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The nucleoprotein (<jats:styled-content style=\"fixed-case\">NP<\/jats:styled-content>) is conserved among all influenza A viruses (<jats:styled-content style=\"fixed-case\">IAV<\/jats:styled-content>s) and has no cellular equivalent. Therefore, <jats:styled-content style=\"fixed-case\">NP<\/jats:styled-content> is an ideal target for the development of new <jats:styled-content style=\"fixed-case\">IAV<\/jats:styled-content> inhibitors. In this study, we identified a novel anti\u2010influenza compound, <jats:styled-content style=\"fixed-case\">ZBMD<\/jats:styled-content>\u20101, from a library of 20,000 compounds using cell\u2010based influenza A infection assays. We found that <jats:styled-content style=\"fixed-case\">ZBMD<\/jats:styled-content>\u20101 inhibited the replication of H1N1 and H3N2 influenza A virus strains <jats:italic>in\u00a0vitro<\/jats:italic>, with an <jats:styled-content style=\"fixed-case\">IC<\/jats:styled-content><jats:sub>50<\/jats:sub> ranging from 0.41\u20131.14\u00a0\u03bcM. Furthermore, <jats:styled-content style=\"fixed-case\">ZBMD<\/jats:styled-content>\u20101 inhibited the polymerase activity and specifically impaired the nuclear export of <jats:styled-content style=\"fixed-case\">NP<\/jats:styled-content>. Further investigation indicated that <jats:styled-content style=\"fixed-case\">ZBMD<\/jats:styled-content>\u20101 binds to the nuclear export signal 3 (<jats:styled-content style=\"fixed-case\">NES<\/jats:styled-content>3) domain and the dimer interface of the <jats:styled-content style=\"fixed-case\">NP<\/jats:styled-content> pocket. <jats:styled-content style=\"fixed-case\">ZBMD<\/jats:styled-content>\u20101 also protected mice that were challenged with lethal doses of A\/<jats:styled-content style=\"fixed-case\">PR<\/jats:styled-content>\/8\/1934 (H1N1) virus, effectively relieving lung histopathology changes, as well as strongly inhibiting the expression of pro\u2010inflammatory cytokines\/chemokines, without inducing toxicity effects in mice. These results suggest that <jats:styled-content style=\"fixed-case\">ZBMD<\/jats:styled-content>\u20101 is a promising anti\u2010influenza compound which can be further investigated as a useful strategy against <jats:styled-content style=\"fixed-case\">IAV<\/jats:styled-content>s in the future.<\/jats:p>","DOI":"10.1111\/jcmm.13467","type":"journal-article","created":{"date-parts":[[2017,11,30]],"date-time":"2017-11-30T05:08:37Z","timestamp":1512018517000},"page":"1826-1839","source":"Crossref","is-referenced-by-count":17,"title":["Identification of a novel compound targeting the nuclear export of influenza A virus nucleoprotein"],"prefix":"10.1111","volume":"22","author":[{"given":"Feng","family":"Huang","sequence":"first","affiliation":[{"name":"Department of Respiration Affiliated Guangzhou Women and Children's Hospital Zhongshan School of Medicine Sun Yat\u2010Sen University Guangzhou China"},{"name":"Institute of Human Virology Zhongshan School of Medicine Sun Yat\u2010sen 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