{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T21:24:07Z","timestamp":1791321847881,"version":"4.3.1"},"reference-count":40,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2023,5,26]],"date-time":"2023-05-26T00:00:00Z","timestamp":1685059200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Tunisian Ministry of Higher Education and Scientific Research","award":["LR20IPT01"],"award-info":[{"award-number":["LR20IPT01"]}]},{"name":"Tunisian Ministry of Higher Education and Scientific Research","award":["LR16IPT03"],"award-info":[{"award-number":["LR16IPT03"]}]},{"name":"the Pasteur Institute of Tunis","award":["LR20IPT01"],"award-info":[{"award-number":["LR20IPT01"]}]},{"name":"the Pasteur Institute of Tunis","award":["LR16IPT03"],"award-info":[{"award-number":["LR16IPT03"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Newcastle disease virus (NDV) is one of the most serious contagions affecting domestic poultry and other avian species. It causes high morbidity and mortality, resulting in huge economic losses to the poultry industry worldwide. Despite vaccination, NDV outbreaks increase the need for alternative prevention and control means. In this study, we have screened fractions of Buthus occitanus tunetanus (Bot) scorpion venom and isolated the first scorpion peptide inhibiting the NDV multiplication. It showed a dose dependent effect on NDV growth in vitro, with an IC50 of 0.69 \u00b5M, and a low cytotoxicity on cultured Vero cells (CC50 &gt; 55 \u00b5M). Furthermore, tests carried out in specific pathogen-free embryonated chicken eggs demonstrated that the isolated peptide has a protective effect on chicken embryos against NDV, and reduced by 73% the virus titer in allantoic fluid. The N-terminal sequence, as well as the number of cysteine residues of the isolated peptide, showed that it belongs to the scorpion venom Chlorotoxin-like peptides family, which led us to designate it \u201cBotCl\u201d. Interestingly, at 10 \u00b5g\/mL, BotCl showed an inhibiting effect three times higher than its analogue AaCtx, from Androctonus australis (Aa) scorpion venom, on NDV development. Altogether, our results highlight the chlorotoxin-like peptides as a new scorpion venom AMPs family.<\/jats:p>","DOI":"10.3390\/molecules28114355","type":"journal-article","created":{"date-parts":[[2023,5,26]],"date-time":"2023-05-26T02:00:19Z","timestamp":1685066419000},"page":"4355","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["BotCl, the First Chlorotoxin-Like Peptide Inhibiting Newcastle Disease Virus: The Emergence of a New Scorpion Venom AMPs Family"],"prefix":"10.3390","volume":"28","author":[{"given":"Abir","family":"Jlassi","sequence":"first","affiliation":[{"name":"LR20IPT01 Laboratoire des Biomol\u00e9cules, Venins et Applications Th\u00e9ranostiques (LBVAT), Institut Pasteur de Tunis, Universit\u00e9 Tunis El Manar, Tunis 1002, Tunisia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marwa","family":"Mekni-Toujani","sequence":"additional","affiliation":[{"name":"LR16IPT03 Laboratoire d\u2019Epid\u00e9miologie et MicrobiologieV\u00e9t\u00e9rinaire, Institut Pasteur de Tunis, Universit\u00e9 de Tunis El Manar, Tunis 1002, Tunisia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Asma","family":"Ferchichi","sequence":"additional","affiliation":[{"name":"LR20IPT01 Laboratoire des Biomol\u00e9cules, Venins et Applications Th\u00e9ranostiques (LBVAT), Institut Pasteur de Tunis, Universit\u00e9 Tunis El Manar, Tunis 1002, Tunisia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2548-0509","authenticated-orcid":false,"given":"Charfeddine","family":"Gharsallah","sequence":"additional","affiliation":[{"name":"LR16IPT02 Laboratoire de Recherche sur la Transmission, le Contr\u00f4le et l\u2019Immunobiologie des Infections, Institut Pasteur de Tunis, Universit\u00e9 de Tunis El Manar, Tunis 1002, Tunisia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Malosse","sequence":"additional","affiliation":[{"name":"Mass Spectrometry for Biology Unit, Institut Pasteur, Universit\u00e9 Paris Cit\u00e9, CNRS UAR 2024, 75015 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia","family":"Chamot-Rooke","sequence":"additional","affiliation":[{"name":"Mass Spectrometry for Biology Unit, Institut Pasteur, Universit\u00e9 Paris Cit\u00e9, CNRS UAR 2024, 75015 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohamed","family":"ElAyeb","sequence":"additional","affiliation":[{"name":"LR20IPT01 Laboratoire des Biomol\u00e9cules, Venins et Applications Th\u00e9ranostiques (LBVAT), Institut Pasteur de Tunis, Universit\u00e9 Tunis El Manar, Tunis 1002, Tunisia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abdeljelil","family":"Ghram","sequence":"additional","affiliation":[{"name":"LR16IPT03 Laboratoire d\u2019Epid\u00e9miologie et MicrobiologieV\u00e9t\u00e9rinaire, Institut Pasteur de Tunis, Universit\u00e9 de Tunis El Manar, Tunis 1002, Tunisia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Najet","family":"Srairi-Abid","sequence":"additional","affiliation":[{"name":"LR20IPT01 Laboratoire des Biomol\u00e9cules, Venins et Applications Th\u00e9ranostiques (LBVAT), Institut Pasteur de Tunis, Universit\u00e9 Tunis El Manar, Tunis 1002, Tunisia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Salma","family":"Daoud","sequence":"additional","affiliation":[{"name":"LR20IPT01 Laboratoire des Biomol\u00e9cules, Venins et Applications Th\u00e9ranostiques (LBVAT), Institut Pasteur de Tunis, Universit\u00e9 Tunis El Manar, Tunis 1002, Tunisia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,5,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"126","DOI":"10.1016\/j.vetmic.2016.12.019","article-title":"Newcastle disease vaccines\u2014A solved problem or a continuous challenge?","volume":"206","author":"Dimitrov","year":"2017","journal-title":"Vet. Microbiol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"443","DOI":"10.20506\/rst.19.2.1231","article-title":"Newcastle disease and other avian paramyxoviruses","volume":"19","author":"Alexander","year":"2000","journal-title":"Rev. Sci. Et Tech.-Off. Int. Des Epizoot."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"2493","DOI":"10.1007\/s00705-017-3311-7","article-title":"Taxonomy of the order Mononegavirales: Update 2017","volume":"162","author":"Amarasinghe","year":"2017","journal-title":"Arch. Virol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1079\/WPS20030011","article-title":"Review of Newcastle disease virus with particular references to immunity and vaccination","volume":"59","author":"Gielkens","year":"2003","journal-title":"World\u2019s Poult. Sci. J."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1186\/1297-9716-42-122","article-title":"Virulence of Newcastle disease virus: What is known so far?","volume":"42","author":"Dortmans","year":"2011","journal-title":"Vet. Res."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"505","DOI":"10.1016\/j.dci.2013.06.007","article-title":"Effects of Newcastle disease virus vaccine antibodies on the shedding and transmission of challenge viruses","volume":"41","author":"Miller","year":"2013","journal-title":"Dev. Comp. Immunol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"7238","DOI":"10.1016\/j.vaccine.2007.07.017","article-title":"Antigenic differences among Newcastle disease virus strains of different genotypes used in vaccine formulation affect viral shedding after a virulent challenge","volume":"25","author":"Miller","year":"2007","journal-title":"Vaccine"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1186\/1743-422X-9-307","article-title":"In vitro characterization of the antiviral activity of fucoidan from Cladosiphonokamuranus against Newcastle Disease Virus","volume":"9","year":"2012","journal-title":"Virol. J."},{"key":"ref_9","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_10","doi-asserted-by":"crossref","first-page":"e148218","DOI":"10.1590\/1678-9199-jvatitd-1482-18","article-title":"Proteome of fraction from Tityus serrulatus venom reveals new enzymes and toxins","volume":"25","author":"Amorim","year":"2019","journal-title":"J. Venom. Anim. Toxins Incl. Trop. Dis."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1016\/j.toxicon.2014.06.006","article-title":"Antimicrobial peptides from scorpion venoms","volume":"88","author":"Harrison","year":"2014","journal-title":"Toxicon"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1186\/s40409-016-0089-0","article-title":"Antiviral activity of animal venom peptides and related compounds","volume":"23","author":"Mata","year":"2017","journal-title":"J. Venom. Anim. Toxins Incl. Trop. Dis."},{"key":"ref_13","first-page":"43","article-title":"Characterisation of a novel toxin active on potassium apamine channels, purified from Buthus occitanus tunetanus scorpion venom","volume":"80","author":"Kharrat","year":"2003","journal-title":"Arch. De L\u2019institut Pasteur De Tunis"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"637","DOI":"10.1016\/j.peptides.2004.02.017","article-title":"Kbot1, a three disulfide bridges toxin from Buthus occitanus tunetanus venom highly active on both SK and Kv channels","volume":"25","author":"Crest","year":"2004","journal-title":"Peptides"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1016\/j.peptides.2015.05.015","article-title":"Kbot55, purified from Buthus occitanus tunetanus venom, represents the first member of a novel \u03b1-KTx subfamily","volume":"80","author":"Peigneur","year":"2016","journal-title":"Peptides"},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"ElFessi, R., Khamessi, O., Srairi-Abid, N., Sabatier, J.-M., Tytgat, J., Peigneur, S., and Kharrat, R. (2022). Purification and Characterization of Bot33: A Non-Toxic Peptide from the Venom of Buthus occitanus tunetanus Scorpion. Molecules, 27.","DOI":"10.3390\/molecules27217278"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"199","DOI":"10.7150\/thno.21425","article-title":"Histidine-rich modification of a scorpion- derived peptide improves bioavailability and inhibitory activity against HSV-1","volume":"8","author":"Zhengyang","year":"2018","journal-title":"Theranostics"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"3256","DOI":"10.1002\/pmic.201300242","article-title":"High throughput screening of disulfide-containing proteins in a complex mixture","volume":"13","author":"Zhao","year":"2013","journal-title":"Proteomics"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"C361","DOI":"10.1152\/ajpcell.1993.264.2.C361","article-title":"Purification and characterization of chlorotoxin, a chloride channel ligand from the venom of the scorpion","volume":"264","author":"DeBin","year":"1993","journal-title":"Am. J. Physiol.-Cell Physiol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"656","DOI":"10.1016\/j.peptides.2011.01.015","article-title":"Purification, synthesis and characterization of AaCtx, the first chlorotoxin-like peptide from Androctonus australis scorpion venom","volume":"32","author":"Rjeibi","year":"2011","journal-title":"Peptides"},{"key":"ref_21","first-page":"996","article-title":"Study of toxic components from the venom of Caucasus subspecies of scorpion Buthus eupeus: Grishin, EV, Volkova, TM and Soldatova, LN (MM Shemyakin Institute of Bioorganic Chemistry, Academy of Sciences of the USSR, Moscow, USSR) Bioorganic eskayaKhimiya 8, 155 (1982)","volume":"22","author":"Kolm","year":"1984","journal-title":"Toxicon"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1068","DOI":"10.1038\/81002","article-title":"Crystal structure of the multifunctional paramyxovirus hemagglutinin-neuraminidase","volume":"7","author":"Crennell","year":"2000","journal-title":"Nat. Struct. Biol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"514","DOI":"10.1111\/j.1432-1033.1970.tb01111.x","article-title":"Purification of animal neurotoxins: Isolation and characterization of eleven neurotoxins from the venoms of the scorpions Androctonus australis Hector, Buthus occitanus tunetanus and Leiurus quinquestriatus quinquestriatus","volume":"16","author":"Miranda","year":"1970","journal-title":"Eur. J. Biochem."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1555","DOI":"10.1002\/ptr.6084","article-title":"Inhibition of HSV-2 infection by pure compounds from Thymus capitatus extract in vitro","volume":"32","author":"Toujani","year":"2018","journal-title":"Phytother. Res."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1016\/j.dci.2004.07.006","article-title":"A hemolysis\u2013hemagglutination assay for characterizing constitutive innate humoral immunity in wild and domestic birds","volume":"29","author":"Matson","year":"2005","journal-title":"Dev. Comp. Immunol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1093\/oxfordjournals.aje.a118408","article-title":"A simple method of estimating fifty per cent endpoints","volume":"27","author":"Reed","year":"1938","journal-title":"Am. J. Epidemiol."},{"key":"ref_27","first-page":"9998420","article-title":"Scorpion-Derived Antiviral Peptides with a Special Focus on Medically Important Viruses: An Update","volume":"2021","author":"Laaradia","year":"2021","journal-title":"BioMed Res. Int."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"811","DOI":"10.1007\/s10989-019-09888-2","article-title":"Smp76, a scorpine-like peptide isolated from the venom of the scorpion Scorpio mauruspalmatus, with a potent antiviral activity against hepatitis C virus and dengue virus","volume":"26","author":"Sarhan","year":"2020","journal-title":"Int. J. Pept. Res. Ther."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"e07454.20","DOI":"10.7554\/eLife.07454","article-title":"Contacts-based prediction of binding affinity in protein\u2013protein complexes","volume":"4","author":"Vangone","year":"2015","journal-title":"eLife"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"3676","DOI":"10.1093\/bioinformatics\/btw514","article-title":"PRODIGY: A web server for predicting the binding affinity of protein\u2013protein complexes","volume":"32","author":"Xue","year":"2016","journal-title":"Bioinformatics"},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Luna-Ramirez, K., Tonk, M., Rahnamaeian, M., and Vilcinskas, A. (2017). Bioactivity of Natural and Engineered Antimicrobial Peptides from Venom of the Scorpions Urodacusyaschenkoi and U. manicatus. Toxins, 9.","DOI":"10.3390\/toxins9010022"},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Chen, Y., Cao, L., Zhong, M., Zhang, Y., Han, C., Li, Q., Yang, J., Zhou, D., Shi, W., and He, B. (2012). Anti-HIV-1 activity of a new scorpion venom peptide derivative Kn2-7. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0034947"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/j.peptides.2010.10.008","article-title":"A new natural \u03b1-helical peptide from the venom of the scorpion Heterometruspetersii kills HCV","volume":"32","author":"Yan","year":"2011","journal-title":"Peptides"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1002\/bip.22748","article-title":"Chlorotoxin: Structure, activity, and potential uses in cancer therapy","volume":"106","author":"Ojeda","year":"2015","journal-title":"Pept. Sci."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"182","DOI":"10.1074\/jbc.RA118.005015","article-title":"A scorpion venom peptide Ev37 restricts viral late entry by alkalizing acidic organelles","volume":"294","author":"Li","year":"2019","journal-title":"J. Biol. Chem."},{"key":"ref_36","first-page":"9","article-title":"Scorpion venom as antimicrobial peptides (AMPs): A review article","volume":"5","author":"Shadi","year":"2015","journal-title":"Int. Arab. J. Antimicrob. Agents"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1016\/j.toxicon.2010.10.008","article-title":"Vejovine, a new antibiotic from the scorpion venom of Vaejovis mexicanus","volume":"57","author":"Balderas","year":"2011","journal-title":"Toxicon"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"3733","DOI":"10.1128\/JVI.78.7.3733-3741.2004","article-title":"Second sialic acid binding site in Newcastle disease virus hemagglutinin-neuraminidase: Implications for fusion","volume":"78","author":"Zaitsev","year":"2004","journal-title":"J. Virol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1007\/s10719-006-5446-8","article-title":"Structural analysis of a designed inhibitor complexed with the hemagglutinin-neuraminidase of Newcastle disease virus","volume":"23","author":"Ryan","year":"2006","journal-title":"Glycoconj. J."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1816","DOI":"10.1128\/JVI.76.4.1816-1824.2002","article-title":"Probing the sialic acid binding site of the hemagglutinin-neuraminidase of Newcastle disease virus: Identification of key amino acids involved in cell binding, catalysis, and fusion","volume":"76","author":"Connaris","year":"2002","journal-title":"J. Virol."}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/28\/11\/4355\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T19:42:29Z","timestamp":1760125349000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/28\/11\/4355"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,5,26]]},"references-count":40,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2023,6]]}},"alternative-id":["molecules28114355"],"URL":"https:\/\/doi.org\/10.3390\/molecules28114355","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,5,26]]}}}