{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,24]],"date-time":"2026-01-24T03:40:50Z","timestamp":1769226050801,"version":"3.49.0"},"reference-count":75,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2023,12,7]],"date-time":"2023-12-07T00:00:00Z","timestamp":1701907200000},"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":["NIBR202333202"],"award-info":[{"award-number":["NIBR202333202"]}],"id":[{"id":"10.13039\/501100005880","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005880","name":"National Institute of Biological Resources","doi-asserted-by":"publisher","award":["NIBR202304103"],"award-info":[{"award-number":["NIBR202304103"]}],"id":[{"id":"10.13039\/501100005880","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Ministry of Environment (MOE) of the Republic of Korea","award":["NIBR202333202"],"award-info":[{"award-number":["NIBR202333202"]}]},{"name":"Ministry of Environment (MOE) of the Republic of Korea","award":["NIBR202304103"],"award-info":[{"award-number":["NIBR202304103"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antibiotics"],"abstract":"<jats:p>With the increasing challenge of controlling infectious diseases due to the emergence of antibiotic-resistant strains, the importance of discovering new antimicrobial agents is rapidly increasing. Animal venoms contain a variety of functional peptides, making them a promising platform for pharmaceutical development. In this study, a novel toxin peptide with antibacterial and anti-inflammatory activities was discovered from the spider venom gland transcriptome by implementing computational approaches. Lycotoxin-Pa2a (Lytx-Pa2a) showed homology to known-spider toxin, where functional prediction indicated the potential of both antibacterial and anti-inflammatory peptides without hemolytic activity. The colony-forming assay and minimum inhibitory concentration test showed that Lytx-Pa2a exhibited comparable or stronger antibacterial activity against pathogenic strains than melittin. Following mechanistic studies revealed that Lytx-Pa2a disrupts both cytoplasmic and outer membranes of bacteria while simultaneously inducing the accumulation of reactive oxygen species. The peptide exerted no significant toxicity when treated to human primary cells, murine macrophages, and bovine red blood cells. Moreover, Lytx-Pa2a alleviated lipopolysaccharide-induced inflammation in mouse macrophages by suppressing the expression of inflammatory mediators. These findings not only suggested that Lytx-Pa2a with dual activity can be utilized as a new antimicrobial agent for infectious diseases but also demonstrated the implementation of in silico methods for discovering a novel functional peptide, which may enhance the future utilization of biological resources.<\/jats:p>","DOI":"10.3390\/antibiotics12121708","type":"journal-article","created":{"date-parts":[[2023,12,7]],"date-time":"2023-12-07T10:45:33Z","timestamp":1701945933000},"page":"1708","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["The Identification of a Novel Spider Toxin Peptide, Lycotoxin-Pa2a, with Antibacterial and Anti-Inflammatory Activities"],"prefix":"10.3390","volume":"12","author":[{"given":"Min Kyoung","family":"Shin","sequence":"first","affiliation":[{"name":"Department of Life Science, Dongguk University-Seoul, Goyang 10326, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"In-Wook","family":"Hwang","sequence":"additional","affiliation":[{"name":"Department of Life Science, Dongguk University-Seoul, Goyang 10326, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bo-Young","family":"Jang","sequence":"additional","affiliation":[{"name":"Department of Life Science, Dongguk University-Seoul, Goyang 10326, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kyung-Bin","family":"Bu","sequence":"additional","affiliation":[{"name":"Department of Life Science, Dongguk University-Seoul, Goyang 10326, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dong-Hee","family":"Han","sequence":"additional","affiliation":[{"name":"Department of Life Science, Dongguk University-Seoul, Goyang 10326, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Seung-Ho","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Life Science, Dongguk University-Seoul, Goyang 10326, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jin Wook","family":"Oh","sequence":"additional","affiliation":[{"name":"Department of Life Science, Dongguk University-Seoul, Goyang 10326, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jung Sun","family":"Yoo","sequence":"additional","affiliation":[{"name":"Species Diversity Research Division, National Institute of Biological Resources, Incheon 22689, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3145-8458","authenticated-orcid":false,"given":"Jung-Suk","family":"Sung","sequence":"additional","affiliation":[{"name":"Department of Life Science, Dongguk University-Seoul, Goyang 10326, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,12,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"273","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":"ref_2","doi-asserted-by":"crossref","first-page":"206","DOI":"10.1038\/s41579-021-00650-4","article-title":"Horizontal gene transfer and adaptive evolution in bacteria","volume":"20","author":"Arnold","year":"2022","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"711","DOI":"10.1038\/nrmicro1234","article-title":"Mechanisms of, and Barriers to, Horizontal Gene Transfer between Bacteria","volume":"3","author":"Thomas","year":"2005","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"599","DOI":"10.1016\/j.copbio.2004.10.007","article-title":"Exploiting natural peptide diversity: Novel research tools and drug leads","volume":"15","author":"Adermann","year":"2004","journal-title":"Curr. Opin. Biotechnol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"415","DOI":"10.2147\/IDR.S287792","article-title":"Encouraging the Development of New Antibiotics: Are Financial Incentives the Right Way Forward? A Systematic Review and Case Study","volume":"14","author":"Dutescu","year":"2021","journal-title":"Infect. Drug Resist."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"185","DOI":"10.4161\/viru.22507","article-title":"New antibiotic agents in the pipeline and how they can help overcome microbial resistance","volume":"4","author":"Gould","year":"2013","journal-title":"Virulence"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Pacios, O., Blasco, L., Bleriot, I., Fernandez-Garcia, L., Gonz\u00e1lez Bardanca, M., Ambroa, A., L\u00f3pez, M., Bou, G., and Tom\u00e1s, M. (2020). Strategies to Combat Multidrug-Resistant and Persistent Infectious Diseases. Antibiotics, 9.","DOI":"10.3390\/antibiotics9020065"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"28","DOI":"10.4331\/wjbc.v6.i2.28","article-title":"Animal venom studies: Current benefits and future developments","volume":"6","author":"Utkin","year":"2015","journal-title":"World J. Biol. Chem."},{"key":"ref_9","first-page":"183","article-title":"Why do we study animal toxins?","volume":"36","author":"Zhang","year":"2015","journal-title":"Dongwuxue Yanjiu"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1016\/j.bcp.2017.03.005","article-title":"Animal venoms as antimicrobial agents","volume":"134","author":"Stiles","year":"2017","journal-title":"Biochem. Pharmacol."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Schendel, V., Rash, L.D., Jenner, R.A., and Undheim, E.A.B. (2019). The Diversity of Venom: The Importance of Behavior and Venom System Morphology in Understanding Its Ecology and Evolution. Toxins, 11.","DOI":"10.3390\/toxins11110666"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"14192","DOI":"10.1074\/jbc.M114.635458","article-title":"Structural and Functional Diversity of Peptide Toxins from Tarantula Haplopelma hainanum (Ornithoctonus hainana) Venom Revealed by Transcriptomic, Peptidomic, and Patch Clamp Approaches","volume":"290","author":"Zhang","year":"2015","journal-title":"J. Biol. Chem."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1016\/j.peptides.2013.10.029","article-title":"Peptide diversity in the venom of the social wasp Polybia paulista (Hymenoptera): A comparison of the intra- and inter-colony compositions","volume":"51","author":"Dias","year":"2014","journal-title":"Peptides"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"2159","DOI":"10.1002\/jcp.25328","article-title":"Bee Venom Accelerates Wound Healing in Diabetic Mice by Suppressing Activating Transcription Factor-3 (ATF-3) and Inducible Nitric Oxide Synthase (iNOS)-Mediated Oxidative Stress and Recruiting Bone Marrow-Derived Endothelial Progenitor Cells","volume":"231","author":"Badr","year":"2016","journal-title":"J. Cell Physiol."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Guilhelmelli, F., Vilela, N., Smidt, K.S., de Oliveira, M.A., da Cunha Morales \u00c1lvares, A., Rigonatto, M.C.L., da Silva Costa, P.H., Tavares, A.H., Freitas, S.M.D., and Nicola, A.M. (2016). Activity of Scorpion Venom-Derived Antifungal Peptides against Planktonic Cells of Candida spp. and Cryptococcus neoformans and Candida albicans Biofilms. Front. Microbiol., 7.","DOI":"10.3389\/fmicb.2016.01844"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"13397","DOI":"10.1038\/s41598-018-31245-4","article-title":"Novel analgesic \u03c9-conotoxins from the vermivorous cone snail Conus moncuri provide new insights into the evolution of conopeptides","volume":"8","author":"Sousa","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1016\/j.toxicon.2020.12.018","article-title":"Immunomodulatory properties of molecules from animal venoms","volume":"191","author":"Vergara","year":"2021","journal-title":"Toxicon"},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Mohamed Abd El-Aziz, T., Garcia Soares, A., and Stockand, J.D. (2019). Snake Venoms in Drug Discovery: Valuable Therapeutic Tools for Life Saving. Toxins, 11.","DOI":"10.3390\/toxins11100564"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Messadi, E. (2023). Snake Venom Components as Therapeutic Drugs in Ischemic Heart Disease. Biomolecules, 13.","DOI":"10.3390\/biom13101539"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Nguyen, L.T.T., Craik, D.J., and Kaas, Q. (2023). Bibliometric Review of the Literature on Cone Snail Peptide Toxins from 2000 to 2022. Mar. Drugs, 21.","DOI":"10.3390\/md21030154"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"2738","DOI":"10.1016\/j.bmc.2017.09.029","article-title":"Peptide therapeutics from venom: Current status and potential","volume":"26","author":"Pennington","year":"2018","journal-title":"Bioorg. Med. Chem."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1469","DOI":"10.1517\/14712598.2011.621940","article-title":"Venoms as a platform for human drugs: Translating toxins into therapeutics","volume":"11","author":"King","year":"2011","journal-title":"Expert Opin. Biol. Ther."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"574","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":"ref_24","unstructured":"Benson, N., Cucurull-Sanchez, L., Demin, O., Smirnov, S., and van der Graaf, P. (2012). Proceedings of the Advances in Systems Biology, Springer. [2012th ed.]."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"114378","DOI":"10.1016\/j.addr.2022.114378","article-title":"Novel antimicrobial agents for combating antibiotic-resistant bacteria","volume":"187","author":"Chang","year":"2022","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Hof, W.V.T., Veerman, E.C.I., Helmerhorst, E.J., and Amerongen, A.V.N. (2001). Antimicrobial Peptides: Properties and Applicability, Walter de Gruyter.","DOI":"10.1515\/BC.2001.072"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"463","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":"ref_28","doi-asserted-by":"crossref","first-page":"1315","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. Divers."},{"key":"ref_29","doi-asserted-by":"crossref","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":"ref_30","doi-asserted-by":"crossref","first-page":"1132","DOI":"10.3389\/fphar.2020.01132","article-title":"From Animal Poisons and Venoms to Medicines: Achievements, Challenges and Perspectives in Drug Discovery","volume":"11","author":"Bordon","year":"2020","journal-title":"Front. Pharmacol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1103","DOI":"10.1016\/j.cell.2016.08.007","article-title":"Toward Accurate and Quantitative Comparative Metagenomics","volume":"166","author":"Nayfach","year":"2016","journal-title":"Cell"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"821070","DOI":"10.3389\/fimmu.2022.821070","article-title":"Designing a Novel Functional Peptide with Dual Antimicrobial and Anti-inflammatory Activities via in Silico Methods","volume":"13","author":"Shin","year":"2022","journal-title":"Front. Immunol."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Nagarajan, N., Yapp, E.K.Y., Le, N.Q.K., Kamaraj, B., Al-Subaie, A.M., and Yeh, H.-Y. (2019). Application of Computational Biology and Artificial Intelligence Technologies in Cancer Precision Drug Discovery. BioMed Res. Int., 2019.","DOI":"10.1155\/2019\/8427042"},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Shin, M.K., Hwang, I.-W., Kim, Y., Kim, S.T., Jang, W., Lee, S., Bang, W.Y., Bae, C.-H., and Sung, J.-S. (2020). Antibacterial and Anti-Inflammatory Effects of Novel Peptide Toxin from the Spider Pardosa astrigera. Antibiotics, 9.","DOI":"10.3390\/antibiotics9070422"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"264","DOI":"10.1016\/j.toxicon.2008.05.020","article-title":"A rational nomenclature for naming peptide toxins from spiders and other venomous animals","volume":"52","author":"King","year":"2008","journal-title":"Toxicon"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"115377","DOI":"10.1016\/j.ejmech.2023.115377","article-title":"Antimicrobial peptides: Structure, mechanism, and modification","volume":"255","author":"Chen","year":"2023","journal-title":"Eur. J. Med. Chem."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"3265","DOI":"10.1007\/s00253-019-09698-y","article-title":"Melittin: From honeybees to superbugs","volume":"103","author":"Memariani","year":"2019","journal-title":"Appl. Microbiol. Biotechnol."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Askari, P., Namaei, M.H., Ghazvini, K., and Hosseini, M. (2021). In vitro and in vivo toxicity and antibacterial efficacy of melittin against clinical extensively drug-resistant bacteria. BMC Pharmacol. Toxicol., 22.","DOI":"10.1186\/s40360-021-00503-z"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"610997","DOI":"10.3389\/fmedt.2020.610997","article-title":"Mode-of-Action of Antimicrobial Peptides: Membrane Disruption vs. Intracellular Mechanisms","volume":"2","author":"Benfield","year":"2020","journal-title":"Front. Med. Technol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"e01493-18","DOI":"10.1128\/AAC.01493-18","article-title":"Pse-T2, an Antimicrobial Peptide with High-Level, Broad-Spectrum Antimicrobial Potency and Skin Biocompatibility against Multidrug-Resistant Pseudomonas aeruginosa Infection","volume":"62","author":"Kang","year":"2018","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1619","DOI":"10.1021\/acsinfecdis.0c00797","article-title":"New Antimicrobial Peptides with Repeating Unit against Multidrug-Resistant Bacteria","volume":"7","author":"Zhong","year":"2021","journal-title":"ACS Infect. Dis."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"17023","DOI":"10.1038\/sigtrans.2017.23","article-title":"NF-\u03baB signaling in inflammation","volume":"2","author":"Liu","year":"2017","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"461","DOI":"10.3389\/fimmu.2014.00461","article-title":"Toll-Like Receptor Signaling Pathways","volume":"5","author":"Kawasaki","year":"2014","journal-title":"Front. Immunol."},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Ain, Q.U., Batool, M., and Choi, S. (2020). TLR4-Targeting Therapeutics: Structural Basis and Computer-Aided Drug Discovery Approaches. Molecules, 25.","DOI":"10.3390\/molecules25030627"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1038\/s41392-022-00904-4","article-title":"Therapeutic peptides: Current applications and future directions","volume":"7","author":"Wang","year":"2022","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Yacoub, T., Rima, M., Karam, M., Sabatier, J.-M., and Fajloun, Z. (2020). Antimicrobials from Venomous Animals: An Overview. Molecules, 25.","DOI":"10.3390\/molecules25102402"},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Lee, A.C.-L., Harris, J.L., Khanna, K.K., and Hong, J.-H. (2019). A Comprehensive Review on Current Advances in Peptide Drug Development and Design. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20102383"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1111\/brv.12793","article-title":"The biology and evolution of spider venoms","volume":"97","author":"Herzig","year":"2022","journal-title":"Biol. Rev."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"2851","DOI":"10.3390\/toxins2122851","article-title":"Spider-venom peptides as therapeutics","volume":"2","author":"Saez","year":"2010","journal-title":"Toxins"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"5067","DOI":"10.1074\/jbc.RA119.012281","article-title":"Manipulation of a spider peptide toxin alters its affinity for lipid bilayers and potency and selectivity for voltage-gated sodium channel subtype 1.7","volume":"295","author":"Agwa","year":"2020","journal-title":"J. Biol. Chem."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"11208","DOI":"10.1074\/jbc.M111099200","article-title":"Cupiennin 1, a New Family of Highly Basic Antimicrobial Peptides in the Venom of the Spider Cupiennius salei(Ctenidae)*","volume":"277","author":"Schaller","year":"2002","journal-title":"J. Biol. Chem."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"2059","DOI":"10.1074\/jbc.273.4.2059","article-title":"Lycotoxins, antimicrobial peptides from venom of the wolf spider Lycosa carolinensis","volume":"273","author":"Yan","year":"1998","journal-title":"J. Biol. Chem."},{"key":"ref_53","first-page":"48","article-title":"Antimicrobial peptides: Mechanism of action, activity and clinical potential","volume":"8","author":"Zhang","year":"2021","journal-title":"Mil. Med. Res."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"6566","DOI":"10.3390\/ijms12106566","article-title":"The Potential of Antimicrobial Peptides as Biocides","volume":"12","author":"Laverty","year":"2011","journal-title":"Int. J. Mol. Sci."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"821535","DOI":"10.3389\/fgene.2021.821535","article-title":"Bacterial Response to Oxidative Stress and RNA Oxidation","volume":"12","author":"Seixas","year":"2022","journal-title":"Front. Genet."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"2377","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":"ref_57","doi-asserted-by":"crossref","unstructured":"Buccini, D.F., Roriz, B.C., Rodrigues, J.M., and Franco, O.L. (2022). Antimicrobial peptides could antagonize uncontrolled inflammation via Toll-like 4 receptor. Front. Bioeng. Biotechnol., 10.","DOI":"10.3389\/fbioe.2022.1037147"},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Robles-Loaiza, A.A., Pinos-Tamayo, E.A., Mendes, B., Ortega-Pila, J.A., Proa\u00f1o-Bola\u00f1os, C., Plisson, F., Teixeira, C., Gomes, P., and Almeida, J.R. (2022). Traditional and Computational Screening of Non-Toxic Peptides and Approaches to Improving Selectivity. Pharmaceuticals, 15.","DOI":"10.3390\/ph15030323"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"2300472","DOI":"10.1002\/advs.202300472","article-title":"Antimicrobial Peptide Synergies for Fighting Infectious Diseases","volume":"10","author":"Mhlongo","year":"2023","journal-title":"Adv. Sci."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"420","DOI":"10.1038\/s41587-019-0036-z","article-title":"SignalP 5.0 improves signal peptide predictions using deep neural networks","volume":"37","author":"Tsirigos","year":"2019","journal-title":"Nat. Biotechnol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1074","DOI":"10.1093\/bioinformatics\/btx661","article-title":"ArachnoServer 3.0: An online resource for automated discovery, analysis and annotation of spider toxins","volume":"34","author":"Pineda","year":"2017","journal-title":"Bioinformatics"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"583","DOI":"10.1038\/s41586-021-03819-2","article-title":"Highly accurate protein structure prediction with AlphaFold","volume":"596","author":"Jumper","year":"2021","journal-title":"Nature"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"1829","DOI":"10.1038\/s41596-020-0312-x","article-title":"The HDOCK server for integrated protein\u2013protein docking","volume":"15","author":"Yan","year":"2020","journal-title":"Nat. Protoc."},{"key":"ref_64","doi-asserted-by":"crossref","unstructured":"Lee, H.-T., Lee, C.-C., Yang, J.-R., Lai, J.Z.C., and Chang, K.Y. (2015). A Large-Scale Structural Classification of Antimicrobial Peptides. BioMed Res. Int., 2015.","DOI":"10.1155\/2015\/475062"},{"key":"ref_65","doi-asserted-by":"crossref","unstructured":"Yan, K., Lv, H., Guo, Y., Peng, W., and Liu, B. (2022). sAMPpred-GAT: Prediction of antimicrobial peptide by graph attention network and predicted peptide structure. Bioinformatics, 39.","DOI":"10.1093\/bioinformatics\/btac715"},{"key":"ref_66","doi-asserted-by":"crossref","unstructured":"Burdukiewicz, M., Sidorczuk, K., Rafacz, D., Pietluch, F., Chilimoniuk, J., R\u00f6diger, S., and Gagat, P. (2020). Proteomic Screening for Prediction and Design of Antimicrobial Peptides with AmpGram. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21124310"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"129","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":"ref_68","doi-asserted-by":"crossref","first-page":"1337","DOI":"10.1109\/TCBB.2022.3183018","article-title":"PreTP-Stack: Prediction of Therapeutic Peptides Based on the Stacked Ensemble Learing","volume":"20","author":"Yan","year":"2023","journal-title":"IEEE\/ACM Trans. Comput. Biol. Bioinform."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"D288","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":"2020","journal-title":"Nucleic Acids Res."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"2019","DOI":"10.2147\/IDR.S215084","article-title":"Synergism of cationic antimicrobial peptide WLBU2 with antibacterial agents against biofilms of multi-drug resistant Acinetobacter baumannii and Klebsiella pneumoniae","volume":"12","author":"Swedan","year":"2019","journal-title":"Infect. Drug Resist."},{"key":"ref_71","doi-asserted-by":"crossref","unstructured":"Dwivedi, S., Wahab, R., Khan, F., Mishra, Y.K., Musarrat, J., and Al-Khedhairy, A.A. (2014). Reactive Oxygen Species Mediated Bacterial Biofilm Inhibition via Zinc Oxide Nanoparticles and Their Statistical Determination. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0111289"},{"key":"ref_72","doi-asserted-by":"crossref","unstructured":"Jang, B.-Y., Shin, M.K., Han, D.-H., and Sung, J.-S. (2023). Curcumin Disrupts a Positive Feedback Loop between ADMSCs and Cancer Cells in the Breast Tumor Microenvironment via the CXCL12\/CXCR4 Axis. Pharmaceutics, 15.","DOI":"10.3390\/pharmaceutics15112627"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"2994","DOI":"10.1128\/AAC.06327-11","article-title":"Strand Length-Dependent Antimicrobial Activity and Membrane-Active Mechanism of Arginine- and Valine-Rich \u03b2-Hairpin-Like Antimicrobial Peptides","volume":"56","author":"Dong","year":"2012","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_74","doi-asserted-by":"crossref","unstructured":"Baek, S.-H., Park, T., Kang, M.-G., and Park, D. (2020). Anti-Inflammatory Activity and ROS Regulation Effect of Sinapaldehyde in LPS-Stimulated RAW 264.7 Macrophages. Molecules, 25.","DOI":"10.3390\/molecules25184089"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"16384","DOI":"10.1038\/s41598-023-43737-z","article-title":"Regulation of base excision repair during adipogenesis and osteogenesis of bone marrow-derived mesenchymal stem cells","volume":"13","author":"Kim","year":"2023","journal-title":"Sci. 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