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Herein, a novel quinolone alkaloid (QLA) derived from marine fungus was discovered with broad\u2010spectrum anti\u2010IAV activities with low toxicity. Distinct from current anti\u2010IAV drugs, QLA may block virus replication and viral RNA (vRNA) export from the nucleus by targeting virus nucleoprotein (NP). QLA can block the binding of chromosome region maintenance 1 to nuclear export signal 3 of NP to inhibit the nuclear export of NP and vRNP. QLA may also affect vRNP assembly by interfering with the binding of NP to RNA rather than NP oligomerization. Arg305 and Phe488\u2010Gly490 may be required for the interaction between QLA and NP, and the binding pocket around these amino acids may be a promising target for anti\u2010IAV drugs. Importantly, oral administration of QLA can protect the mice against IAV\u2010induced death and weight loss, superior to the effects of the clinical drug oseltamivir. In summary, the marine derived compound QLA has the potential to be developed into a novel anti\u2010IAV agent targeting virus NP protein in the future.<\/jats:p>","DOI":"10.1002\/jmv.28499","type":"journal-article","created":{"date-parts":[[2023,1,18]],"date-time":"2023-01-18T23:28:25Z","timestamp":1674084505000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Inhibition of influenza A virus replication by a marine derived quinolone alkaloid targeting virus nucleoprotein"],"prefix":"10.1002","volume":"95","author":[{"given":"Yang","family":"Zhang","sequence":"first","affiliation":[{"name":"School of Medicine and Pharmacy, Key Laboratory of Marine Drugs, Ministry of Education Ocean University of China  Qingdao China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei\u2010Feng","family":"Xu","sequence":"additional","affiliation":[{"name":"School of Medicine and Pharmacy, Key Laboratory of Marine 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