{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T19:58:29Z","timestamp":1790798309055,"version":"4.1.0"},"reference-count":40,"publisher":"MDPI AG","issue":"21","license":[{"start":{"date-parts":[[2025,10,31]],"date-time":"2025-10-31T00:00:00Z","timestamp":1761868800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000038","name":"Natural Sciences and Engineering Research Council (NSERC) of Canada","doi-asserted-by":"publisher","award":["123456"],"award-info":[{"award-number":["123456"]}],"id":[{"id":"10.13039\/501100000038","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000038","name":"Natural Sciences and Engineering Research Council (NSERC) of Canada","doi-asserted-by":"publisher","award":["20234"],"award-info":[{"award-number":["20234"]}],"id":[{"id":"10.13039\/501100000038","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Natural peptides derived from plants have been an important source of medical substances for several decades. Due to their mechanism of action, chemical potential, and favourable side effect profile, these peptides represent a safer alternative to synthetic pharmaceutical treatments. In this study, we report the discovery of a natural peptide derived from the Brassica napus (Canola) proteome that exhibits high functional similarity to an artificial intelligence (AI)-generated peptide that is designed to bind to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike 1 (S1) protein receptor-binding domain (RBD) region. The results of a series of experiments including molecular docking simulations, as well as binding and inhibition assays suggest that the natural peptide exhibits functions similar to those of the AI-generated peptide in binding to the RBD region and disrupting its interaction with the human host receptor angiotensin-converting enzyme 2 (ACE2). This study demonstrates the potential of AI-designed peptides to facilitate the identification of natural peptides with similar functional properties.<\/jats:p>","DOI":"10.3390\/ijms262110607","type":"journal-article","created":{"date-parts":[[2025,11,3]],"date-time":"2025-11-03T13:15:14Z","timestamp":1762175714000},"page":"10607","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Artificial Intelligence Reveals Nature: Functional Parallels Between a Designed and a Natural Peptide"],"prefix":"10.3390","volume":"26","author":[{"given":"Jiashu","family":"Wang","sequence":"first","affiliation":[{"name":"Ottawa Institute of Systems Biology, Faculty of Medicine, University of Ottawa, Ottawa, ON K1H 8M5, Canada"},{"name":"Department of Biology, Faculty of Science, Carleton University, Ottawa, ON K1S 5B6, Canada"},{"name":"Institute of Biochemistry, Faculty of Science, Carleton University, Ottawa, ON K1S 5B6, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas David Daniel","family":"Kazmirchuk","sequence":"additional","affiliation":[{"name":"Ottawa Institute of Systems Biology, Faculty of Medicine, University of Ottawa, Ottawa, ON K1H 8M5, Canada"},{"name":"Department of Biology, Faculty of Science, Carleton University, Ottawa, ON K1S 5B6, Canada"},{"name":"Institute of Biochemistry, Faculty of Science, Carleton University, Ottawa, ON K1S 5B6, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0762-3465","authenticated-orcid":false,"given":"Maryam","family":"Hajikarimlou","sequence":"additional","affiliation":[{"name":"Ottawa Institute of Systems Biology, Faculty of Medicine, University of Ottawa, Ottawa, ON K1H 8M5, Canada"},{"name":"Department of Biology, Faculty of Science, Carleton University, Ottawa, ON K1S 5B6, Canada"},{"name":"Institute of Biochemistry, Faculty of Science, Carleton University, Ottawa, ON K1S 5B6, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3877-6707","authenticated-orcid":false,"given":"Mustafa","family":"Al-Gafari","sequence":"additional","affiliation":[{"name":"Ottawa Institute of Systems Biology, Faculty of Medicine, University of Ottawa, Ottawa, ON K1H 8M5, Canada"},{"name":"Department of Biology, Faculty of Science, Carleton University, Ottawa, ON K1S 5B6, Canada"},{"name":"Institute of Biochemistry, Faculty of Science, Carleton University, Ottawa, ON K1S 5B6, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-8349-3771","authenticated-orcid":false,"given":"Sarah","family":"Takallou","sequence":"additional","affiliation":[{"name":"Ottawa Institute of Systems Biology, Faculty of Medicine, University of Ottawa, Ottawa, ON K1H 8M5, Canada"},{"name":"Department of Biology, Faculty of Science, Carleton University, Ottawa, ON K1S 5B6, Canada"},{"name":"Institute of Biochemistry, Faculty of Science, Carleton University, Ottawa, ON K1S 5B6, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Houman","family":"Moteshareie","sequence":"additional","affiliation":[{"name":"Ottawa Institute of Systems Biology, Faculty of Medicine, University of Ottawa, Ottawa, ON K1H 8M5, Canada"},{"name":"Heathy Environments and Consumer Safety Brance, Health Canada, Ottawa, ON K1A 0K9, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frank","family":"Dehne","sequence":"additional","affiliation":[{"name":"School of Computer Science, Faculty of Science, Carleton University, Ottawa, ON K1S 5B6, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6625-2153","authenticated-orcid":false,"given":"Bahram","family":"Samanfar","sequence":"additional","affiliation":[{"name":"Department of Biology, Faculty of Science, Carleton University, Ottawa, ON K1S 5B6, Canada"},{"name":"Ottawa Research and Development Centre, Agriculture and Agri-Food Canada, Ottawa, ON K1A 0C6, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohan","family":"Babu","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, University of Regina, Regina, SK S4S 0A2, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taha","family":"Azad","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Infectiology, Faculty of Medicine and Health Sciences, Universit\u00e9 de Sherbrooke Cancer Research Institute, Universit\u00e9 de Sherbrooke, Sherbrooke, QC J1E 4K8, Canada"},{"name":"Centre de Recherche du Centre Hospitalier Universitaire de Sherbrooke, Centre Int\u00e9gr\u00e9 Universitaire de Sant\u00e9 et de Services Sociaux de l\u2019Estrie\u2013Centre Hospitalier Universitaire de Sherbrooke, Sherbrooke, QC J1H 5N4, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ashkan","family":"Golshani","sequence":"additional","affiliation":[{"name":"Ottawa Institute of Systems Biology, Faculty of Medicine, University of Ottawa, Ottawa, ON K1H 8M5, Canada"},{"name":"Department of Biology, Faculty of Science, Carleton University, Ottawa, ON K1S 5B6, Canada"},{"name":"Institute of Biochemistry, Faculty of Science, Carleton University, Ottawa, ON K1S 5B6, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,10,31]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Singh, N., Vayer, P., Tanwar, S., Poyet, J.-L., Tsaioun, K., and Villoutreix, B.O. (2023). Drug Discovery and Development: Introduction to the General Public and Patient Groups. Front. Drug Discov., 3.","DOI":"10.3389\/fddsv.2023.1201419"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"e2415445","DOI":"10.1001\/jamanetworkopen.2024.15445","article-title":"Costs of Drug Development and Research and Development Intensity in the US, 2000\u20132018","volume":"7","author":"Sertkaya","year":"2024","journal-title":"JAMA Netw. Open"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1007\/s10989-023-10524-3","article-title":"Strategic Approaches to Improvise Peptide Drugs as Next Generation Therapeutics","volume":"29","author":"Barman","year":"2023","journal-title":"Int. J. Pept. Res. Ther."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Kazmirchuk, T.D.D., Bradbury-Jost, C., Withey, T.A., Gessese, T., Azad, T., Samanfar, B., Dehne, F., and Golshani, A. (2023). Peptides of a Feather: How Computation Is Taking Peptide Therapeutics under Its Wing. Genes, 14.","DOI":"10.3390\/genes14061194"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Pechenov, S., Revell, J., Will, S., Naylor, J., Tyagi, P., Patel, C., Liang, L., Tseng, L., Huang, Y., and Rosenbaum, A.I. (2021). Development of an Orally Delivered GLP-1 Receptor Agonist through Peptide Engineering and Drug Delivery to Treat Chronic Disease. Sci. Rep., 11.","DOI":"10.1038\/s41598-021-01750-0"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"18536","DOI":"10.1021\/jacs.1c08132","article-title":"Rational Design of Potent Peptide Inhibitors of the PD-1:PD-L1 Interaction for Cancer Immunotherapy","volume":"143","author":"Yin","year":"2021","journal-title":"J. Am. Chem. Soc."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"587","DOI":"10.1038\/nrd1133","article-title":"Large-Scale Manufacture of Peptide Therapeutics by Chemical Synthesis","volume":"2","author":"Bray","year":"2003","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1038\/s41573-020-00135-8","article-title":"Trends in Peptide Drug Discovery","volume":"20","author":"Muttenthaler","year":"2021","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1016\/j.isci.2018.11.038","article-title":"In Silico Engineering of Synthetic Binding Proteins from Random Amino Acid Sequences","volume":"11","author":"Burnside","year":"2019","journal-title":"iScience"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"320","DOI":"10.1038\/nature19946","article-title":"The Coming of Age of de Novo Protein Design","volume":"537","author":"Huang","year":"2016","journal-title":"Nature"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Kazmirchuk, T.D.D., Wang, J., Bury, L., Falcinelli, E., Bradbury-Jost, C., Koziar, A., Al-gafari, M., Takallou, S., Willmore, W.G., and Dehne, F. (Blood Adv., 2025). Developing an AI-Generated Peptide Targeting Platelet-Type von Willebrand Disease, Blood Adv., in press.","DOI":"10.1182\/bloodadvances.2025017674"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"7124","DOI":"10.1038\/s41467-024-51067-5","article-title":"Rapid Single-Tier Serodiagnosis of Lyme Disease","volume":"15","author":"Ghosh","year":"2024","journal-title":"Nat. Commun."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"540","DOI":"10.1038\/s41423-023-01001-4","article-title":"SARS-CoV-2 Peptides\/Epitopes for Specific and Sensitive Diagnosis","volume":"20","author":"Jiang","year":"2023","journal-title":"Cell. Mol. Immunol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"5784","DOI":"10.1038\/s41467-025-60949-1","article-title":"Human Protein Interaction Networks of Ancestral and Variant SARS-CoV-2 in Organ-Specific Cells and Bodily Fluids","volume":"16","author":"Broderick","year":"2025","journal-title":"Nat. Commun."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"602","DOI":"10.1021\/acscentsci.2c01513","article-title":"Computational Protein Design for COVID-19 Research and Emerging Therapeutics","volume":"9","author":"Kalita","year":"2023","journal-title":"ACS Cent. Sci."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Hajikarimlou, M., Hooshyar, M., Moutaoufik, M.T., Aly, K.A., Azad, T., Takallou, S., Jagadeesan, S., Phanse, S., Said, K.B., and Samanfar, B. (2022). A Computational Approach to Rapidly Design Peptides That Detect SARS-CoV-2 Surface Protein S. NAR Genom. Bioinform., 4.","DOI":"10.1093\/nargab\/lqac058"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1641","DOI":"10.1002\/jmv.27526","article-title":"Omicron and Delta Variant of SARS-CoV-2: A Comparative Computational Study of Spike Protein","volume":"94","author":"Kumar","year":"2022","journal-title":"J. Med. Virol."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Mart\u00ednez, L., Malaina, I., Salcines-Cuevas, D., Ter\u00e1n-Navarro, H., Zeoli, A., Alonso, S., De la Fuente, I.M., Gonzalez-Lopez, E., Ocejo-Vinyals, J.G., and Gozalo-Marg\u00fcello, M. (2022). First Computational Design Using Lambda-Superstrings and in Vivo Validation of SARS-CoV-2 Vaccine. Sci. Rep., 12.","DOI":"10.1038\/s41598-022-09615-w"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"2673","DOI":"10.1080\/07391102.2020.1752802","article-title":"Computational Studies of Drug Repurposing and Synergism of Lopinavir, Oseltamivir and Ritonavir Binding with SARS-CoV-2 Protease against COVID-19","volume":"39","author":"Muralidharan","year":"2021","journal-title":"J. Biomol. Struct. Dyn."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1186\/s40529-021-00312-x","article-title":"Plant Antimicrobial Peptides: Structures, Functions, and Applications","volume":"62","author":"Li","year":"2021","journal-title":"Bot. Stud."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1413","DOI":"10.4155\/fmc-2016-0035","article-title":"Natural and Synthetic Peptides with Antifungal Activity","volume":"8","author":"Ciociola","year":"2016","journal-title":"Future Med. Chem."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1038\/nrmicro2095","article-title":"Antimicrobial Peptides: Linking Partition, Activity and High Membrane-Bound Concentrations","volume":"7","author":"Melo","year":"2009","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"254","DOI":"10.1002\/2211-5463.13847","article-title":"Structural Information in Therapeutic Peptides: Emerging Applications in Biomedicine","volume":"15","author":"Iglesias","year":"2025","journal-title":"FEBS Open Bio"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"2679","DOI":"10.1007\/s12033-023-00873-1","article-title":"Peptide-Based Therapeutics in Cancer Therapy","volume":"66","author":"Jalil","year":"2024","journal-title":"Mol. Biotechnol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"117149","DOI":"10.1016\/j.ejmech.2024.117149","article-title":"The Novel \u03b2-Hairpin Antimicrobial Peptide D-G(RF)3 Demonstrates Exceptional Antibacterial Efficacy","volume":"283","author":"Li","year":"2025","journal-title":"Eur. J. Med. Chem."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Purohit, K., Reddy, N., and Sunna, A. (2024). Exploring the Potential of Bioactive Peptides: From Natural Sources to Therapeutics. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25031391"},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Tang, S., Chen, D., Shen, H., Yuan, Z., Wei, H., Feng, Y., Li, L., Dong, J., and Zhang, L. (2025). Discovery of Two Novel ACE Inhibitory Peptides from Soybeans: Stability, Molecular Interactions, and in Vivo Antihypertensive Effects. Int. J. Biol. Macromol., 308.","DOI":"10.1016\/j.ijbiomac.2025.142247"},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Xu, B., Dong, Q., Yu, C., Chen, H., Zhao, Y., Zhang, B., Yu, P., and Chen, M. (2024). Advances in Research on the Activity Evaluation, Mechanism and Structure-Activity Relationships of Natural Antioxidant Peptides. Antioxidants, 13.","DOI":"10.3390\/antiox13040479"},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Al Musaimi, O., AlShaer, D., de la Torre, B.G., and Albericio, F. (2025). 2024 FDA TIDES (Peptides and Oligonucleotides) Harvest. Pharmaceuticals, 18.","DOI":"10.3390\/ph18030291"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"467","DOI":"10.1016\/j.tibs.2025.01.009","article-title":"From Lead to Market: Chemical Approaches to Transform Peptides into Therapeutics","volume":"50","author":"Gare","year":"2025","journal-title":"Trends Biochem. Sci."},{"key":"ref_31","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_32","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1038\/s41586-024-07487-w","article-title":"Accurate Structure Prediction of Biomolecular Interactions with AlphaFold 3","volume":"630","author":"Abramson","year":"2024","journal-title":"Nature"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"105920","DOI":"10.1016\/j.isci.2022.105920","article-title":"How Good Are AlphaFold Models for Docking-Based Virtual Screening?","volume":"26","author":"Scardino","year":"2023","journal-title":"iScience"},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Wong, F., Krishnan, A., Zheng, E.J., St\u00e4rk, H., Manson, A.L., Earl, A.M., Jaakkola, T., and Collins, J.J. (2022). Benchmarking AlphaFold Enabled Molecular Docking Predictions for Antibiotic Discovery. Mol. Syst. Biol., 18.","DOI":"10.15252\/msb.202211081"},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Xia, X. (2021). Domains and Functions of Spike Protein in SARS-Cov-2 in the Context of Vaccine Design. Viruses, 13.","DOI":"10.3390\/v13010109"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1984","DOI":"10.1016\/j.ymthe.2021.02.007","article-title":"Nanoluciferase Complementation-Based Bioreporter Reveals the Importance of N-Linked Glycosylation of SARS-CoV-2 S for Viral Entry","volume":"29","author":"Azad","year":"2021","journal-title":"Mol. Ther."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Cruz-Cardenas, J.A., Gutierrez, M., L\u00f3pez-Arredondo, A., Casta\u00f1eda-Delgado, J.E., Rojas-Martinez, A., Nakamura, Y., Enciso-Moreno, J.A., Palomares, L.A., and Brunck, M.E.G. (2022). A Pseudovirus-Based Platform to Measure Neutralizing Antibodies in Mexico Using SARS-CoV-2 as Proof-of-Concept. Sci. Rep., 12.","DOI":"10.1038\/s41598-022-22921-7"},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Dick, K., Samanfar, B., Barnes, B., Cober, E.R., Mimee, B., Tan, L.H., Molnar, S.J., Biggar, K.K., Golshani, A., and Dehne, F. (2020). PIPE4: Fast PPI Predictor for Comprehensive Inter- and Cross-Species Interactomes. Sci. Rep., 10.","DOI":"10.1038\/s41598-019-56895-w"},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Brown, E.E.F., Rezaei, R., Jamieson, T.R., Dave, J., Martin, N.T., Singaravelu, R., Crupi, M.J.F., Boulton, S., Tucker, S., and Duong, J. (2021). Characterization of Critical Determinants of ACE2\u2013SARS CoV-2 RBD Interaction. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22052268"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1016\/j.cellsig.2018.08.012","article-title":"TAZ Enhances Mammary Cell Proliferation in 3D Culture through Transcriptional Regulation of IRS1","volume":"52","author":"Lai","year":"2018","journal-title":"Cell. Signal."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/21\/10607\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,11,3]],"date-time":"2025-11-03T13:17:58Z","timestamp":1762175878000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/21\/10607"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10,31]]},"references-count":40,"journal-issue":{"issue":"21","published-online":{"date-parts":[[2025,11]]}},"alternative-id":["ijms262110607"],"URL":"https:\/\/doi.org\/10.3390\/ijms262110607","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,10,31]]}}}