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一种基于雉鸡cathelicidin的环肽可抑制甲型H1N1流感病毒感染。

A Cyclic Peptide Based on Pheasant Cathelicidin Inhibits Influenza A H1N1 Virus Infection.

作者信息

Pei Yaping, Chen Zhihua, Zhao Ruihan, An Yanxing, Yisihaer Haiche, Wang Chaojie, Bai Yaning, Liang Libin, Jin Lin, Hu Yongting

机构信息

Shanxi Key Laboratory for Modernization of TCVM, College of Veterinary Medicine, Shanxi Agricultural University, Taigu 030801, China.

出版信息

Antibiotics (Basel). 2024 Jun 28;13(7):606. doi: 10.3390/antibiotics13070606.

DOI:10.3390/antibiotics13070606
PMID:39061288
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11273436/
Abstract

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 ± 3.94 µM and 2.47 ± 1.95 µM, 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.

摘要

流感病毒是上呼吸道感染的主要病因,引发了数次全球大流行,对公众健康构成威胁。由于甲型流感病毒不断变异,持续需要开发新型抗病毒疗法。最近,天然抗菌肽为抗流感分子的发现提供了契机。在此,我们基于雉鸡cathelicidin设计了几种肽,并测试了它们对H1N1病毒的抗病毒活性及作用机制。值得注意的是,所设计的肽Pc-4和Pc-5被发现能够抑制H1N1病毒的复制,其IC50分别为8.14±3.94µM和2.47±1.95µM。此外,发现环肽Pc-5可诱导I型干扰素及干扰素诱导基因的表达。一项动物研究表明,环肽Pc-5在小鼠模型中有效抑制了H1N1病毒感染。综上所述,我们的工作揭示了一种设计环肽的策略,并提供了具有抗甲型流感病毒感染治疗潜力的新型分子。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9334/11273436/6c492827467a/antibiotics-13-00606-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9334/11273436/ad5d4987aa97/antibiotics-13-00606-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9334/11273436/deb72c2ac062/antibiotics-13-00606-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9334/11273436/2ba4bdbd4f1c/antibiotics-13-00606-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9334/11273436/6c492827467a/antibiotics-13-00606-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9334/11273436/ad5d4987aa97/antibiotics-13-00606-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9334/11273436/deb72c2ac062/antibiotics-13-00606-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9334/11273436/2ba4bdbd4f1c/antibiotics-13-00606-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9334/11273436/6c492827467a/antibiotics-13-00606-g004.jpg

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本文引用的文献

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The role of cathelicidins in neutrophil biology.抗菌肽 cathelicidins 在中性粒细胞生物学中的作用。
J Leukoc Biol. 2024 Oct 1;116(4):689-705. doi: 10.1093/jleuko/qiae112.
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A multi-species, multi-pathogen avian viral disease outbreak event: Investigating potential for virus transmission at the wild bird - poultry interface.多物种、多病原体禽类病毒病暴发事件:调查野鸟-家禽界面病毒传播的可能性。
Emerg Microbes Infect. 2024 Dec;13(1):2348521. doi: 10.1080/22221751.2024.2348521. Epub 2024 Jun 10.
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Retracted and republished from: "The current state of research on influenza antiviral drug development: drugs in clinical trial and licensed drugs".
撤回并重新发布自:“流感抗病毒药物研发的现状:临床试验药物和已获许可药物”。
mBio. 2024 May 8;15(5):e0017524. doi: 10.1128/mbio.00175-24. Epub 2024 Mar 29.
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LL-37_Renalexin hybrid peptide exhibits antimicrobial activity at lower MICs than its counterpart single peptides.LL-37 肾素灵杂合肽在较低 MIC 下表现出比其相应的单一肽更强的抗菌活性。
Appl Microbiol Biotechnol. 2024 Dec;108(1):126. doi: 10.1007/s00253-023-12887-5. Epub 2024 Jan 13.
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Hylin-a1: A Pan-Inhibitor against Emerging and Re-Emerging Respiratory Viruses.Hylin-a1:一种针对新兴和重现呼吸道病毒的泛抑制剂。
Int J Mol Sci. 2023 Sep 9;24(18):13888. doi: 10.3390/ijms241813888.
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Viral recognition and the antiviral interferon response.病毒识别与抗病毒干扰素反应。
EMBO J. 2023 Jul 17;42(14):e112907. doi: 10.15252/embj.2022112907. Epub 2023 Jun 27.
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Cathelicidin-derived antiviral peptide inhibits herpes simplex virus 1 infection.cathelicidin衍生的抗病毒肽抑制单纯疱疹病毒1型感染。
Front Microbiol. 2023 Jun 5;14:1201505. doi: 10.3389/fmicb.2023.1201505. eCollection 2023.
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A review of the antiviral activity of cationic antimicrobial peptides.阳离子抗菌肽的抗病毒活性研究综述。
Peptides. 2023 Aug;166:171024. doi: 10.1016/j.peptides.2023.171024. Epub 2023 May 10.
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Influenza.流感。
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