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However, oseltamivir\u2010resistant H1N1 influenza viruses carrying the H275Y NA mutation spontaneously emerged as a result of natural genetic drift and drug treatment. Because H275Y and other potential mutations may generate a future pandemic influenza strain that is oseltamivir\u2010resistant, alternative therapy options are needed. Herein, we show that a structure\u2010based computational method can be used to identify existing drugs that inhibit resistant viruses, thereby providing a first line of pharmaceutical defense against this possible scenario. We identified two drugs, nalidixic acid and dorzolamide, that potently inhibit the NA activity of oseltamivir\u2010resistant H1N1 viruses with the H275Y NA mutation at very low concentrations, but have no effect on wild\u2010type H1N1 NA even at a much higher concentration, suggesting that the oseltamivir\u2010resistance mutation itself caused susceptibility to these drugs.<\/jats:p>","DOI":"10.1002\/anie.201511361","type":"journal-article","created":{"date-parts":[[2016,2,2]],"date-time":"2016-02-02T11:24:39Z","timestamp":1454412279000},"page":"3438-3441","source":"Crossref","is-referenced-by-count":25,"title":["Drug Repurposing Identifies Inhibitors of Oseltamivir\u2010Resistant Influenza Viruses"],"prefix":"10.1002","volume":"55","author":[{"given":"Ju","family":"Bao","sequence":"first","affiliation":[{"name":"Department of Structural Biology St. Jude Children's Research Hospital  Memphis TN 38105 USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bindumadhav","family":"Marathe","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases St. Jude Children's Research Hospital  Memphis TN 38105 USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elena A.","family":"Govorkova","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases St. Jude Children's Research Hospital  Memphis TN 38105 USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6524-6800","authenticated-orcid":false,"given":"Jie J.","family":"Zheng","sequence":"additional","affiliation":[{"name":"Department of Structural Biology St. Jude Children's Research Hospital  Memphis TN 38105 USA"},{"name":"Stein Eye Institute Department of Ophthalmology David Geffen School of Medicine at UCLA  Los Angeles CA 90095 USA"},{"name":"Department of Infectious Diseases St. Jude Children's Research Hospital  Memphis TN 38105 USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2016,2,2]]},"reference":[{"key":"e_1_2_2_1_1","unstructured":"\u00a0"},{"key":"e_1_2_2_2_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1750-2659.2009.00090.x"},{"key":"e_1_2_2_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2009.01.029"},{"key":"e_1_2_2_4_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.med.050908.132031"},{"key":"e_1_2_2_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2009.06.034"},{"key":"e_1_2_2_6_1","unstructured":"\u00a0"},{"key":"e_1_2_2_7_2","doi-asserted-by":"crossref","first-page":"552","DOI":"10.3201\/eid1504.181280","volume":"15","author":"Meijer A.","year":"2009","journal-title":"Emerging Infect. 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