{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T09:17:34Z","timestamp":1787735854403,"version":"build-2784847793"},"reference-count":83,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T00:00:00Z","timestamp":1787702400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100007155","name":"Medical Research Council","doi-asserted-by":"publisher","award":["MR\/W019353\/1"],"award-info":[{"award-number":["MR\/W019353\/1"]}],"id":[{"id":"10.13039\/501100007155","id-type":"DOI","asserted-by":"publisher"}]},{"award":["MR\/W019353\/1"],"award-info":[{"award-number":["MR\/W019353\/1"]}],"id":[{"id":"https:\/\/ror.org\/03x94j517","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Toxins"],"abstract":"<jats:p>Venoms of African spitting cobras, including Naja mossambica, N. nigricincta, and N. pallida, are widely recognised for their cytotoxicity. However, their effects on platelets and blood coagulation remain poorly characterised. To address this gap, we characterised their enzymatic profiles and evaluated their effects on haemostasis and cell viability using functional blood-based and cellular assays, respectively. All three venoms markedly impaired haemostatic regulation by affecting intrinsic coagulation, significantly inhibiting platelet function, and inducing haemolysis. They also exerted potent myotoxic effects on cultured myoblasts\/myotubes while causing only minimal cytotoxicity towards platelets. Fractionation by reversed-phase HPLC followed by mass spectrometry identified three-finger toxins that reproduced the potent platelet-inhibitory and myotoxic activities of the crude venoms but only partially accounted for the haemolytic and anticoagulant effects. These findings demonstrate that African spitting cobra venoms induce coordinated, multifaceted effects on human blood, with three-finger toxins serving as key functional mediators alongside other potential venom components. Overall, this study advances our understanding of the effects of spitting cobra envenoming, provides a foundation for developing improved snakebite therapies, and highlights venom-derived components as potential scaffolds for developing novel antithrombotic agents.<\/jats:p>","DOI":"10.3390\/toxins18090368","type":"journal-article","created":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T08:11:15Z","timestamp":1787731875000},"page":"368","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Effects of Selective African Spitting Cobra Venoms and Their Three-Finger Toxins on the Modulation of Platelet Function and Blood Clotting"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-7598-3011","authenticated-orcid":false,"given":"Mahtab","family":"Khatibi","sequence":"first","affiliation":[{"name":"School of Pharmacy, University of Reading, Reading RG6 6UB, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4637-4468","authenticated-orcid":false,"given":"Jos\u00e9 R.","family":"Almeida","sequence":"additional","affiliation":[{"name":"School of Pharmacy, University of Reading, Reading RG6 6UB, UK"},{"name":"Butantan Institute, Sao Paulo 05503-900, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ashifa","family":"Al Juwaiser","sequence":"additional","affiliation":[{"name":"School of Pharmacy, University of Reading, Reading RG6 6UB, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Soheil","family":"Gilabadi","sequence":"additional","affiliation":[{"name":"School of Pharmacy, University of Reading, Reading RG6 6UB, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ketan","family":"Patel","sequence":"additional","affiliation":[{"name":"School of Biological Sciences, University of Reading, Reading RG6 6UB, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6006-6517","authenticated-orcid":false,"given":"Sakthivel","family":"Vaiyapuri","sequence":"additional","affiliation":[{"name":"School of Pharmacy, University of Reading, Reading RG6 6UB, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,26]]},"reference":[{"key":"ref_1","unstructured":"World Health Organization (2026, April 13). Snakebite Envenoming. Available online: https:\/\/www.who.int\/news-room\/fact-sheets\/detail\/snakebite-envenoming."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"9598","DOI":"10.1038\/s41467-024-54070-y","article-title":"Snakebite envenoming in Africa remains widely neglected and demands multidisciplinary attention","volume":"15","author":"Berg","year":"2024","journal-title":"Nat. Commun."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"17063","DOI":"10.1038\/nrdp.2017.63","article-title":"Snakebite envenoming","volume":"3","author":"Calvete","year":"2017","journal-title":"Nat. Rev. Dis. Prim."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Katali, O., Shipingana, L., Nyarang\u00f3, P., P\u00e4\u00e4kk\u00f6nen, M., Haindongo, E., Rennie, T., James, P., Eriksson, J., and Hunter, C.J. (2020). Protein Identification of Venoms of the African Spitting Cobras, Naja mossambica and Naja nigricincta nigricincta. Toxins, 12.","DOI":"10.3390\/toxins12080520"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Panagides, N., Jackson, T.N., Ikonomopoulou, M.P., Arbuckle, K., Pretzler, R., Yang, D.C., Ali, S.A., Koludarov, I., Dobson, J., and Sanker, B. (2017). How the Cobra Got Its Flesh-Eating Venom: Cytotoxicity as a Defensive Innovation and Its Co-Evolution with Hooding, Aposematic Marking, and Spitting. Toxins, 9.","DOI":"10.3390\/toxins9030103"},{"key":"ref_6","unstructured":"Uetz, P., Freed, P., Aguilar, R., Reyes, F., Kudera, J., and Ho\u0161ek, J. (2026, March 27). The Reptile Database. Available online: http:\/\/www.reptile-database.org."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Chowdhury, A., Lewin, M.R., Zdenek, C.N., Carter, R., and Fry, B.G. (2021). The Relative Efficacy of Chemically Diverse Small-Molecule Enzyme-Inhibitors Against Anticoagulant Activities of African Spitting Cobra (Naja Species) Venoms. Front. Immunol., 12.","DOI":"10.3389\/fimmu.2021.752442"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"e2315597121","DOI":"10.1073\/pnas.2315597121","article-title":"Dermonecrosis caused by a spitting cobra snakebite results from toxin potentiation and is prevented by the repurposed drug varespladib","volume":"121","author":"Bartlett","year":"2024","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Babo Martins, S., Bolon, I., Chappuis, F., Ray, N., Alcoba, G., Ochoa, C., Kumar Sharma, S., Nkwescheu, A.S., Wanda, F., and Durso, A.M. (2019). Snakebite and its impact in rural communities: The need for a One Health approach. PLoS Negl. Trop. Dis., 13.","DOI":"10.1371\/journal.pntd.0007608"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1016\/S0140-6736(09)61754-2","article-title":"Snake bite","volume":"375","author":"Warrell","year":"2010","journal-title":"Lancet"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Habib, A.G., Kuznik, A., Hamza, M., Abdullahi, M.I., Chedi, B.A., Chippaux, J.P., and Warrell, D.A. (2015). Snakebite is Under Appreciated: Appraisal of Burden from West Africa. PLoS Negl. Trop. Dis., 9.","DOI":"10.1371\/journal.pntd.0004088"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"587","DOI":"10.1016\/j.etp.2009.08.002","article-title":"Systemic pathological effects induced by cobra (Naja naja) venom from geographically distinct origins of Indian peninsula","volume":"62","author":"Shashidharamurthy","year":"2010","journal-title":"Exp. Toxicol. Pathol."},{"key":"ref_13","unstructured":"World Health Organization (2016). Guidelines for the Management of Snakebites, World Health Organization, Regional Office for South-East Asia. [2nd ed.]."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Ranawaka, U.K., Lalloo, D.G., and de Silva, H.J. (2013). Neurotoxicity in snakebite--the limits of our knowledge. PLoS Negl. Trop. Dis., 7.","DOI":"10.1371\/journal.pntd.0002302"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"100125","DOI":"10.1016\/j.toxcx.2022.100125","article-title":"Evaluation of lethality and cytotoxic effects induced by Naja ashei (large brown spitting cobra) venom and the envenomation-neutralizing efficacy of selected commercial antivenoms in Kenya","volume":"14","author":"Manson","year":"2022","journal-title":"Toxicon X"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"107637","DOI":"10.1016\/j.toxicon.2024.107637","article-title":"Distinct cardiotoxic effects by venoms of a spitting cobra (Naja pallida) and a rattlesnake (Crotalus atrox) revealed using an ex vivo Langendorff heart model","volume":"240","author":"Vlasblom","year":"2024","journal-title":"Toxicon"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Bittenbinder, M.A., Zdenek, C.N., Op den Brouw, B., Youngman, N.J., Dobson, J.S., Naude, A., Vonk, F.J., and Fry, B.G. (2018). Coagulotoxic Cobras: Clinical Implications of Strong Anticoagulant Actions of African Spitting Naja Venoms That Are Not Neutralised by Antivenom but Are by LY315920 (Varespladib). Toxins, 10.","DOI":"10.3390\/toxins10120516"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"6940798","DOI":"10.1155\/2018\/6940798","article-title":"Quantitative Characterization of the Hemorrhagic, Necrotic, Coagulation-Altering Properties and Edema-Forming Effects of Zebra Snake (Naja nigricincta nigricincta) Venom","volume":"2018","author":"Kandiwa","year":"2018","journal-title":"J. Toxicol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"386","DOI":"10.1126\/science.abb9303","article-title":"Convergent evolution of pain-inducing defensive venom components in spitting cobras","volume":"371","author":"Kazandjian","year":"2021","journal-title":"Science"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Offor, B.C., Muller, B., and Piater, L.A. (2022). A Review of the Proteomic Profiling of African Viperidae and Elapidae Snake Venoms and Their Antivenom Neutralisation. Toxins, 14.","DOI":"10.3390\/toxins14110723"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1000181","DOI":"10.4172\/2161-0495.1000181","article-title":"Snake Venom Cytotoxins, Phospholipase A2s, and Zn2+-dependent Metalloproteinases: Mechanisms of Action and Pharmacological Relevance","volume":"4","author":"Gasanov","year":"2014","journal-title":"J. Clin. Toxicol."},{"key":"ref_22","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_23","doi-asserted-by":"crossref","first-page":"101398","DOI":"10.1016\/j.jpha.2025.101398","article-title":"Profiling cytotoxicity of nanofractionated elapid snake venoms in human cell lines representing different tissues","volume":"16","author":"Xu","year":"2026","journal-title":"J. Pharm. Anal."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"550","DOI":"10.1016\/j.bbrc.2013.10.125","article-title":"Anti-platelet activity of a three-finger toxin (3FTx) from Indian monocled cobra (Naja kaouthia) venom","volume":"441","author":"Chanda","year":"2013","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"17","DOI":"10.4331\/wjbc.v10.i1.17","article-title":"Last decade update for three-finger toxins: Newly emerging structures and biological activities","volume":"10","author":"Utkin","year":"2019","journal-title":"World J. Biol. Chem."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1147","DOI":"10.1016\/j.toxicon.2005.02.018","article-title":"Structure\u2013function relationships and mechanism of anticoagulant phospholipase A2 enzymes from snake venoms","volume":"45","author":"Kini","year":"2005","journal-title":"Toxicon"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"947","DOI":"10.1016\/j.toxicon.2003.11.006","article-title":"Inflammatory effects of snake venom myotoxic phospholipases A2","volume":"42","author":"Teixeira","year":"2003","journal-title":"Toxicon"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"6592820","DOI":"10.1155\/2017\/6592820","article-title":"Snake Venom PLA2, a Promising Target for Broad-Spectrum Antivenom Drug Development","volume":"2017","author":"Xiao","year":"2017","journal-title":"Biomed. Res. Int."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Kazandjian, T.D., Arrahman, A., Still, K.B.M., Somsen, G.W., Vonk, F.J., Casewell, N.R., Wilkinson, M.C., and Kool, J. (2021). Anticoagulant Activity of Naja nigricollis Venom Is Mediated by Phospholipase A2 Toxins and Inhibited by Varespladib. Toxins, 13.","DOI":"10.3390\/toxins13050302"},{"key":"ref_30","unstructured":"African Snakebite Institute (2026, April 13). Everything You Need to Know About Antivenom. Available online: https:\/\/www.africansnakebiteinstitute.com\/articles\/everything-you-need-to-know-about-antivenom\/."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Menzies, S.K., Litschka-Koen, T., Edge, R.J., Alsolaiss, J., Crittenden, E., Hall, S.R., Westhorpe, A., Thomas, B., Murray, J., and Shongwe, N. (2022). Two snakebite antivenoms have potential to reduce Eswatini\u2019s dependency upon a single, increasingly unavailable product: Results of preclinical efficacy testing. PLoS Negl. Trop. Dis., 16.","DOI":"10.1101\/2022.05.16.492230"},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Vanuopadath, M., Rajan, K., Alangode, A., Nair, S.S., and Nair, B.G. (2023). The Need for Next-Generation Antivenom for Snakebite Envenomation in India. Toxins, 15.","DOI":"10.3390\/toxins15080510"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"114135","DOI":"10.1016\/j.bcp.2020.114135","article-title":"Snake antivenom: Challenges and alternate approaches","volume":"181","author":"Alangode","year":"2020","journal-title":"Biochem. Pharmacol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1007\/s10534-017-0066-2","article-title":"Carbon monoxide inhibits hemotoxic activity of Elapidae venoms: Potential role of heme","volume":"31","author":"Nielsen","year":"2018","journal-title":"BioMetals"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1097\/MBC.0000000000000842","article-title":"Anticoagulant activity of krait, coral snake, and cobra neurotoxic venoms with diverse proteomes are inhibited by carbon monoxide","volume":"30","author":"Turchioe","year":"2019","journal-title":"Blood Coagul. Fibrinolysis"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"107792","DOI":"10.1016\/j.toxicon.2024.107792","article-title":"A comparison of the venom proteomes and potential therapeutics of 3 African naja subgenera","volume":"245","author":"Offor","year":"2024","journal-title":"Toxicon"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"2055","DOI":"10.1002\/jat.4825","article-title":"The Proteome of African Spitting and Non-Spitting Cobra Venoms and Cytotoxicity Against Pancreatic Cancer Cells","volume":"45","author":"Offor","year":"2025","journal-title":"J. Appl. Toxicol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1266","DOI":"10.1021\/pr101040f","article-title":"Snake Venomics of African Spitting Cobras: Toxin Composition and Assessment of Congeneric Cross-Reactivity of the Pan-African EchiTAb-Plus-ICP Antivenom by Antivenomics and Neutralization Approaches","volume":"10","author":"Petras","year":"2011","journal-title":"J. Proteome Res."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Hus, K.K., Buczkowicz, J., Petrilla, V., Petrillov\u00e1, M., \u0141yskowski, A., Leg\u00e1th, J., and Bocian, A. (2018). First Look at the Venom of Naja ashei. Molecules, 23.","DOI":"10.3390\/molecules23030609"},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Tasoulis, T., and Isbister, G.K. (2017). A Review and Database of Snake Venom Proteomes. Toxins, 9.","DOI":"10.3390\/toxins9090290"},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Tasoulis, T., Pukala, T.L., and Isbister, G.K. (2021). Investigating Toxin Diversity and Abundance in Snake Venom Proteomes. Front. Pharmacol., 12.","DOI":"10.3389\/fphar.2021.768015"},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Damm, M., Hempel, B.F., and S\u00fcssmuth, R.D. (2021). Old World Vipers-A Review about Snake Venom Proteomics of Viperinae and Their Variations. Toxins, 13.","DOI":"10.3390\/toxins13060427"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"330","DOI":"10.1016\/j.tiv.2019.05.026","article-title":"Differential destructive (non-clotting) fibrinogenolytic activity in Afro-Asian elapid snake venoms and the links to defensive hooding behavior","volume":"60","author":"Bittenbinder","year":"2019","journal-title":"Toxicol. Vitr."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1180","DOI":"10.3892\/ijmm.2014.1864","article-title":"Purification and biochemical characterization of a fibrin(ogen)olytic metalloprotease from Macrovipera mauritanica snake venom which induces vascular permeability","volume":"34","author":"Lee","year":"2014","journal-title":"Int. J. Mol. Med."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1021","DOI":"10.1016\/j.toxicon.2005.02.027","article-title":"Snake venom fibrin(ogen)olytic enzymes","volume":"45","author":"Swenson","year":"2005","journal-title":"Toxicon"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"100052","DOI":"10.1016\/j.toxcx.2020.100052","article-title":"Snake Venom Metalloproteinases (SVMPs): A structure-function update","volume":"7","author":"Olaoba","year":"2020","journal-title":"Toxicon X"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1016\/0049-3848(88)90078-3","article-title":"Mechanism of platelet effects of cardiotoxins from Naja nigricollis crawshawii (spitting cobra) snake venom","volume":"52","author":"Kini","year":"1988","journal-title":"Thromb. Res."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1016\/j.biochi.2004.02.003","article-title":"Purification of a Class B1 platelet aggregation inhibitor phospholipase A2 from Indian cobra (Naja naja) venom","volume":"86","author":"Satish","year":"2004","journal-title":"Biochimie"},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Alsolaiss, J., Evans, C.A., Oluoch, G.O., Casewell, N.R., and Harrison, R.A. (2022). Profiling the Murine Acute Phase and Inflammatory Responses to African Snake Venom: An Approach to Inform Acute Snakebite Pathology. Toxins, 14.","DOI":"10.3390\/toxins14040229"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"4929","DOI":"10.1021\/bi952456c","article-title":"Mocarhagin, a novel cobra venom metalloproteinase, cleaves the platelet von Willebrand factor receptor glycoprotein Ibalpha. Identification of the sulfated tyrosine\/anionic sequence Tyr-276-Glu-282 of glycoprotein Ibalpha as a binding site for von Willebrand factor and alpha-thrombin","volume":"35","author":"Ward","year":"1996","journal-title":"Biochemistry"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1749","DOI":"10.1016\/S0041-0101(98)00126-3","article-title":"Snake venoms and the hemostatic system","volume":"36","author":"Markland","year":"1998","journal-title":"Toxicon"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"2887","DOI":"10.2174\/138161207782023702","article-title":"Snake venom proteins affecting platelets and their applications to anti-thrombotic research","volume":"13","author":"Clemetson","year":"2007","journal-title":"Curr. Pharm. Des."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"19827","DOI":"10.1016\/S0021-9258(19)77710-2","article-title":"Echistatin. A potent platelet aggregation inhibitor from the venom of the viper, Echis carinatus","volume":"263","author":"Gan","year":"1988","journal-title":"J. Biol. Chem."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1023\/A:1006457903545","article-title":"Contortrostatin, a dimeric disintegrin from Agkistrodon contortrix contortrix, inhibits breast cancer progression","volume":"61","author":"Zhou","year":"2000","journal-title":"Breast Cancer Res. Treat."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1093\/oxfordjournals.qjmed.a067448","article-title":"Necrosis, haemorrhage and complement depletion following bites by the spitting cobra (Naja nigricollis)","volume":"45","author":"Warrell","year":"1976","journal-title":"Q. J. Med."},{"key":"ref_56","first-page":"31","article-title":"Biochemical and biological characterization of Naja kaouthia venom from North-East India and its neutralization by polyvalent antivenom","volume":"4","author":"Das","year":"2013","journal-title":"J. Venom. Res."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"e30969","DOI":"10.1016\/j.heliyon.2024.e30969","article-title":"Atrase A, a P-III class metalloproteinase purified from cobra venom, exhibits potent anticoagulant activity by inhibiting coagulation pathway and activating the fibrinolytic system","volume":"10","author":"Zhong","year":"2024","journal-title":"Heliyon"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"107836","DOI":"10.1016\/j.toxicon.2024.107836","article-title":"Anticoagulant activity in Australasian elapid snake venoms and neutralisation with antivenom and varespladib","volume":"247","author":"Murphy","year":"2024","journal-title":"Toxicon"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1046\/j.1432-1327.1999.00623.x","article-title":"Snake venom alpha-neurotoxins and other \u2018three-finger\u2019 proteins","volume":"264","author":"Tsetlin","year":"1999","journal-title":"Eur. J. Biochem."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"815","DOI":"10.1046\/j.1440-1681.2002.03725.x","article-title":"Molecular moulds with multiple missions: Functional sites in three-finger toxins","volume":"29","author":"Kini","year":"2002","journal-title":"Clin. Exp. Pharmacol. Physiol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1016\/j.toxicon.2012.09.007","article-title":"Three-finger toxins, a deadly weapon of elapid venom--milestones of discovery","volume":"62","author":"Utkin","year":"2013","journal-title":"Toxicon"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1042\/BJ20041892","article-title":"Cancer cell injury by cytotoxins from cobra venom is mediated through lysosomal damage","volume":"390","author":"Feofanov","year":"2005","journal-title":"Biochem. J."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1007\/s002329900165","article-title":"Cobra venom cytotoxin free of phospholipase A2 and its effect on model membranes and T leukemia cells","volume":"155","author":"Gasanov","year":"1997","journal-title":"J. Membr. Biol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"1012","DOI":"10.1016\/0006-291X(88)90729-2","article-title":"Non-enzymatic inhibitors of coagulation and platelet aggregation from Naja nigricollis venom are cardiotoxins","volume":"150","author":"Kini","year":"1988","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"42601","DOI":"10.1074\/jbc.M508987200","article-title":"Hemextin AB complex, a unique anticoagulant protein complex from Hemachatus haemachatus (African Ringhals cobra) venom that inhibits clot initiation and factor VIIa activity","volume":"280","author":"Banerjee","year":"2005","journal-title":"J. Biol. Chem."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"25935","DOI":"10.1038\/srep25935","article-title":"Ringhalexin from Hemachatus haemachatus: A novel inhibitor of extrinsic tenase complex","volume":"6","author":"Barnwal","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"591","DOI":"10.1042\/bj2900591","article-title":"Snake venom cardiotoxin can rapidly induce actin polymerization in intact platelets","volume":"290","author":"Liou","year":"1993","journal-title":"Biochem. J."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"602","DOI":"10.1016\/j.toxicon.2009.01.011","article-title":"Paraspecific neutralization of the venom of African species of cobra by an equine antiserum against Naja melanoleuca: A comparative study","volume":"53","author":"Casasola","year":"2009","journal-title":"Toxicon"},{"key":"ref_69","doi-asserted-by":"crossref","unstructured":"Koh, C.Y., and Kini, R.M. (2025). Orphan Three-Finger Toxins from Snake Venoms: Unexplored Library of Novel Biological Ligands with Potential New Structures and Functions. Int. J. Mol. Sci., 26.","DOI":"10.3390\/ijms26188792"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1016\/j.toxicon.2011.03.017","article-title":"From snake venom toxins to therapeutics\u2014Cardiovascular examples","volume":"59","author":"Koh","year":"2012","journal-title":"Toxicon"},{"key":"ref_71","doi-asserted-by":"crossref","unstructured":"Lazarovici, P., Marcinkiewicz, C., and Lelkes, P.I. (2019). From Snake Venom\u2019s Disintegrins and C-Type Lectins to Anti-Platelet Drugs. Toxins, 11.","DOI":"10.3390\/toxins11050303"},{"key":"ref_72","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_73","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1016\/j.thromres.2019.04.019","article-title":"Modulation of the mammalian coagulation system by venoms and other proteins from snakes, arthropods, nematodes and insects","volume":"178","author":"Sachetto","year":"2019","journal-title":"Thromb. Res."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"1171","DOI":"10.1016\/j.toxicon.2005.02.016","article-title":"Practical applications of snake venom toxins in haemostasis","volume":"45","author":"Marsh","year":"2005","journal-title":"Toxicon"},{"key":"ref_75","doi-asserted-by":"crossref","unstructured":"Samuel, S., Merkel, J., and Bickler, P. (2016). Varespladib (LY315920) Appears to Be a Potent, Broad-Spectrum, Inhibitor of Snake Venom Phospholipase A2 and a Possible Pre-Referral Treatment for Envenomation. Toxins, 8.","DOI":"10.3390\/toxins8090248"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"e015985","DOI":"10.1136\/bmjgh-2024-015985","article-title":"Oral varespladib for the treatment of snakebite envenoming in India and the USA (BRAVO): A phase II randomised clinical trial","volume":"9","author":"Gerardo","year":"2024","journal-title":"BMJ Glob. Health"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"6094","DOI":"10.1038\/s41467-020-19981-6","article-title":"A therapeutic combination of two small molecule toxin inhibitors provides broad preclinical efficacy against viper snakebite","volume":"11","author":"Albulescu","year":"2020","journal-title":"Nat. Commun."},{"key":"ref_78","doi-asserted-by":"crossref","unstructured":"Clare, R.H., Westhorpe, A., Stars, E., Kazandjian, T.D., Albulescu, L.O., Menzies, S.K., and Casewell, N.R. (2026). Repurposed small molecule toxin inhibitors neutralise a diversity of venoms from the Neotropical viperid snake genus Bothrops. eLife, 15.","DOI":"10.7554\/eLife.110419"},{"key":"ref_79","unstructured":"World Health Organization (2019). Snakebite Envenoming: A Strategy for Prevention and Control, World Health Organization."},{"key":"ref_80","doi-asserted-by":"crossref","unstructured":"Bartlett, K.E., Hall, S.R., Rasmussen, S.A., Crittenden, E., Dawson, C.A., Albulescu, L.-O., Laprade, W., Harrison, R.A., Saviola, A.J., and Jenkins, T.P. (2023). Dermonecrosis caused by spitting cobra snakebite is the result of toxin potentiation and is prevented by the repurposed drug varespladib. bioRxiv.","DOI":"10.1101\/2023.07.20.549878"},{"key":"ref_81","doi-asserted-by":"crossref","unstructured":"Harrison, R.A., Oluoch, G.O., Ainsworth, S., Alsolaiss, J., Bolton, F., Arias, A.S., Guti\u00e9rrez, J.M., Rowley, P., Kalya, S., and Ozwara, H. (2017). Preclinical antivenom-efficacy testing reveals potentially disturbing deficiencies of snakebite treatment capability in East Africa. PLoS Negl. Trop. Dis., 11.","DOI":"10.1371\/journal.pntd.0005969"},{"key":"ref_82","doi-asserted-by":"crossref","unstructured":"Umoh, I., Boro, E., McLoughlin, C., Tianyi, F.L., Oluoch, G.O., Ajose, O., Irowa-Omoregie, D., Burn, I., Jones-Phillips, B., and Casewell, N.R. (2026). From scarcity to sustainability: Policy pathways for equitable snakebite antivenom access in Africa. PLoS Glob. Public Health, 6.","DOI":"10.1371\/journal.pgph.0006490"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"107942","DOI":"10.1016\/j.toxicon.2024.107942","article-title":"Small molecule therapeutics for neutralising venom toxins\u2014A drug discovery approach","volume":"248","author":"Albulescu","year":"2024","journal-title":"Toxicon"}],"container-title":["Toxins"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6651\/18\/9\/368\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T08:18:15Z","timestamp":1787732295000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6651\/18\/9\/368"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,26]]},"references-count":83,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2026,9]]}},"alternative-id":["toxins18090368"],"URL":"https:\/\/doi.org\/10.3390\/toxins18090368","relation":{},"ISSN":["2072-6651"],"issn-type":[{"value":"2072-6651","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,26]]}}}