{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,3]],"date-time":"2026-11-03T11:56:43Z","timestamp":1793707003270,"version":"4.6.1"},"reference-count":46,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,4,1]],"date-time":"2022-04-01T00:00:00Z","timestamp":1648771200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100005880","name":"National Institute of Biological Resources","doi-asserted-by":"publisher","award":["NIBR202134205"],"award-info":[{"award-number":["NIBR202134205"]}],"id":[{"id":"10.13039\/501100005880","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>\n                    As spider venom is composed of various bioactive substances, it can be utilized as a platform for discovering future therapeutics. Host defense peptides are great candidates for developing novel antimicrobial agents due to their multifunctional properties. In this study, novel functional peptides were rationally designed to have dual antibacterial and anti-inflammatory activities with high cytocompatibility. Based on a template sequence from the transcriptome of spider\u00a0\n                    <jats:italic>Agelena koreana<\/jats:italic>\n                    , a series of\n                    <jats:italic>via in silico<\/jats:italic>\n                    analysis were conducted, incorporating web-based machine learning tools along with the alteration of amino acid residues. Two peptides, Ak-N\u2019 and Ak-N\u2019m, were designed and were subjected to functional validation. The peptides inhibited gram-negative and gram-positive bacteria by disrupting the outer and bacterial cytoplasmic membrane. Moreover, the peptides down-regulated the expression of pro-inflammatory mediators, tumor necrosis factor-\u03b1, interleukin (IL)-1\u03b2, and IL6. Along with low cytotoxicity, Ak-N\u2019m was shown to interact with macrophage surface receptors, inhibiting both Myeloid differentiation primary response 88-dependent and TIR-domain-containing adapter-inducing interferon-\u03b2-dependent pathways of Toll-like receptor 4 signaling on lipopolysaccharide-stimulated THP-1-derived macrophages. Here, we rationally designed functional peptides based on the suggested\n                    <jats:italic>in silico<\/jats:italic>\n                    strategy, demonstrating new insights for utilizing biological resources as well as developing therapeutic agents with enhanced properties.\n                  <\/jats:p>","DOI":"10.3389\/fimmu.2022.821070","type":"journal-article","created":{"date-parts":[[2022,4,1]],"date-time":"2022-04-01T01:24:10Z","timestamp":1648776250000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":22,"title":["Designing a Novel Functional Peptide With Dual Antimicrobial and Anti-inflammatory Activities via in Silico Methods"],"prefix":"10.3389","volume":"13","author":[{"given":"Min Kyoung","family":"Shin","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Byungjo","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seung Tae","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jung Sun","family":"Yoo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jung-Suk","family":"Sung","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,4,1]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"4065603","DOI":"10.1155\/2016\/4065603","article-title":"Multidrug Resistant and Extensively Drug Resistant Bacteria: A Study","volume":"2016","author":"Basak","year":"2016","journal-title":"J Pathog"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.12968\/jowc.2018.27.5.273","article-title":"Antibiotic Resistance and Biofilm Tolerance: A Combined Threat in the Treatment of Chronic Infections","volume":"27","author":"Bowler","year":"2018","journal-title":"J Wound Care"},{"key":"B3","doi-asserted-by":"publisher","first-page":"761820","DOI":"10.1155\/2015\/761820","article-title":"Peptide-Based Treatment: A Promising Cancer Therapy","volume":"2015","author":"Xiao","year":"2015","journal-title":"J Immunol Res"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1007\/s12602-017-9289-3","article-title":"Bactericidal Activity and Synergy Studies of Peptide AP-CECT7121 Against Multi-Resistant Bacteria Isolated from Human and Animal Soft Tissue Infections","volume":"9","author":"Delpech","year":"2017","journal-title":"Probiotics Antimicrob Proteins"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2018.04.025","article-title":"Peptide Based Therapeutics and Their Use for the Treatment of Neurodegenerative and Other Diseases","volume":"103","author":"Baig","year":"2018","journal-title":"BioMed Pharmacother"},{"key":"B6","doi-asserted-by":"publisher","first-page":"666","DOI":"10.3390\/toxins11110666","article-title":"The Diversity of Venom: The Importance of Behavior and Venom System Morphology in Understanding Its Ecology and Evolution","volume":"11","author":"Schendel","year":"2019","journal-title":"Toxins"},{"key":"B7","doi-asserted-by":"publisher","first-page":"114096","DOI":"10.1016\/j.bcp.2020.114096","article-title":"Animal Toxins \u2014 Nature\u2019s Evolutionary-Refined Toolkit for Basic Research and Drug Discovery","volume":"181","author":"Herzig","year":"2020","journal-title":"Biochem Pharmacol"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.49.5.1727-1732.2005","article-title":"Immunomodulatory Activities of Small Host Defense Peptides","volume":"49","author":"Bowdish","year":"2005","journal-title":"Antimicrob Agents Chemother"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.2174\/15665240113139990045","article-title":"Antimicrobial Potential of Lycosin-I, a Cationic and Amphiphilic Peptide From the Venom of the Spider Lycosa Singorensis","volume":"13","author":"Tan","year":"2013","journal-title":"Curr Mol Med"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcp.2017.03.005","article-title":"Animal Venoms as Antimicrobial Agents","volume":"134","author":"Perumal Samy","year":"2017","journal-title":"Biochem Pharmacol"},{"key":"B11","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1016\/j.exppara.2019.01.009","article-title":"Anti-Parasitic Effect on Toxoplasma Gondii Induced by a Spider Peptide Lycosin-I","volume":"198","author":"Tang","year":"2019","journal-title":"Exp Parasitol"},{"key":"B12","doi-asserted-by":"publisher","first-page":"22","DOI":"10.1016\/j.copbio.2012.09.004","article-title":"Transcriptome Analysis Using Next-Generation Sequencing","volume":"24","author":"Mutz","year":"2013","journal-title":"Curr Opin Biotechnol"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1007\/s10989-019-09970-9","article-title":"Insilico Studies on Antimicrobial Peptides (AMPs) From Earthworm","volume":"26","author":"Ghosh","year":"2020","journal-title":"Int J Pept Res Ther"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1038\/s41573-019-0024-5","article-title":"Applications of Machine Learning in Drug Discovery and Development","volume":"18","author":"Vamathevan","year":"2019","journal-title":"Nat Rev Drug Discov"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1007\/s11030-021-10217-3","article-title":"Artificial Intelligence to Deep Learning: Machine Intelligence Approach for Drug Discovery","volume":"25","author":"Gupta","year":"2021","journal-title":"Mol Diversity"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2018.00276","article-title":"AIPpred: Sequence-Based Prediction of Anti-inflammatory Peptides Using Random Forest","volume":"9","author":"Manavalan","year":"2018","journal-title":"Front Pharmacol"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.3389\/fgene.2019.00129","article-title":"). PreAIP: Computational Prediction of Anti-inflammatory Peptides by Integrating Multiple Complementary Features","volume":"10","author":"Khatun","year":"2019","journal-title":"Front Genet"},{"key":"B18","doi-asserted-by":"publisher","first-page":"7","DOI":"10.1186\/s12967-016-1103-6","article-title":"Prediction of Anti-Inflammatory Proteins\/Peptides: an Insilico Approach","volume":"15","author":"Gupta","year":"2017","journal-title":"J Trans Med"},{"key":"B19","doi-asserted-by":"publisher","first-page":"475062","DOI":"10.1155\/2015\/475062","article-title":"A Large-Scale Structural Classification of Antimicrobial Peptides","volume":"2015","author":"Lee","year":"2015","journal-title":"BioMed Res Int"},{"key":"B20","doi-asserted-by":"publisher","first-page":"4310","DOI":"10.3390\/ijms21124310","article-title":"Proteomic Screening for Prediction and Design of Antimicrobial Peptides with AmpGram","volume":"21","author":"Burdukiewicz","year":"2020","journal-title":"Int J Mol Sci"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkv1051","article-title":"CAMPR3: a Database on Sequences, Structures and Signatures of Antimicrobial Peptides","volume":"44","author":"Waghu","year":"2016","journal-title":"Nucleic Acids Res"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkaa991","article-title":"DBAASP v3: Database of Antimicrobial\/Cytotoxic Activity and Structure of Peptides as a Resource for Development of new Therapeutics","volume":"49","author":"Pirtskhalava","year":"2021","journal-title":"Nucleic Acids Res"},{"key":"B23","doi-asserted-by":"publisher","first-page":"10869","DOI":"10.1038\/s41598-020-67701-3","article-title":"Happenn Is a Novel Tool for Hemolytic Activity Prediction for Therapeutic Peptides Which Employs Neural Networks","volume":"10","author":"Timmons","year":"2020","journal-title":"Sci Rep"},{"key":"B24","doi-asserted-by":"publisher","first-page":"22843","DOI":"10.1038\/srep22843","article-title":"A Web Server and Mobile App for Computing Hemolytic Potency of Peptides","volume":"6","author":"Chaudhary","year":"2016","journal-title":"Sci Rep"},{"key":"B25","doi-asserted-by":"publisher","first-page":"8469","DOI":"10.3390\/ijms22168469","article-title":"Effect of L- to D-Amino Acid Substitution on Stability and Activity of Antitumor Peptide RDP215 against Human Melanoma and Glioblastoma","volume":"22","author":"Maxian","year":"2021","journal-title":"Int J Mol Sci"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M200511200","article-title":"Oxyopinins, Large Amphipathic Peptides Isolated From the Venom of the Wolf Spider Oxyopes Kitabensis With Cytolytic Properties and Positive Insecticidal Cooperativity With Spider Neurotoxins","volume":"277","author":"Corzo","year":"2002","journal-title":"J Biol Chem"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.2174\/0929866053406084","article-title":"Amphiphilic Alpha-Helical Antimicrobial Peptides and Their Structure\/Function Relationships","volume":"12","author":"Dennison","year":"2005","journal-title":"Protein Pept Lett"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1007\/s13238-010-0004-3","article-title":"Alpha-Helical Cationic Antimicrobial Peptides: Relationships of Structure and Function","volume":"1","author":"Huang","year":"2010","journal-title":"Protein Cell"},{"key":"B29","doi-asserted-by":"publisher","first-page":"e56217","DOI":"10.1371\/journal.pone.0056217","article-title":"De Novo Transcriptome Assembly (NGS) of Curcuma longa L. Rhizome Reveals Novel Transcripts Related to Anticancer and Antimalarial Terpenoids","volume":"8","author":"Annadurai","year":"2013","journal-title":"PloS One"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1016\/S1226-8615(08)60090-4","article-title":"Accumulated Heavy Metal Content in Wolf Spider, Pardosa astrigera (Araneae: Lycosidae), as a Bioindicator of Exposure","volume":"8","author":"Jung","year":"2005","journal-title":"J Asia-Pacific Entomology"},{"key":"B31","doi-asserted-by":"publisher","first-page":"712","DOI":"10.1186\/s12859-019-3225-3","article-title":"The Coming Era of Artificial Intelligence in Biological Data Science","volume":"20","author":"Han","year":"2019","journal-title":"BMC Bioinf"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.2174\/138161209788682325","article-title":"The Roles of Antimicrobial Peptides in Innate Host Defense","volume":"15","author":"Diamond","year":"2009","journal-title":"Curr Pharm Des"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1016\/j.tibtech.2011.05.001","article-title":"The Expanding Scope of Antimicrobial Peptide Structures and Their Modes of Action","volume":"29","author":"Nguyen","year":"2011","journal-title":"Trends Biotechnol"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.49.7.2845-2850.2005","article-title":"Antimicrobial and Chemoattractant Activity, Lipopolysaccharide Neutralization, Cytotoxicity, and Inhibition by Serum of Analogs of Human Cathelicidin LL-37","volume":"49","author":"Ciornei","year":"2005","journal-title":"Antimicrobial Agents Chemother"},{"key":"B35","doi-asserted-by":"publisher","first-page":"167572","DOI":"10.1155\/2015\/167572","article-title":"Inhibitory Effects of Antimicrobial Peptides on Lipopolysaccharide-Induced Inflammation","volume":"2015","author":"Sun","year":"2015","journal-title":"Mediators Inflammation"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1016\/j.semcdb.2018.02.002","article-title":"Modulation of Toll-Like Receptor Signaling by Antimicrobial Peptides","volume":"88","author":"Lee","year":"2019","journal-title":"Semin Cell Dev Biol"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.3390\/biom10040511","article-title":"Octominin Inhibits LPS-Induced Chemokine and Pro-inflammatory Cytokine Secretion from RAW 264.7 Macrophages via Blocking TLRs\/NF-\u03baB Signal Transduction","volume":"10","author":"Sanjeewa","year":"2020","journal-title":"Biomolecules"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.3390\/antibiotics9070422","article-title":"Antibacterial and Anti-Inflammatory Effects of Novel Peptide Toxin from the Spider Pardosa astrigera","volume":"9","author":"Shin","year":"2020","journal-title":"Antibiotics (Basel)"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1097\/00024382-200309000-00005","article-title":"Modulation of Toll-Like Receptor 4 Expression on Human Monocytes by Tumor Necrosis Factor and Interleukin-6: Tumor Necrosis Factor Evokes Lipopolysaccharide Hyporesponsiveness, Whereas Interleukin-6 Enhances Lipopolysaccharide Activity","volume":"20","author":"Tamandl","year":"2003","journal-title":"Shock"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2019.01000","article-title":"Regulation of Toll-Like Receptor (TLR) Signaling Pathway by Polyphenols in the Treatment of Age-Linked Neurodegenerative Diseases: Focus on TLR4 Signaling","volume":"10","author":"Azam","year":"2019","journal-title":"Front Immunol"},{"key":"B41","doi-asserted-by":"publisher","first-page":"187","DOI":"10.1186\/s42269-019-0227-2","article-title":"Toll-Like Receptors Activation, Signaling, and Targeting: an Overview","volume":"43","author":"El-Zayat","year":"2019","journal-title":"Bull Natl Res Centre"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2015.10.008","article-title":"Mechanisms of Toll-like Receptor 4 Endocytosis Reveal a Common Immune-Evasion Strategy Used by Pathogenic and Commensal Bacteria","volume":"43","author":"Tan","year":"2015","journal-title":"Immunity"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2017.00508","article-title":"Inhibition of Toll-Like Receptor Signaling as a Promising Therapy for Inflammatory Diseases: A Journey from Molecular to Nano Therapeutics","volume":"8","author":"Gao","year":"2017","journal-title":"Front Physiol"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbamem.2016.07.001","article-title":"Selective Amino Acid Substitution Reduces Cytotoxicity of the Antimicrobial Peptide Mastoparan","volume":"1858","author":"Irazazabal","year":"2016","journal-title":"Biochim Biophys Acta"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1093\/abbs\/gmx091","article-title":"D-Akmino Acid Substitution Enhances the Stability of Antimicrobial Peptide Polybia-CP","volume":"49","author":"Jia","year":"2017","journal-title":"Acta Biochim Biophys Sin"},{"key":"B46","doi-asserted-by":"publisher","first-page":"23","DOI":"10.3390\/antibiotics9010023","article-title":"Designed Antimicrobial Peptides for Topical Treatment of Antibiotic Resistant Acne Vulgaris","volume":"9","author":"Woodburn","year":"2020","journal-title":"Antibiotics (Basel Switzerland)"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2022.821070\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,4,1]],"date-time":"2022-04-01T01:24:12Z","timestamp":1648776252000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2022.821070\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,4,1]]},"references-count":46,"alternative-id":["10.3389\/fimmu.2022.821070"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2022.821070","relation":{"has-review":[{"id-type":"doi","id":"10.32388\/H9ZKVZ","asserted-by":"object"},{"id-type":"doi","id":"10.32388\/OUM7TB","asserted-by":"object"}]},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,4,1]]},"article-number":"821070"}}