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Severe complications are often related to secondary pneumonia caused by <jats:italic>Streptococcus pneumoniae<\/jats:italic> (pneumococci), which also express NAs. Recently, a NA-mediated lethal synergism between influenza A viruses and pneumococci was described. Therefore, dual inhibitors of both viral and bacterial NAs are expected to be advantageous for the treatment of influenza. We investigated the traditional Chinese herbal drug s\u0101ng b\u00e1i p\u00ed (mulberry root bark) as source for anti-infectives. Two prenylated flavonoid derivatives, sanggenon G (<jats:bold>4<\/jats:bold>) and sanggenol A (<jats:bold>5<\/jats:bold>) inhibited influenza A viral and pneumococcal NAs and, in contrast to the approved NA inhibitor oseltamivir, also planktonic growth and biofilm formation of pneumococci. Evaluation of <jats:bold>27<\/jats:bold> congeners of <jats:bold>5<\/jats:bold> revealed a correlation between the degree of prenylation and bioactivity. Abyssinone-V 4\u2032-methyl ether (<jats:bold>27<\/jats:bold>) inhibited pneumococcal NA with IC<jats:sub>50<\/jats:sub>\u2009=\u20092.18\u2009\u03bcM, pneumococcal growth with MIC\u2009=\u20095.63\u2009\u03bcM and biofilm formation with MBIC\u2009=\u20094.21\u2009\u03bcM, without harming lung epithelial cells. Compounds <jats:bold>5<\/jats:bold> and <jats:bold>27<\/jats:bold> also disrupt the synergism between influenza A virus and pneumococcal NA <jats:italic>in vitro<\/jats:italic>, hence functioning as dual-acting anti-infectives. The results warrant further studies on whether the observed disruption of this synergism is transferable to <jats:italic>in vivo<\/jats:italic> systems.<\/jats:p>","DOI":"10.1038\/srep27156","type":"journal-article","created":{"date-parts":[[2016,6,3]],"date-time":"2016-06-03T09:34:39Z","timestamp":1464946479000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":69,"title":["Discovery of prenylated flavonoids with dual activity against influenza virus and Streptococcus pneumoniae"],"prefix":"10.1038","volume":"6","author":[{"given":"Ulrike","family":"Grienke","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martina","family":"Richter","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisabeth","family":"Walther","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anja","family":"Hoffmann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johannes","family":"Kirchmair","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vadim","family":"Makarov","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandor","family":"Nietzsche","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michaela","family":"Schmidtke","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Judith M.","family":"Rollinger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2016,6,3]]},"reference":[{"key":"BFsrep27156_CR1","unstructured":"WHO Influenza Fact Sheets. 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