{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T22:09:39Z","timestamp":1787695779005,"version":"build-2784847793"},"reference-count":40,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2024,6,28]],"date-time":"2024-06-28T00:00:00Z","timestamp":1719532800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Natural Science Foundation of China","award":["32322014"],"award-info":[{"award-number":["32322014"]}]},{"name":"National Natural Science Foundation of China","award":["32070444"],"award-info":[{"award-number":["32070444"]}]},{"name":"National Natural Science Foundation of China","award":["2022JQPYGC03"],"award-info":[{"award-number":["2022JQPYGC03"]}]},{"name":"Excellent Young Scholar Cultivation Project of Shanxi Agricultural University","award":["32322014"],"award-info":[{"award-number":["32322014"]}]},{"name":"Excellent Young Scholar Cultivation Project of Shanxi Agricultural University","award":["32070444"],"award-info":[{"award-number":["32070444"]}]},{"name":"Excellent Young Scholar Cultivation Project of Shanxi Agricultural University","award":["2022JQPYGC03"],"award-info":[{"award-number":["2022JQPYGC03"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antibiotics"],"abstract":"<jats:p>Influenza viruses are the leading cause of upper respiratory tract infections, leading to several global pandemics and threats to public health. Due to the continuous mutation of influenza A viruses, there is a constant need for the development of novel antiviral therapeutics. Recently, natural antimicrobial peptides have provided an opportunity for the discovery of anti-influenza molecules. Here, we designed several peptides based on pheasant cathelicidin and tested their antiviral activities and mechanisms against the H1N1 virus. Of note, the designed peptides Pc-4 and Pc-5 were found to inhibit replication of the H1N1 virus with an IC50 = 8.14 \u00b1 3.94 \u00b5M and 2.47 \u00b1 1.95 \u00b5M, respectively. In addition, the cyclic peptide Pc-5 was found to induce type I interferons and the expression of interferon-induced genes. An animal study showed that the cyclic peptide Pc-5 effectively inhibited H1N1 virus infection in a mouse model. Taken together, our work reveals a strategy for designing cyclic peptides and provides novel molecules with therapeutic potential against influenza A virus infection.<\/jats:p>","DOI":"10.3390\/antibiotics13070606","type":"journal-article","created":{"date-parts":[[2024,7,2]],"date-time":"2024-07-02T11:33:53Z","timestamp":1719920033000},"page":"606","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["A Cyclic Peptide Based on Pheasant Cathelicidin Inhibits Influenza A H1N1 Virus Infection"],"prefix":"10.3390","volume":"13","author":[{"given":"Yaping","family":"Pei","sequence":"first","affiliation":[{"name":"Shanxi Key Laboratory for Modernization of TCVM, College of Veterinary Medicine, Shanxi Agricultural University, Taigu 030801, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhihua","family":"Chen","sequence":"additional","affiliation":[{"name":"Shanxi Key Laboratory for Modernization of TCVM, College of Veterinary Medicine, Shanxi Agricultural University, Taigu 030801, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruihan","family":"Zhao","sequence":"additional","affiliation":[{"name":"Shanxi Key Laboratory for Modernization of TCVM, College of Veterinary Medicine, Shanxi Agricultural University, Taigu 030801, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanxing","family":"An","sequence":"additional","affiliation":[{"name":"Shanxi Key Laboratory for Modernization of TCVM, College of Veterinary Medicine, Shanxi Agricultural University, Taigu 030801, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haiche","family":"Yisihaer","sequence":"additional","affiliation":[{"name":"Shanxi Key Laboratory for Modernization of TCVM, College of Veterinary Medicine, Shanxi Agricultural University, Taigu 030801, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chaojie","family":"Wang","sequence":"additional","affiliation":[{"name":"Shanxi Key Laboratory for Modernization of TCVM, College of Veterinary Medicine, Shanxi Agricultural University, Taigu 030801, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yaning","family":"Bai","sequence":"additional","affiliation":[{"name":"Shanxi Key Laboratory for Modernization of TCVM, College of Veterinary Medicine, Shanxi Agricultural University, Taigu 030801, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Libin","family":"Liang","sequence":"additional","affiliation":[{"name":"Shanxi Key Laboratory for Modernization of TCVM, College of Veterinary Medicine, Shanxi Agricultural University, Taigu 030801, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6273-9140","authenticated-orcid":false,"given":"Lin","family":"Jin","sequence":"additional","affiliation":[{"name":"Shanxi Key Laboratory for Modernization of TCVM, College of Veterinary Medicine, Shanxi Agricultural University, Taigu 030801, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongting","family":"Hu","sequence":"additional","affiliation":[{"name":"Shanxi Key Laboratory for Modernization of TCVM, College of Veterinary Medicine, Shanxi Agricultural University, Taigu 030801, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,6,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1038\/nrmicro.2017.118","article-title":"The evolution of seasonal influenza viruses","volume":"16","author":"Petrova","year":"2018","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1038\/s41579-018-0115-z","article-title":"Host and viral determinants of influenza A virus species specificity","volume":"17","author":"Long","year":"2019","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"S1","DOI":"10.1093\/infdis\/jiy633","article-title":"Influenza Vaccines: Good, but We Can Do Better","volume":"219","author":"Paules","year":"2019","journal-title":"J. Infect. Dis."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1109","DOI":"10.1007\/s40265-020-01350-8","article-title":"Baloxavir Marboxil: A Review in Acute Uncomplicated Influenza","volume":"80","author":"Shirley","year":"2020","journal-title":"Drugs"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Kosik, I., and Yewdell, J.W. (2019). Influenza Hemagglutinin and Neuraminidase: Yin\u2013Yang Proteins Coevolving to Thwart Immunity. Viruses, 11.","DOI":"10.3390\/v11040346"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1358\/dot.2019.55.6.2999889","article-title":"Baloxavir marboxil: A novel cap-dependent endonuclease (CEN) inhibitor for the treatment of acute uncomplicated influenza","volume":"55","author":"Locke","year":"2019","journal-title":"Drugs Today"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Li, Y., Huo, S., Yin, Z., Tian, Z., Huang, F., Liu, P., Liu, Y., and Yu, F. (2024). Retracted and republished from: \u201cThe current state of research on influenza antiviral drug development: Drugs in clinical trial and licensed drugs\u201d. mBio, 15.","DOI":"10.1128\/mbio.00175-24"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"693","DOI":"10.1016\/S0140-6736(22)00982-5","article-title":"Influenza","volume":"400","author":"Uyeki","year":"2022","journal-title":"Lancet"},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Dufrasne, F. (2021). Baloxavir Marboxil: An Original New Drug against Influenza. Pharmaceuticals, 15.","DOI":"10.3390\/ph15010028"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1016\/j.bcp.2016.09.018","article-title":"Antimicrobial peptides (AMPs): Ancient compounds that represent novel weapons in the fight against bacteria","volume":"133","author":"Ageitos","year":"2017","journal-title":"Biochem. Pharmacol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"3525","DOI":"10.1007\/s00018-019-03138-w","article-title":"Antiviral peptides as promising therapeutic drugs","volume":"76","author":"Campos","year":"2019","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"171024","DOI":"10.1016\/j.peptides.2023.171024","article-title":"A review of the antiviral activity of cationic antimicrobial peptides","volume":"166","author":"Urmi","year":"2023","journal-title":"Peptides"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"001661","DOI":"10.1099\/jgv.0.001661","article-title":"Natural antimicrobial peptides as a source of new antiviral agents","volume":"102","author":"Zakaryan","year":"2021","journal-title":"J. Gen. Virol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1007\/BF00362792","article-title":"Host range of avian influenza virus in free-living birds","volume":"12","author":"Stallknecht","year":"1988","journal-title":"Vet. Res. Commun."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"669","DOI":"10.1111\/tbed.14033","article-title":"H9N2 influenza virus spillover into wild birds from poultry in China bind to human-type receptors and transmit in mammals via respiratory droplets","volume":"69","author":"Zhang","year":"2022","journal-title":"Transbound. Emerg. Dis."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"2348521","DOI":"10.1080\/22221751.2024.2348521","article-title":"A multi-species, multi-pathogen avian viral disease outbreak event: Investigating potential for virus transmission at the wild bird\u2013poultry interface","volume":"13","author":"Reid","year":"2024","journal-title":"Emerg. Microbes Infect."},{"key":"ref_17","first-page":"179","article-title":"The role of cathelicidins in the innate host defenses of mammals","volume":"7","author":"Zanetti","year":"2005","journal-title":"Curr. Issues Mol. Biol."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Scheenstra, M.R., van Harten, R.M., Veldhuizen, E.J.A., Haagsman, H.P., and Coorens, M. (2020). Cathelicidins Modulate TLR-Activation and Inflammation. Front. Immunol., 11.","DOI":"10.3389\/fimmu.2020.01137"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Amagai, R., Takahashi, T., Terui, H., Fujimura, T., Yamasaki, K., Aiba, S., and Asano, Y. (2023). The Antimicrobial Peptide Cathelicidin Exerts Immunomodulatory Effects via Scavenger Receptors. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24010875"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Yoon, G., Puentes, R., Tran, J., Multani, A., and Cobo, E.R. (2024). The role of cathelicidins in neutrophil biology. J. Leukoc. Biol.","DOI":"10.1093\/jleuko\/qiae112"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Narh, J.K., Casillas-Vega, N.G., and Zarate, X. (2024). LL-37_Renalexin hybrid peptide exhibits antimicrobial activity at lower MICs than its counterpart single peptides. Appl. Microbiol. Biotechnol., 108.","DOI":"10.1007\/s00253-023-12887-5"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1016\/j.peptides.2017.07.013","article-title":"Cathelicidins display conserved direct antiviral activity towards rhinovirus","volume":"95","author":"Sousa","year":"2017","journal-title":"Peptides"},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Guo, X., An, Y., Tan, W., Ma, L., Wang, M., Li, J., Li, B., Hou, W., and Wu, L. (2023). Cathelicidin-derived antiviral peptide inhibits herpes simplex virus 1 infection. Front. Microbiol., 14.","DOI":"10.3389\/fmicb.2023.1201505"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Damour, A., Garcia, M., Cho, H.-S., Larivi\u00e8re, A., L\u00e9v\u00eaque, N., Park, C., and Bodet, C. (2021). Characterisation of Antiviral Activity of Cathelicidins from Naked Mole Rat and Python bivittatus on Human Herpes Simplex Virus 1. Pharmaceuticals, 14.","DOI":"10.3390\/ph14080715"},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Peng, L., Du, W., Balhuizen, M.D., Haagsman, H.P., de Haan, C.A.M., and Veldhuizen, E.J.A. (2020). Antiviral Activity of Chicken Cathelicidin B1 Against Influenza A Virus. Front. Microbiol., 11.","DOI":"10.3389\/fmicb.2020.00426"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"e24234","DOI":"10.1002\/pep2.24234","article-title":"Antiviral activity of selected cathelicidins against infectious bronchitis virus","volume":"114","author":"Verheije","year":"2022","journal-title":"Pept. Sci."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"314","DOI":"10.1016\/j.dci.2010.10.004","article-title":"Molecular cloning and characterization of novel cathelicidin-derived myeloid antimicrobial peptide from Phasianus colchicus","volume":"35","author":"Wang","year":"2011","journal-title":"Dev. Comp. Immunol."},{"key":"ref_28","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_29","doi-asserted-by":"crossref","first-page":"394","DOI":"10.1126\/science.1122818","article-title":"Host species barriers to influenza virus infections","volume":"312","author":"Kuiken","year":"2006","journal-title":"Science"},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Chianese, A., Zannella, C., Monti, A., Doti, N., Sanna, G., Manzin, A., De Filippis, A., and Galdiero, M. (2023). Hylin-a1: A Pan-Inhibitor against Emerging and Re-Emerging Respiratory Viruses. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms241813888"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"757","DOI":"10.1093\/jb\/mvab019","article-title":"Antiviral activity and mechanism of ESC-1GN from skin secretion of Hylarana guentheri against influenza A virus","volume":"169","author":"Yang","year":"2021","journal-title":"J. Biochem."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1016\/j.theriogenology.2017.12.047","article-title":"Innate antiviral immune response against infectious bronchitis virus and involvement of prostaglandin E2 in the uterine mucosa of laying hens","volume":"110","author":"Elhamouly","year":"2018","journal-title":"Theriogenology"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"e112907","DOI":"10.15252\/embj.2022112907","article-title":"Viral recognition and the antiviral interferon response","volume":"42","author":"Dalskov","year":"2023","journal-title":"EMBO J."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"672","DOI":"10.1080\/00071668.2021.1919993","article-title":"Antimicrobial peptides as an alternative to relieve antimicrobial growth promoters in poultry","volume":"62","author":"Nazeer","year":"2021","journal-title":"Br. Poult. Sci."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1016\/j.antiviral.2019.02.002","article-title":"Human cathelicidin peptide LL-37 as a therapeutic antiviral targeting Venezuelan equine encephalitis virus infections","volume":"164","author":"Ahmed","year":"2019","journal-title":"Antivir. Res."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"105021","DOI":"10.1016\/j.antiviral.2021.105021","article-title":"Cathelicidin antimicrobial peptides suppress EV71 infection via regulating antiviral response and inhibiting viral binding","volume":"187","author":"Yu","year":"2021","journal-title":"Antivir. Res."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1016\/j.ajpath.2011.03.013","article-title":"Excessive neutrophils and neutrophil extracellular traps contribute to acute lung injury of influenza pneumonitis","volume":"179","author":"Narasaraju","year":"2011","journal-title":"Am. J. Pathol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"314","DOI":"10.1016\/j.antiviral.2011.07.008","article-title":"Synergistic activity of baicalein with ribavirin against influenza A (H1N1) virus infections in cell culture and in mice","volume":"91","author":"Chen","year":"2011","journal-title":"Antivir. Res."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"153150","DOI":"10.1016\/j.phymed.2019.153150","article-title":"Flavonoids from Houttuynia cordata attenuate H1N1-induced acute lung injury in mice via inhibition of influenza virus and Toll-like receptor signalling","volume":"67","author":"Ling","year":"2020","journal-title":"Phytomedicine"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"725","DOI":"10.1165\/rcmb.2009-0210ST","article-title":"An official American Thoracic Society workshop report: Features and measurements of experimental acute lung injury in animals","volume":"44","author":"Downey","year":"2011","journal-title":"Am. J. Respir. Cell Mol. Biol."}],"container-title":["Antibiotics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2079-6382\/13\/7\/606\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T15:07:26Z","timestamp":1760108846000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2079-6382\/13\/7\/606"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,6,28]]},"references-count":40,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2024,7]]}},"alternative-id":["antibiotics13070606"],"URL":"https:\/\/doi.org\/10.3390\/antibiotics13070606","relation":{},"ISSN":["2079-6382"],"issn-type":[{"value":"2079-6382","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,6,28]]}}}