{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T13:28:34Z","timestamp":1790947714659,"version":"4.1.0"},"reference-count":55,"publisher":"Public Library of Science (PLoS)","issue":"7","license":[{"start":{"date-parts":[[2015,7,29]],"date-time":"2015-07-29T00:00:00Z","timestamp":1438128000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"DOI":"10.1371\/journal.ppat.1005062","type":"journal-article","created":{"date-parts":[[2015,7,29]],"date-time":"2015-07-29T18:17:38Z","timestamp":1438193858000},"page":"e1005062","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":42,"title":["A Novel Antiviral Target Structure Involved in the RNA Binding, Dimerization, and Nuclear Export Functions of the Influenza A Virus Nucleoprotein"],"prefix":"10.1371","volume":"11","author":[{"given":"Michinori","family":"Kakisaka","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yutaka","family":"Sasaki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazunori","family":"Yamada","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasumitsu","family":"Kondoh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hirokazu","family":"Hikono","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroyuki","family":"Osada","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kentaro","family":"Tomii","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takehiko","family":"Saito","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoko","family":"Aida","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2015,7,29]]},"reference":[{"key":"ref1","doi-asserted-by":"crossref","first-page":"440","DOI":"10.1016\/j.chom.2010.05.009","article-title":"Influenza virus evolution, host adaptation, and pandemic formation","volume":"7","author":"JK Taubenberger","year":"2010","journal-title":"Cell Host Microbe"},{"key":"ref2","doi-asserted-by":"crossref","first-page":"3021","DOI":"10.1002\/j.1460-2075.1985.tb04038.x","article-title":"The molecular basis of the specific anti-influenza action of Amantadine","volume":"4","author":"AJ Hay","year":"1985","journal-title":"EMBO J"},{"key":"ref3","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1146\/annurev.med.59.061506.213121","article-title":"Medical management of influenza infection","volume":"59","author":"A Moscona","year":"2008","journal-title":"Annu Rev Med"},{"key":"ref4","doi-asserted-by":"crossref","first-page":"891","DOI":"10.1001\/jama.295.8.joc60020","article-title":"Adamantane resistance among influenza A viruses isolated early during the 2005\u20132006 influenza season in the United States","volume":"295","author":"RA Bright","year":"2006","journal-title":"JAMA"},{"key":"ref5","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1016\/j.antiviral.2009.03.003","article-title":"Emergence and spread of oseltamivir-resistant A(H1N1) influenza viruses in Oceania, South East Asia and South Africa","volume":"83","author":"AC Hurt","year":"2009","journal-title":"Antiviral Res"},{"key":"ref6","doi-asserted-by":"crossref","first-page":"1034","DOI":"10.1001\/jama.2009.294","article-title":"Infections with oseltamivir resistant influenza A(H1N1) virus in the United States","volume":"301","author":"NJ Dharan","year":"2009","journal-title":"JAMA"},{"key":"ref7","doi-asserted-by":"crossref","first-page":"981","DOI":"10.1128\/AAC.49.3.981-986.2005","article-title":"Mechanism of action of T-705 against influenza virus","volume":"49","author":"Y Furuta","year":"2005","journal-title":"Antimicrob Agents Chemother"},{"key":"ref8","doi-asserted-by":"crossref","first-page":"1350","DOI":"10.1136\/gut.2005.076646","article-title":"Treating viral hepatitis C: efficacy, side effects, and complications","volume":"55","author":"MP Manns","year":"2006","journal-title":"Gut"},{"key":"ref9","doi-asserted-by":"crossref","first-page":"1248","DOI":"10.1093\/emboj\/16.6.1248","article-title":"Roles of the influenza virus polymerase and nucleoprotein in forming a functional RNP structure","volume":"16","author":"K Klumpp","year":"1997","journal-title":"EMBO J"},{"key":"ref10","doi-asserted-by":"crossref","first-page":"1634","DOI":"10.1126\/science.1228172","article-title":"The structure of native influenza virion ribonucleoproteins","volume":"338","author":"R Arranz","year":"2012","journal-title":"Science"},{"key":"ref11","doi-asserted-by":"crossref","first-page":"1078","DOI":"10.1038\/nature05379","article-title":"The mechanism by which influenza A virus nucleoprotein forms oligomers and binds RNA","volume":"444","author":"Q Ye","year":"2006","journal-title":"Nature"},{"key":"ref12","first-page":"e00467","article-title":"Biochemical and structural evidence in support of a coherent model for the formation of the double-helical influenza A virus ribonucleoprotein","volume":"4","author":"Q Ye","year":"2012","journal-title":"MBio"},{"key":"ref13","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1006\/viro.1993.1473","article-title":"Molecular assembly of influenza virus: association of the NS2 protein with virion matrix","volume":"196","author":"J Yasuda","year":"1993","journal-title":"Virology"},{"key":"ref14","doi-asserted-by":"crossref","first-page":"4646","DOI":"10.1093\/emboj\/cdg449","article-title":"Crystal structure of the M1 protein-binding domain of the influenza A virus nuclear export protein (NEP\/NS2)","volume":"22","author":"H Akarsu","year":"2003","journal-title":"EMBO J"},{"key":"ref15","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1016\/j.febslet.2010.11.017","article-title":"Crucial role of the influenza virus NS2 (NEP) C-terminal domain in M1 binding and nuclear export of vRNP","volume":"585","author":"T Shimizu","year":"2011","journal-title":"FEBS Lett"},{"key":"ref16","doi-asserted-by":"crossref","first-page":"7467","DOI":"10.1128\/JVI.73.9.7467-7473.1999","article-title":"Association of influenza virus matrix protein with ribonucleoproteins","volume":"73","author":"Z Ye","year":"1999","journal-title":"J Virol"},{"key":"ref17","doi-asserted-by":"crossref","first-page":"2280","DOI":"10.1099\/vir.0.82809-0","article-title":"Identification of the domains of the influenza A virus M1 matrix protein required for NP binding, oligomerization and incorporation into virions","volume":"88","author":"SL Noton","year":"2007","journal-title":"J Gen Virol"},{"key":"ref18","doi-asserted-by":"crossref","first-page":"4970","DOI":"10.1128\/JVI.06159-11","article-title":"Identification and characterization of three novel nuclear export signals in the influenza A virus nucleoprotein","volume":"86","author":"M Yu","year":"2012","journal-title":"J Virol"},{"key":"ref19","doi-asserted-by":"crossref","first-page":"e105081","DOI":"10.1371\/journal.pone.0105081","article-title":"Comparative Analysis of Seven Viral Nuclear Export Signals (NESs) Reveals the Crucial Role of Nuclear Export Mediated by the Third NES Consensus Sequence of Nucleoprotein (NP) in Influenza A Virus Replication","volume":"9","author":"N Chutiwitoonchai","year":"2014","journal-title":"PLoS One"},{"key":"ref20","doi-asserted-by":"crossref","first-page":"408","DOI":"10.1128\/JVI.75.1.408-419.2001","article-title":"Interaction of the influenza virus nucleoprotein with the cellular CRM1-mediated nuclear export pathway","volume":"75","author":"D Elton","year":"2001","journal-title":"J Virol"},{"key":"ref21","first-page":"99","article-title":"Discovery of Novel Antiviral Agents Directed Against the Influenza A Virus Nucleoprotein","author":"Y Aida","year":"2012","journal-title":"Antiviral Drugs\u2014Aspects of Clinical Use and Recent Advances"},{"key":"ref22","doi-asserted-by":"crossref","first-page":"721","DOI":"10.1016\/j.bbrc.2010.03.058","article-title":"Discovery of novel antiviral agents directed against the influenza A virus nucleoprotein using photo-cross-linked chemical arrays","volume":"394","author":"K Hagiwara","year":"2010","journal-title":"Biochem Biophys Res Commun"},{"key":"ref23","doi-asserted-by":"crossref","first-page":"16515","DOI":"10.1073\/pnas.1113107108","article-title":"E339\u2026R416 salt bridge of nucleoprotein as a feasible target for influenza virus inhibitors","volume":"108","author":"YF Shen","year":"2011","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ref24","doi-asserted-by":"crossref","first-page":"600","DOI":"10.1038\/nbt.1638","article-title":"Identification of influenza A nucleoprotein as an antiviral target","volume":"28","author":"RY Kao","year":"2010","journal-title":"Nat Biotechnol"},{"key":"ref25","doi-asserted-by":"crossref","first-page":"15366","DOI":"10.1073\/pnas.1107906108","article-title":"Inhibition of influenza virus replication via small molecules that induce the formation of higher-order nucleoprotein oligomers","volume":"108","author":"SW Gerritz","year":"2011","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ref26","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1016\/j.bbrc.2014.05.058","article-title":"Identification of a novel multiple kinase inhibitor with potent antiviral activity against influenza virus by reducing viral polymerase activity","volume":"450","author":"Y Sasaki","year":"2014","journal-title":"Biochem Biophys Res Commun"},{"key":"ref27","doi-asserted-by":"crossref","first-page":"1093","DOI":"10.1023\/A:1018943613122","article-title":"Physiological parameters in laboratory animals and humans","volume":"10","author":"B Davies","year":"1993","journal-title":"Pharm Res"},{"key":"ref28","doi-asserted-by":"crossref","first-page":"1834","DOI":"10.1128\/AAC.01608-09","article-title":"Detection of E119V and E119I mutations in influenza A (H3N2) viruses isolated from an immunocompromised patient: challenges in diagnosis of oseltamivir resistance","volume":"54","author":"M Okomo-Adhiambo","year":"2010","journal-title":"Antimicrob Agents Chemother"},{"key":"ref29","doi-asserted-by":"crossref","first-page":"e1003358","DOI":"10.1371\/journal.ppat.1003358","article-title":"Colocalization of different influenza viral RNA segments in the cytoplasm before viral budding as shown by single-molecule sensitivity FISH analysis","volume":"9","author":"YY Chou","year":"2013","journal-title":"PLoS Pathog"},{"key":"ref30","doi-asserted-by":"crossref","first-page":"e1002187","DOI":"10.1371\/journal.ppat.1002187","article-title":"Influenza virus ribonucleoprotein complexes gain preferential access to cellular export machinery through chromatin targeting","volume":"7","author":"GP Chase","year":"2011","journal-title":"PLoS Pathog"},{"key":"ref31","doi-asserted-by":"crossref","first-page":"2785","DOI":"10.1002\/jcc.21256","article-title":"AutoDock4 and AutoDockTools4: Automated docking with selective receptor flexibility","volume":"30","author":"GM Morris","year":"2009","journal-title":"J Comput Chem"},{"key":"ref32","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1186\/1471-2121-9-22","article-title":"Application of bioinformatics-coupled experimental analysis reveals a new transport-competent nuclear localization signal in the nucleoprotein of influenza A virus strain","volume":"9","author":"KM Ketha","year":"2008","journal-title":"BMC Cell Biol"},{"key":"ref33","doi-asserted-by":"crossref","first-page":"776","DOI":"10.1016\/j.biochi.2011.11.009","article-title":"Oligomerization paths of the nucleoprotein of influenza A virus","volume":"94","author":"B Tarus","year":"2012","journal-title":"Biochimie"},{"key":"ref34","doi-asserted-by":"crossref","first-page":"3638","DOI":"10.1096\/fj.08-112110","article-title":"Structure of the influenza virus A H5N1 nucleoprotein: implications for RNA binding, oligomerization, and vaccine design","volume":"22","author":"AK Ng","year":"2008","journal-title":"FASEB J"},{"key":"ref35","doi-asserted-by":"crossref","first-page":"795","DOI":"10.1128\/JVI.10.4.795-800.1972","article-title":"Structure of the ribonucleoprotein of influenza virus","volume":"10","author":"RW Compans","year":"1972","journal-title":"J Virol"},{"key":"ref36","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1128\/JVI.74.1.156-163.2000","article-title":"Ultrastructural and functional analyses of recombinant influenza virus ribonucleoproteins suggest dimerization of nucleoprotein during virus amplification","volume":"74","author":"J Ortega","year":"2000","journal-title":"J Virol"},{"key":"ref37","doi-asserted-by":"crossref","first-page":"7337","DOI":"10.1128\/JVI.02474-09","article-title":"Functional analysis of the influenza virus H5N1 nucleoprotein tail loop reveals amino acids that are crucial for oligomerization and ribonucleoprotein activities","volume":"84","author":"WH Chan","year":"2010","journal-title":"J Virol"},{"key":"ref38","doi-asserted-by":"crossref","first-page":"D541","DOI":"10.1093\/nar\/gkr1130","article-title":"PoSSuM: a database of similar protein-ligand binding and putative pockets","volume":"40","author":"J Ito","year":"2012","journal-title":"Nucleic Acids Res"},{"key":"ref39","doi-asserted-by":"crossref","first-page":"W214","DOI":"10.1093\/nar\/gks435","article-title":"ProBiS-2012: web server and web services for detection of structurally similar binding sites in proteins","volume":"40","author":"J Konc","year":"2012","journal-title":"Nucleic Acids Res"},{"key":"ref40","doi-asserted-by":"crossref","first-page":"914","DOI":"10.1038\/nature07745","article-title":"The cap-snatching endonuclease of influenza virus polymerase resides in the PA subunit","volume":"458","author":"A Dias","year":"2009","journal-title":"Nature"},{"key":"ref41","doi-asserted-by":"crossref","first-page":"909","DOI":"10.1038\/nature07720","article-title":"Crystal structure of an avian influenza polymerase PA(N) reveals an endonuclease active site","volume":"458","author":"P Yuan","year":"2009","journal-title":"Nature"},{"key":"ref42","doi-asserted-by":"crossref","first-page":"e1002830","DOI":"10.1371\/journal.ppat.1002830","article-title":"Structural and biochemical basis for development of influenza virus inhibitors targeting the PA endonuclease","volume":"8","author":"RM DuBois","year":"2012","journal-title":"PLoS Pathog"},{"key":"ref43","doi-asserted-by":"crossref","first-page":"e1003275","DOI":"10.1371\/journal.ppat.1003275","article-title":"Monomeric nucleoprotein of influenza A virus","volume":"9","author":"S Chenavas","year":"2013","journal-title":"PLoS Pathog"},{"key":"ref44","doi-asserted-by":"crossref","first-page":"4153","DOI":"10.1128\/JVI.02642-08","article-title":"Mutational analysis of conserved amino acids in the influenza A virus nucleoprotein","volume":"83","author":"Z Li","year":"2009","journal-title":"J Virol"},{"key":"ref45","doi-asserted-by":"crossref","first-page":"e1002993","DOI":"10.1371\/journal.ppat.1002993","article-title":"Mapping the phosphoproteome of influenza A and B viruses by mass spectrometry","volume":"8","author":"EC Hutchinson","year":"2012","journal-title":"PLoS Pathog"},{"key":"ref46","doi-asserted-by":"crossref","first-page":"1303","DOI":"10.1073\/pnas.1217203110","article-title":"Nuclear export inhibition through covalent conjugation and hydrolysis of Leptomycin B by CRM1","volume":"110","author":"Q Sun","year":"2013","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ref47","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1006\/viro.1996.0454","article-title":"Intracellular oligomerization of influenza virus nucleoprotein","volume":"223","author":"EN Prokudina-Kantorovich","year":"1996","journal-title":"Virology"},{"key":"ref48","doi-asserted-by":"crossref","first-page":"190","DOI":"10.1006\/viro.1999.9818","article-title":"Oligomerization of the influenza virus nucleoprotein: identification of positive and negative sequence elements","volume":"260","author":"D Elton","year":"1999","journal-title":"Virology"},{"key":"ref49","doi-asserted-by":"crossref","first-page":"e83533","DOI":"10.1371\/journal.pone.0083533","article-title":"Identification of distant drug off-targets by direct superposition of binding pocket surfaces","volume":"8","author":"M Schumann","year":"2013","journal-title":"PLoS One"},{"key":"ref50","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1128\/MMBR.56.1.152-179.1992","article-title":"Evolution and ecology of influenza A viruses","volume":"56","author":"RG Webster","year":"1992","journal-title":"Microbiol Rev"},{"key":"ref51","doi-asserted-by":"crossref","first-page":"977","DOI":"10.1128\/AAC.46.4.977-981.2002","article-title":"In vitro and in vivo activities of anti-influenza virus compound T-705","volume":"46","author":"Y Furuta","year":"2002","journal-title":"Antimicrob Agents Chemother"},{"key":"ref52","doi-asserted-by":"crossref","first-page":"863","DOI":"10.1517\/17460441.2012.714363","article-title":"The influence of lipophilicity in drug discovery and design","volume":"7","author":"JA Arnott","year":"2012","journal-title":"Expert Opin Drug Discov"},{"key":"ref53","doi-asserted-by":"crossref","first-page":"596","DOI":"10.1128\/JVI.02005-07","article-title":"The influenza virus resource at the National Center for Biotechnology Information","volume":"82","author":"Y Bao","year":"2008","journal-title":"J Virol"},{"key":"ref54","doi-asserted-by":"crossref","first-page":"3059","DOI":"10.1093\/nar\/gkf436","article-title":"MAFFT: a novel method for rapid multiple sequence alignment based on fast Fourier transform","volume":"30","author":"K Katoh","year":"2002","journal-title":"Nucleic Acids Res"},{"key":"ref55","unstructured":"Molecular Operating Environment (MOE), 2013.08; Chemical Computing Group Inc., 1010 Sherbooke St. West, Suite #910, Montreal, QC, Canada, H3A 2R7, 2014."}],"container-title":["PLOS Pathogens"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/dx.plos.org\/10.1371\/journal.ppat.1005062","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,9,6]],"date-time":"2020-09-06T16:50:29Z","timestamp":1599411029000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.ppat.1005062"}},"subtitle":[],"editor":[{"given":"Paul G.","family":"Thomas","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2015,7,29]]},"references-count":55,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2015,7,29]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.ppat.1005062","relation":{},"ISSN":["1553-7374"],"issn-type":[{"value":"1553-7374","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,7,29]]}}}