{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T21:16:22Z","timestamp":1792790182218,"version":"4.5.0"},"reference-count":98,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2015,10,20]],"date-time":"2015-10-20T00:00:00Z","timestamp":1445299200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100006435","name":"Central European Institute of Technology","doi-asserted-by":"publisher","award":["CZ.1.05\/1.1.00\/02.0068"],"award-info":[{"award-number":["CZ.1.05\/1.1.00\/02.0068"]}],"id":[{"id":"10.13039\/501100006435","id-type":"DOI","asserted-by":"publisher"}]},{"name":"EXAM","award":["CZ.1.05\/2.1.00\/03.0124"],"award-info":[{"award-number":["CZ.1.05\/2.1.00\/03.0124"]}]},{"DOI":"10.13039\/501100006109","name":"VEGA","doi-asserted-by":"publisher","award":["2\/0146\/15"],"award-info":[{"award-number":["2\/0146\/15"]}],"id":[{"id":"10.13039\/501100006109","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100006109","name":"VEGA","doi-asserted-by":"publisher","award":["2\/0100\/13"],"award-info":[{"award-number":["2\/0100\/13"]}],"id":[{"id":"10.13039\/501100006109","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>The threat of a worldwide influenza pandemic has greatly increased over the past decade with the emergence of highly virulent avian influenza strains. The increased frequency of drug-resistant influenza strains against currently available antiviral drugs requires urgent development of new strategies for antiviral therapy, too. The research in the field of therapeutic peptides began to develop extensively in the second half of the 20th century. Since then, the mechanisms of action for several peptides and their antiviral prospect received large attention due to the global threat posed by viruses. Here, we discussed the therapeutic properties of peptides used in influenza treatment. Peptides with antiviral activity against influenza can be divided into three main groups. First, entry blocker peptides such as a Flupep that interact with influenza hemagglutinin, block its binding to host cells and prevent viral fusion. Second, several peptides display virucidal activity, disrupting viral envelopes, e.g., Melittin. Finally, a third set of peptides interacts with the viral polymerase complex and act as viral replication inhibitors such as PB1 derived peptides. Here, we present a review of the current literature describing the antiviral activity, mechanism and future therapeutic potential of these influenza antiviral peptides.<\/jats:p>","DOI":"10.3390\/v7102883","type":"journal-article","created":{"date-parts":[[2015,10,20]],"date-time":"2015-10-20T16:21:51Z","timestamp":1445358111000},"page":"5428-5442","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":130,"title":["Perspective of Use of Antiviral Peptides against Influenza Virus"],"prefix":"10.3390","volume":"7","author":[{"given":"Sylvie","family":"Skalickova","sequence":"first","affiliation":[{"name":"Department of Chemistry and Biochemistry, Mendel University in Brno, Zemedelska 1, Brno CZ-613 00, Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zbynek","family":"Heger","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Biochemistry, Mendel University in Brno, Zemedelska 1, Brno CZ-613 00, Czech Republic"},{"name":"Central European Institute of Technology, Brno University of Technology, Technicka 3058\/10, Brno CZ-616 00, Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ludmila","family":"Krejcova","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Biochemistry, Mendel University in Brno, Zemedelska 1, Brno CZ-613 00, Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vladimir","family":"Pekarik","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Biochemistry, Mendel University in Brno, Zemedelska 1, Brno CZ-613 00, Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karel","family":"Bastl","sequence":"additional","affiliation":[{"name":"Wool and Knitting Research Institute, Brno, Sujanovo namesti 3, Brno CZ-602 00, Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jozef","family":"Janda","sequence":"additional","affiliation":[{"name":"Laboratory of Tumour Biology, Institute of Animal Physiology and Genetics, Academy of Sciences of the Czech Republic, Libechov CZ-277 21, Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frantisek","family":"Kostolansky","sequence":"additional","affiliation":[{"name":"Institute of Virology, Slovak Academy of Sciences, Dubravska cesta 9, 84505 Bratislava, Slovak Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6386-651X","authenticated-orcid":false,"given":"Eva","family":"Vareckova","sequence":"additional","affiliation":[{"name":"Institute of Virology, Slovak Academy of Sciences, Dubravska cesta 9, 84505 Bratislava, Slovak Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ondrej","family":"Zitka","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Biochemistry, Mendel University in Brno, Zemedelska 1, Brno CZ-613 00, Czech Republic"},{"name":"Central European Institute of Technology, Brno University of Technology, Technicka 3058\/10, Brno CZ-616 00, Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vojtech","family":"Adam","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Biochemistry, Mendel University in Brno, Zemedelska 1, Brno CZ-613 00, Czech Republic"},{"name":"Central European Institute of Technology, Brno University of Technology, Technicka 3058\/10, Brno CZ-616 00, Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rene","family":"Kizek","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Biochemistry, Mendel University in Brno, Zemedelska 1, Brno CZ-613 00, Czech Republic"},{"name":"Central European Institute of Technology, Brno University of Technology, Technicka 3058\/10, Brno CZ-616 00, Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2015,10,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"440","DOI":"10.4161\/viru.1.5.12983","article-title":"Antimicrobial peptides the ancient arm of the human immune system","volume":"1","author":"Wiesner","year":"2010","journal-title":"Virulence"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1045","DOI":"10.1016\/j.drudis.2014.05.019","article-title":"Recombinant probiotics with antimicrobial peptides: A dual strategy to improve immune response in immunocompromised patients","volume":"19","author":"Mandal","year":"2014","journal-title":"Drug Discov. Today"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"454","DOI":"10.1038\/35106587","article-title":"Innate antimicrobial peptide protects the skin from invasive bacterial infection","volume":"414","author":"Nizet","year":"2001","journal-title":"Nature"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1387","DOI":"10.1016\/j.bbamem.2006.03.001","article-title":"Antimicrobial activity of an abiotic host defense peptide mimic","volume":"1758","author":"Tew","year":"2006","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3389\/fmicb.2014.00443","article-title":"Optical and dielectric sensors based on an microbial peptides for microorganism diagnosis","volume":"5","author":"Silva","year":"2014","journal-title":"Front. Microbiol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"951","DOI":"10.1586\/14787210.5.6.951","article-title":"Alternative mechanisms of action of cationic antimicrobial peptides on bacteria","volume":"5","author":"Hale","year":"2007","journal-title":"Expert Rev. Anti Infect. Ther."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1872","DOI":"10.2174\/156802610793176648","article-title":"Strategies for the discovery and advancement of novel cationic antimicrobial peptides","volume":"10","author":"Hadley","year":"2010","journal-title":"Curr. Top. Med. Chem."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1016\/j.drudis.2014.10.003","article-title":"Peptide therapeutics: Current status and future directions","volume":"20","author":"Fosgerau","year":"2015","journal-title":"Drug Discov. Today"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1097\/00001432-198906000-00013","article-title":"Potential of new drugs in the prophylaxis and therapy of influenza A virus-infections","volume":"2","author":"Sim","year":"1989","journal-title":"Curr. Opin. Infect. Dis."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1136","DOI":"10.1016\/S1473-3099(14)70828-X","article-title":"Emerging novel and antimicrobial-resistant respiratory tract infections: New drug development and therapeutic options","volume":"14","author":"Zumla","year":"2014","journal-title":"Lancet Infect. Dis."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1016\/j.antiviral.2011.04.002","article-title":"Molecular strategies to design an escape-proof antiviral therapy","volume":"92","author":"Berkhout","year":"2011","journal-title":"Antivir. Res."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"389","DOI":"10.2174\/1389450033491019","article-title":"Recent strategies in the search for new anti-influenza therapies","volume":"4","author":"Wilson","year":"2003","journal-title":"Curr. Drug Targets"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Air, G.M., and Brouillette, W.J. (2009). Influenza virus antiviral targets. Antiviral Res., 187\u2013207.","DOI":"10.1128\/9781555815493.ch11"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"495","DOI":"10.18388\/abp.2014_1870","article-title":"Antivirals\u2014Current trends in fighting influenza","volume":"61","author":"Krol","year":"2014","journal-title":"Acta Biochim. Pol."},{"key":"ref_15","first-page":"367","article-title":"Noninvasive routes of proteins and peptides drug delivery","volume":"73","author":"Jitendra","year":"2011","journal-title":"Indian J. Pharm. Sci."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1016\/j.drudis.2009.10.009","article-title":"Synthetic therapeutic peptides: Science and market","volume":"15","author":"Vlieghe","year":"2010","journal-title":"Drug Discov. Today"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1155\/2013\/376219","article-title":"Secondary bacterial infections in patients with seasonal influenza A and pandemic H1N1","volume":"2013","author":"Liderot","year":"2013","journal-title":"Biomed. Res. Int."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1016\/j.plipres.2011.12.005","article-title":"Role of lipids in the interaction of antimicrobial peptides with membranes","volume":"51","author":"Teixeira","year":"2012","journal-title":"Prog. Lipid Res."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"5589","DOI":"10.1046\/j.1432-1033.2001.02494.x","article-title":"Amphipathic alpha helical antimicrobial peptides\u2014A systematic study of the effects of structural and physical properties on biological activity","volume":"268","author":"Giangaspero","year":"2001","journal-title":"Eur. J. Biochem."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"7738","DOI":"10.1074\/jbc.M111.303602","article-title":"Roles of hydrophobicity and charge distribution of cationic antimicrobial peptides in peptide-membrane interactions","volume":"287","author":"Yin","year":"2012","journal-title":"J. Biol. Chem."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"S183","DOI":"10.1016\/S1525-0016(16)35489-2","article-title":"The therapeutic potential of secreted antiviral entry inhibitor (SAVE) peptides expressed by transduced MSCs to block HIV infection","volume":"22","author":"Lee","year":"2014","journal-title":"Mol. Ther."},{"key":"ref_22","first-page":"302","article-title":"Dramatic increase of antiviral potency of an HIV peptide fusion inhibitor by targeting to lipid rafts via addition of a cholesterol group","volume":"92","author":"Pessi","year":"2009","journal-title":"Biopolymers"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1111\/j.1348-0421.2007.tb03882.x","article-title":"Tandem repeats of lactoferrin-derived anti-hepatitis C virus peptide enhance antiviral activity in cultured human hepatocytes","volume":"51","author":"Abe","year":"2007","journal-title":"Microbiol. Immunol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"3002","DOI":"10.1007\/s00018-005-5228-7","article-title":"Anti herpes simplex virus activity of lactoferrin\/lactoferricin\u2014An example of antiviral activity of antimicrobial protein\/peptide","volume":"62","author":"Jenssen","year":"2005","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1932","DOI":"10.1128\/JVI.02979-14","article-title":"Characterization of a proteolytically stable d-peptide that suppresses herpes simplex virus 1 infection: Implications for the development of entry-based antiviral therapy","volume":"89","author":"Jaishankar","year":"2015","journal-title":"J. Virol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1527","DOI":"10.4155\/fmc.12.94","article-title":"Therapeutic peptides foreword","volume":"4","author":"Albericio","year":"2012","journal-title":"Future Med. Chem."},{"key":"ref_27","first-page":"81","article-title":"Effect of rabbit sacculus rotundus antimicrobial peptides on serum antibody titers after vaccination with newcastle disease virus vaccine and avian influenza virus vaccine in chickens","volume":"87","author":"She","year":"2008","journal-title":"Poult. Sci."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1055\/s-0031-1283281","article-title":"Influenza drug resistance","volume":"32","author":"Pizzorno","year":"2011","journal-title":"Semin. Respir. Crit. Care Med."},{"key":"ref_29","first-page":"273","article-title":"Transcription and replication of the influenza A virus genome","volume":"44","author":"Mikulasova","year":"2000","journal-title":"Acta Virol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"530","DOI":"10.1038\/nsmb.1779","article-title":"Structures of influenza A proteins and insights into antiviral drug targets","volume":"17","author":"Das","year":"2010","journal-title":"Nat. Struct. Mol. Biol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"20067","DOI":"10.1074\/jbc.M114.569178","article-title":"The nuclear export protein of H5N1 influenza A viruses recruits matrix 1 (M1) protein to the viral ribonucleoprotein to mediate nuclear export","volume":"289","author":"Brunotte","year":"2014","journal-title":"J. Biol. Chem."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"863","DOI":"10.2217\/fvl.14.66","article-title":"The RNA-dependent RNA polymerase of the influenza A virus","volume":"9","author":"Stubbs","year":"2014","journal-title":"Future Virol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1016\/j.virol.2005.09.049","article-title":"Influenza virus assembly and budding in raft-derived microdomains: A quantitative analysis of the surface distribution of HA, NA and M2 proteins","volume":"342","author":"Leser","year":"2005","journal-title":"Virology"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"14610","DOI":"10.1073\/pnas.2235620100","article-title":"Influenza virus hemagglutinin concentrates in lipid raft microdomains for efficient viral fusion","volume":"100","author":"Takeda","year":"2003","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_35","first-page":"495","article-title":"Influenza virus assembly and budding in lipid rafts","volume":"42","author":"Ma","year":"2015","journal-title":"Prog. Biochem. Biophys."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"902","DOI":"10.1016\/j.cell.2010.08.029","article-title":"Influenza virus M2 protein mediates ESCRT-independent membrane scission","volume":"142","author":"Rossman","year":"2010","journal-title":"Cell"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"11960","DOI":"10.1128\/JVI.01678-06","article-title":"Inhibition of influenza virus infection by a novel antiviral peptide that targets viral attachment to cells","volume":"80","author":"Jones","year":"2006","journal-title":"J. Virol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1810","DOI":"10.1128\/AAC.01428-10","article-title":"Identification of the minimal active sequence of an anti-influenza virus peptide","volume":"55","author":"Jones","year":"2011","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/1743-422X-6-74","article-title":"Identification and characterisation of a novel anti-viral peptide against avian influenza virus H9N2","volume":"6","author":"Rajik","year":"2009","journal-title":"Virol. J."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"980","DOI":"10.1099\/vir.0.038679-0","article-title":"A novel family of peptides with potent activity against influenza A viruses","volume":"93","author":"Nicol","year":"2012","journal-title":"J. Gen. Virol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"4441","DOI":"10.1021\/jm1002183","article-title":"Sialic acid-mimic peptides as hemagglutinin inhibitors for anti-influenza therapy","volume":"53","author":"Matsubara","year":"2010","journal-title":"J. Med. Chem."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/1472-6750-13-51","article-title":"Self-assembled peptide amphiphiles function as multivalent binder with increased hemagglutinin affinity","volume":"13","author":"Huttl","year":"2013","journal-title":"BMC Biotechnol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"3942","DOI":"10.1111\/j.1742-4658.2011.08302.x","article-title":"Antimicrobial peptides important in innate immunity","volume":"278","author":"Cederlund","year":"2011","journal-title":"FEBS J."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1016\/j.antiviral.2014.01.015","article-title":"A new class of synthetic anti-lipopolysaccharide peptides inhibits influenza A virus replication by blocking cellular attachment","volume":"104","author":"Hoffmann","year":"2014","journal-title":"Antivir. Res."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"7878","DOI":"10.4049\/jimmunol.0804049","article-title":"Interactions of \u03b1-, \u03b2-, and \u03b8-defensins with influenza A virus and surfactant protein D","volume":"182","author":"Doss","year":"2009","journal-title":"J. Immunol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1179\/2047773212Y.0000000004","article-title":"Bovine lactoferrin-derived peptides as novel broad-spectrum inhibitors of influenza virus","volume":"106","author":"Ammendolia","year":"2012","journal-title":"Pathog. Glob. Health"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1518","DOI":"10.1016\/j.peptides.2011.05.015","article-title":"Virucidal activity of a scorpion venom peptide variant mucroporin-M1 against measles, SARS-CoV and influenza H5N1 viruses","volume":"32","author":"Li","year":"2011","journal-title":"Peptides"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1099\/vir.0.045013-0","article-title":"The human cathelicidin LL-37 inhibits influenza A viruses through a mechanism distinct from that of surfactant protein D or defensins","volume":"94","author":"Tripathi","year":"2013","journal-title":"J. Gen. Virol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"7801","DOI":"10.1128\/JVI.00724-07","article-title":"Peptide-mediated interference with influenza A virus polymerase","volume":"81","author":"Ghanem","year":"2007","journal-title":"J. Virol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"188","DOI":"10.1016\/j.ymeth.2011.08.007","article-title":"Identification of influenza virus inhibitors which disrupt of viral polymerase protein-protein interactions","volume":"55","author":"Chase","year":"2011","journal-title":"Methods"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"352","DOI":"10.3390\/v5010352","article-title":"Influenza A virus entry inhibitors targeting the hemagglutinin","volume":"5","author":"Yang","year":"2013","journal-title":"Viruses"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1371\/journal.pone.0007517","article-title":"Identification of a PA-binding peptide with inhibitory activity against influenza A and B virus replication","volume":"4","author":"Wunderlich","year":"2009","journal-title":"PLoS ONE"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"4331","DOI":"10.1128\/AAC.00506-08","article-title":"Therapeutic activity of an anti-idiotypic antibody-derived killer peptide against influenza A virus experimental infection","volume":"52","author":"Conti","year":"2008","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"835","DOI":"10.1086\/521027","article-title":"\u03b1-Defensin inhibits influenza virus replication by cell-mediated mechanism(s)","volume":"196","author":"Salvatore","year":"2007","journal-title":"J. Infect. Dis."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"687","DOI":"10.1128\/AAC.41.3.687","article-title":"In vivo anti-influenza virus activity of a zinc finger peptide","volume":"41","author":"Judd","year":"1997","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"8639","DOI":"10.1128\/jvi.70.12.8639-8644.1996","article-title":"Antiviral activity of influenza virus M1 zinc finger peptides","volume":"70","author":"Nasser","year":"1996","journal-title":"J. Virol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1402","DOI":"10.1128\/JVI.01138-08","article-title":"SOCS-1 mimetics protect mice against lethal poxvirus infection: Identification of a novel endogenous antiviral system","volume":"83","author":"Ahmed","year":"2009","journal-title":"J. Virol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1016\/j.ab.2005.01.020","article-title":"Using surface plasmon resonance to directly determine binding affinities of combinatorially selected cyclopeptides and their linear analogs to a streptavidin chip","volume":"340","author":"Chang","year":"2005","journal-title":"Anal. Biochem."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"653","DOI":"10.1002\/bip.20983","article-title":"Conformational constraint in protein ligand design and the inconsistency of binding entropy","volume":"89","author":"Udugamasooriya","year":"2008","journal-title":"Biopolymers"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"4708","DOI":"10.4049\/jimmunol.170.9.4708","article-title":"Retrocyclin, an antiretroviral \u03b8-defensin, is a lectin","volume":"170","author":"Wang","year":"2003","journal-title":"J. Immunol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1189\/jlb.0609382","article-title":"Human defensins and LL-37 in mucosal immunity","volume":"87","author":"Doss","year":"2010","journal-title":"J. Leukoc. Biol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"3817","DOI":"10.1128\/AAC.00534-10","article-title":"New antiseptic peptides to protect against endotoxin-mediated shock","volume":"54","author":"Gutsmann","year":"2010","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"1654","DOI":"10.1093\/infdis\/jis273","article-title":"A new class of synthetic peptide inhibitors blocks attachment and entry of human pathogenic viruses","volume":"205","author":"Krepstakies","year":"2012","journal-title":"J. Infect. Dis."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"467","DOI":"10.1038\/nrmicro3047","article-title":"Fortifying the barrier: The impact of lipid a remodelling on bacterial pathogenesis","volume":"11","author":"Needham","year":"2013","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"180","DOI":"10.3109\/1040841X.2012.699025","article-title":"Bacterial resistance to cationic antimicrobial peptides","volume":"39","year":"2013","journal-title":"Crit. Rev. Microbiol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"315","DOI":"10.4155\/fmc.12.213","article-title":"Peptides as the next generation of anti-infectives","volume":"5","author":"Mercer","year":"2013","journal-title":"Future Med. Chem."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"659","DOI":"10.1517\/17460440902992888","article-title":"Antimicrobial peptides: To membranes and beyond","volume":"4","author":"Marcos","year":"2009","journal-title":"Expert Opin. Drug Discov."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1038\/nrd2897","article-title":"Subcellular targeting strategies for drug design and delivery","volume":"9","author":"Rajendran","year":"2010","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"149","DOI":"10.3389\/fimmu.2012.00149","article-title":"Multiple immune-modulatory functions of cathelicidin host defense peptides","volume":"3","author":"Choi","year":"2012","journal-title":"Front. Immun."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1371\/journal.pone.0025333","article-title":"Antiviral activity and increased host defense against influenza infection elicited by the human cathelicidin LL-37","volume":"6","author":"Barlow","year":"2011","journal-title":"PLoS ONE"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"1966","DOI":"10.1016\/j.peptides.2010.07.028","article-title":"A carpet-based mechanism for direct antimicrobial peptide activity against vaccinia virus membranes","volume":"31","author":"Dean","year":"2010","journal-title":"Peptides"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"2688","DOI":"10.1128\/AAC.47.8.2688-2691.2003","article-title":"Bovine lactoferrin inhibits adenovirus infection by interacting with viral structural polypeptides","volume":"47","author":"Pietrantoni","year":"2003","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"465","DOI":"10.1007\/s10534-010-9323-3","article-title":"Bovine lactoferrin inhibits influenza A virus induced programmed cell death in vitro","volume":"23","author":"Pietrantoni","year":"2010","journal-title":"Biometals"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1016\/j.foodhyd.2013.02.004","article-title":"Nanoencapsulation of bovine lactoferrin for food and biopharmaceutical applications","volume":"32","author":"Balcao","year":"2013","journal-title":"Food Hydrocoll."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"262","DOI":"10.3109\/02652048.2011.646330","article-title":"Trigger release liposome systems: Local and remote controlled delivery?","volume":"29","author":"Bibi","year":"2012","journal-title":"J. Microencapsul."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1007\/s10540-006-9030-z","article-title":"Melittin: A membrane-active peptide with diverse functions","volume":"27","author":"Raghuraman","year":"2007","journal-title":"Biosci. Rep."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"5087","DOI":"10.1073\/pnas.0710625105","article-title":"Mechanism and kinetics of pore formation in membranes by water-soluble amphipathic peptides","volume":"105","author":"Lee","year":"2008","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1016\/S0005-2736(01)00382-0","article-title":"\u2018Detergent-like\u2019 permeabilization of anionic lipid vesicles by melittin","volume":"1514","author":"Ladokhin","year":"2001","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"11709","DOI":"10.1128\/JVI.05040-11","article-title":"Crystal structure of swine major histocompatibility complex class I SLA-1*0401 and identification of 2009 pandemic swine-origin influenza A H1N1 virus cytotoxic t lymphocyte epitope peptides","volume":"85","author":"Zhang","year":"2011","journal-title":"J. Virol."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1021\/jp207159z","article-title":"Investigation of model membrane disruption mechanism by melittin using pulse electron paramagnetic resonance spectroscopy and cryogenic transmission electron microscopy","volume":"116","author":"Zimmermann","year":"2012","journal-title":"J. Phys. Chem. B"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"15128","DOI":"10.1021\/jp909559d","article-title":"A combined pulse EPR and monte carlo simulation study provides molecular insight on peptide-membrane interactions","volume":"113","author":"Gofman","year":"2009","journal-title":"J. Phys. Chem. B"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"451","DOI":"10.1002\/(SICI)1097-0282(1998)47:6<451::AID-BIP4>3.0.CO;2-F","article-title":"Mode of action of linear amphipathic \u03b1-helical antimicrobial peptides","volume":"47","author":"Oren","year":"1998","journal-title":"Biopolymers"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"452","DOI":"10.1016\/0005-2736(95)80035-E","article-title":"Study of vesicle leakage induced by melittin","volume":"1235","author":"Benachir","year":"1995","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"1918","DOI":"10.1016\/j.bbamem.2013.04.013","article-title":"Vesicle deposition and subsequent membrane-melittin interactions on different substrates: A QCM-D experiment","volume":"1828","author":"Lu","year":"2013","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"1979","DOI":"10.1007\/s00705-011-1087-8","article-title":"Inhibition of influenza A virus replication by RNA interference targeted against the PB1 subunit of the RNA polymerase gene","volume":"156","author":"Li","year":"2011","journal-title":"Arch. Virol."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"1254","DOI":"10.1128\/JVI.01533-09","article-title":"Nuclear import and assembly of influenza A virus RNA polymerase studied in live cells by fluorescence cross-correlation spectroscopy","volume":"84","author":"Huet","year":"2010","journal-title":"J. Virol."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"8414","DOI":"10.1074\/jbc.M110.205534","article-title":"Disruption of the viral polymerase complex assembly as a novel approach to attenuate influenza A virus","volume":"286","author":"Manz","year":"2011","journal-title":"J. Biol. Chem."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1016\/j.sbi.2009.12.007","article-title":"Towards an atomic resolution understanding of the influenza virus replication machinery","volume":"20","author":"Ruigrok","year":"2010","journal-title":"Curr. Opin. Struct. Biol."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"1666","DOI":"10.1021\/bm2000583","article-title":"Effects of side group functionality and molecular weight on the activity of synthetic antimicrobial polypeptides","volume":"12","author":"Engler","year":"2011","journal-title":"Biomacromolecules"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"520","DOI":"10.1002\/psc.1360","article-title":"Cell selectivity and interaction with model membranes of Val\/Arg-rich peptides","volume":"17","author":"Ma","year":"2011","journal-title":"J. Pept. Sci."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"20381","DOI":"10.1074\/jbc.M300130200","article-title":"Two aromatic residues in the PB2 subunit of influenza A RNA polymerase are crucial for cap binding","volume":"278","author":"Fechter","year":"2003","journal-title":"J. Biol. Chem."},{"key":"ref_92","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":"Dias","year":"2009","journal-title":"Nature"},{"key":"ref_93","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":"Yuan","year":"2009","journal-title":"Nature"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"1458","DOI":"10.1073\/pnas.1218509110","article-title":"Hemagglutinin homologue from H17N10 bat influenza virus exhibits divergent receptor-binding and pH-dependent fusion activities","volume":"110","author":"Zhu","year":"2013","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1016\/j.femsle.2004.12.007","article-title":"The mode of action of the plant antimicrobial peptide MiAMP1 differs from that of its structural homologue, the yeast killer toxin WmKT","volume":"243","author":"Stephens","year":"2005","journal-title":"FEMS Microbiol. Lett."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"4965","DOI":"10.1016\/j.jmb.2013.09.038","article-title":"Antiviral mechanisms of human defensins","volume":"425","author":"Wilson","year":"2013","journal-title":"J. Mol. Biol."},{"key":"ref_97","unstructured":"Shah, R., and Chang, T.L. (2012). Small Wonders: Peptides for Disease Control, American Chemical Society."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"1707","DOI":"10.1016\/j.vaccine.2013.01.041","article-title":"Modulation of HIV peptide antigen specific cellular immune response by synthetic \u03b1- and \u03b2-defensin peptides","volume":"31","author":"Mohan","year":"2013","journal-title":"Vaccine"}],"container-title":["Viruses"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4915\/7\/10\/2883\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T20:50:31Z","timestamp":1760215831000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4915\/7\/10\/2883"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,10,20]]},"references-count":98,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2015,10]]}},"alternative-id":["v7102883"],"URL":"https:\/\/doi.org\/10.3390\/v7102883","relation":{},"ISSN":["1999-4915"],"issn-type":[{"value":"1999-4915","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,10,20]]}}}