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After screening different plant extracts with potential anti-influenza activity, a water extract of <jats:italic>Taxodium distichum<\/jats:italic> stems (TDSWex) showed excellent activity against influenza viruses. The EC<jats:sub>50<\/jats:sub> of TDSWex was 0.051\u2009\u00b1\u20090.024\u2009mg\/mL against influenza virus A\/WSN\/33. TDSWex had excellent antiviral efficacy against various strains of human influenza A and B viruses, particularly oseltamivir-resistant clinical isolates and a swine-origin influenza strain. We observed that the synthesis of viral RNA and protein were inhibited in the presence of TDSWex. The results of the time-of-addition assay suggested that TDSWex inhibited viral entry and budding. In the hemagglutination inhibition assay, TDSWex inhibited the hemagglutination of red blood cells, implying that the extract targeted hemagglutin-related functions such as viral entry. In the attachment and penetration assay, TDSWex showed antiviral activity with EC<jats:sub>50<\/jats:sub>s of 0.045\u2009\u00b1\u20090.026 and 0.012\u2009\u00b1\u20090.003\u2009mg\/mL, respectively. In addition, TDSWex blocked neuraminidase activity. We conclude that TDSWex has bimodal activities against both hemagglutinin and neuraminidase during viral replication.<\/jats:p>","DOI":"10.1038\/srep36015","type":"journal-article","created":{"date-parts":[[2016,10,31]],"date-time":"2016-10-31T10:58:14Z","timestamp":1477911494000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["An extract from Taxodium distichum targets hemagglutinin- and neuraminidase-related activities of influenza virus in vitro"],"prefix":"10.1038","volume":"6","author":[{"given":"Chung-Fan","family":"Hsieh","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu-Li","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chwan-Fwu","family":"Lin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jin-Yuan","family":"Ho","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chun-Hsun","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cheng-Hsun","family":"Chiu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pei-Wen","family":"Hsieh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jim-Tong","family":"Horng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2016,10,31]]},"reference":[{"key":"BFsrep36015_CR1","doi-asserted-by":"publisher","first-page":"197","DOI":"10.1126\/science.1176225","volume":"325","author":"RJ Garten","year":"2009","unstructured":"Garten, R. 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