{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T17:54:34Z","timestamp":1785434074100,"version":"3.56.0"},"reference-count":94,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2026,5,5]],"date-time":"2026-05-05T00:00:00Z","timestamp":1777939200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"UE","award":["MCIN\/AEI\/10.13039\/501100011033\/FEDER"],"award-info":[{"award-number":["MCIN\/AEI\/10.13039\/501100011033\/FEDER"]}]},{"award":["MCIN\/AEI\/10.13039\/501100011033\/FEDER"],"award-info":[{"award-number":["MCIN\/AEI\/10.13039\/501100011033\/FEDER"]}],"id":[{"id":"https:\/\/ror.org\/01rm1r711","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003030","name":"AGAUR","doi-asserted-by":"publisher","award":["2021\/SGR\/0113"],"award-info":[{"award-number":["2021\/SGR\/0113"]}],"id":[{"id":"10.13039\/501100003030","id-type":"DOI","asserted-by":"publisher"}]},{"award":["2021\/SGR\/0113"],"award-info":[{"award-number":["2021\/SGR\/0113"]}],"id":[{"id":"https:\/\/ror.org\/01n4pqe45","id-type":"ROR","asserted-by":"publisher"}]},{"name":"PROGRAMAS DE BECAS MAEC-AECID"},{"id":[{"id":"https:\/\/ror.org\/00r6akf90","id-type":"ROR","asserted-by":"publisher"}]},{"name":"fellowships","award":["PREP2022-000394"],"award-info":[{"award-number":["PREP2022-000394"]}]},{"name":"fellowships","award":["PRE2020-093993"],"award-info":[{"award-number":["PRE2020-093993"]}]},{"name":"fellowships","award":["FPU21-06217"],"award-info":[{"award-number":["FPU21-06217"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Animal venoms induce systemic inflammatory response syndrome through their interaction, inter alia, with pattern recognition receptors (PRRs) of the innate immune system. CD5 and CD6 are lymphoid members of the scavenger receptor cysteine-rich superfamily, endowed with PRR activity against microbial-associated molecular patterns (MAMPs) derived from bacteria, fungi, viruses and\/or parasites. In this study, we aimed to investigate CD5 and CD6 interaction with cobra (Naja haje), scorpion (Androctonus australis) and honeybee (Apis mellifera) venoms. Binding assays revealed direct, dose-dependent and specific interaction of soluble human CD5 and CD6 receptors with protein nature components from the three venoms. Proteomic analysis identified venom nerve growth factor, basic phospholipase A2 (PLA2) and cobra venom factor, in cobra venom, and scorpion venom toxins targeting potassium (\u03b1-KTx 8.1) and sodium channels (Neurotoxin-1\u2033 and G-TI) as potentially interacting components with CD5 and CD6. Further studies confirmed direct binding of bee venom main components, phospholipase A2 and melittin, to both soluble CD5 and CD6 receptors. Interestingly, in vitro PLA2 activity from cobra and bee venom was significantly reduced by both soluble CD5 and CD6 receptors. These findings broaden the PRR properties of CD5 and CD6 and support their potential involvement in envenomation pathophysiology.<\/jats:p>","DOI":"10.3390\/biom16050681","type":"journal-article","created":{"date-parts":[[2026,5,5]],"date-time":"2026-05-05T10:01:30Z","timestamp":1777975290000},"page":"681","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Interaction of Human Lymphocyte Scavenger Receptors CD5 and CD6 with Toxins from Naja haje, Androctonus australis and Apis mellifera Venoms"],"prefix":"10.3390","volume":"16","author":[{"given":"Dalila","family":"Khemili","sequence":"first","affiliation":[{"name":"Laboratory of Cellular and Molecular Biology-Tamayouz, Faculty of Biological Sciences, University of Science and Technology Houari Boumediene (USTHB), BP 32, El Alia, Bab Ezzouar, Algiers 16111, Algeria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Carrillo-Serradell","sequence":"additional","affiliation":[{"name":"Group of Immunoreceptors of the Innate and Adaptive System, Institut d\u2019Investigacions Biom\u00e8diques August Pi i Sunyer (IDIBAPS), 08036 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6511-6440","authenticated-orcid":false,"given":"Violeta","family":"Planells-Romeo","sequence":"additional","affiliation":[{"name":"Group of Immunoreceptors of the Innate and Adaptive System, Institut d\u2019Investigacions Biom\u00e8diques August Pi i Sunyer (IDIBAPS), 08036 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luc\u00eda","family":"Arag\u00f3n-Serrano","sequence":"additional","affiliation":[{"name":"Group of Immunoreceptors of the Innate and Adaptive System, Institut d\u2019Investigacions Biom\u00e8diques August Pi i Sunyer (IDIBAPS), 08036 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Selma","family":"Djilani","sequence":"additional","affiliation":[{"name":"Research and Development Laboratory, Institut Pasteur Alg\u00e9rie, University of Health Sciences, Algiers 16000, Algeria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Djelila","family":"Hammoudi-Triki","sequence":"additional","affiliation":[{"name":"Laboratory of Cellular and Molecular Biology-Tamayouz, Faculty of Biological Sciences, University of Science and Technology Houari Boumediene (USTHB), BP 32, El Alia, Bab Ezzouar, Algiers 16111, Algeria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Khedidja","family":"Zerouti","sequence":"additional","affiliation":[{"name":"Laboratory of Cellular and Molecular Biology-Tamayouz, Faculty of Biological Sciences, University of Science and Technology Houari Boumediene (USTHB), BP 32, El Alia, Bab Ezzouar, Algiers 16111, Algeria"},{"name":"Faculty of Natural Sciences and Life, Department of Biology, Saad Dahlab-Blida 1 University, P.O. Box 270 Soumaa Road, Blida 09000, Algeria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7515-4651","authenticated-orcid":false,"given":"Abdenacer","family":"Mouffok","sequence":"additional","affiliation":[{"name":"Laboratory of Applied Microbiology, Department of Microbiology, Faculty of Nature and Life Sciences, Setif 1 University\u2014Ferhat ABBAS, Setif 19000, Algeria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1119-4368","authenticated-orcid":false,"given":"Francisco","family":"Lozano","sequence":"additional","affiliation":[{"name":"Group of Immunoreceptors of the Innate and Adaptive System, Institut d\u2019Investigacions Biom\u00e8diques August Pi i Sunyer (IDIBAPS), 08036 Barcelona, Spain"},{"name":"Servei d\u2019Immunologia, Hospital Cl\u00ednic de Barcelona, 08036 Barcelona, Spain"},{"name":"Departament de Biomedicina, Facultat de Medicina, Universitat de Barcelona, 08036 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1230-3845","authenticated-orcid":false,"given":"Mar\u00eda","family":"Velasco-de-Andr\u00e9s","sequence":"additional","affiliation":[{"name":"Group of Immunoreceptors of the Innate and Adaptive System, Institut d\u2019Investigacions Biom\u00e8diques August Pi i Sunyer (IDIBAPS), 08036 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,5]]},"reference":[{"key":"ref_1","first-page":"399","article-title":"Venom peptide modulators of the immune system","volume":"10","author":"Inserra","year":"2011","journal-title":"Inflamm. Allergy-Drug Targets (Former. Curr. Drug Targets-Inflamm. Allergy) (Discontin.)"},{"key":"ref_2","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_3","doi-asserted-by":"crossref","first-page":"1968","DOI":"10.1016\/j.drudis.2019.06.012","article-title":"Neurobiology and therapeutic utility of neurotoxins targeting postsynaptic mechanisms of neuromuscular transmission","volume":"24","author":"Ayvazyan","year":"2019","journal-title":"Drug Discov. Today"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"828","DOI":"10.1124\/pharmrev.123.000923","article-title":"Conotoxins targeting voltage-gated sodium ion channels","volume":"76","author":"Pei","year":"2024","journal-title":"Pharmacol. Rev."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"e21835","DOI":"10.1002\/jbt.21835","article-title":"Biochemical and biological characterization of a dermonecrotic metalloproteinase isolated from Cerastes cerastes snake venom","volume":"31","author":"Ami","year":"2017","journal-title":"J. Biochem. Mol. Toxicol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"455","DOI":"10.33549\/physiolres.935125","article-title":"Bee venom causes oxidative stress, biochemical and histopathological changes in the kidney of mice","volume":"72","author":"Dahdouh","year":"2023","journal-title":"Physiol. Res."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"841","DOI":"10.1016\/S0300-9084(00)01163-9","article-title":"Snake venom metalloproteinases: Their role in the pathogenesis of local tissue damage","volume":"82","author":"Rucavado","year":"2000","journal-title":"Biochimie"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"915","DOI":"10.1016\/j.toxicon.2003.11.005","article-title":"Skeletal muscle degeneration induced by venom phospholipases A2: Insights into the mechanisms of local and systemic myotoxicity","volume":"42","author":"Ownby","year":"2003","journal-title":"Toxicon"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"105274","DOI":"10.1016\/j.actatropica.2019.105274","article-title":"Myotoxicity induced by Cerastes cerastes venom: Beneficial effect of heparin in skeletal muscle tissue regeneration","volume":"202","author":"Nourreddine","year":"2020","journal-title":"Acta Trop."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"697","DOI":"10.1016\/0041-0101(93)90376-T","article-title":"Cardiotoxin 1 from cobra (Naja naja atra) venom causes necrosis of skeletal muscle in vivo","volume":"31","author":"Ownby","year":"1993","journal-title":"Toxicon"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"703","DOI":"10.1016\/S0041-0101(00)00200-2","article-title":"Evidence for a direct action of Tityus serrulatus scorpion venom on the cardiac muscle","volume":"39","author":"Teixeira","year":"2001","journal-title":"Toxicon"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1002\/9783527692156.ch5","article-title":"Venoms","volume":"5","author":"Teixeira","year":"2017","journal-title":"Inflamm. Mol. Cell. Mech. Clin."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"11175","DOI":"10.1038\/s41598-019-47557-y","article-title":"Inhibition of snake venom induced sterile inflammation and PLA2 activity by Titanium dioxide Nanoparticles in experimental animals","volume":"9","author":"Chakrabartty","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1016\/j.toxicon.2022.05.043","article-title":"Role of Toll-like receptors in local effects in a model of experimental envenoming induced by Bothrops jararacussu snake venom and by two phospholipases A2","volume":"214","author":"Fontana","year":"2022","journal-title":"Toxicon"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1007\/s10753-019-01105-y","article-title":"Involvement of toll-like receptor 4 in neutrophil-mediated inflammation, oxidative stress and tissue damage induced by scorpion venom","volume":"43","author":"Khemili","year":"2020","journal-title":"Inflammation"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1016\/j.toxicon.2016.04.042","article-title":"The role of TLR2 in the acute inflammatory response induced by Bothrops atrox snake venom","volume":"118","author":"Moreira","year":"2016","journal-title":"Toxicon"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Zornetta, I., Caccin, P., Fernandez, J., Lomonte, B., Gutierrez, J.M., and Montecucco, C. (2012). Envenomations by Bothrops and Crotalus snakes induce the release of mitochondrial alarmins. PLoS Neglected Trop. Dis., 6.","DOI":"10.1371\/journal.pntd.0001526"},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Resiere, D., Mehdaoui, H., and Neviere, R. (2022). Inflammation and oxidative stress in snakebite envenomation: A brief descriptive review and clinical implications. Toxins, 14.","DOI":"10.3390\/toxins14110802"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"602","DOI":"10.1016\/j.ijbiomac.2020.05.169","article-title":"Naja kaouthia venom protein, Nk-CRISP, upregulates inflammatory gene expression in human macrophages","volume":"160","author":"Deka","year":"2020","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"174","DOI":"10.1016\/j.toxicon.2019.06.219","article-title":"Scorpion envenomation and inflammation: Beyond neurotoxic effects","volume":"167","author":"Reis","year":"2019","journal-title":"Toxicon"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Ryan, R.Y., Seymour, J., Loukas, A., Lopez, J.A., Ikonomopoulou, M.P., and Miles, J.J. (2021). Immunological responses to envenomation. Front. Immunol., 12.","DOI":"10.3389\/fimmu.2021.661082"},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Zoccal, K.F., Bitencourt, C.d.S., Paula-Silva, F.W.G., Sorgi, C.A., de Castro Figueiredo Bordon, K., Arantes, E.C., and Faccioli, L.H. (2014). TLR2, TLR4 and CD14 recognize venom-associated molecular patterns from Tityus serrulatus to induce macrophage-derived inflammatory mediators. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0088174"},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Zoccal, K.F., Gardinassi, L.G., Sorgi, C.A., Meirelles, A.F., Bordon, K.C., Glezer, I., Cupo, P., Matsuno, A.K., Bollela, V.R., and Arantes, E.C. (2018). CD36 shunts eicosanoid metabolism to repress CD14 licensed interleukin-1\u03b2 release and inflammation. Front. Immunol., 9.","DOI":"10.3389\/fimmu.2018.00890"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"773","DOI":"10.1007\/s10753-018-0731-9","article-title":"Involvement of alveolar macrophages and neutrophils in acute lung injury after scorpion envenomation: New pharmacological targets","volume":"41","author":"Saidi","year":"2018","journal-title":"Inflammation"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"556","DOI":"10.1016\/j.ijbiomac.2019.08.108","article-title":"First report on BaltCRP, a cysteine-rich secretory protein (CRISP) from Bothrops alternatus venom: Effects on potassium channels and inflammatory processes","volume":"140","author":"Bernardes","year":"2019","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"42673","DOI":"10.1038\/srep42673","article-title":"CR-LAAO, an L-amino acid oxidase from Calloselasma rhodostoma venom, as a potential tool for developing novel immunotherapeutic strategies against cancer","volume":"7","author":"Costa","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Li, R., Tang, Y., Chen, Z., and Liu, Y. (2024). Screening TLR4 Binding Peptide from Naja atra Venom Glands Based on Phage Display. Toxins, 16.","DOI":"10.3390\/toxins16030113"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"R790","DOI":"10.1016\/j.cub.2020.05.051","article-title":"Scavenger receptors","volume":"30","author":"Alquraini","year":"2020","journal-title":"Curr. Biol."},{"key":"ref_29","first-page":"255","article-title":"PRR function of innate immune receptors in recognition of bacteria or bacterial ligands","volume":"1112","author":"Gulati","year":"2019","journal-title":"Biochem. Biophys. Roles Cell Surf. Mol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"967","DOI":"10.1124\/pr.111.004523","article-title":"The conserved scavenger receptor cysteine-rich superfamily in therapy and diagnosis","volume":"63","author":"Moestrup","year":"2011","journal-title":"Pharmacol. Rev."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"3775","DOI":"10.4049\/jimmunol.1700373","article-title":"A consensus definitive classification of scavenger receptors and their roles in health and disease","volume":"198","author":"PrabhuDas","year":"2017","journal-title":"J. Immunol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1186\/s12964-021-00812-0","article-title":"Scavenger receptors in host defense: From functional aspects to mode of action","volume":"20","author":"Taban","year":"2022","journal-title":"Cell Commun. Signal."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1111\/imr.12646","article-title":"TCR tuning of T cell subsets","volume":"283","author":"Cho","year":"2018","journal-title":"Immunol. Rev."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"2519682","DOI":"10.1080\/07853890.2025.2519682","article-title":"The multiple functions of CD5 in diseases related to immune disorders","volume":"57","author":"Dong","year":"2025","journal-title":"Ann. Med."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Velasco-de Andr\u00e9s, M., Casad\u00f3-Llombart, S., Catal\u00e0, C., Leyton-Pereira, A., Lozano, F., and Aranda, F. (2020). Soluble CD5 and CD6: Lymphocytic class I scavenger receptors as immunotherapeutic agents. Cells, 9.","DOI":"10.3390\/cells9122589"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1506","DOI":"10.1073\/pnas.0805846106","article-title":"The CD5 ectodomain interacts with conserved fungal cell wall components and protects from zymosan-induced septic shock-like syndrome","volume":"106","author":"Vera","year":"2009","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"3723","DOI":"10.1128\/JVI.06956-11","article-title":"Hepatitis C virus infection of human T lymphocytes is mediated by CD5","volume":"86","author":"Sarhan","year":"2012","journal-title":"J. Virol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"11724","DOI":"10.1073\/pnas.0702815104","article-title":"CD6 binds to pathogen-associated molecular patterns and protects from LPS-induced septic shock","volume":"104","author":"Sarrias","year":"2007","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"A49","DOI":"10.1089\/aid.2014.5085.abstract","article-title":"A role for scavenger-like lymphocyte receptor CD6 in HIV-1 viral infection","volume":"30","author":"Carrasco","year":"2014","journal-title":"AIDS Res. Hum. Retroviruses"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"3718","DOI":"10.1016\/j.ijbiomac.2020.08.219","article-title":"Interactome analysis of CD5 and CD6 ectodomains with tegumental antigens from the helminth parasite Echinococcus granulosus sensu lato","volume":"164","author":"Miles","year":"2020","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Mourglia-Ettlin, G., Miles, S., Velasco-De-Andres, M., Armiger-Borras, N., Cucher, M., Dematteis, S., and Lozano, F. (2018). The ectodomains of the lymphocyte scavenger receptors CD5 and CD6 interact with tegumental antigens from Echinococcus granulosus sensu lato and protect mice against secondary cystic echinococcosis. PLoS Neglected Trop. Dis., 12.","DOI":"10.1371\/journal.pntd.0006891"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"e13034","DOI":"10.1111\/pim.13034","article-title":"Recombinant CD5 and CD6 Ectodomains Induce Antiparasitic and Immunomodulatory Effects in Secondary Cystic Echinococcosis","volume":"46","author":"Arbildi","year":"2024","journal-title":"Parasite Immunol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1077","DOI":"10.1093\/infdis\/jit624","article-title":"Targeting of key pathogenic factors from gram-positive bacteria by the soluble ectodomain of the scavenger-like lymphocyte receptor CD6","volume":"209","author":"Vila","year":"2014","journal-title":"J. Infect. Dis."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"4307","DOI":"10.4049\/jimmunol.159.9.4307","article-title":"The cytoplasmic domain of CD5 mediates both TCR\/CD3-dependent and-independent diacylglycerol production","volume":"159","author":"Simarro","year":"1997","journal-title":"J. Immunol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1128\/JCM.00375-20","article-title":"A method to prevent SARS-CoV-2 IgM false positives in gold immunochromatography and enzyme-linked immunosorbent assays","volume":"58","author":"Wang","year":"2020","journal-title":"J. Clin. Microbiol."},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Wang, Q., Lei, Y., Lu, X., Wang, G., Du, Q., Guo, X., Xing, Y., Zhang, G., and Wang, D. (2019). Urea-mediated dissociation alleviate the false-positive Treponema pallidum-specific antibodies detected by ELISA. PLoS ONE, 14.","DOI":"10.1371\/journal.pone.0212893"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1016\/j.mcp.2012.01.002","article-title":"Development and application of a GuHCl-modified ELISA to measure the avidity of anti-HPV L1 VLP antibodies in vaccinated individuals","volume":"26","author":"Dauner","year":"2012","journal-title":"Mol. Cell. Probes"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"680","DOI":"10.1038\/227680a0","article-title":"Cleavage of structural proteins during the assembly of the head of bacteriophage T4","volume":"227","author":"Laemmli","year":"1970","journal-title":"Nature"},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Arndt, C., Koristka, S., Feldmann, A., and Bachmann, M. (2018). Native polyacrylamide gels. Electrophoretic Separation of Proteins: Methods and Protocols, Springer.","DOI":"10.1007\/978-1-4939-8793-1_8"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1016\/j.biochi.2014.12.020","article-title":"Anticoagulant mechanism and platelet deaggregation property of a non-cytotoxic, acidic phospholipase A2 purified from Indian cobra (Naja naja) venom: Inhibition of anticoagulant activity by low molecular weight heparin","volume":"110","author":"Dutta","year":"2015","journal-title":"Biochimie"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1111\/j.1432-1033.1980.tb06112.x","article-title":"Purification, some properties and amino-acid sequences of two phospholipases A (CM-II and CM-III) from Naja naja kaouthia venom","volume":"112","author":"Joubert","year":"1980","journal-title":"Eur. J. Biochem."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1016\/j.bpc.2016.11.010","article-title":"Effect of urea on protein-ligand association","volume":"231","author":"Stepanian","year":"2017","journal-title":"Biophys. Chem."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1016\/j.toxicon.2016.01.062","article-title":"Human scFv antibodies (Afribumabs) against Africanized bee venom: Advances in melittin recognition","volume":"112","author":"Pessenda","year":"2016","journal-title":"Toxicon"},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Pucca, M.B., Cerni, F.A., Oliveira, I.S., Jenkins, T.P., Argem\u00ed, L., S\u00f8rensen, C.V., Ahmadi, S., Barbosa, J.E., and Laustsen, A.H. (2019). Bee updated: Current knowledge on bee venom and bee envenoming therapy. Front. Immunol., 10.","DOI":"10.3389\/fimmu.2019.02090"},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Wehbe, R., Frangieh, J., Rima, M., El Obeid, D., Sabatier, J.-M., and Fajloun, Z. (2019). Bee venom: Overview of main compounds and bioactivities for therapeutic interests. Molecules, 24.","DOI":"10.3390\/molecules24162997"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"2851","DOI":"10.1007\/s00018-009-0050-2","article-title":"Protein complexes in snake venom","volume":"66","author":"Doley","year":"2009","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1080\/15569543.2016.1220397","article-title":"Toxin synergism in snake venoms","volume":"35","author":"Laustsen","year":"2016","journal-title":"Toxin Rev."},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"McFarlane, L.O., and Pukala, T.L. (2024). Proteomic investigation of cape cobra (Naja nivea) venom reveals first evidence of quaternary protein structures. Toxins, 16.","DOI":"10.3390\/toxins16020063"},{"key":"ref_59","first-page":"37","article-title":"Non-covalent interaction of phospholipase A2 (PLA2) and kaouthiotoxin (KTX) from venom of Naja kaouthia exhibits marked synergism to potentiate their cytotoxicity on target cells","volume":"1","author":"Mukherjee","year":"2010","journal-title":"J. Venom Res."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"103680","DOI":"10.1016\/j.jprot.2020.103680","article-title":"Interrogating the higher order structures of snake venom proteins using an integrated mass spectrometric approach","volume":"216","author":"Wang","year":"2020","journal-title":"J. Proteom."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1016\/j.toxlet.2018.02.004","article-title":"Synergistic strategies of predominant toxins in snake venoms","volume":"287","author":"Xiong","year":"2018","journal-title":"Toxicol. Lett."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1016\/j.toxicon.2021.03.014","article-title":"Proteomic analysis of three medically important Nigerian Naja (Naja haje, Naja katiensis and Naja nigricollis) snake venoms","volume":"197","author":"Adamude","year":"2021","journal-title":"Toxicon"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"240","DOI":"10.1016\/j.jprot.2013.11.012","article-title":"Proteomic analysis of Moroccan cobra Naja haje legionis venom using tandem mass spectrometry","volume":"96","author":"Malih","year":"2014","journal-title":"J. Proteom."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"526","DOI":"10.1007\/s00203-022-03139-7","article-title":"Egyptian cobra (Naja haje haje) venom phospholipase A2: A promising antiviral agent with potent virucidal activity against simian rotavirus and bovine coronavirus","volume":"204","author":"Salama","year":"2022","journal-title":"Arch. Microbiol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"32835","DOI":"10.1016\/S0021-9258(20)30067-3","article-title":"The kaliotoxin family enlarged. Purification, characterization, and precursor nucleotide sequence of KTX2 from Androctonus australis venom","volume":"269","author":"Legros","year":"1994","journal-title":"J. Biol. Chem."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"19259","DOI":"10.1016\/S0021-9258(19)47295-5","article-title":"Precursors of Androctonus australis scorpion neurotoxins: Structures of precursors, processing outcomes, and expression of a functional recombinant toxin II","volume":"264","author":"Bougis","year":"1989","journal-title":"J. Biol. Chem."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"310","DOI":"10.1080\/15569543.2019.1614064","article-title":"Nontoxic fraction of scorpion venom reduces bacterial growth and inflammatory response in a mouse model of infection","volume":"40","author":"Zerouti","year":"2021","journal-title":"Toxin Rev."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1016\/S0307-4412(00)00029-7","article-title":"Enzyme kinetics: Partial and complete uncompetitive inhibition","volume":"28","author":"Whiteley","year":"2000","journal-title":"Biochem. Educ."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"550","DOI":"10.1038\/ki.2015.147","article-title":"Phospholipase A2 inhibits cisplatin-induced acute kidney injury by modulating regulatory T cells by the CD206 mannose receptor","volume":"88","author":"Kim","year":"2015","journal-title":"Kidney Int."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1006\/abbi.1995.9926","article-title":"Bee venom Phospholipase A2Is recognized by the Macrophage Mannose receptor","volume":"324","author":"Mukhopadhyay","year":"1995","journal-title":"Arch. Biochem. Biophys."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"7443","DOI":"10.1073\/pnas.85.20.7443","article-title":"Orthorhombic crystals and three-dimensional structure of the potent toxin II from the scorpion Androctonus australis hector","volume":"85","author":"Rochat","year":"1988","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s00249-018-1323-1","article-title":"Differential effect of Androctonus australis hector venom components on macrophage KV channels: Electrophysiological characterization","volume":"48","author":"Khemili","year":"2019","journal-title":"Eur. Biophys. J."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1016\/j.biochi.2015.04.010","article-title":"Electrophysiological characterization of the first Tityus serrulatus alpha-like toxin, Ts5: Evidence of a pro-inflammatory toxin on macrophages","volume":"115","author":"Pucca","year":"2015","journal-title":"Biochimie"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1016\/j.toxicon.2014.02.011","article-title":"Macrophage alteration induced by inflammatory toxins isolated from Tityus discrepans scorpion venom. The role of Na+\/Ca2+ exchangers","volume":"82","author":"Sevcik","year":"2014","journal-title":"Toxicon"},{"key":"ref_75","doi-asserted-by":"crossref","unstructured":"Mendes, L.C., Viana, G.M.M., Nencioni, A.L.A., Pimenta, D.C., and Beraldo-Neto, E. (2023). Scorpion peptides and ion channels: An insightful review of mechanisms and drug development. Toxins, 15.","DOI":"10.3390\/toxins15040238"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"661","DOI":"10.1016\/j.toxicon.2004.02.021","article-title":"Quantitative variability in the biodistribution and in toxinokinetic studies of the three main alpha toxins from the Androctonus australis hector scorpion venom","volume":"43","author":"Devaux","year":"2004","journal-title":"Toxicon"},{"key":"ref_77","doi-asserted-by":"crossref","unstructured":"Vogel, C.-W., Bredehorst, R., Fritzinger, D.C., Grunwald, T., Ziegelm\u00fcller, P., and Kock, M.A. (1996). Structure and function of cobra venom factor, the complement-activating protein in cobra venom. Natural Toxins 2: Structure, Mechanism of Action, and Detection, Springer.","DOI":"10.1007\/978-1-4613-0361-9_6"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"1198","DOI":"10.1016\/j.toxicon.2010.04.007","article-title":"Cobra venom factor: Structure, function, and humanization for therapeutic complement depletion","volume":"56","author":"Vogel","year":"2010","journal-title":"Toxicon"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/j.toxicon.2012.09.006","article-title":"Phospholipases A2: Unveiling the secrets of a functionally versatile group of snake venom toxins","volume":"62","author":"Lomonte","year":"2013","journal-title":"Toxicon"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"451","DOI":"10.1038\/s41570-022-00393-7","article-title":"The chemistry of snake venom and its medicinal potential","volume":"6","author":"Oliveira","year":"2022","journal-title":"Nat. Rev. Chem."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1186\/1678-9199-20-42","article-title":"Hepatotoxicity and oxidative stress induced by Naja haje crude venom","volume":"20","author":"Dkhil","year":"2014","journal-title":"J. Venom. Anim. Toxins Incl. Trop. Dis."},{"key":"ref_82","doi-asserted-by":"crossref","unstructured":"Mejri, H., Mokrani, R., Ksouri, A., Seddik, M., Awad, N., Ayme, G., Chagour, T., Mokrani, A., Louchene, C.E., and Salhi, I. (2024). Neutralizing nanobodies against venoms from Naja haje species captured in north africa. Toxins, 16.","DOI":"10.3390\/toxins16090393"},{"key":"ref_83","doi-asserted-by":"crossref","unstructured":"Silva, A., Hodgson, W.C., and Isbister, G.K. (2017). Antivenom for neuromuscular paralysis resulting from snake envenoming. Toxins, 9.","DOI":"10.3390\/toxins9040143"},{"key":"ref_84","doi-asserted-by":"crossref","unstructured":"Bickler, P.E. (2020). Amplification of snake venom toxicity by endogenous signaling pathways. Toxins, 12.","DOI":"10.3390\/toxins12020068"},{"key":"ref_85","doi-asserted-by":"crossref","unstructured":"Ivanu\u0161ec, A., \u0160ribar, J., Verani\u010d, P., and Kri\u017eaj, I. (2022). The phospholipase activity of ammodytoxin, a prototype snake venom \u03b2-neurotoxin, is not obligatory for cell Internalisation and translocation to mitochondria. Toxins, 14.","DOI":"10.3390\/toxins14060375"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1186\/s40409-018-0170-y","article-title":"Cytotoxic and inflammatory potential of a phospholipase A 2 from Bothrops jararaca snake venom","volume":"24","author":"Cedro","year":"2018","journal-title":"J. Venom. Anim. Toxins Incl. Trop. Dis."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"e21945","DOI":"10.1002\/jbt.21945","article-title":"Purification and partial characterization of an anticoagulant PLA2 from the venom of Indian Daboia russelii that induces inflammation through upregulation of proinflammatory mediators","volume":"31","author":"Deka","year":"2017","journal-title":"J. Biochem. Mol. Toxicol."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1016\/j.cbi.2017.12.022","article-title":"Evaluation of pro-inflammatory events induced by Bothrops alternatus snake venom","volume":"281","author":"Echeverria","year":"2018","journal-title":"Chem.-Biol. Interact."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"428","DOI":"10.1016\/j.toxicon.2008.06.012","article-title":"Secretory phospholipases A2 isolated from Bothrops asper and from Crotalus durissus terrificus snake venoms induce distinct mechanisms for biosynthesis of prostaglandins E2 and D2 and expression of cyclooxygenases","volume":"52","author":"Moreira","year":"2008","journal-title":"Toxicon"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"483","DOI":"10.1146\/annurev.genom.9.081307.164356","article-title":"The toxicogenomic multiverse: Convergent recruitment of proteins into animal venoms","volume":"10","author":"Fry","year":"2009","journal-title":"Annu. Rev. Genom. Hum. Genet."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"386","DOI":"10.1007\/s12016-017-8597-4","article-title":"Immunology of bee venom","volume":"54","author":"Shafaghat","year":"2018","journal-title":"Clin. Rev. Allergy Immunol."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1007\/s000110300026","article-title":"Analysis of the inflammatory response in the rat paw caused by the venom of Apis melifera bee","volume":"52","author":"Calixto","year":"2003","journal-title":"Inflamm. Res."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1007\/BF01993245","article-title":"Comparison of antiinflammatory and antiallergic drugs in the melittin-and D49 PLA2-induced mouse paw edema models","volume":"34","author":"Hartman","year":"1991","journal-title":"Agents Actions"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"976","DOI":"10.1016\/j.immuni.2013.10.006","article-title":"Bee venom phospholipase A2 induces a primary type 2 response that is dependent on the receptor ST2 and confers protective immunity","volume":"39","author":"Palm","year":"2013","journal-title":"Immunity"}],"container-title":["Biomolecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2218-273X\/16\/5\/681\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,7]],"date-time":"2026-05-07T04:18:52Z","timestamp":1778127532000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2218-273X\/16\/5\/681"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,5]]},"references-count":94,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2026,5]]}},"alternative-id":["biom16050681"],"URL":"https:\/\/doi.org\/10.3390\/biom16050681","relation":{},"ISSN":["2218-273X"],"issn-type":[{"value":"2218-273X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,5]]}}}