{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T08:17:36Z","timestamp":1788337056967,"version":"build-2803163510"},"reference-count":47,"publisher":"American Chemical Society (ACS)","issue":"11","license":[{"start":{"date-parts":[[2015,5,4]],"date-time":"2015-05-04T00:00:00Z","timestamp":1430697600000},"content-version":"vor","delay-in-days":365,"URL":"https:\/\/pubs.acs.org\/page\/policy\/authorchoice_termsofuse.html"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2014,6,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>A series of 2-adamantanamines with alkyl adducts of various lengths were examined for efficacy against strains of influenza A including those having an S31N mutation in M2 proton channel that confer resistance to amantadine and rimantadine. The addition of as little as one CH2 group to the methyl adduct of the amantadine\/rimantadine analogue, 2-methyl-2-aminoadamantane, led to activity in vitro against two M2 S31N viruses A\/Calif\/07\/2009 (H1N1) and A\/PR\/8\/34 (H1N1) but not to a third A\/WS\/33 (H1N1). Solid state NMR of the transmembrane domain (TMD) with a site mutation corresponding to S31N shows evidence of drug binding. But electrophysiology using the full length S31N M2 protein in HEK cells showed no blockade. A wild type strain, A\/Hong Kong\/1\/68 (H3N2) developed resistance to representative drugs within one passage with mutations in M2 TMD, but A\/Calif\/07\/2009 S31N was slow (&amp;gt;8 passages) to develop resistance in vitro, and the resistant virus had no mutations in M2 TMD. The results indicate that 2-alkyl-2-aminoadamantane derivatives with sufficient adducts can persistently block p2009 influenza A in vitro through an alternative mechanism. The observations of an HA1 mutation, N160D, near the sialic acid binding site in both 6-resistant A\/Calif\/07\/2009(H1N1) and the broadly resistant A\/WS\/33(H1N1) and of an HA1 mutation, I325S, in the 6-resistant virus at a cell-culture stable site suggest that the drugs tested here may block infection by direct binding near these critical sites for virus entry to the host cell.<\/jats:p>","DOI":"10.1021\/jm500598u","type":"journal-article","created":{"date-parts":[[2014,5,4]],"date-time":"2014-05-04T13:06:37Z","timestamp":1399208797000},"page":"4629-4639","source":"Crossref","is-referenced-by-count":68,"title":["Aminoadamantanes with Persistent in Vitro Efficacy\nagainst H1N1 (2009) Influenza A"],"prefix":"10.1021","volume":"57","author":[{"given":"Antonios","family":"Kolocouris","sequence":"first","affiliation":[{"name":"National and Kapodistrian University of Athens , , ,","place":["Athens, Greece, 15771"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christina","family":"Tzitzoglaki","sequence":"additional","affiliation":[{"name":"National and Kapodistrian University of Athens , , ,","place":["Athens, Greece, 15771"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"F. Brent","family":"Johnson","sequence":"additional","affiliation":[{"name":"Brigham Young University , , , ,","place":["Provo, Utah, United States, 84602"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roland","family":"Zell","sequence":"additional","affiliation":[{"name":"Jena University Hospital , , CMB Building, R. 443, Hans Knoell Strasse 2 , ,","place":["Jena, Germany, D-07745"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna K.","family":"Wright","sequence":"additional","affiliation":[{"name":"Florida State University , , , ,","place":["Tallahassee, Florida, United States, 32306"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timothy A.","family":"Cross","sequence":"additional","affiliation":[{"name":"Florida State University , , , ,","place":["Tallahassee, Florida, United States, 32306"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ian","family":"Tietjen","sequence":"additional","affiliation":[{"name":"University of British Columbia , , , , ,","place":["Vancouver, British Columbia, Canada, V6T 1Z3"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Fedida","sequence":"additional","affiliation":[{"name":"University of British Columbia , , , , ,","place":["Vancouver, British Columbia, Canada, V6T 1Z3"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David D.","family":"Busath","sequence":"additional","affiliation":[{"name":"Brigham Young University , , , ,","place":["Provo, Utah, United States, 84602"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2014,5,4]]},"reference":[{"key":"2026090203413575000_cit1","doi-asserted-by":"crossref","first-page":"1175","DOI":"10.1016\/S0140-6736(05)67338-2","article-title":"Incidence of adamantane resistance\namong influenza A (H3N2) viruses isolated worldwide from 1994 to 2005:\na cause for concern","volume":"366","author":"Bright","year":"2005","journal-title":"Lancet"},{"key":"2026090203413575000_cit2a","doi-asserted-by":"crossref","first-page":"891","DOI":"10.1001\/jama.295.8.joc60020","article-title":"Adamantane resistance among influenza\nA viruses isolated\nearly during the 2005\u20132006 influenza season in the United States","volume":"295","author":"Bright","year":"2006","journal-title":"JAMA, J. 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