt signaling pathway. Our results suggest that abietane diterpenoids isolated from T. nucifera may be potent antiviral candidates for new influenza therapies.<\/jats:p>","DOI":"10.3390\/cimb45030147","type":"journal-article","created":{"date-parts":[[2023,3,10]],"date-time":"2023-03-10T03:35:42Z","timestamp":1678419342000},"page":"2284-2295","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Abietane Diterpenoids Isolated from Torreya nucifera Disrupt Replication of Influenza Virus by Blocking the Phosphatidylinositol-3-Kinase (PI3K)-Akt and ERK Signaling Pathway"],"prefix":"10.3390","volume":"45","author":[{"given":"Jaehoon","family":"Bae","sequence":"first","affiliation":[{"name":"Functional Biomaterial Research Center, Korea Research Institute of Bioscience and Biotechnology, 181 Ipsin-gil, Jeongeup-si 56212, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hyung-Jun","family":"Kwon","sequence":"additional","affiliation":[{"name":"Functional Biomaterial Research Center, Korea Research Institute of Bioscience and Biotechnology, 181 Ipsin-gil, Jeongeup-si 56212, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ji Sun","family":"Park","sequence":"additional","affiliation":[{"name":"Functional Biomaterial Research Center, Korea Research Institute of Bioscience and Biotechnology, 181 Ipsin-gil, Jeongeup-si 56212, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jinseok","family":"Jung","sequence":"additional","affiliation":[{"name":"Functional Biomaterial Research Center, Korea Research Institute of Bioscience and Biotechnology, 181 Ipsin-gil, Jeongeup-si 56212, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Young Bae","family":"Ryu","sequence":"additional","affiliation":[{"name":"Functional Biomaterial Research Center, Korea Research Institute of Bioscience and Biotechnology, 181 Ipsin-gil, Jeongeup-si 56212, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Woo Sik","family":"Kim","sequence":"additional","affiliation":[{"name":"Functional Biomaterial Research Center, Korea Research Institute of Bioscience and Biotechnology, 181 Ipsin-gil, Jeongeup-si 56212, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ju Huck","family":"Lee","sequence":"additional","affiliation":[{"name":"Biological Resource Center, Korea Research Institute of Bioscience and Biotechnology, 181 Ipsin-gil, Jeongeup-si 56212, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jae-Ho","family":"Jeong","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Chonnam National University Medical School, Gwangju 61468, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jae Sung","family":"Lim","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Chonnam National University, Gwangju 61186, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Woo Song","family":"Lee","sequence":"additional","affiliation":[{"name":"Functional Biomaterial Research Center, Korea Research Institute of Bioscience and Biotechnology, 181 Ipsin-gil, Jeongeup-si 56212, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1893-2714","authenticated-orcid":false,"given":"Su-Jin","family":"Park","sequence":"additional","affiliation":[{"name":"Functional Biomaterial Research Center, Korea Research Institute of Bioscience and Biotechnology, 181 Ipsin-gil, Jeongeup-si 56212, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,3,9]]},"reference":[{"key":"ref_1","unstructured":"Knipe, D.M., and Howley, P.M. 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