{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T22:50:12Z","timestamp":1777416612269,"version":"3.51.4"},"reference-count":39,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2021,7,13]],"date-time":"2021-07-13T00:00:00Z","timestamp":1626134400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["2020R1A5A8029280"],"award-info":[{"award-number":["2020R1A5A8029280"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["2019R1I1A1A01060238"],"award-info":[{"award-number":["2019R1I1A1A01060238"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003716","name":"Korea Basic Science Institute","doi-asserted-by":"publisher","award":["C140360"],"award-info":[{"award-number":["C140360"]}],"id":[{"id":"10.13039\/501100003716","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>Influenza viruses cause respiratory infections in humans and animals, which have high morbidity and mortality rates. Although several drugs that inhibit viral neuraminidase are used to treat influenza infections, the emergence of resistant viruses necessitates the urgent development of new antiviral drugs. Chrysin (5,7-dihydroxyflavone) is a natural flavonoid that exhibits antiviral activity against enterovirus 71 (EV71) by inhibiting viral 3C protease activity. In this study, we evaluated the antiviral activity of chrysin against influenza A\/Puerto Rico\/8\/34 (A\/PR\/8). Chrysin significantly inhibited A\/PR\/8-mediated cell death and the replication of A\/PR\/8 at concentrations up to 2 \u03bcM. Viral hemagglutinin expression was also markedly decreased by the chrysin treatment in A\/PR\/8-infected cells. Through the time course experiment and time-of-addition assay, we found that chrysin inhibited viral infection at the early stages of the replication cycle. Additionally, the nucleoprotein expression of A\/PR\/8 in A549 cells was reduced upon treatment with chrysin. Regarding the mechanism of action, we found that chrysin inhibited autophagy activation by increasing the phosphorylation of mammalian target of rapamycin (mTOR). We also confirmed a decrease in LC3B expression and LC3-positive puncta levels in A\/PR\/8-infected cells. These results suggest that chrysin exhibits antiviral activity by activating mTOR and inhibiting autophagy to inhibit the replication of A\/PR\/8 in the early stages of infection.<\/jats:p>","DOI":"10.3390\/v13071350","type":"journal-article","created":{"date-parts":[[2021,7,13]],"date-time":"2021-07-13T04:26:06Z","timestamp":1626150366000},"page":"1350","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":27,"title":["Antiviral Activity of Chrysin against Influenza Virus Replication via Inhibition of Autophagy"],"prefix":"10.3390","volume":"13","author":[{"given":"Seong-Ryeol","family":"Kim","sequence":"first","affiliation":[{"name":"Department of Pharmacy, Kangwon National University, Chuncheon 24341, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Myeong-Seon","family":"Jeong","sequence":"additional","affiliation":[{"name":"Chuncheon Center, Korea Basic Science Institute (KBSI), Chuncheon 24341, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Seo-Hyeon","family":"Mun","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Kangwon National University, Chuncheon 24341, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jaewon","family":"Cho","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Kangwon National University, Chuncheon 24341, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Min-Duk","family":"Seo","sequence":"additional","affiliation":[{"name":"College of Pharmacy and Research Institute of Pharmaceutical Science and Technology (RIPST), Ajou University, Suwon 16499, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2774-8727","authenticated-orcid":false,"given":"Hyoungsu","family":"Kim","sequence":"additional","affiliation":[{"name":"College of Pharmacy and Research Institute of Pharmaceutical Science and Technology (RIPST), Ajou University, Suwon 16499, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jooeun","family":"Lee","sequence":"additional","affiliation":[{"name":"Chuncheon Center, Korea Basic Science Institute (KBSI), Chuncheon 24341, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jae-Hyoung","family":"Song","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Kangwon National University, Chuncheon 24341, Korea"},{"name":"Kangwon Institute of Inclusive Technology, Kangwon National University, Chuncheon 24341, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hyun-Jeong","family":"Ko","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Kangwon National University, Chuncheon 24341, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,7,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1363","DOI":"10.1056\/NEJMra050740","article-title":"Neuraminidase inhibitors for influenza","volume":"353","author":"Moscona","year":"2005","journal-title":"N. 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