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Thus there is an unmet medical need to develop new anti\u2010influenza agents. In this study, we show that punicalagin from plants possesses strong anti\u2010influenza activity with a low micromolar IC<jats:sub>50<\/jats:sub> value in tissue culture. Using a battery of bioassays such as single\u2010cycle replication assay, neuraminidase (NA) inhibition assay, and virus yield reduction assay, we demonstrate that the primary mechanism of action (MOA) of punicalagin is the NA\u2010mediated viral release. Moreover, punicalagin can inhibit replication of different strains of influenza A and B viruses, including oseltamivir\u2010resistant virus (NA\/H274Y), indicating that punicalagin is a broad spectrum antiviral against both IAV and IBV. Further, although punicalagin targets NA like oseltamivir, it has a different MOA. These results suggest that punicalagin is an influenza NA inhibitor that may be further developed as a novel antiviral against influenza viruses.<\/jats:p>","DOI":"10.1002\/jmv.26449","type":"journal-article","created":{"date-parts":[[2020,8,22]],"date-time":"2020-08-22T14:12:20Z","timestamp":1598105540000},"page":"3465-3472","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":34,"title":["Punicalagin is a neuraminidase inhibitor of influenza viruses"],"prefix":"10.1002","volume":"93","author":[{"given":"Ping","family":"Li","sequence":"first","affiliation":[{"name":"College of Pharmacy Shandong University of Traditional Chinese Medicine Jinan China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ruikun","family":"Du","sequence":"additional","affiliation":[{"name":"College of Pharmacy Shandong University of Traditional Chinese Medicine Jinan China"},{"name":"Qingdao Academy of Chinese Medicinal Sciences Shandong University of Traditional Chinese Medicine Qingdao China"},{"name":"Research Center, College of Medicine Shandong University of Traditional Chinese Medicine Jinan China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zinuo","family":"Chen","sequence":"additional","affiliation":[{"name":"College of Pharmacy Shandong University of Traditional Chinese Medicine Jinan China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yanyan","family":"Wang","sequence":"additional","affiliation":[{"name":"College of Pharmacy Shandong University of Traditional Chinese Medicine Jinan China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peng","family":"Zhan","sequence":"additional","affiliation":[{"name":"Department of Medicinal Chemistry Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences Shandong University Jinan China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xinyong","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Medicinal Chemistry Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences Shandong University Jinan China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dongwei","family":"Kang","sequence":"additional","affiliation":[{"name":"Department of Medicinal Chemistry Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences Shandong University Jinan China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhaoyu","family":"Chen","sequence":"additional","affiliation":[{"name":"College of Pharmacy Shandong University of Traditional Chinese Medicine Jinan China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiujuan","family":"Zhao","sequence":"additional","affiliation":[{"name":"College of Pharmacy Shandong University of Traditional Chinese Medicine Jinan China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lin","family":"Wang","sequence":"additional","affiliation":[{"name":"College of Pharmacy Shandong University of Traditional Chinese Medicine Jinan China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lijun","family":"Rong","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology College of Medicine University of Illinois at Chicago Chicago Illinois"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qinghua","family":"Cui","sequence":"additional","affiliation":[{"name":"College of Pharmacy Shandong University of Traditional Chinese Medicine Jinan China"},{"name":"Qingdao Academy of Chinese Medicinal Sciences Shandong University of Traditional Chinese Medicine Qingdao China"},{"name":"Research Center, College of Medicine Shandong University of Traditional Chinese Medicine Jinan China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2020,9,29]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.3390\/v10060325"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms18081650"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(18)30364-5"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1353\/bhm.2002.0022"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(12)70121-4"},{"key":"e_1_2_10_7_1","unstructured":"World Health Organization (WHO).2018Influenza (Seasonal) Fact Sheet; WHO: Geneva Switzerland 2018;http:\/\/www.who.int\/mediacentre\/factsheets\/fs211\/en\/. 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