{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,5]],"date-time":"2026-06-05T10:49:12Z","timestamp":1780656552939,"version":"3.54.1"},"publisher-location":"Singapore","reference-count":172,"publisher":"Springer Singapore","isbn-type":[{"value":"9789811602665","type":"print"},{"value":"9789811602672","type":"electronic"}],"license":[{"start":{"date-parts":[[2021,1,1]],"date-time":"2021-01-01T00:00:00Z","timestamp":1609459200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.springer.com\/tdm"},{"start":{"date-parts":[[2021,1,1]],"date-time":"2021-01-01T00:00:00Z","timestamp":1609459200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.springer.com\/tdm"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021]]},"DOI":"10.1007\/978-981-16-0267-2_8","type":"book-chapter","created":{"date-parts":[[2021,7,13]],"date-time":"2021-07-13T20:02:36Z","timestamp":1626206556000},"page":"195-218","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Anti-Influenza Drug Discovery and Development: Targeting the Virus and Its Host by All Possible Means"],"prefix":"10.1007","author":[{"given":"Olivier","family":"Terrier","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anny","family":"Slama-Schwok","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,7,14]]},"reference":[{"key":"8_CR1","doi-asserted-by":"crossref","unstructured":"Iuliano AD, Roguski KM, Chang HH et al (2018) Estimates of global seasonal influenza-associated respiratory mortality: a modelling study. Lancet 391:1285\u20131300","DOI":"10.1016\/S0140-6736(17)33293-2"},{"key":"8_CR2","unstructured":"World Health Organization (2018) Influenza (seasonal). http\/\/www\/cho.int\/fact-sheets\/details\/influenza-(seasonal). Accessed 18 Jul 2020"},{"key":"8_CR3","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1038\/s41572-018-0002-y","volume":"4","author":"F Krammer","year":"2018","unstructured":"Krammer F, Smith GJD, Fouchier RM et al (2018) Influenza. Nat Rev Dis Primers 4:3","journal-title":"Nat Rev Dis Primers"},{"key":"8_CR4","doi-asserted-by":"publisher","first-page":"104780","DOI":"10.1016\/j.antiviral.2020.104780","volume":"178","author":"PH Jalily","year":"2020","unstructured":"Jalily PH, Duncan MC, Fedida D et al (2020) Put a cork in it: plugging the M2 viral ion channel to sink influenza. Antiviral Res 178:104780","journal-title":"Antiviral Res"},{"key":"8_CR5","doi-asserted-by":"publisher","first-page":"505","DOI":"10.1126\/science.1191714","volume":"330","author":"F Hu","year":"2010","unstructured":"Hu F, Luo W, Hong M (2010) Mechanisms of proton conduction and gating in influenza M2 proton channels from solid-state NMR. Science 330:505\u2013508","journal-title":"Science"},{"key":"8_CR6","doi-asserted-by":"publisher","first-page":"8592","DOI":"10.1074\/jbc.275.12.8592","volume":"275","author":"JA Mould","year":"2000","unstructured":"Mould JA, Li HC, Dudlak CS et al (2000) Mechanism for proton conduction of the M(2) ion channel of influenza A virus. J Biol Chem 275:8592\u20138599","journal-title":"J Biol Chem"},{"key":"8_CR7","doi-asserted-by":"publisher","first-page":"509","DOI":"10.1126\/science.1191750","volume":"330","author":"M Sharma","year":"2010","unstructured":"Sharma M, Yi M, Dong H et al (2010) Insight into the mechanism of the influenza A proton channel from a structure in a lipid bilayer. Science 330:509\u2013512","journal-title":"Science"},{"key":"8_CR8","doi-asserted-by":"publisher","first-page":"39880","DOI":"10.1074\/jbc.M206582200","volume":"277","author":"Y Tang","year":"2002","unstructured":"Tang Y, Zaitseva F, Lamb RA et al (2002) The gate of the influenza virus M2 proton channel is formed by a single tryptophan residue. J Biol Chem 277:39880\u201339886","journal-title":"J Biol Chem"},{"key":"8_CR9","doi-asserted-by":"publisher","first-page":"15219","DOI":"10.1021\/jacs.8b06741","volume":"140","author":"JL Thomaston","year":"2018","unstructured":"Thomaston JL, Polizzi NF, Konstantinidi A et al (2018) Inhibitors of the M2 proton channel engage and disrupt transmembrane networks of hydrogen-bonded waters. J Am Chem Soc 140:15219\u201315226","journal-title":"J Am Chem Soc"},{"key":"8_CR10","doi-asserted-by":"publisher","first-page":"627","DOI":"10.1021\/acs.biochem.9b00971","volume":"59","author":"JL Thomaston","year":"2020","unstructured":"Thomaston JL, Konstantinidi A, Liu L et al (2020) X-ray crystal structures of the influenza M2 Proton Channel drug-resistant V27A mutant bound to a Spiro-Adamantyl amine inhibitor reveal the mechanism of Adamantane resistance. Biochemistry 59:627\u2013634","journal-title":"Biochemistry"},{"key":"8_CR11","doi-asserted-by":"publisher","first-page":"11481","DOI":"10.1021\/jacs.9b02196","volume":"141","author":"JL Thomaston","year":"2019","unstructured":"Thomaston JL, Wu Y, Polizzi N et al (2019) X-ray crystal structure of the influenza a M2 Proton Channel S31N mutant in two conformational states: an open and shut case. J Am Chem Soc 141:11481\u201311488","journal-title":"J Am Chem Soc"},{"key":"8_CR12","doi-asserted-by":"publisher","first-page":"105124","DOI":"10.1016\/j.ejps.2019.105124","volume":"141","author":"R Musharrafieh","year":"2020","unstructured":"Musharrafieh R, Ma C, Wang J (2020) Discovery of M2 channel blockers targeting the drug-resistant double mutants M2-S31N\/L26I and M2-S31N\/V27A from the influenza A viruses. Eur J Pharm Sci 141:105124","journal-title":"Eur J Pharm Sci"},{"key":"8_CR13","doi-asserted-by":"crossref","unstructured":"Yao Y, Kadam RU, Lee CD et al (2020) An influenza A hemagglutinin small-molecule fusion inhibitor identified by a new high-throughput fluorescence polarization screen. Proc Natl Acad Sci U S A 117:18431\u201318438","DOI":"10.1073\/pnas.2006893117"},{"key":"8_CR14","doi-asserted-by":"publisher","first-page":"689","DOI":"10.1038\/nature08722","volume":"463","author":"SD Cady","year":"2010","unstructured":"Cady SD, Schmidt-Rohr K, Wang J et al (2010) Structure of the amantadine binding site of influenza M2 proton channels in lipid bilayers. Nature 463:689\u2013692","journal-title":"Nature"},{"key":"8_CR15","doi-asserted-by":"publisher","first-page":"591","DOI":"10.1038\/nature06531","volume":"451","author":"JR Schnell","year":"2008","unstructured":"Schnell JR, Chou JJ (2008) Structure and mechanism of the M2 proton channel of influenza a virus. Nature 451:591\u2013595","journal-title":"Nature"},{"key":"8_CR16","doi-asserted-by":"publisher","first-page":"45","DOI":"10.1038\/nature05114","volume":"443","author":"RJ Russell","year":"2006","unstructured":"Russell RJ, Haire LF, Stevens DJ et al (2006) The structure of H5N1 avian influenza neuraminidase suggests new opportunities for drug design. Nature 443:45\u201349","journal-title":"Nature"},{"key":"8_CR17","doi-asserted-by":"publisher","first-page":"1258","DOI":"10.1038\/nature06956","volume":"453","author":"PJ Collins","year":"2008","unstructured":"Collins PJ, Haire LF, Lin YP et al (2008) Crystal structures of oseltamivir-resistant influenza virus neuraminidase mutants. Nature 453:1258\u20131261","journal-title":"Nature"},{"key":"8_CR18","doi-asserted-by":"publisher","first-page":"182","DOI":"10.3389\/fmicb.2020.00182","volume":"11","author":"P Li","year":"2020","unstructured":"Li P, Du R, Wang Y et al (2020) Identification of Chebulinic acid and Chebulagic acid as novel influenza viral neuraminidase inhibitors. Front Microbiol 11:182","journal-title":"Front Microbiol"},{"key":"8_CR19","first-page":"191","volume":"112147","author":"W Ai","year":"2020","unstructured":"Ai W, Zhang J, Zalloum WA et al (2020) Discovery of novel \"dual-site\" binding oseltamivir derivatives as potent influenza virus neuraminidase inhibitors. Eur J Med Chem 112147:191","journal-title":"Eur J Med Chem"},{"key":"8_CR20","doi-asserted-by":"crossref","unstructured":"Jia R, Zhang J, Ai W et al (2019) Design, synthesis and biological evaluation of \u201cmulti-site\u201d-binding influenza virus neuraminidase inhibitors. Eur J Med Chem 178:64\u201380","DOI":"10.1016\/j.ejmech.2019.05.076"},{"key":"8_CR21","doi-asserted-by":"publisher","first-page":"6379","DOI":"10.1021\/acs.jmedchem.8b00929","volume":"61","author":"J Zhang","year":"2018","unstructured":"Zhang J, Poongavanam V, Kang D et al (2018b) Optimization of N-substituted Oseltamivir derivatives as potent inhibitors of Group-1 and -2 influenza a neuraminidases, including a drug-resistant variant. J Med Chem 61:6379\u20136397","journal-title":"J Med Chem"},{"key":"8_CR22","doi-asserted-by":"publisher","first-page":"111940","DOI":"10.1016\/j.ejmech.2019.111940","volume":"187","author":"H Ju","year":"2020","unstructured":"Ju H, Xiu S, Ding X et al (2020) Discovery of novel 1,2,3-triazole oseltamivir derivatives as potent influenza neuraminidase inhibitors targeting the 430-cavity. Eur J Med Chem 187:111940","journal-title":"Eur J Med Chem"},{"key":"8_CR23","doi-asserted-by":"publisher","first-page":"e0119115","DOI":"10.1371\/journal.pone.0119115","volume":"10","author":"G Dong","year":"2015","unstructured":"Dong G, Peng C, Luo J et al (2015) Adamantane-resistant influenza a viruses in the world (1902-2013): frequency and distribution of M2 gene mutations. PLoS One 10:e0119115","journal-title":"PLoS One"},{"key":"8_CR24","doi-asserted-by":"publisher","first-page":"206","DOI":"10.1073\/pnas.1617020114","volume":"114","author":"RU Kadam","year":"2017","unstructured":"Kadam RU, Wilson IA (2017) Structural basis of influenza virus fusion inhibition by the antiviral drug Arbidol. Proc Natl Acad Sci U S A 114:206\u2013214","journal-title":"Proc Natl Acad Sci U S A"},{"key":"8_CR25","doi-asserted-by":"publisher","first-page":"393","DOI":"10.1016\/j.biopha.2017.04.091","volume":"91","author":"Y Wang","year":"2017","unstructured":"Wang Y, Ding Y, Yang C et al (2017) Inhibition of the infectivity and inflammatory response of influenza virus by Arbidol hydrochloride in vitro and in vivo (mice and ferret). Biomed Pharmacother 91:393\u2013401","journal-title":"Biomed Pharmacother"},{"key":"8_CR26","doi-asserted-by":"publisher","first-page":"3744","DOI":"10.1016\/j.bmcl.2017.06.074","volume":"27","author":"ZVF Wright","year":"2017","unstructured":"Wright ZVF, Wu NC, Kadam RU et al (2017) Structure-based optimization and synthesis of antiviral drug Arbidol analogues with significantly improved affinity to influenza hemagglutinin. Bioorg Med Chem Lett 27:3744\u20133748","journal-title":"Bioorg Med Chem Lett"},{"key":"8_CR27","doi-asserted-by":"crossref","unstructured":"Van Dongen MJP, Kadam RU, Juraszek J et al (2019) A small-molecule fusion inhibitor of influenza virus is orally active in mice. Science 363:eaar6221","DOI":"10.1126\/science.aar6221"},{"key":"8_CR28","doi-asserted-by":"crossref","unstructured":"Kim JI, Lee S, Lee GY et al (2019) Novel small molecule targeting the hemagglutinin stalk of influenza viruses. J Virol 93:e00878-19","DOI":"10.1128\/JVI.00878-19"},{"key":"8_CR29","doi-asserted-by":"crossref","unstructured":"Antanasijevic A, Durst MA, Cheng H et al (2020) Structure of avian influenza hemagglutinin in complex with a small molecule entry inhibitor. Life Sci Alliance 3(8):e202000724","DOI":"10.26508\/lsa.202000724"},{"key":"8_CR30","doi-asserted-by":"publisher","first-page":"3120","DOI":"10.1021\/acs.jmedchem.9b01900","volume":"63","author":"IN Gaisina","year":"2020","unstructured":"Gaisina IN, Peet NP, Cheng H et al (2020) Optimization of 4-aminopiperidines as inhibitors of influenza a viral entry that are synergistic with Oseltamivir. J Med Chem 63:3120\u20133130","journal-title":"J Med Chem"},{"key":"8_CR31","doi-asserted-by":"publisher","first-page":"104782","DOI":"10.1016\/j.antiviral.2020.104782","volume":"177","author":"AFA Hussein","year":"2020","unstructured":"Hussein AFA, Cheng H, Tundup S et al (2020) Identification of entry inhibitors with 4-aminopiperidine scaffold targeting group 1 influenza a virus. Antiviral Res 177:104782","journal-title":"Antiviral Res"},{"key":"8_CR32","doi-asserted-by":"publisher","first-page":"330","DOI":"10.1021\/acsinfecdis.6b00194","volume":"3","author":"A Basu","year":"2017","unstructured":"Basu A, Komazin-Meredith G, Mccarthy C et al (2017) Molecular mechanism underlying the action of influenza a virus fusion inhibitor MBX2546. ACS Infect Dis 3:330\u2013335","journal-title":"ACS Infect Dis"},{"key":"8_CR33","doi-asserted-by":"publisher","first-page":"667","DOI":"10.1038\/nbt.3907","volume":"35","author":"EM Strauch","year":"2017","unstructured":"Strauch EM, Bernard SM, La D et al (2017) Computational design of trimeric influenza-neutralizing proteins targeting the hemagglutinin receptor binding site. Nat Biotechnol 35:667\u2013671","journal-title":"Nat Biotechnol"},{"key":"8_CR34","doi-asserted-by":"publisher","first-page":"6924","DOI":"10.1021\/acs.jmedchem.0c00312","volume":"63","author":"G Wu","year":"2020","unstructured":"Wu G, Yu G, Yu Y et al (2020) Chemoreactive-inspired discovery of influenza a virus dual inhibitor to block Hemagglutinin-mediated adsorption and membrane fusion. J Med Chem 63:6924\u20136940","journal-title":"J Med Chem"},{"key":"8_CR35","doi-asserted-by":"publisher","first-page":"84","DOI":"10.1016\/j.antiviral.2014.04.006","volume":"107","author":"J Blaising","year":"2014","unstructured":"Blaising J, Polyak SJ, Pecheur EI (2014) Arbidol as a broad-spectrum antiviral: an update. Antiviral Res 107:84\u201394","journal-title":"Antiviral Res"},{"key":"8_CR36","doi-asserted-by":"publisher","first-page":"1136","DOI":"10.1016\/j.cell.2019.04.011","volume":"177","author":"S Bangaru","year":"2019","unstructured":"Bangaru S, Lang S, Schotsaert M et al (2019) A site of vulnerability on the influenza virus Hemagglutinin head domain trimer interface. Cell 177:1136\u20131152.e1118","journal-title":"Cell"},{"key":"8_CR37","doi-asserted-by":"publisher","first-page":"914","DOI":"10.1038\/nature07745","volume":"458","author":"A Dias","year":"2009","unstructured":"Dias A, Bouvier D, Crepin T et al (2009) The cap-snatching endonuclease of influenza virus polymerase resides in the PA subunit. Nature 458:914\u2013918","journal-title":"Nature"},{"key":"8_CR38","doi-asserted-by":"publisher","first-page":"9438","DOI":"10.1021\/acs.jmedchem.9b00747","volume":"62","author":"CV Credille","year":"2019","unstructured":"Credille CV, Morrison CN, Stokes RW et al (2019) SAR exploration of tight-binding inhibitors of influenza virus PA endonuclease. J Med Chem 62:9438\u20139449","journal-title":"J Med Chem"},{"key":"8_CR39","doi-asserted-by":"publisher","first-page":"6668","DOI":"10.1021\/jm5007275","volume":"57","author":"MP Clark","year":"2014","unstructured":"Clark MP, Ledeboer MW, Davies I et al (2014) Discovery of a novel, first-in-class, orally bioavailable azaindole inhibitor (VX-787) of influenza PB2. J Med Chem 57:6668\u20136678","journal-title":"J Med Chem"},{"key":"8_CR40","doi-asserted-by":"publisher","first-page":"7202","DOI":"10.1021\/acs.jmedchem.8b00557","volume":"61","author":"S Dilly","year":"2018","unstructured":"Dilly S, Fotso Fotso A, Lejal N et al (2018) From naproxen repurposing to naproxen analogues and their antiviral activity against influenza a virus. J Med Chem 61:7202\u20137217","journal-title":"J Med Chem"},{"key":"8_CR41","doi-asserted-by":"publisher","first-page":"9633","DOI":"10.1038\/s41598-018-27890-4","volume":"8","author":"S Omoto","year":"2018","unstructured":"Omoto S, Speranzini V, Hashimoto T et al (2018) Characterization of influenza virus variants induced by treatment with the endonuclease inhibitor baloxavir marboxil. Sci Rep 8:9633","journal-title":"Sci Rep"},{"key":"8_CR42","doi-asserted-by":"publisher","first-page":"3669","DOI":"10.1073\/pnas.1519772113","volume":"113","author":"MS Song","year":"2016","unstructured":"Song MS, Kumar G, Shadrick WR et al (2016) Identification and characterization of influenza variants resistant to a viral endonuclease inhibitor. Proc Natl Acad Sci U S A 113:3669\u20133674","journal-title":"Proc Natl Acad Sci U S A"},{"key":"8_CR43","doi-asserted-by":"crossref","unstructured":"Jones JC, Kumar G, Barman S et al (2018) Identification of the I38T PA substitution as a resistance marker for next-generation influenza virus endonuclease inhibitors. mBio 9:e00430-18. Erratum in: mBio. 2018 Nov 13;9(6)","DOI":"10.1128\/mBio.01868-18"},{"key":"8_CR44","doi-asserted-by":"crossref","unstructured":"Kowalinski E, Zubieta C, Wolkerstorfer A et al (2012) Structural analysis of specific metal chelating inhibitor binding to the endonuclease domain of influenza pH1N1 (2009) polymerase. PLoS Pathog 8:e1002831","DOI":"10.1371\/journal.ppat.1002831"},{"key":"8_CR45","doi-asserted-by":"publisher","first-page":"22880","DOI":"10.1038\/srep22880","volume":"6","author":"S Yuan","year":"2016","unstructured":"Yuan S, Chu H, Singh K et al (2016) A novel small-molecule inhibitor of influenza A virus acts by suppressing PA endonuclease activity of the viral polymerase. Sci Rep 6:22880","journal-title":"Sci Rep"},{"key":"8_CR46","doi-asserted-by":"publisher","first-page":"31500","DOI":"10.1038\/srep31500","volume":"6","author":"M Carcelli","year":"2016","unstructured":"Carcelli M, Rogolino D, Gatti A et al (2016) N-acylhydrazone inhibitors of influenza virus PA endonuclease with versatile metal binding modes. Sci Rep 6:31500","journal-title":"Sci Rep"},{"key":"8_CR47","doi-asserted-by":"publisher","first-page":"2280","DOI":"10.1038\/s41598-018-20772-9","volume":"8","author":"CY Lo","year":"2018","unstructured":"Lo CY, Li OT, Tang WP et al (2018) Identification of influenza polymerase inhibitors targeting C-terminal domain of PA through surface plasmon resonance screening. Sci Rep 8:2280","journal-title":"Sci Rep"},{"key":"8_CR48","doi-asserted-by":"publisher","first-page":"4653","DOI":"10.1038\/s41598-018-22875-9","volume":"8","author":"J Zhang","year":"2018","unstructured":"Zhang J, Hu Y, Foley C et al (2018a) Exploring Ugi-Azide four-component reaction products for broad-Spectrum influenza antivirals with a high genetic barrier to drug resistance. Sci Rep 8:4653","journal-title":"Sci Rep"},{"key":"8_CR49","doi-asserted-by":"publisher","first-page":"743","DOI":"10.1016\/j.ejmech.2018.08.032","volume":"157","author":"I D\u2019agostino","year":"2018","unstructured":"D\u2019agostino I, Giacchello I, Nannetti G et al (2018) Synthesis and biological evaluation of a library of hybrid derivatives as inhibitors of influenza virus PA-PB1 interaction. Eur J Med Chem 157:743\u2013758","journal-title":"Eur J Med Chem"},{"key":"8_CR50","doi-asserted-by":"publisher","first-page":"128","DOI":"10.1016\/j.ejmech.2017.06.015","volume":"138","author":"J Desantis","year":"2017","unstructured":"Desantis J, Nannetti G, Massari S et al (2017) Exploring the cycloheptathiophene-3-carboxamide scaffold to disrupt the interactions of the influenza polymerase subunits and obtain potent anti-influenza activity. Eur J Med Chem 138:128\u2013139","journal-title":"Eur J Med Chem"},{"key":"8_CR51","doi-asserted-by":"publisher","first-page":"55","DOI":"10.1016\/j.antiviral.2019.03.003","volume":"165","author":"G Nannetti","year":"2019","unstructured":"Nannetti G, Massari S, Mercorelli B et al (2019) Potent and broad-spectrum cycloheptathiophene-3-carboxamide compounds that target the PA-PB1 interaction of influenza virus RNA polymerase and possess a high barrier to drug resistance. Antiviral Res 165:55\u201364","journal-title":"Antiviral Res"},{"key":"8_CR52","doi-asserted-by":"publisher","first-page":"74","DOI":"10.1021\/acschembio.9b00552","volume":"15","author":"J Zhang","year":"2020","unstructured":"Zhang J, Hu Y, Wu N et al (2020) Discovery of influenza polymerase PA-PB1 interaction inhibitors using an in vitro Split-luciferase complementation-based assay. ACS Chem Biol 15:74\u201382","journal-title":"ACS Chem Biol"},{"key":"8_CR53","doi-asserted-by":"crossref","unstructured":"Yoon JJ, Toots M, Lee S et al (2018) Orally efficacious broad-Spectrum Ribonucleoside analog inhibitor of influenza and respiratory syncytial viruses. Antimicrob Agents Chemother 62:e00766-18.\u00a0","DOI":"10.1128\/AAC.00766-18"},{"key":"8_CR54","doi-asserted-by":"crossref","unstructured":"Sheahan TP, Sims AC, Zhou S et al (2020) An orally bioavailable broad-spectrum antiviral inhibits SARS-CoV-2 in human airway epithelial cell cultures and multiple coronaviruses in mice. Sci Transl Med 12:eabb5883","DOI":"10.1126\/scitranslmed.abb5883"},{"key":"8_CR55","doi-asserted-by":"publisher","first-page":"16","DOI":"10.1016\/j.trsl.2019.12.002","volume":"218","author":"M Toots","year":"2020","unstructured":"Toots M, Yoon JJ, Hart M et al (2020) Quantitative efficacy paradigms of the influenza clinical drug candidate EIDD-2801 in the ferret model. Transl Res 218:16\u201328","journal-title":"Transl Res"},{"key":"8_CR56","doi-asserted-by":"publisher","first-page":"1569","DOI":"10.1128\/AAC.04623-14","volume":"59","author":"RA Byrn","year":"2015","unstructured":"Byrn RA, Jones SM, Bennett HB et al (2015) Preclinical activity of VX-787, a first-in-class, orally bioavailable inhibitor of the influenza virus polymerase PB2 subunit. Antimicrob Agents Chemother 59:1569\u20131582","journal-title":"Antimicrob Agents Chemother"},{"key":"8_CR57","doi-asserted-by":"publisher","first-page":"9680","DOI":"10.1021\/acs.jmedchem.9b01091","volume":"62","author":"DC Mcgowan","year":"2019","unstructured":"Mcgowan DC, Balemans W, Embrechts W et al (2019) Design, synthesis, and biological evaluation of novel Indoles targeting the influenza PB2 cap binding region. J Med Chem 62:9680\u20139690","journal-title":"J Med Chem"},{"key":"8_CR58","doi-asserted-by":"publisher","first-page":"4110","DOI":"10.1021\/acs.molpharmaceut.8b00531","volume":"15","author":"T Liu","year":"2018","unstructured":"Liu T, Liu M, Chen F et al (2018) A small-molecule compound has anti-influenza a virus activity by acting as a ''PB2 inhibitor. Mol Pharm 15:4110\u20134120","journal-title":"Mol Pharm"},{"key":"8_CR59","doi-asserted-by":"publisher","first-page":"8915","DOI":"10.1021\/jm401369y","volume":"56","author":"S Pautus","year":"2013","unstructured":"Pautus S, Sehr P, Lewis J et al (2013) New 7-methylguanine derivatives targeting the influenza polymerase PB2 cap-binding domain. J Med Chem 56:8915\u20138930","journal-title":"J Med Chem"},{"key":"8_CR60","doi-asserted-by":"crossref","unstructured":"Yuan S, Chu H, Ye J et al (2017) Identification of a novel small-molecule compound targeting the influenza A virus polymerase PB1-PB2 interface. Antiviral Res 137:58\u201366","DOI":"10.1016\/j.antiviral.2016.11.005"},{"key":"8_CR61","doi-asserted-by":"publisher","first-page":"600","DOI":"10.1038\/nbt.1638","volume":"28","author":"RY Kao","year":"2010","unstructured":"Kao RY, Yang D, Lau LS et al (2010) Identification of influenza A nucleoprotein as an antiviral target. Nat Biotechnol 28:600\u2013605","journal-title":"Nat Biotechnol"},{"key":"8_CR62","doi-asserted-by":"publisher","first-page":"29684","DOI":"10.1038\/srep29684","volume":"6","author":"B Pang","year":"2016","unstructured":"Pang B, Cheung NN, Zhang W et al (2016) Structural characterization of H1N1 nucleoprotein-Nucleozin binding sites. Sci Rep 6:29684","journal-title":"Sci Rep"},{"key":"8_CR63","doi-asserted-by":"publisher","first-page":"15366","DOI":"10.1073\/pnas.1107906108","volume":"108","author":"SW Gerritz","year":"2011","unstructured":"Gerritz SW, Cianci C, Kim S et al (2011) Inhibition of influenza virus replication via small molecules that induce the formation of higher-order nucleoprotein oligomers. Proc Natl Acad Sci U S A 108:15366\u201315371","journal-title":"Proc Natl Acad Sci U S A"},{"key":"8_CR64","doi-asserted-by":"publisher","first-page":"16515","DOI":"10.1073\/pnas.1113107108","volume":"108","author":"YF Shen","year":"2011","unstructured":"Shen YF, Chen YH, Chu SY et al (2011) E339...R416 salt bridge of nucleoprotein as a feasible target for influenza virus inhibitors. Proc Natl Acad Sci U S A 108:16515\u201316520","journal-title":"Proc Natl Acad Sci U S A"},{"key":"8_CR65","doi-asserted-by":"publisher","first-page":"205","DOI":"10.1021\/acs.jmedchem.9b01244","volume":"63","author":"JL Woodring","year":"2020","unstructured":"Woodring JL, Lu SH, Krasnova L et al (2020) Disrupting the conserved salt bridge in the Trimerization of influenza a nucleoprotein. J Med Chem 63:205\u2013215","journal-title":"J Med Chem"},{"key":"8_CR66","doi-asserted-by":"publisher","first-page":"2231","DOI":"10.1128\/AAC.02335-12","volume":"57","author":"N Lejal","year":"2013","unstructured":"Lejal N, Tarus B, Bouguyon E et al (2013) Structure-based discovery of the novel antiviral properties of naproxen against the nucleoprotein of influenza A virus. Antimicrob Agents Chemother 57:2231\u20132242","journal-title":"Antimicrob Agents Chemother"},{"key":"8_CR67","doi-asserted-by":"publisher","first-page":"1899","DOI":"10.1080\/07391102.2014.979230","volume":"33","author":"B Tarus","year":"2015","unstructured":"Tarus B, Bertrand H, Zedda G et al (2015) Structure-based design of novel naproxen derivatives targeting monomeric nucleoprotein of influenza A virus. J Biomol Struct Dyn 33:1899\u20131912","journal-title":"J Biomol Struct Dyn"},{"key":"8_CR68","doi-asserted-by":"publisher","first-page":"e0173582","DOI":"10.1371\/journal.pone.0173582","volume":"12","author":"JN Makau","year":"2017","unstructured":"Makau JN, Watanabe K, Ishikawa T et al (2017) Identification of small molecule inhibitors for influenza a virus using in silico and in vitro approaches. PLoS One 12:e0173582","journal-title":"PLoS One"},{"key":"8_CR69","doi-asserted-by":"publisher","first-page":"14659","DOI":"10.1074\/jbc.RA118.004012","volume":"293","author":"AB Kleinpeter","year":"2018","unstructured":"Kleinpeter AB, Jureka AS, Falahat SM et al (2018) Structural analyses reveal the mechanism of inhibition of influenza virus NS1 by two antiviral compounds. J Biol Chem 293:14659\u201314668","journal-title":"J Biol Chem"},{"key":"8_CR70","doi-asserted-by":"publisher","first-page":"1113","DOI":"10.1016\/j.bmcl.2019.02.027","volume":"29","author":"S Patnaik","year":"2019","unstructured":"Patnaik S, Basu D, Southall N et al (2019) Identification, design and synthesis of novel pyrazolopyridine influenza virus nonstructural protein 1 antagonists. Bioorg Med Chem Lett 29:1113\u20131119","journal-title":"Bioorg Med Chem Lett"},{"key":"8_CR71","doi-asserted-by":"publisher","first-page":"9096","DOI":"10.1128\/JVI.00995-10","volume":"84","author":"T Crepin","year":"2010","unstructured":"Crepin T, Dias A, Palencia A et al (2010) Mutational and metal binding analysis of the endonuclease domain of the influenza virus polymerase PA subunit. J Virol 84:9096\u20139104","journal-title":"J Virol"},{"key":"8_CR72","doi-asserted-by":"publisher","first-page":"500","DOI":"10.1038\/nsmb.1421","volume":"15","author":"D Guilligay","year":"2008","unstructured":"Guilligay D, Tarendeau F, Resa-Infante P et al (2008) The structural basis for cap binding by influenza virus polymerase subunit PB2. Nat Struct Mol Biol 15:500\u2013506","journal-title":"Nat Struct Mol Biol"},{"key":"8_CR73","doi-asserted-by":"publisher","first-page":"1127","DOI":"10.1038\/nature07225","volume":"454","author":"E Obayashi","year":"2008","unstructured":"Obayashi E, Yoshida H, Kawai F et al (2008) The structural basis for an essential subunit interaction in influenza virus RNA polymerase. Nature 454:1127\u20131131","journal-title":"Nature"},{"key":"8_CR74","doi-asserted-by":"publisher","first-page":"355","DOI":"10.1038\/nature14008","volume":"516","author":"A Pflug","year":"2014","unstructured":"Pflug A, Guilligay D, Reich S et al (2014) Structure of influenza a polymerase bound to the viral RNA promoter. Nature 516:355\u2013360","journal-title":"Nature"},{"key":"8_CR75","doi-asserted-by":"publisher","first-page":"361","DOI":"10.1038\/nature14009","volume":"516","author":"S Reich","year":"2014","unstructured":"Reich S, Guilligay D, Pflug A et al (2014) Structural insight into cap-snatching and RNA synthesis by influenza polymerase. Nature 516:361\u2013366","journal-title":"Nature"},{"key":"8_CR76","doi-asserted-by":"publisher","first-page":"1803","DOI":"10.1038\/emboj.2009.138","volume":"28","author":"K Sugiyama","year":"2009","unstructured":"Sugiyama K, Obayashi E, Kawaguchi A et al (2009) Structural insight into the essential PB1-PB2 subunit contact of the influenza virus RNA polymerase. EMBO J 28:1803\u20131811","journal-title":"EMBO J"},{"key":"8_CR77","doi-asserted-by":"publisher","first-page":"877","DOI":"10.1016\/j.cell.2020.03.061","volume":"181","author":"JM Wandzik","year":"2020","unstructured":"Wandzik JM, Kouba T, Karuppasamy M et al (2020b) A structure-based model for the complete transcription cycle of influenza polymerase. Cell 181:877\u2013893.e821","journal-title":"Cell"},{"key":"8_CR78","doi-asserted-by":"publisher","first-page":"e1000491","DOI":"10.1371\/journal.ppat.1000491","volume":"5","author":"R Coloma","year":"2009","unstructured":"Coloma R, Valpuesta JM, Arranz R et al (2009) The structure of a biologically active influenza virus ribonucleoprotein complex. PLoS Pathog 5:e1000491","journal-title":"PLoS Pathog"},{"key":"8_CR79","doi-asserted-by":"publisher","first-page":"287","DOI":"10.1038\/s41586-019-1530-7","volume":"573","author":"H Fan","year":"2019","unstructured":"Fan H, Walker AP, Carrique L et al (2019) Structures of influenza a virus RNA polymerase offer insight into viral genome replication. Nature 573:287\u2013290","journal-title":"Nature"},{"key":"8_CR80","doi-asserted-by":"crossref","unstructured":"Fodor E, Te Velthuis AJW (2019) Structure and function of the influenza virus transcription and replication machinery. Cold Spring Harb Perspect Med 10:a038398\u00a0","DOI":"10.1101\/cshperspect.a038398"},{"key":"8_CR81","doi-asserted-by":"publisher","first-page":"6466","DOI":"10.1093\/nar\/gkz313","volume":"47","author":"NC Robb","year":"2019","unstructured":"Robb NC, Te Velthuis AJW, Fodor E et al (2019) Real-time analysis of single influenza virus replication complexes reveals large promoter-dependent differences in initiation dynamics. Nucleic Acids Res 47:6466\u20136477","journal-title":"Nucleic Acids Res"},{"key":"8_CR82","doi-asserted-by":"publisher","first-page":"398","DOI":"10.1016\/j.tim.2018.12.013","volume":"27","author":"AP Walker","year":"2019","unstructured":"Walker AP, Fodor E (2019) Interplay between influenza virus and the host RNA polymerase II transcriptional machinery. Trends Microbiol 27:398\u2013407","journal-title":"Trends Microbiol"},{"key":"8_CR83","doi-asserted-by":"publisher","first-page":"3533","DOI":"10.1021\/acs.jmedchem.6b01227","volume":"60","author":"H Ju","year":"2017","unstructured":"Ju H, Zhang J, Huang B et al (2017) Inhibitors of influenza virus polymerase acidic (PA) endonuclease: contemporary developments and perspectives. J Med Chem 60:3533\u20133551","journal-title":"J Med Chem"},{"key":"8_CR84","doi-asserted-by":"publisher","unstructured":"Ju H, Zhan P, Liu X (2019) Designing influenza polymerase acidic endonuclease inhibitors via \u2018privileged scaffold\u2019 re-evolution\/refining strategy. Future Med Chem. https:\/\/doi.org\/10.4155\/fmc-2018-0489.","DOI":"10.4155\/fmc-2018-0489"},{"key":"8_CR85","doi-asserted-by":"publisher","first-page":"345","DOI":"10.1517\/17460441.2015.1019859","volume":"10","author":"A Monod","year":"2015","unstructured":"Monod A, Swale C, Tarus B et al (2015) Learning from structure-based drug design and new antivirals targeting the ribonucleoprotein complex for the treatment of influenza. Expert Opin Drug Discov 10:345\u2013371","journal-title":"Expert Opin Drug Discov"},{"key":"8_CR86","doi-asserted-by":"publisher","first-page":"503","DOI":"10.1016\/j.drudis.2018.01.028","volume":"23","author":"Z Zhou","year":"2018","unstructured":"Zhou Z, Liu T, Zhang J et al (2018) Influenza a virus polymerase: an attractive target for next-generation anti-influenza therapeutics. Drug Discov Today 23:503\u2013518","journal-title":"Drug Discov Today"},{"key":"8_CR87","doi-asserted-by":"publisher","first-page":"7699","DOI":"10.1021\/acs.jmedchem.5b01474","volume":"59","author":"S Massari","year":"2016","unstructured":"Massari S, Goracci L, Desantis J et al (2016) Polymerase acidic protein-basic protein 1 (PA-PB1) protein-protein interaction as a target for next-generation anti-influenza therapeutics. J Med Chem 59:7699\u20137718","journal-title":"J Med Chem"},{"key":"8_CR88","doi-asserted-by":"publisher","first-page":"24727","DOI":"10.1038\/srep24727","volume":"6","author":"C Swale","year":"2016","unstructured":"Swale C, Monod A, Tengo L et al (2016) Structural characterization of recombinant IAV polymerase reveals a stable complex between viral PA-PB1 heterodimer and host RanBP5. Sci Rep 6:24727","journal-title":"Sci Rep"},{"key":"8_CR89","doi-asserted-by":"publisher","first-page":"727","DOI":"10.1038\/s41564-020-0675-3","volume":"5","author":"R Coloma","year":"2020","unstructured":"Coloma R, Arranz R, De La Rosa-Trevin JM et al (2020) Structural insights into influenza A virus ribonucleoproteins reveal a processive helical track as transcription mechanism. Nat Microbiol 5:727\u2013734","journal-title":"Nat Microbiol"},{"key":"8_CR90","doi-asserted-by":"crossref","unstructured":"Wandzik JM, Kouba T, Cusack S (2020a) Structure and function of influenza polymerase. Cold Spring Harb Perspect Med,\u00a0a038372","DOI":"10.1101\/cshperspect.a038372"},{"key":"8_CR91","doi-asserted-by":"publisher","first-page":"1634","DOI":"10.1126\/science.1228172","volume":"338","author":"R Arranz","year":"2012","unstructured":"Arranz R, Coloma R, Chichon FJ et al (2012) The structure of native influenza virion ribonucleoproteins. Science 338:1634\u20131637","journal-title":"Science"},{"key":"8_CR92","doi-asserted-by":"publisher","first-page":"1078","DOI":"10.1038\/nature05379","volume":"444","author":"Q Ye","year":"2006","unstructured":"Ye Q, Krug RM, Tao YJ (2006) The mechanism by which influenza a virus nucleoprotein forms oligomers and binds RNA. Nature 444:1078\u20131082","journal-title":"Nature"},{"key":"8_CR93","doi-asserted-by":"crossref","unstructured":"Chenavas S, Estrozi LF, Slama-Schwok A et al (2013b) Monomeric nucleoprotein of influenza A virus. PLoS Pathog 9:e1003275","DOI":"10.1371\/journal.ppat.1003275"},{"key":"8_CR94","doi-asserted-by":"publisher","first-page":"1537","DOI":"10.2217\/fmb.13.128","volume":"8","author":"S Chenavas","year":"2013","unstructured":"Chenavas S, Crepin T, Delmas B et al (2013a) Influenza virus nucleoprotein: structure, RNA binding, oligomerization and antiviral drug target. Future Microbiol 8:1537\u20131545","journal-title":"Future Microbiol"},{"key":"8_CR95","doi-asserted-by":"publisher","first-page":"776","DOI":"10.1016\/j.biochi.2011.11.009","volume":"94","author":"B Tarus","year":"2012","unstructured":"Tarus B, Bakowiez O, Chenavas S et al (2012) Oligomerization paths of the nucleoprotein of influenza A virus. Biochimie 94:776\u2013785","journal-title":"Biochimie"},{"key":"8_CR96","doi-asserted-by":"publisher","first-page":"1875","DOI":"10.1016\/j.celrep.2019.04.053","volume":"27","author":"W Zheng","year":"2019","unstructured":"Zheng W, Fan W, Zhang S et al (2019) Naproxen exhibits broad anti-influenza virus activity in mice by impeding viral nucleoprotein nuclear export. Cell Rep 27:1875\u20131885.e1875","journal-title":"Cell Rep"},{"key":"8_CR97","doi-asserted-by":"publisher","first-page":"4259","DOI":"10.1021\/acs.biochem.6b00514","volume":"55","author":"J Vidic","year":"2016","unstructured":"Vidic J, Noiray M, Bagchi A et al (2016) Identification of a novel complex between the nucleoprotein and PA(1-27) of influenza a virus polymerase. Biochemistry 55:4259\u20134262","journal-title":"Biochemistry"},{"key":"8_CR98","doi-asserted-by":"publisher","first-page":"6550","DOI":"10.1073\/pnas.1920582117","volume":"117","author":"JH Cho","year":"2020","unstructured":"Cho JH, Zhao B, Shi J et al (2020) Molecular recognition of a host protein by NS1 of pandemic and seasonal influenza A viruses. Proc Natl Acad Sci U S A 117:6550\u20136558","journal-title":"Proc Natl Acad Sci U S A"},{"key":"8_CR99","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1038\/cmi.2015.74","volume":"13","author":"Q Liu","year":"2016","unstructured":"Liu Q, Zhou YH, Yang ZQ (2016) The cytokine storm of severe influenza and development of immunomodulatory therapy. Cell Mol Immunol 13:3\u201310","journal-title":"Cell Mol Immunol"},{"key":"8_CR100","doi-asserted-by":"publisher","first-page":"818","DOI":"10.1038\/nature08760","volume":"463","author":"A Karlas","year":"2010","unstructured":"Karlas A, Machuy N, Shin Y et al (2010) Genome-wide RNAi screen identifies human host factors crucial for influenza virus replication. Nature 463:818\u2013822","journal-title":"Nature"},{"key":"8_CR101","doi-asserted-by":"publisher","first-page":"813","DOI":"10.1038\/nature08699","volume":"463","author":"R K\u00f6nig","year":"2010","unstructured":"K\u00f6nig R, Stertz S, Zhou Y et al (2010) Human host factors required for influenza virus replication. Nature 463:813\u2013817","journal-title":"Nature"},{"key":"8_CR102","doi-asserted-by":"publisher","first-page":"1372","DOI":"10.1096\/fj.11-193466","volume":"26","author":"VA Meliopoulos","year":"2012","unstructured":"Meliopoulos VA, Andersen LE, Birrer KF et al (2012) Host gene targets for novel influenza therapies elucidated by high-throughput RNA interference screens. FASEB J 26:1372\u20131386","journal-title":"FASEB J"},{"key":"8_CR103","doi-asserted-by":"publisher","first-page":"516","DOI":"10.1016\/j.micinf.2011.01.012","volume":"13","author":"S Stertz","year":"2011","unstructured":"Stertz S, Shaw ML (2011) Uncovering the global host cell requirements for influenza virus replication via RNAi screening. Microbes Infect 13:516\u2013525","journal-title":"Microbes Infect"},{"key":"8_CR104","doi-asserted-by":"crossref","unstructured":"Powell JD, Waters KM (2017) Influenza-Omics and the host response: recent advances and future prospects. Pathogens 6:25","DOI":"10.3390\/pathogens6020025"},{"key":"8_CR105","doi-asserted-by":"publisher","first-page":"71","DOI":"10.1016\/j.coviro.2015.08.008","volume":"14","author":"T Watanabe","year":"2015","unstructured":"Watanabe T, Kawaoka Y (2015) Influenza virus-host interactomes as a basis for antiviral drug development. Curr Opin Virol 14:71\u201378","journal-title":"Curr Opin Virol"},{"key":"8_CR106","doi-asserted-by":"publisher","first-page":"1844","DOI":"10.1093\/infdis\/jis622","volume":"206","author":"RB Moss","year":"2012","unstructured":"Moss RB, Hansen C, Sanders RL et al (2012) A phase II study of DAS181, a novel host directed antiviral for the treatment of influenza infection. J Infect Dis 206:1844\u20131851","journal-title":"J Infect Dis"},{"key":"8_CR107","doi-asserted-by":"crossref","unstructured":"Zenilman JM, Fuchs EJ, Hendrix CW et al (2015) Phase 1 clinical trials of DAS181, an inhaled sialidase, in healthy adults. Antiviral Res 123:114\u2013119","DOI":"10.1016\/j.antiviral.2015.09.008"},{"key":"8_CR108","doi-asserted-by":"publisher","first-page":"L270","DOI":"10.1152\/ajplung.00011.2014","volume":"308","author":"B Yeganeh","year":"2015","unstructured":"Yeganeh B, Ghavami S, Kroeker AL et al (2015) Suppression of influenza A virus replication in human lung epithelial cells by noncytotoxic concentrations bafilomycin A1. Am J Physiol Lung Cell Mol Physiol 308:L270\u2013L286","journal-title":"Am J Physiol Lung Cell Mol Physiol"},{"key":"8_CR109","doi-asserted-by":"publisher","first-page":"344","DOI":"10.1111\/j.1476-5381.2011.01346.x","volume":"164","author":"KH Muller","year":"2011","unstructured":"Muller KH, Kainov DE, El Bakkouri K et al (2011) The proton translocation domain of cellular vacuolar ATPase provides a target for the treatment of influenza A virus infections. Br J Pharmacol 164:344\u2013357","journal-title":"Br J Pharmacol"},{"key":"8_CR110","doi-asserted-by":"publisher","first-page":"371","DOI":"10.1016\/j.antiviral.2013.06.014","volume":"99","author":"HW Chen","year":"2013","unstructured":"Chen HW, Cheng JX, Liu MT et al (2013) Inhibitory and combinatorial effect of diphyllin, a v-ATPase blocker, on influenza viruses. Antiviral Res 99:371\u2013382","journal-title":"Antiviral Res"},{"key":"8_CR111","doi-asserted-by":"publisher","first-page":"6884","DOI":"10.1021\/nn402062f","volume":"7","author":"LM Bimbo","year":"2013","unstructured":"Bimbo LM, Denisova OV, Makila E et al (2013) Inhibition of influenza A virus infection in vitro by saliphenylhalamide-loaded porous silicon nanoparticles. ACS Nano 7:6884\u20136893","journal-title":"ACS Nano"},{"key":"8_CR112","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1016\/j.antiviral.2011.07.014","volume":"92","author":"OP Zhirnov","year":"2011","unstructured":"Zhirnov OP, Klenk HD, Wright PF (2011) Aprotinin and similar protease inhibitors as drugs against influenza. Antiviral Res 92:27\u201336","journal-title":"Antiviral Res"},{"key":"8_CR113","doi-asserted-by":"publisher","first-page":"66","DOI":"10.1016\/j.pupt.2015.07.001","volume":"33","author":"M Yamaya","year":"2015","unstructured":"Yamaya M, Shimotai Y, Hatachi Y et al (2015) The serine protease inhibitor camostat inhibits influenza virus replication and cytokine production in primary cultures of human tracheal epithelial cells. Pulm Pharmacol Ther 33:66\u201374","journal-title":"Pulm Pharmacol Ther"},{"key":"8_CR114","doi-asserted-by":"publisher","first-page":"e1001329","DOI":"10.1371\/journal.ppat.1001329","volume":"7","author":"E De Vries","year":"2011","unstructured":"De Vries E, Tscherne DM, Wienholts MJ et al (2011) Dissection of the influenza A virus endocytic routes reveals macropinocytosis as an alternative entry pathway. PLoS Pathog 7:e1001329","journal-title":"PLoS Pathog"},{"key":"8_CR115","doi-asserted-by":"publisher","first-page":"196","DOI":"10.1111\/j.1462-5822.2006.00781.x","volume":"9","author":"S Harada","year":"2007","unstructured":"Harada S, Yokomizo K, Monde K et al (2007) A broad antiviral neutral glycolipid, fattiviracin FV-8, is a membrane fluidity modulator. Cell Microbiol 9:196\u2013203","journal-title":"Cell Microbiol"},{"key":"8_CR116","doi-asserted-by":"publisher","first-page":"23138","DOI":"10.1038\/srep23138","volume":"6","author":"V G\u00f6tz","year":"2016","unstructured":"G\u00f6tz V, Magar L, Dornfeld D et al (2016) Influenza A viruses escape from MxA restriction at the expense of efficient nuclear vRNP import. Sci Rep 6:23138","journal-title":"Sci Rep"},{"key":"8_CR117","doi-asserted-by":"publisher","first-page":"19735","DOI":"10.3390\/molecules201119653","volume":"20","author":"M Zu","year":"2015","unstructured":"Zu M, Li C, Fang J-S et al (2015) Drug discovery of host CLK1 inhibitors for influenza treatment. Molecules 20:19735\u201319747","journal-title":"Molecules"},{"key":"8_CR118","doi-asserted-by":"crossref","unstructured":"Slaine PD, Kleer M, Smith NK et al (2017) Stress granule-inducing eukaryotic translation initiation factor 4A inhibitors block influenza a virus replication. Viruses 9:388","DOI":"10.3390\/v9120388"},{"key":"8_CR119","doi-asserted-by":"publisher","first-page":"582","DOI":"10.1128\/AAC.7.5.582","volume":"7","author":"FE Durr","year":"1975","unstructured":"Durr FE, Lindh HF, Forbes M (1975) Efficacy of 1-beta-D-ribofuranosyl-1,2,4-triazole-3-carboxamide against influenza virus infections in mice. Antimicrob Agents Chemother 7:582\u2013586","journal-title":"Antimicrob Agents Chemother"},{"key":"8_CR120","doi-asserted-by":"crossref","unstructured":"Sidwell RW, Bailey KW, Wong MH et al (2005) In vitro and in vivo influenza virus-inhibitory effects of viramidine. Antiviral Res 68:10\u201317","DOI":"10.1016\/j.antiviral.2005.06.003"},{"key":"8_CR121","doi-asserted-by":"publisher","first-page":"10228","DOI":"10.1128\/JVI.01774-14","volume":"88","author":"O Perwitasari","year":"2014","unstructured":"Perwitasari O, Johnson S, Yan X et al (2014) Verdinexor, a novel selective inhibitor of nuclear export, reduces influenza a virus replication in vitro and in vivo. J Virol 88:10228\u201310243","journal-title":"J Virol"},{"key":"8_CR122","doi-asserted-by":"publisher","first-page":"32","DOI":"10.1016\/j.virol.2017.04.001","volume":"507","author":"N Chutiwitoonchai","year":"2017","unstructured":"Chutiwitoonchai N, Mano T, Kakisaka M et al (2017) Inhibition of CRM1-mediated nuclear export of influenza A nucleoprotein and nuclear export protein as a novel target for antiviral drug development. Virology 507:32\u201339","journal-title":"Virology"},{"key":"8_CR123","doi-asserted-by":"crossref","unstructured":"Haasbach E, Reiling SJ, Ehrhardt C et al (2013) The NF-kappaB inhibitor SC75741 protects mice against highly pathogenic avian influenza A virus. Antiviral Res 99:336\u2013344","DOI":"10.1016\/j.antiviral.2013.06.008"},{"key":"8_CR124","doi-asserted-by":"crossref","unstructured":"Pleschka S, Wolff T, Ehrhardt C et al (2001) Influenza virus propagation is impaired by inhibition of the Raf\/MEK\/ERK signalling cascade. Nat Cell Biol 3:301\u2013305","DOI":"10.1038\/35060098"},{"key":"8_CR125","doi-asserted-by":"publisher","first-page":"252","DOI":"10.1016\/j.antiviral.2017.05.001","volume":"143","author":"N Courtin","year":"2017","unstructured":"Courtin N, Fotso AF, Fautrad P et al (2017) Antiviral activity of formyl peptide receptor 2 antagonists against influenza viruses. Antiviral Res 143:252\u2013261","journal-title":"Antiviral Res"},{"key":"8_CR126","doi-asserted-by":"crossref","unstructured":"Schr\u00e4der T, Dudek SE, Schreiber A et al (2018) The clinically approved MEK inhibitor Trametinib efficiently blocks influenza A virus propagation and cytokine expression. Antiviral Res 157:80\u201392","DOI":"10.1016\/j.antiviral.2018.07.006"},{"key":"8_CR127","doi-asserted-by":"publisher","first-page":"103","DOI":"10.1016\/j.antiviral.2017.07.016","volume":"145","author":"Y Hu","year":"2017","unstructured":"Hu Y, Zhang J, Musharrafieh RG et al (2017) Discovery of dapivirine, a nonnucleoside HIV-1 reverse transcriptase inhibitor, as a broad-spectrum antiviral against both influenza A and B viruses. Antiviral Res 145:103\u2013113","journal-title":"Antiviral Res"},{"key":"8_CR128","doi-asserted-by":"publisher","first-page":"29798","DOI":"10.1074\/jbc.M109.029470","volume":"284","author":"JF Rossignol","year":"2009","unstructured":"Rossignol JF, La Frazia S, Chiappa L et al (2009) Thiazolides, a new class of anti-influenza molecules targeting viral hemagglutinin at the post-translational level. J Biol Chem 284:29798\u201329808","journal-title":"J Biol Chem"},{"key":"8_CR129","doi-asserted-by":"crossref","unstructured":"Musiol A, Gran S, Ehrhardt C et al (2013) Annexin A6-balanced late endosomal cholesterol controls influenza A replication and propagation. mBio 4:e00608\u201313","DOI":"10.1128\/mBio.00608-13"},{"key":"8_CR130","doi-asserted-by":"publisher","first-page":"4631","DOI":"10.1038\/s41598-018-22927-0","volume":"8","author":"K Matsui","year":"2018","unstructured":"Matsui K, Ozawa M, Kiso M et al (2018) Stimulation of alpha2-adrenergic receptors impairs influenza virus infection. Sci Rep 8:4631","journal-title":"Sci Rep"},{"key":"8_CR131","doi-asserted-by":"publisher","first-page":"1470","DOI":"10.1128\/AAC.50.4.1470-1479.2006","volume":"50","author":"MP Malakhov","year":"2006","unstructured":"Malakhov MP, Aschenbrenner LM, Smee DF et al (2006) Sialidase fusion protein as a novel broad-spectrum inhibitor of influenza virus infection. Antimicrob Agents Chemother 50:1470\u20131479","journal-title":"Antimicrob Agents Chemother"},{"key":"8_CR132","doi-asserted-by":"crossref","unstructured":"Dubois J, Terrier O, Rosa-Calatrava M (2014) Influenza viruses and mRNA splicing: doing more with less. mBio 5:e00070\u201314","DOI":"10.1128\/mBio.00070-14"},{"key":"8_CR133","doi-asserted-by":"crossref","unstructured":"Dubois J, Traversier A, Julien T et al (2019) The nonstructural NS1 protein of influenza viruses modulates TP53 splicing through host factor CPSF4. J Virol 93:e02168-18","DOI":"10.1128\/JVI.02168-18"},{"key":"8_CR134","doi-asserted-by":"publisher","first-page":"16557","DOI":"10.1073\/pnas.2002828117","volume":"117","author":"A Schreiber","year":"2020","unstructured":"Schreiber A, Boff L, Anhlan D et al (2020) Dissecting the mechanism of signaling-triggered nuclear export of newly synthesized influenza virus ribonucleoprotein complexes. Proc Natl Acad Sci U S A 117:16557\u201316566","journal-title":"Proc Natl Acad Sci U S A"},{"key":"8_CR135","doi-asserted-by":"crossref","unstructured":"Rossignol J-F (2014) Nitazoxanide: a first-in-class broad-spectrum antiviral agent. Antiviral Res 110:94\u2013103","DOI":"10.1016\/j.antiviral.2014.07.014"},{"key":"8_CR136","doi-asserted-by":"publisher","first-page":"142","DOI":"10.1016\/j.antiviral.2017.10.002","volume":"147","author":"D Tilmanis","year":"2017","unstructured":"Tilmanis D, Van Baalen C, Oh DY et al (2017) The susceptibility of circulating human influenza viruses to tizoxanide, the active metabolite of nitazoxanide. Antiviral Res 147:142\u2013148","journal-title":"Antiviral Res"},{"key":"8_CR137","doi-asserted-by":"publisher","first-page":"609","DOI":"10.1016\/S1473-3099(14)70717-0","volume":"14","author":"J Haffizulla","year":"2014","unstructured":"Haffizulla J, Hartman A, Hoppers M et al (2014) Effect of nitazoxanide in adults and adolescents with acute uncomplicated influenza: a double-blind, randomised, placebo-controlled, phase 2b\/3 trial. Lancet Infect Dis 14:609\u2013618","journal-title":"Lancet Infect Dis"},{"key":"8_CR138","doi-asserted-by":"publisher","first-page":"1683","DOI":"10.1111\/j.1462-5822.2007.00902.x","volume":"9","author":"I Mazur","year":"2007","unstructured":"Mazur I, Wurzer WJ, Ehrhardt C et al (2007) Acetylsalicylic acid (ASA) blocks influenza virus propagation via its NF-kappaB-inhibiting activity. Cell Microbiol 9:1683\u20131694","journal-title":"Cell Microbiol"},{"key":"8_CR139","doi-asserted-by":"publisher","first-page":"115","DOI":"10.1007\/s00430-010-0182-x","volume":"200","author":"N Wiesener","year":"2011","unstructured":"Wiesener N, Zimmer C, Jarasch-Althof N et al (2011) Therapy of experimental influenza virus infection with pyrrolidine dithiocarbamate. Med Microbiol Immunol 200:115\u2013126","journal-title":"Med Microbiol Immunol"},{"key":"8_CR140","doi-asserted-by":"publisher","first-page":"1198","DOI":"10.1111\/cmi.12108","volume":"15","author":"C Ehrhardt","year":"2013","unstructured":"Ehrhardt C, R\u00fcckle A, Hrincius ER et al (2013) The NF-\u03baB inhibitor SC75741 efficiently blocks influenza virus propagation and confers a high barrier for development of viral resistance. Cell Microbiol 15:1198\u20131211","journal-title":"Cell Microbiol"},{"key":"8_CR141","doi-asserted-by":"publisher","first-page":"2130","DOI":"10.3389\/fmicb.2017.02130","volume":"8","author":"K Droebner","year":"2017","unstructured":"Droebner K, Haasbach E, Dudek SE et al (2017) Pharmacodynamics, pharmacokinetics, and antiviral activity of BAY 81-8781, a novel NF-kappaB inhibiting anti-influenza drug. Front Microbiol 8:2130","journal-title":"Front Microbiol"},{"key":"8_CR142","doi-asserted-by":"publisher","first-page":"21","DOI":"10.1038\/s41426-018-0023-3","volume":"7","author":"G Scheuch","year":"2018","unstructured":"Scheuch G, Canisius S, Nocker K et al (2018) Targeting intracellular signaling as an antiviral strategy: aerosolized LASAG for the treatment of influenza in hospitalized patients. Emerg Microbes Infect 7:21","journal-title":"Emerg Microbes Infect"},{"key":"8_CR143","doi-asserted-by":"publisher","first-page":"525","DOI":"10.1515\/hsz-2011-0270","volume":"393","author":"W Nacken","year":"2012","unstructured":"Nacken W, Ehrhardt C, Ludwig S (2012) Small molecule inhibitors of the c-Jun N-terminal kinase (JNK) possess antiviral activity against highly pathogenic avian and human pandemic influenza A viruses. Biol Chem 393:525\u2013534","journal-title":"Biol Chem"},{"key":"8_CR144","doi-asserted-by":"publisher","first-page":"311","DOI":"10.1016\/j.bbrc.2016.06.111","volume":"477","author":"MS Choi","year":"2016","unstructured":"Choi MS, Heo J, Yi CM et al (2016) A novel p38 mitogen activated protein kinase (MAPK) specific inhibitor suppresses respiratory syncytial virus and influenza A virus replication by inhibiting virus-induced p38 MAPK activation. Biochem Biophys Res Commun 477:311\u2013316","journal-title":"Biochem Biophys Res Commun"},{"key":"8_CR145","doi-asserted-by":"publisher","first-page":"417","DOI":"10.1016\/j.antiviral.2013.06.018","volume":"99","author":"DS Fedson","year":"2013","unstructured":"Fedson DS (2013) Treating influenza with statins and other immunomodulatory agents. Antiviral Res 99:417\u2013435","journal-title":"Antiviral Res"},{"key":"8_CR146","doi-asserted-by":"publisher","DOI":"10.1155\/2014\/872370","volume":"2014","author":"P Mehrbod","year":"2014","unstructured":"Mehrbod P, Omar AR, Hair-Bejo M et al (2014) Mechanisms of action and efficacy of statins against influenza. Biomed Res Int 2014:872370","journal-title":"Biomed Res Int"},{"key":"8_CR147","doi-asserted-by":"publisher","first-page":"R301","DOI":"10.1186\/cc13171","volume":"17","author":"X Shi","year":"2013","unstructured":"Shi X, Zhou W, Huang H et al (2013) Inhibition of the inflammatory cytokine tumor necrosis factor-alpha with etanercept provides protection against lethal H1N1 influenza infection in mice. Crit Care 17:R301","journal-title":"Crit Care"},{"key":"8_CR148","doi-asserted-by":"publisher","first-page":"2672","DOI":"10.1128\/JVI.03529-14","volume":"89","author":"S Ye","year":"2015","unstructured":"Ye S, Lowther S, Stambas J (2015) Inhibition of reactive oxygen species production ameliorates inflammation induced by influenza a viruses via upregulation of SOCS1 and SOCS3. J Virol 89:2672\u20132683","journal-title":"J Virol"},{"key":"8_CR149","doi-asserted-by":"publisher","first-page":"20983","DOI":"10.1038\/srep20983","volume":"6","author":"LC Oostwoud","year":"2016","unstructured":"Oostwoud LC, Gunasinghe P, Seow HJ et al (2016) Apocynin and ebselen reduce influenza A virus-induced lung inflammation in cigarette smoke-exposed mice. Sci Rep 6:20983","journal-title":"Sci Rep"},{"key":"8_CR150","doi-asserted-by":"publisher","first-page":"1946","DOI":"10.3389\/fimmu.2018.01946","volume":"9","author":"S Davidson","year":"2018","unstructured":"Davidson S (2018) Treating influenza infection, from now and into the future. Front Immunol 9:1946","journal-title":"Front Immunol"},{"key":"8_CR151","doi-asserted-by":"publisher","first-page":"e11610","DOI":"10.1371\/journal.pone.0011610","volume":"5","author":"MA Carey","year":"2010","unstructured":"Carey MA, Bradbury JA, Rebolloso YD et al (2010) Pharmacologic inhibition of COX-1 and COX-2 in influenza A viral infection in mice. PLoS One 5:e11610","journal-title":"PLoS One"},{"key":"8_CR152","doi-asserted-by":"publisher","first-page":"8091","DOI":"10.1073\/pnas.0711942105","volume":"105","author":"B-J Zheng","year":"2008","unstructured":"Zheng B-J, Chan K-W, Lin Y-P et al (2008) Delayed antiviral plus immunomodulator treatment still reduces mortality in mice infected by high inoculum of influenza a\/H5N1 virus. Proc Natl Acad Sci U S A 105:8091\u20138096","journal-title":"Proc Natl Acad Sci U S A"},{"key":"8_CR153","doi-asserted-by":"publisher","first-page":"1099","DOI":"10.15252\/emmm.201606413","volume":"8","author":"S Davidson","year":"2016","unstructured":"Davidson S, Mccabe TM, Crotta S et al (2016) IFN\u03bb is a potent anti-influenza therapeutic without the inflammatory side effects of IFN\u03b1 treatment. EMBO Mol Med 8:1099\u20131112","journal-title":"EMBO Mol Med"},{"key":"8_CR154","doi-asserted-by":"publisher","first-page":"202","DOI":"10.1165\/rcmb.2016-0373OC","volume":"56","author":"S Kim","year":"2017","unstructured":"Kim S, Kim M-J, Kim C-H et al (2017) The superiority of IFN-\u03bb as a therapeutic candidate to control acute influenza viral lung infection. Am J Respir Cell Mol Biol 56:202\u2013212","journal-title":"Am J Respir Cell Mol Biol"},{"key":"8_CR155","doi-asserted-by":"publisher","first-page":"531","DOI":"10.3389\/fimmu.2019.00531","volume":"10","author":"A Pizzorno","year":"2019","unstructured":"Pizzorno A, Padey B, Terrier O et al (2019a) Drug repurposing approaches for the treatment of influenza viral infection: reviving old drugs to fight against a long-lived enemy. Front Immunol 10:531","journal-title":"Front Immunol"},{"key":"8_CR156","doi-asserted-by":"publisher","first-page":"60","DOI":"10.3389\/fimmu.2019.00060","volume":"10","author":"A Pizzorno","year":"2019","unstructured":"Pizzorno A, Terrier O, Nicolas De Lamballerie C et al (2019b) Repurposing of drugs as novel influenza inhibitors from clinical gene expression infection signatures. Front Immunol 10:60","journal-title":"Front Immunol"},{"key":"8_CR157","doi-asserted-by":"publisher","first-page":"30931","DOI":"10.1074\/jbc.M403258200","volume":"279","author":"WJ Wurzer","year":"2004","unstructured":"Wurzer WJ, Ehrhardt C, Pleschka S et al (2004) NF-kappaB-dependent induction of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and Fas\/FasL is crucial for efficient influenza virus propagation. J Biol Chem 279:30931\u201330937","journal-title":"J Biol Chem"},{"key":"8_CR158","doi-asserted-by":"publisher","first-page":"77","DOI":"10.1038\/23948","volume":"396","author":"MJ Yin","year":"1998","unstructured":"Yin MJ, Yamamoto Y, Gaynor RB (1998) The anti-inflammatory agents aspirin and salicylate inhibit the activity of I(kappa)B kinase-beta. Nature 396:77\u201380","journal-title":"Nature"},{"key":"8_CR159","doi-asserted-by":"publisher","first-page":"42","DOI":"10.1016\/j.virol.2013.01.017","volume":"439","author":"JA Belser","year":"2013","unstructured":"Belser JA, Szretter KJ, Katz JM et al (2013) Simvastatin and oseltamivir combination therapy does not improve the effectiveness of oseltamivir alone following highly pathogenic avian H5N1 influenza virus infection in mice. Virology 439:42\u201346","journal-title":"Virology"},{"key":"8_CR160","doi-asserted-by":"publisher","first-page":"801","DOI":"10.2217\/fvl.12.71","volume":"7","author":"Y Kumaki","year":"2012","unstructured":"Kumaki Y, Morrey JD, Barnard DL (2012) Effect of statin treatments on highly pathogenic avian influenza H5N1, seasonal and H1N1pdm09 virus infections in BALB\/c mice. Future Virol 7:801\u2013818","journal-title":"Future Virol"},{"key":"8_CR161","doi-asserted-by":"publisher","first-page":"12479","DOI":"10.1073\/pnas.0705289104","volume":"104","author":"R Salomon","year":"2007","unstructured":"Salomon R, Hoffmann E, Webster RG (2007) Inhibition of the cytokine response does not protect against lethal H5N1 influenza infection. Proc Natl Acad Sci U S A 104:12479\u201312481","journal-title":"Proc Natl Acad Sci U S A"},{"key":"8_CR162","doi-asserted-by":"crossref","unstructured":"Enserink M (2005) Infectious disease. Old drugs losing effectiveness against flu; could statins fill gap? Science 309:1976\u20131977","DOI":"10.1126\/science.309.5743.1976a"},{"key":"8_CR163","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1093\/infdis\/jir695","volume":"205","author":"ML Vandermeer","year":"2012","unstructured":"Vandermeer ML, Thomas AR, Kamimoto L et al (2012) Association between use of statins and mortality among patients hospitalized with laboratory-confirmed influenza virus infections: a multistate study. J Infect Dis 205:13\u201319","journal-title":"J Infect Dis"},{"key":"8_CR164","doi-asserted-by":"publisher","first-page":"1069","DOI":"10.1016\/j.chest.2016.11.012","volume":"151","author":"IFN Hung","year":"2017","unstructured":"Hung IFN, To KKW, Chan JFW et al (2017) Efficacy of clarithromycin-naproxen-Oseltamivir combination in the treatment of patients hospitalized for influenza a(H3N2) infection: an open-label randomized, controlled, phase IIb\/III trial. Chest 151:1069\u20131080","journal-title":"Chest"},{"key":"8_CR165","doi-asserted-by":"crossref","unstructured":"Lejal N, Truchet S, Bechor E et al (2018) Turning off NADPH oxidase-2 by impeding p67(phox) activation in infected mouse macrophages reduced viral entry and inflammation. Biochim Biophys Acta 1862:1263\u20131275","DOI":"10.1016\/j.bbagen.2018.03.004"},{"key":"8_CR166","doi-asserted-by":"publisher","first-page":"76","DOI":"10.1016\/j.antiviral.2018.05.005","volume":"155","author":"S Chaudhuri","year":"2018","unstructured":"Chaudhuri S, Symons JA, Deval J (2018) Innovation and trends in the development and approval of antiviral medicines: 1987-2017 and beyond. Antiviral Res 155:76\u201388","journal-title":"Antiviral Res"},{"key":"8_CR167","doi-asserted-by":"crossref","unstructured":"Escuret V, Cornu C, Boutitie F et al (2012) Oseltamivir-zanamivir bitherapy compared to oseltamivir monotherapy in the treatment of pandemic 2009 influenza a(H1N1) virus infections. Antiviral Res 96:130\u2013137","DOI":"10.1016\/j.antiviral.2012.08.002"},{"key":"8_CR168","doi-asserted-by":"crossref","unstructured":"Pizzorno A, Abed Y, Rh\u00e9aume C et al (2014) Oseltamivir-zanamivir combination therapy is not superior to zanamivir monotherapy in mice infected with influenza A(H3N2) and A(H1N1)pdm09 viruses. Antiviral Res 105:54\u201358","DOI":"10.1016\/j.antiviral.2014.02.017"},{"key":"8_CR169","doi-asserted-by":"crossref","unstructured":"Schloer S, Goretzko J, Pleschka S et al (2020) Combinatory treatment with Oseltamivir and Itraconazole targeting both virus and host factors in influenza a virus infection. Viruses 12:703","DOI":"10.3390\/v12070703"},{"key":"8_CR170","doi-asserted-by":"publisher","unstructured":"Terrier O, Dilly S, Pizzorno A et al (2020) Broad-spectrum antiviral activity of naproxen: from influenza A to SARS-CoV-2 coronavirus. bioRxiv. https:\/\/doi.org\/10.1101\/2020.04.30.069922","DOI":"10.1101\/2020.04.30.069922"},{"key":"8_CR171","doi-asserted-by":"crossref","unstructured":"Pizzorno A, Padey B, Dubois J et al (2020a) In vitro evaluation of antiviral activity of single and combined repurposable drugs against SARS-CoV-2. Antiviral Res:104878","DOI":"10.1016\/j.antiviral.2020.104878"},{"key":"8_CR172","doi-asserted-by":"crossref","unstructured":"Pizzorno A, Padey B, Julien T et al (2020b) Characterization and treatment of SARS-CoV-2 in nasal and bronchial human airway epithelia.\u00a0Cell Rep Med 1:100059","DOI":"10.1016\/j.xcrm.2020.100059"}],"container-title":["Advances in Experimental Medicine and Biology","Antiviral Drug Discovery and Development"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/978-981-16-0267-2_8","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,7,13]],"date-time":"2021-07-13T20:04:29Z","timestamp":1626206669000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/978-981-16-0267-2_8"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021]]},"ISBN":["9789811602665","9789811602672"],"references-count":172,"URL":"https:\/\/doi.org\/10.1007\/978-981-16-0267-2_8","relation":{},"ISSN":["0065-2598","2214-8019"],"issn-type":[{"value":"0065-2598","type":"print"},{"value":"2214-8019","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021]]},"assertion":[{"value":"14 July 2021","order":1,"name":"first_online","label":"First Online","group":{"name":"ChapterHistory","label":"Chapter History"}}]}}