{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T15:35:04Z","timestamp":1791041704877,"version":"4.1.0"},"reference-count":218,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2021,6,29]],"date-time":"2021-06-29T00:00:00Z","timestamp":1624924800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100005299","name":"Vicerrector\u00eda de Investigaci\u00f3n, Universidad de Costa Rica","doi-asserted-by":"publisher","award":["No grant number"],"award-info":[{"award-number":["No grant number"]}],"id":[{"id":"10.13039\/501100005299","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Toxins"],"abstract":"<jats:p>A global strategy, under the coordination of the World Health Organization, is being unfolded to reduce the impact of snakebite envenoming. One of the pillars of this strategy is to ensure safe and effective treatments. The mainstay in the therapy of snakebite envenoming is the administration of animal-derived antivenoms. In addition, new therapeutic options are being explored, including recombinant antibodies and natural and synthetic toxin inhibitors. In this review, snake venom toxins are classified in terms of their abundance and toxicity, and priority actions are being proposed in the search for snake venom metalloproteinase (SVMP), phospholipase A2 (PLA2), three-finger toxin (3FTx), and serine proteinase (SVSP) inhibitors. Natural inhibitors include compounds isolated from plants, animal sera, and mast cells, whereas synthetic inhibitors comprise a wide range of molecules of a variable chemical nature. Some of the most promising inhibitors, especially SVMP and PLA2 inhibitors, have been developed for other diseases and are being repurposed for snakebite envenoming. In addition, the search for drugs aimed at controlling endogenous processes generated in the course of envenoming is being pursued. The present review summarizes some of the most promising developments in this field and discusses issues that need to be considered for the effective translation of this knowledge to improve therapies for tackling snakebite envenoming.<\/jats:p>","DOI":"10.3390\/toxins13070451","type":"journal-article","created":{"date-parts":[[2021,6,29]],"date-time":"2021-06-29T22:39:43Z","timestamp":1625006383000},"page":"451","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":96,"title":["The Search for Natural and Synthetic Inhibitors That Would Complement Antivenoms as Therapeutics for Snakebite Envenoming"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8385-3081","authenticated-orcid":false,"given":"Jos\u00e9 Mar\u00eda","family":"Guti\u00e9rrez","sequence":"first","affiliation":[{"name":"Facultad de Microbiolog\u00eda, Instituto Clodomiro Picado, Universidad de Costa Rica, San Jos\u00e9 11501, Costa Rica"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura-Oana","family":"Albulescu","sequence":"additional","affiliation":[{"name":"Centre for Snakebite Research & Interventions, Liverpool School of Tropical Medicine, Liverpool L3 5QA, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rachel H.","family":"Clare","sequence":"additional","affiliation":[{"name":"Centre for Snakebite Research & Interventions, Liverpool School of Tropical Medicine, Liverpool L3 5QA, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8035-4719","authenticated-orcid":false,"given":"Nicholas R.","family":"Casewell","sequence":"additional","affiliation":[{"name":"Centre for Snakebite Research & Interventions, Liverpool School of Tropical Medicine, Liverpool L3 5QA, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3441-9673","authenticated-orcid":false,"given":"Tarek Mohamed","family":"Abd El-Aziz","sequence":"additional","affiliation":[{"name":"Zoology Department, Faculty of Science, Minia University, El-Minia 61519, Egypt"},{"name":"Department of Cellular and Integrative Physiology, University of Texas Health Science Center at San Antonio, San Antonio, TX 78229-3900, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Teresa","family":"Escalante","sequence":"additional","affiliation":[{"name":"Facultad de Microbiolog\u00eda, Instituto Clodomiro Picado, Universidad de Costa Rica, San Jos\u00e9 11501, Costa Rica"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandra","family":"Rucavado","sequence":"additional","affiliation":[{"name":"Facultad de Microbiolog\u00eda, Instituto Clodomiro Picado, Universidad de Costa Rica, San Jos\u00e9 11501, Costa Rica"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,6,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1591","DOI":"10.1371\/journal.pmed.0050218","article-title":"The global burden of snakebite: A literature analysis and modelling based on regional estimates of envenoming and deaths","volume":"5","author":"Kasturiratne","year":"2008","journal-title":"PLoS Med."},{"key":"ref_2","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_3","unstructured":"Republic of Costa Rica (2021, March 15). Recommendation for the Adoption of an Additional Disease as a Neglected Tropical Disease. The Case for Snakebite Envenoming, Available online: https:\/\/www.who.int\/snakebites\/news\/Recommendation_for_snakebite_envenoming_for_adoption_of_additional_NTD.pdf."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Harrison, R.A., Hargreaves, A., Wagstaff, S.C., Faragher, B., and Lalloo, D.G. (2009). Snake envenoming: A disease of poverty. PLoS Negl. Trop. Dis., 3.","DOI":"10.1371\/journal.pntd.0000569"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Chaves, L.F., Chuang, T.W., Sasa, M., and Guti\u00e9rrez, J.M. (2015). Snakebites are associated with poverty, weather fluctuations, and El Ni\u00f1o. Sci. Adv., 1.","DOI":"10.1126\/sciadv.1500249"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1570","DOI":"10.1016\/S0140-6736(09)60233-6","article-title":"Rescuing the bottom billion through control of neglected tropical diseases","volume":"373","author":"Hotez","year":"2009","journal-title":"Lancet"},{"key":"ref_7","first-page":"623","article-title":"The London Declaration on Neglected Tropical Diseases: 5 years on","volume":"110","author":"Molyneux","year":"2016","journal-title":"Trans. R. Soc. Trop. Med. Hyg."},{"key":"ref_8","first-page":"0727","article-title":"Confronting the neglected problem of snake bite envenoming: The need for a global partnership","volume":"3","author":"Theakston","year":"2006","journal-title":"PLoS Med."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Guti\u00e9rrez, J.M., Warrell, D.A., Williams, D.J., Jensen, S., Brown, N., Calvete, J.J., and Harrison, R.A. (2013). The Need for Full Integration of Snakebite Envenoming within a Global Strategy to Combat the Neglected Tropical Diseases: The Way Forward. PLoS Negl. Trop. Dis., 7.","DOI":"10.1371\/journal.pntd.0002162"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1016\/S0140-6736(09)61159-4","article-title":"The Global Snake Bite Initiative: An antidote for snake bite","volume":"375","author":"Williams","year":"2010","journal-title":"Lancet"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Williams, D.J., Faiz, M.A., Abela-Ridder, B., Ainsworth, S., Bulfone, T.C., Nickerson, A.D., Habib, A.G., Junghanss, T., Fan, H.W., and Turner, M. (2019). Strategy for a globally coordinated response to a priority neglected tropical disease: Snakebite envenoming. PLoS Negl. Trop. Dis., 13.","DOI":"10.1371\/journal.pntd.0007059"},{"key":"ref_12","unstructured":"World Health Assembly (2021, March 11). Addressing the Burden of Snakebite Envenoming. Available online: https:\/\/www.who.int\/neglected_diseases\/mediacentre\/WHA_71.5_Eng.pdf?ua=1."},{"key":"ref_13","unstructured":"World Health Organization (2021, March 15). Snakebite Envenoming. A Strategy for Prevention and Control. Available online: https:\/\/www.who.int\/snakebites\/resources\/9789241515641\/en\/."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1016\/j.toxicon.2018.05.008","article-title":"The history of antivenoms development: Beyond Calmette and Vital Brazil","volume":"150","author":"Marcelino","year":"2018","journal-title":"Toxicon"},{"key":"ref_15","unstructured":"World Health Organization (2021, April 02). Guidelines for the Production, Control and Regulation of Snake Antivenom Immunoglobulins. Available online: https:\/\/www.who.int\/bloodproducts\/snake_antivenoms\/snakeantivenomguide\/en\/."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1016\/j.toxicon.2018.06.084","article-title":"Current technology for the industrial manufacture of snake antivenoms","volume":"151","author":"Vargas","year":"2018","journal-title":"Toxicon"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1016\/j.toxicon.2013.09.010","article-title":"Pathogenic mechanisms underlying adverse reactions induced by intravenous administration of snake antivenoms","volume":"76","author":"Herrera","year":"2013","journal-title":"Toxicon"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"446","DOI":"10.1111\/bcp.12739","article-title":"Adverse reactions to snake antivenom, and their prevention and treatment","volume":"81","author":"Ryan","year":"2016","journal-title":"Br. J. Clin. Pharmacol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"234","DOI":"10.4269\/ajtmh.2004.71.234","article-title":"Impact of snake bites and determinants of fatal outcomes in Southeastern Nepal","volume":"71","author":"Sharma","year":"2004","journal-title":"Am. J. Trop. Med. Hyg."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1016\/j.inhe.2010.08.001","article-title":"Factors affecting snakebite mortality in north-eastern Nigeria","volume":"3","author":"Habib","year":"2011","journal-title":"Int. Health"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"586","DOI":"10.1016\/j.toxicon.2010.12.022","article-title":"Estimate of the burden of snakebites in sub-Saharan Africa: A meta-analytic approach","volume":"57","author":"Chippaux","year":"2011","journal-title":"Toxicon"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1016\/j.toxicon.2018.02.041","article-title":"Snakebites as cause of deaths in the Western Brazilian Amazon: Why and who dies? Deaths from snakebites in the Amazon","volume":"145","author":"Sachett","year":"2018","journal-title":"Toxicon"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1529","DOI":"10.1016\/S0041-0101(98)00145-7","article-title":"Neutralization of local tissue damage induced by Bothrops asper (terciopelo) snake venom","volume":"36","author":"Rojas","year":"1998","journal-title":"Toxicon"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1016\/j.toxicon.2016.06.006","article-title":"Pathogenesis of dermonecrosis induced by venom of the spitting cobra, Naja nigricollis: An experimental study in mice","volume":"119","author":"Rivel","year":"2016","journal-title":"Toxicon"},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Williams, S.S., Wijesinghe, C.A., Jayamanne, S.F., Buckley, N.A., Dawson, A.H., Lalloo, D.G., and de Silva, H.J. (2011). Delayed psychological morbidity associated with snakebite envenoming. PLoS Negl. Trop. Dis., 5.","DOI":"10.1371\/journal.pntd.0001255"},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Waiddyanatha, S., Silva, A., Siribaddana, S., and Isbister, G.K. (2019). Long-term effects of snake envenoming. Toxins, 11.","DOI":"10.3390\/toxins11040193"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"676","DOI":"10.1016\/j.toxicon.2012.02.008","article-title":"Improving antivenom availability and accessibility: Science, technology, and beyond","volume":"60","year":"2012","journal-title":"Toxicon"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1223","DOI":"10.1016\/j.toxicon.2009.11.020","article-title":"Snakebite envenoming from a global perspective: Towards an integrated approach","volume":"56","author":"Williams","year":"2010","journal-title":"Toxicon"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1016\/j.toxicon.2018.06.070","article-title":"History and perspectives on how to ensure antivenom accessibility in the most remote areas in Brazil","volume":"151","author":"Fan","year":"2018","journal-title":"Toxicon"},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Cristino, J.S., Salazar, G.M., Machado, V.A., Honorato, E., Farias, A.S., Vissoci, J.R.N., Neto, A.V.S., Lacerda, M., Wen, F.H., and Monteiro, W.M. (2021). A painful journey to antivenom: The therapeutic itinerary of snakebite patients in the Brazilian Amazon (the QUALISnake study). PLoS Negl. Trop. Dis., 15.","DOI":"10.1371\/journal.pntd.0009245"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"570","DOI":"10.1016\/j.tips.2020.05.006","article-title":"Causes and Consequences of Snake Venom Variation","volume":"41","author":"Casewell","year":"2020","journal-title":"Trends Pharmacol. Sci."},{"key":"ref_32","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_33","doi-asserted-by":"crossref","first-page":"1816","DOI":"10.1021\/pr101091a","article-title":"Venomic and Antivenomic Analyses of the Central American Coral Snake, Micrurus nigrocinctus (Elapidae)","volume":"10","author":"Angulo","year":"2011","journal-title":"J. Proteome Res."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Ainsworth, S., Menzies, S.K., Casewell, N.R., and Harrison, R.A. (2020). An analysis of preclinical efficacy testing of antivenoms for sub-Saharan Africa: Inadequate independent scrutiny and poor-quality reporting are barriers to improving snakebite treatment and management. PLoS Negl. Trop. Dis., 14.","DOI":"10.1371\/journal.pntd.0008579"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"5270","DOI":"10.2174\/1381612822666160623073438","article-title":"From Fangs to Pharmacology: The Future of Snakebite Envenoming Therapy","volume":"22","author":"Laustsen","year":"2016","journal-title":"Curr. Pharm. Des."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1016\/j.toxicon.2018.03.004","article-title":"Pros and cons of different therapeutic antibody formats for recombinant antivenom development","volume":"146","author":"Laustsen","year":"2018","journal-title":"Toxicon"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"727","DOI":"10.1111\/pbi.12823","article-title":"A synthetic biology approach for consistent production of plant-made recombinant polyclonal antibodies against snake venom toxins","volume":"16","author":"Huet","year":"2018","journal-title":"Plant Biotechnol. J."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"340","DOI":"10.1016\/j.tips.2021.02.005","article-title":"Small Molecule Drug Discovery for Neglected Tropical Snakebite","volume":"42","author":"Clare","year":"2021","journal-title":"Trends Pharmacol. Sci."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1016\/j.jprot.2009.01.009","article-title":"Evolution and diversification of the Toxicofera reptile venom system","volume":"72","author":"Fry","year":"2009","journal-title":"J. Proteom."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"611","DOI":"10.1042\/BCJ20160577","article-title":"Venomics: Integrative venom proteomics and beyond","volume":"474","author":"Calvete","year":"2017","journal-title":"Biochem. J."},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Lomonte, B., and Calvete, J.J. (2017). Strategies in \u201csnake venomics\u201d aiming at an integrative view of compositional, functional, and immunological characteristics of venoms. J. Venom. Anim. Toxins Incl. Trop. Dis., 23.","DOI":"10.1186\/s40409-017-0117-8"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1038\/s41588-019-0559-8","article-title":"The Indian cobra reference genome and transcriptome enables comprehensive identification of venom toxins","volume":"52","author":"Suryamohan","year":"2020","journal-title":"Nat. Genet."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"3388","DOI":"10.3390\/toxins6123388","article-title":"Omics meets biology: Application to the design and preclinical assessment of antivenoms","volume":"6","author":"Calvete","year":"2014","journal-title":"Toxins"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1016\/j.toxicon.2015.07.334","article-title":"Selecting key toxins for focused development of elapid snake antivenoms and inhibitors guided by a Toxicity Score","volume":"104","author":"Laustsen","year":"2015","journal-title":"Toxicon"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1016\/j.jprot.2014.02.020","article-title":"Venomous snakes of Costa Rica: Biological and medical implications of their venom proteomic profiles analyzed through the strategy of snake venomics","volume":"105","author":"Lomonte","year":"2014","journal-title":"J. Proteom."},{"key":"ref_46","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_47","doi-asserted-by":"crossref","unstructured":"Junqueira-de-Azevedo, I.L.M., Campos, P.F., Ching, A.T.C., and Mackessy, S.P. (2016). Colubrid Venom Composition: An-Omics Perspective. Toxins, 8.","DOI":"10.3390\/toxins8080230"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"969","DOI":"10.1016\/j.toxicon.2005.02.012","article-title":"Structural considerations of the snake venom metalloproteinases, key members of the M12 reprolysin family of metalloproteinases","volume":"45","author":"Fox","year":"2005","journal-title":"Toxicon"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"3016","DOI":"10.1111\/j.1742-4658.2008.06466.x","article-title":"Insights into and speculations about snake venom metalloproteinase (SVMP) synthesis, folding and disulfide bond formation and their contribution to venom complexity","volume":"275","author":"Fox","year":"2008","journal-title":"FEBS J."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"3419","DOI":"10.1021\/acs.jproteome.9b00325","article-title":"Deep Profiling of the Cleavage Specificity and Human Substrates of Snake Venom Metalloprotease HF3 by Proteomic Identification of Cleavage Site Specificity (PICS) Using Proteome Derived Peptide Libraries and Terminal Amine Isotopic Labeling of Substrates (TAILS) N-Terminomics","volume":"18","author":"Zelanis","year":"2019","journal-title":"J. Proteome Res."},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Kalogeropoulos, K., Treschow, A.F., Auf Dem Keller, U., Escalante, T., Rucavado, A., Guti\u00e9rrez, J.M., Laustsen, A.H., and Workman, C.T. (2019). Protease activity profiling of snake venoms using high-throughput peptide screening. Toxins, 11.","DOI":"10.3390\/toxins11030170"},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"De Lima, M.E., De Castro, A.M., Martin-Eauclaire, M.F., and Rochat, H. (2009). Snake venom metalloproteinases. Structure, function and effects on snake bite pathology. Animal Toxins: State of the Art\u2014Perspectives in Health and Biotechnology, Editora UFMG.","DOI":"10.1590\/S1678-91992009000300021"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1590\/S0074-02762005000900031","article-title":"Inflammatory effects of snake venom metalloproteinases","volume":"100","author":"Teixeira","year":"2005","journal-title":"Mem. Inst. Oswaldo Cruz"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"2421","DOI":"10.1038\/jid.2008.118","article-title":"Skin Pathology Induced by Snake Venom Metalloproteinase: Acute Damage, Revascularization, and Re-epithelization in a Mouse Ear Model","volume":"128","author":"Escalante","year":"2008","journal-title":"J. Investig. Dermatol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1006\/exmp.1995.1004","article-title":"Skeletal muscle necrosis and regeneration after injection of BaH1, a hemorrhagic metalloproteinase isolated from the venom of the snake Bothrops asper (Terciopelo)","volume":"62","author":"Romero","year":"1995","journal-title":"Exp. Mol. Pathol."},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Hern\u00e1ndez, R., Cabalceta, C., Saravia-Otten, P., Chaves, A., Guti\u00e9rrez, J.M., and Rucavado, A. (2011). Poor regenerative outcome after skeletal muscle necrosis induced by Bothrops asper venom: Alterations in microvasculature and nerves. PLoS ONE, 6.","DOI":"10.1371\/annotation\/9caa2be8-b5e6-4553-8575-f0b575442172"},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Williams, H.F., Mellows, B.A., Mitchell, R., Sfyri, P., Layfield, H.J., Salamah, M., Vaiyapuri, R., Collins-Hooper, H., Bicknell, A.B., and Matsakas, A. (2019). Mechanisms underpinning the permanent muscle damage induced by snake venom metalloprotease. PLoS Negl. Trop. Dis., 13.","DOI":"10.1371\/journal.pntd.0007041"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1613","DOI":"10.1016\/S0041-0101(00)00089-1","article-title":"Mass spectrophotometric evidence for P-III\/P-IV metalloproteinases in the venom of the Boomslang (Dispholidus typus)","volume":"38","author":"Kamiguti","year":"2000","journal-title":"Toxicon"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"827","DOI":"10.1016\/j.toxicon.2003.11.002","article-title":"Excitement ahead: Structure, function and mechanism of snake venom phospholipase A2 enzymes","volume":"42","author":"Kini","year":"2003","journal-title":"Toxicon"},{"key":"ref_60","unstructured":"Kini, R.M. (1997). Phospholipase A2: Structure and catalytic properties. Venom Phospholipase A2 Enzymes. Structure, Function and Mechanism, Wiley."},{"key":"ref_61","unstructured":"Fry, B.G. (2015). Group I phospholipase A2 enzymes. Venomous Reptiles & Their Toxins. Evolution, Pathophysiology & Biodiscovery, Oxford University Press."},{"key":"ref_62","unstructured":"Fry, B.G. (2015). Group II phospholipase A2 enzymes. Venomous Reptiles & Their Toxins. Evolution, Pathophysiology & Biodiscovery, Oxford University Press."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"613","DOI":"10.1016\/0041-0101(89)90013-5","article-title":"A model to explain the pharmacological effects of snake venom phospholipases A2","volume":"27","author":"Kini","year":"1989","journal-title":"Toxicon"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"520","DOI":"10.1016\/j.toxicon.2012.02.007","article-title":"Snake venom Lys49 myotoxins: From phospholipases A 2 to non-enzymatic membrane disruptors","volume":"60","author":"Lomonte","year":"2012","journal-title":"Toxicon"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1111\/jnc.13975","article-title":"The three-finger toxin fold: A multifunctional structural scaffold able to modulate cholinergic functions","volume":"142","author":"Kessler","year":"2017","journal-title":"J. Neurochem."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"855","DOI":"10.1016\/j.toxicon.2010.07.010","article-title":"Structure, function and evolution of three-finger toxins: Mini proteins with multiple targets","volume":"56","author":"Kini","year":"2010","journal-title":"Toxicon"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"1285","DOI":"10.1042\/BCJ20180909","article-title":"Novel long-chain neurotoxins from Bungarus candidus distinguish the two binding sites in muscle-type nicotinic acetylcholine receptors","volume":"476","author":"Utkin","year":"2019","journal-title":"Biochem. J."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1254\/jphs.94.1","article-title":"Three-Finger \u03b1-Neurotoxins and the Nicotinic Acetylcholine Receptor, Forty Years On","volume":"94","author":"Nirthanan","year":"2004","journal-title":"J. Pharmacol. Sci."},{"key":"ref_69","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_70","unstructured":"Mackessy, S.P. (2010). Fasciculins. Toxins from mamba venoms that inhibit acetylcholinesterase. Handbook of Venoms and Toxins of Reptiles, CRC Press."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"3963","DOI":"10.1529\/biophysj.106.100164","article-title":"Biophysical characterization of anticoagulant hemextin AB complex from the venom of snake Hemachatus haemachatus","volume":"93","author":"Banerjee","year":"2007","journal-title":"Biophys. J."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1016\/0005-2736(83)90474-1","article-title":"Effect of phospholipase A on actions of cobra venom cardiotoxins on erythrocytes and skeletal muscle","volume":"728","author":"Harvey","year":"1983","journal-title":"BBA Biomembr."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"570","DOI":"10.2174\/138920312803582960","article-title":"Structure and Dynamics of Cardiotoxins","volume":"13","author":"Konshina","year":"2012","journal-title":"Curr. Protein Pept. Sci."},{"key":"ref_74","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_75","unstructured":"WHO\/Regional Office for Africa (2010). Guidelines for the Prevention and Clinical Management of Snakebite in Africa, WHO."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"1523","DOI":"10.1016\/S0264-410X(97)00098-4","article-title":"Production of highly potent horse antivenom against the Thai cobra (Naja kaouthia)","volume":"15","author":"Pratanaphon","year":"1997","journal-title":"Vaccine"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"881","DOI":"10.1016\/j.toxicon.2008.09.002","article-title":"Characterization of a new polyvalent antivenom (Antivipmyn\u00ae Africa) against African vipers and elapids","volume":"52","author":"Chippaux","year":"2008","journal-title":"Toxicon"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1016\/j.jprot.2017.01.018","article-title":"Venomics of Naja sputatrix, the Javan spitting cobra: A short neurotoxin-driven venom needing improved antivenom neutralization","volume":"157","author":"Tan","year":"2017","journal-title":"J. Proteom."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"1115","DOI":"10.1016\/j.toxicon.2005.02.020","article-title":"Snake venom serine proteinases: Sequence homology vs. substrate specificity, a paradox to be solved","volume":"45","author":"Serrano","year":"2005","journal-title":"Toxicon"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"763","DOI":"10.6026\/97320630008563","article-title":"Sequence and phylogenetic analysis of viper venom serine proteases","volume":"8","author":"Vaiyapuri","year":"2012","journal-title":"Bioinformation"},{"key":"ref_81","unstructured":"Mackessy, S.P. (2010). Thrombin-like snake venom serine proteinases. Handbook of Venoms and Toxins of Reptiles, CRC Press."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"788","DOI":"10.1016\/j.ijbiomac.2018.03.164","article-title":"Thrombin-like enzymes from snake venom: Structural characterization and mechanism of action","volume":"114","author":"Ullah","year":"2018","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1016\/j.tiv.2018.11.008","article-title":"Habu coagulotoxicity: Clinical implications of the functional diversification of Protobothrops snake venoms upon blood clotting factors","volume":"55","author":"Debono","year":"2019","journal-title":"Toxicol. Vitr."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"951","DOI":"10.1016\/j.toxicon.2005.02.030","article-title":"Snake venoms and coagulopathy","volume":"45","author":"White","year":"2005","journal-title":"Toxicon"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"1133","DOI":"10.1016\/j.toxicon.2005.02.019","article-title":"The intriguing world of prothrombin activators from snake venom","volume":"45","author":"Kini","year":"2005","journal-title":"Toxicon"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"119","DOI":"10.5694\/mja17.00094","article-title":"The Australian snakebite project, 2005\u20132015 (ASP-20)","volume":"207","author":"Johnston","year":"2017","journal-title":"Med. J. Aust."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"3065","DOI":"10.2174\/0929867043363820","article-title":"Dendrotoxins: Structure-Activity Relationships and Effects on Potassium Ion Channels","volume":"11","author":"Harvey","year":"2012","journal-title":"Curr. Med. Chem."},{"key":"ref_88","unstructured":"Warrell, D.A. (1995). Clinical toxicology of snakebite in Africa and the Middle East\/Arabian peninsula. Handbook of Clinical Toxicology of Animal Venoms and Poisons, CRC Press."},{"key":"ref_89","unstructured":"Mackessy, S.P. (2010). Sarafotoxins, the snake venom homologs of the endothelins. Handbook of Venoms and Toxins of Reptiles, CRC Press."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"16088","DOI":"10.1038\/s41598-018-34363-1","article-title":"Systemic vascular leakage induced in mice by Russell\u2019s viper venom from Pakistan","volume":"8","author":"Rucavado","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1093\/trstmh\/try026","article-title":"Capillary leak syndrome in Daboia russelii bite\u2014A complication associated with poor outcome","volume":"112","author":"Kendre","year":"2018","journal-title":"Trans. R. Soc. Trop. Med. Hyg."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1016\/0163-7258(90)90081-C","article-title":"Myotoxic components of snake venoms: Their biochemical and biological activities","volume":"48","author":"Mebs","year":"1990","journal-title":"Pharmacol. Ther."},{"key":"ref_93","doi-asserted-by":"crossref","unstructured":"Ullah, A. (2020). Structure\u2013Function Studies and Mechanism of Action of Snake Venom L-Amino Acid Oxidases. Front. Pharmacol., 11.","DOI":"10.3389\/fphar.2020.00110"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"1099","DOI":"10.1016\/j.toxicon.2005.02.021","article-title":"Structures and functions of snake venom CLPs (C-type lectin-like proteins) with anticoagulant-, procoagulant-, and platelet-modulating activities","volume":"45","author":"Morita","year":"2005","journal-title":"Toxicon"},{"key":"ref_95","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_96","doi-asserted-by":"crossref","first-page":"1075","DOI":"10.1016\/j.toxicon.2005.02.023","article-title":"Structure and function of snake venom toxins interacting with human von Willebrand factor","volume":"45","author":"Matsui","year":"2005","journal-title":"Toxicon"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"710","DOI":"10.1055\/s-0037-1615657","article-title":"Characterization of aspercetin, a platelet aggregating component from the venom of the snake Bothrops asper which induces thrombocytopenia and potentiates metalloproteinase-induced hemorrhage","volume":"85","author":"Rucavado","year":"2001","journal-title":"Thromb. Haemost."},{"key":"ref_98","first-page":"123","article-title":"Thrombocytopenia and platelet hypoaggregation induced by Bothrops asper snake venom hemorrhage","volume":"91","author":"Rucavado","year":"2005","journal-title":"Thromb. Haemost."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"1440","DOI":"10.1016\/j.toxicon.2008.03.018","article-title":"Haematological evaluation of patients bitten by the jararaca, Bothrops jararaca, in Brazil","volume":"51","author":"Santoro","year":"2008","journal-title":"Toxicon"},{"key":"ref_100","doi-asserted-by":"crossref","unstructured":"Oliveira, S.S., Alves, E.C., Santos, A.S., Pereira, J.P.T., Sarraff, L.K.S., Nascimento, E.F., De-Brito-sousa, J.D., Sampaio, V.S., Lacerda, M.V.G., and Sachett, J.A.G. (2019). Factors associated with systemic bleeding in Bothrops envenomation in a tertiary hospital in the Brazilian Amazon. Toxins, 11.","DOI":"10.3390\/toxins11010022"},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"1063","DOI":"10.1016\/j.toxicon.2005.02.024","article-title":"Snake venom disintegrins: Evolution of structure and function","volume":"45","author":"Calvete","year":"2005","journal-title":"Toxicon"},{"key":"ref_102","doi-asserted-by":"crossref","unstructured":"Tadokoro, T., Modahl, C.M., Maenaka, K., and Aoki-Shioi, N. (2020). Cysteine-rich secretory proteins (CRISPs) from venomous snakes: An overview of the functional diversity in a large and underappreciated superfamily. Toxins, 12.","DOI":"10.3390\/toxins12030175"},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"1163","DOI":"10.1016\/j.toxicon.2005.02.017","article-title":"The Bradykinin-potentiating peptides from venom gland and brain of Bothrops jararaca contain highly site specific inhibitors of the somatic angiotensin-converting enzyme","volume":"45","author":"Hayashi","year":"2005","journal-title":"Toxicon"},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1016\/j.jprot.2013.05.028","article-title":"Snake venomics of Lachesis muta rhombeata and genus-wide antivenomics assessment of the paraspecific immunoreactivity of two antivenoms evidence the high compositional and immunological conservation across Lachesis","volume":"89","author":"Pla","year":"2013","journal-title":"J. Proteom."},{"key":"ref_105","doi-asserted-by":"crossref","unstructured":"Cavaillon, J.M., and Singer, M.E. (2018). Venoms. Inflammation: From Molecular and Cellular Mechanisms to the Clinic, Wiley.","DOI":"10.1002\/9783527692156"},{"key":"ref_106","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_107","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 Negl. Trop. Dis., 6.","DOI":"10.1371\/journal.pntd.0001526"},{"key":"ref_108","doi-asserted-by":"crossref","unstructured":"Rucavado, A., Nicolau, C.A., Escalante, T., Kim, J., Herrera, C., Guti\u00e9rrez, J.M., and Fox, J.W. (2016). Viperid envenomation wound exudate contributes to increased vascular permeability via a DAMPs\/TLR-4 mediated pathway. Toxins, 8.","DOI":"10.3390\/toxins8120349"},{"key":"ref_109","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_110","doi-asserted-by":"crossref","unstructured":"Zoccal, K.F., Bitencourt, C.S., Paula-Silva, F.W.G., Sorgi, C.A., Bordon, K.C.F., 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_111","doi-asserted-by":"crossref","first-page":"240","DOI":"10.1111\/jpi.12256","article-title":"Oxidative stress-induced methemoglobinemia is the silent killer during snakebite: A novel and strategic neutralization by melatonin","volume":"59","author":"Sharma","year":"2015","journal-title":"J. Pineal Res."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1016\/S0196-0644(96)70142-7","article-title":"Neostigmine for the treatment of neurotoxicity following envenomation by the Asiatic cobra","volume":"28","author":"Gold","year":"1996","journal-title":"Ann. Emerg. Med."},{"key":"ref_113","doi-asserted-by":"crossref","unstructured":"Lewin, M.R., Samuel, S.P., Wexler, D.S., Bickler, P., Vaiyapuri, S., and Mensh, B.D. (2014). Early treatment with intranasal neostigmine reduces mortality in a mouse model of Naja naja (Indian cobra) envenomation. J. Trop. Med., 2014.","DOI":"10.1155\/2014\/131835"},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"876","DOI":"10.4269\/ajtmh.16-0842","article-title":"Bites by the Monocled Cobra, Naja kaouthia, in Chittagong Division, Bangladesh: Epidemiology, clinical features of envenoming and management of 70 identified cases","volume":"96","author":"Faiz","year":"2017","journal-title":"Am. J. Trop. Med. Hyg."},{"key":"ref_115","doi-asserted-by":"crossref","unstructured":"Stazi, M., D\u2019este, G., Mattarei, A., Negro, S., Lista, F., Rigoni, M., Megighian, A., and Montecucco, C. (2020). An agonist of the cxcr4 receptor accelerates the recovery from the peripheral neuroparalysis induced by taipan snake envenomation. PLoS Negl. Trop. Dis., 14.","DOI":"10.1371\/journal.pntd.0008547"},{"key":"ref_116","doi-asserted-by":"crossref","unstructured":"Guti\u00e9rrez, J.M., Escalante, T., Hern\u00e1ndez, R., Gastaldello, S., Saravia-Otten, P., and Rucavado, A. (2018). Why is skeletal muscle regeneration impaired after myonecrosis induced by viperid snake venoms?. Toxins, 10.","DOI":"10.3390\/toxins10050182"},{"key":"ref_117","doi-asserted-by":"crossref","unstructured":"Sanchez-Castro, E.E., Pajuelo-Reyes, C., Tejedo, R., Soria-Juan, B., Tapia-Limonchi, R., Andreu, E., Hitos, A.B., Martin, F., Cahuana, G.M., and Guerra-Duarte, C. (2021). Mesenchymal Stromal Cell-Based Therapies as Promising Treatments for Muscle Regeneration after Snakebite Envenoming. Front. Immunol., 11.","DOI":"10.3389\/fimmu.2020.609961"},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1016\/j.toxicon.2019.06.005","article-title":"Engineering and design considerations for next-generation snakebite antivenoms","volume":"167","author":"Knudsen","year":"2019","journal-title":"Toxicon"},{"key":"ref_119","doi-asserted-by":"crossref","unstructured":"Knudsen, C., Casewell, N.R., Lomonte, B., Guti\u00e9rrez, J.M., Vaiyapuri, S., and Laustsen, A.H. (2020). Novel Snakebite Therapeutics Must Be Tested in Appropriate Rescue Models to Robustly Assess Their Preclinical Efficacy. Toxins, 12.","DOI":"10.3390\/toxins12090528"},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"627","DOI":"10.1016\/S0031-9422(00)00229-6","article-title":"Plant natural products active against snake bite\u2014The molecular approach","volume":"55","author":"Mors","year":"2000","journal-title":"Phytochemistry"},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"2625","DOI":"10.2174\/092986705774370655","article-title":"Medicinal Plants with Inhibitory Properties Against Snake Venoms","volume":"12","author":"Soares","year":"2005","journal-title":"Curr. Med. Chem."},{"key":"ref_122","doi-asserted-by":"crossref","unstructured":"Carvalho, B.M.A., Santos, J.D.L., Xavier, B.M., Almeida, J.R., Resende, L.M., Martins, W., Marcussi, S., Marangoni, S., St\u00e1beli, R.G., and Calderon, L.A. (2013). Snake venom PLA2s inhibitors isolated from Brazilian plants: Synthetic and natural molecules. BioMed Res. Int., 2013.","DOI":"10.1155\/2013\/153045"},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"222","DOI":"10.1016\/j.jep.2014.09.039","article-title":"Protective activity of medicinal plants and their isolated compounds against the toxic effects from the venom of Naja (cobra) species","volume":"157","author":"Shabbir","year":"2014","journal-title":"J. Ethnopharmacol."},{"key":"ref_124","doi-asserted-by":"crossref","unstructured":"F\u00e9lix-Silva, J., Silva-Junior, A.A., Zucolotto, S.M., and Fernandes-Pedrosa, M.D.F. (2017). Medicinal Plants for the Treatment of Local Tissue Damage Induced by Snake Venoms: An Overview from Traditional Use to Pharmacological Evidence. Evid. Based Complementary Altern. Med., 2017.","DOI":"10.1155\/2017\/5748256"},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"168","DOI":"10.1016\/j.jep.2016.12.031","article-title":"The potential of aqueous extracts of Bellucia dichotoma Cogn. (Melastomataceae) to inhibit the biological activities of Bothrops atrox venom: A comparison of specimens collected in the states of Par\u00e1 and Amazonas, Brazil","volume":"196","year":"2017","journal-title":"J. Ethnopharmacol."},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"969","DOI":"10.1590\/S0100-879X2004000700005","article-title":"Neutralization of the edema-forming, defibrinating and coagulant effects of Bothrops asper venom by extracts of plants used by healers in Columbia","volume":"37","author":"Otero","year":"2004","journal-title":"Braz. J. Med. Biol. Res."},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"1017","DOI":"10.1016\/j.phytochem.2005.03.026","article-title":"Inhibitory effects of Piper umbellatum and Piper peltatum extracts towards myotoxic phospholipases A2 from Bothrops snake venoms: Isolation of 4-nerolidylcatechol as active principle","volume":"66","author":"Castro","year":"2005","journal-title":"Phytochemistry"},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"224","DOI":"10.1016\/j.jep.2014.12.020","article-title":"Plants used to treat snakebites in Santar\u00e9m, western Par\u00e1, Brazil: An assessment of their effectiveness in inhibiting hemorrhagic activity induced by Bothrops jararaca venom","volume":"161","year":"2015","journal-title":"J. Ethnopharmacol."},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"1532","DOI":"10.3390\/toxins7051532","article-title":"Extracts of Renealmia alpinia (rottb.) MAAS protect against lethality and systemic hemorrhage induced by Bothrops asper venom: Insights from a model with extract administration before venom injection","volume":"7","author":"Quintana","year":"2015","journal-title":"Toxins"},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"505","DOI":"10.1016\/S0378-8741(99)00197-X","article-title":"Snakebites and ethnobotany in the northwest region of Colombia. Part II: Neutralization of lethal and enzymatic effects of Bothrops atrox venom","volume":"71","author":"Otero","year":"2000","journal-title":"J. Ethnopharmacol."},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1016\/S0378-8741(02)00028-4","article-title":"Medical ethnobotany of the tribals of Sonaghati of Sonbhadra district, Uttar Pradesh, India","volume":"81","author":"Singh","year":"2002","journal-title":"J. Ethnopharmacol."},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1016\/S0254-6272(14)60069-8","article-title":"Effect of externally applied Jidesheng anti-venom on skin and soft-tissue necrosis after Chinese cobra bite: A retrospective study","volume":"34","author":"Chen","year":"2014","journal-title":"J. Tradit. Chin. Med."},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"10914","DOI":"10.1021\/bi0258593","article-title":"Structural basis of phospholipase A2 inhibition for the synthesis of prostaglandins by the plant alkaloid aristolochic acid from a 1.7 \u00c5 crystal structure","volume":"41","author":"Chandra","year":"2002","journal-title":"Biochemistry"},{"key":"ref_134","doi-asserted-by":"crossref","unstructured":"Dos Santos, J.I., Cardoso, F.F., Soares, A.M., dal Pai Silva, M., Gallacci, M., and Fontes, M.R.M. (2011). Structural and functional studies of a bothropic myotoxin complexed to rosmarinic acid: New insights into Lys49-PLA 2 inhibition. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0028521"},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1107\/S1744309110051407","article-title":"Crystallization and preliminary X-ray diffraction analysis of a Lys49-phospholipase A2 complexed with caffeic acid, a molecule with inhibitory properties against snake venoms","volume":"67","author":"Shimabuku","year":"2011","journal-title":"Acta Crystallogr. Sect. F Struct. Biol. Cryst. Commun."},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1016\/j.cbi.2014.06.015","article-title":"The biflavonoid morelloflavone inhibits the enzymatic and biological activities of a snake venom phospholipase A2","volume":"220","author":"Osorio","year":"2014","journal-title":"Chem. Biol. Interact."},{"key":"ref_137","doi-asserted-by":"crossref","unstructured":"Preciado, L.M., Comer, J., N\u00fa\u00f1ez, V., Rey-S\u00faarez, P., and Perea\u00f1ez, J.A. (2018). Inhibition of a snake venom metalloproteinase by the flavonoid myricetin. Molecules, 23.","DOI":"10.3390\/molecules23102662"},{"key":"ref_138","doi-asserted-by":"crossref","unstructured":"Kumar, M.S., Amjesh, R., Bhaskaran, S., Delphin, R.D., Nair, A.S., and Sudhakaran, P.R. (2019). Molecular docking and dynamic studies of crepiside E beta glucopyranoside as an inhibitor of snake venom PLA2. J. Mol. Model., 25.","DOI":"10.1007\/s00894-019-3954-2"},{"key":"ref_139","unstructured":"Mackessy, S.P. (2010). Natural inhibitors. Innate immunity to snake venoms. Handbook of Venoms and Toxins of Reptiles, CRC Press."},{"key":"ref_140","doi-asserted-by":"crossref","unstructured":"Bastos, V.A., Gomes-Neto, F., Perales, J., Neves-Ferreira, A.G.C., and Valente, R.H. (2016). Natural inhibitors of snake venom metalloendopeptidases: History and current challenges. Toxins, 8.","DOI":"10.3390\/toxins8090250"},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"963","DOI":"10.1016\/j.toxicon.2003.11.007","article-title":"Natural phospholipase A2 myotoxin inhibitor proteins from snakes, mammals and plants","volume":"42","author":"Lizano","year":"2003","journal-title":"Toxicon"},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"6052","DOI":"10.1046\/j.1432-1033.2002.03308.x","article-title":"Functional analysis of DM64, an antimyotoxic protein with immunoglobulin-like structure from Didelphis marsupialis serum","volume":"269","author":"Rocha","year":"2002","journal-title":"Eur. J. Biochem."},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"526","DOI":"10.1126\/science.1128877","article-title":"Mast cells can enhance resistance to snake and honeybee venoms","volume":"313","author":"Metz","year":"2006","journal-title":"Science"},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1007\/s40629-020-00118-6","article-title":"Mast cells and IgE in defense against lethality of venoms: Possible \u201cbenefit\u201d of allergy","volume":"29","author":"Galli","year":"2020","journal-title":"Allergo J. Int."},{"key":"ref_145","doi-asserted-by":"crossref","unstructured":"Anderson, E., Stavenhagen, K., Kolarich, D., Sommerhoff, C.P., Maurer, M., and Metz, M. (2018). Human mast cell tryptase is a potential treatment for snakebite envenoming across multiple snake species. Front. Immunol., 9.","DOI":"10.3389\/fimmu.2018.01532"},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1016\/0041-0101(93)90146-A","article-title":"Antagonism of the myotoxic effects of Bothrops jararacussu venom and bothropstoxin by polyanions","volume":"31","author":"Melo","year":"1993","journal-title":"Toxicon"},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"1509","DOI":"10.1016\/0006-2952(94)90525-8","article-title":"Neutralization of the cytolytic and myotoxic activities of phospholipases A2 from Bothrops asper snake venom by glycosaminoglycans of the heparin\/heparan sulfate family","volume":"47","author":"Lomonte","year":"1994","journal-title":"Biochem. Pharmacol."},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1042\/bse0380021","article-title":"Matrix metalloproteinases in cancer","volume":"38","author":"Itoh","year":"2002","journal-title":"Essays Biochem."},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"2571","DOI":"10.1016\/j.bbagen.2014.03.007","article-title":"Matrix metalloproteinases in inflammation","volume":"1840","author":"Nissinen","year":"2014","journal-title":"Biochim. Biophys. Acta Gen. Subj."},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1016\/j.matbio.2018.01.018","article-title":"Matrix metalloproteinases in emphysema","volume":"73","author":"Gharib","year":"2018","journal-title":"Matrix Biol."},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1042\/CS20180906","article-title":"ADAM8 in invasive cancers: Links to tumor progression, metastasis, and chemoresistance","volume":"133","author":"Conrad","year":"2019","journal-title":"Clin. Sci."},{"key":"ref_152","doi-asserted-by":"crossref","first-page":"7960","DOI":"10.1002\/chem.201805361","article-title":"Design and Structural Evolution of Matrix Metalloproteinase Inhibitors","volume":"25","author":"Fischer","year":"2019","journal-title":"Chem. A Eur. J."},{"key":"ref_153","doi-asserted-by":"crossref","first-page":"285","DOI":"10.2174\/1568009054064615","article-title":"Matrix Metalloproteinase Inhibitors as Anticancer Therapeutics","volume":"5","author":"Mannello","year":"2005","journal-title":"Curr. Cancer Drug Targets"},{"key":"ref_154","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1080\/17460441.2018.1398732","article-title":"Recent opportunities in matrix metalloproteinase inhibitor drug design for cancer","volume":"13","author":"Zhong","year":"2018","journal-title":"Expert Opin. Drug Discov."},{"key":"ref_155","doi-asserted-by":"crossref","first-page":"4977","DOI":"10.1158\/0008-5472.CAN-10-4552","article-title":"Small-molecule anticancer compounds selectively target the hemopexin domain of matrix metalloproteinase-9","volume":"71","author":"Dufour","year":"2011","journal-title":"Cancer Res."},{"key":"ref_156","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1016\/S0006-2952(00)00302-6","article-title":"Effectiveness of batimastat, a synthetic inhibitor of matrix metalloproteinases, in neutralizing local tissue damage induced by BaP1, a hemorrhagic metalloproteinase from the venom of the snake Bothrops asper","volume":"60","author":"Escalante","year":"2000","journal-title":"Biochem. Pharmacol."},{"key":"ref_157","doi-asserted-by":"crossref","first-page":"313","DOI":"10.4269\/ajtmh.2000.63.313","article-title":"Inhibition of local hemorrhage and dermonecrosis induced by Bothrops asper snake venom: Effectiveness of early in situ administration of the peptidomimetic metalloproteinase inhibitor batimastat and the chelating agent CaNa2EDTA","volume":"63","author":"Rucavado","year":"2000","journal-title":"Am. J. Trop. Med. Hyg."},{"key":"ref_158","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1016\/j.toxicon.2017.04.001","article-title":"Peptidomimetic hydroxamate metalloproteinase inhibitors abrogate local and systemic toxicity induced by Echis ocellatus (saw-scaled) snake venom","volume":"132","author":"Arias","year":"2017","journal-title":"Toxicon"},{"key":"ref_159","doi-asserted-by":"crossref","unstructured":"Albulescu, L.O., Xie, C., Ainsworth, S., Alsolaiss, J., Crittenden, E., Dawson, C.A., Softley, R., Bartlett, K.E., Harrison, R.A., and Kool, J. (2020). A therapeutic combination of two small molecule toxin inhibitors provides broad preclinical efficacy against viper snakebite. Nat. Commun., 11.","DOI":"10.1038\/s41467-020-19981-6"},{"key":"ref_160","doi-asserted-by":"crossref","first-page":"442","DOI":"10.1006\/taap.1997.8285","article-title":"Inhibition of toxic activities of Bothrops asper venom and other crotalid snake venoms by a novel neutralizing mixture","volume":"147","author":"Borkow","year":"1997","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"ref_161","doi-asserted-by":"crossref","unstructured":"Albulescu, L.O., Hale, M.S., Ainsworth, S., Alsolaiss, J., Crittenden, E., Calvete, J.J., Evans, C., Wilkinson, M.C., Harrison, R.A., and Kool, J. (2020). Preclinical validation of a repurposed metal chelator as an early-intervention therapeutic for hemotoxic snakebite. Sci. Transl. Med., 12.","DOI":"10.1126\/scitranslmed.aay8314"},{"key":"ref_162","doi-asserted-by":"crossref","unstructured":"Rudresha, G.V., Urs, A.P., Manjuprasanna, V.N., Milan Gowda, M.D., Jayachandra, K., Rajaiah, R., and Vishwanath, B.S. (2021). Echis carinatus snake venom metalloprotease-induced toxicities in mice: Therapeutic intervention by a repurposed drug, tetraethyl thiuram disulfide (Disulfiram). PLoS Negl. Trop. Dis., 15.","DOI":"10.1371\/journal.pntd.0008596"},{"key":"ref_163","doi-asserted-by":"crossref","first-page":"754","DOI":"10.1016\/j.toxicon.2008.08.009","article-title":"Assessment of metalloproteinase inhibitors clodronate and doxycycline in the neutralization of hemorrhage and coagulopathy induced by Bothrops asper snake venom","volume":"52","author":"Rucavado","year":"2008","journal-title":"Toxicon"},{"key":"ref_164","doi-asserted-by":"crossref","unstructured":"Nakamoto, M., Escalante, T., Guti\u00e9rrez, J.M., and Shea, K.J. (2021). A Biomimetic of Endogenous Tissue Inhibitors of Metalloproteinases: Inhibition Mechanism and Contribution of Composition, Polymer Size and Shape to the Inhibitory Effect. Nano Lett., in press.","DOI":"10.1021\/acs.nanolett.1c01357"},{"key":"ref_165","doi-asserted-by":"crossref","first-page":"6130","DOI":"10.1021\/cr200085w","article-title":"Phospholipase A2 enzymes: Physical structure, biological function, disease implication, chemical inhibition, and therapeutic intervention","volume":"111","author":"Dennis","year":"2011","journal-title":"Chem. Rev."},{"key":"ref_166","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1517\/13543776.2013.754425","article-title":"Phospholipase A2 inhibitors for the treatment of inflammatory diseases: A patent review (2010-present)","volume":"23","author":"Magrioti","year":"2013","journal-title":"Expert Opin. Ther. Pat."},{"key":"ref_167","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1615\/CritRevImmunol.v37.i2-6.20","article-title":"Regulatory functions of phospholipase A2","volume":"37","author":"Murakami","year":"2017","journal-title":"Crit. Rev. Immunol."},{"key":"ref_168","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1097\/MOL.0b013e32832dd4c7","article-title":"Phospholipase A2 inhibitors","volume":"20","author":"Serruys","year":"2009","journal-title":"Curr. Opin. Lipidol."},{"key":"ref_169","doi-asserted-by":"crossref","first-page":"137","DOI":"10.2165\/11533650-000000000-00000","article-title":"Varespladib","volume":"11","author":"Adis","year":"2011","journal-title":"Am. J. Cardiovasc. Drugs"},{"key":"ref_170","doi-asserted-by":"crossref","first-page":"252","DOI":"10.1001\/jama.2013.282836","article-title":"Varespladib and cardiovascular events in patients with an acute coronary syndrome: The VISTA-16 randomized clinical trial","volume":"311","author":"Nicholls","year":"2014","journal-title":"JAMA J. Am. Med. Assoc."},{"key":"ref_171","doi-asserted-by":"crossref","first-page":"1079","DOI":"10.1016\/j.jacc.2010.06.015","article-title":"Effects of varespladib methyl on biomarkers and major cardiovascular events in acute coronary syndrome patients","volume":"56","author":"Rosenson","year":"2010","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_172","doi-asserted-by":"crossref","unstructured":"Lewin, M., 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_173","doi-asserted-by":"crossref","unstructured":"Lewin, M.R., Guti\u00e9rrez, J.M., Samuel, S.P., Herrera, M., Bryan-Quir\u00f3s, W., Lomonte, B., Bickler, P.E., Bulfone, T.C., and Williams, D.J. (2018). Delayed oral LY333013 rescues mice from highly neurotoxic, lethal doses of papuan taipan (Oxyuranus scutellatus) venom. Toxins, 10.","DOI":"10.3390\/toxins10100380"},{"key":"ref_174","doi-asserted-by":"crossref","unstructured":"Lewin, M.R., Gilliam, L.L., Gilliam, J., Samuel, S.P., Bulfone, T.C., Bickler, P.E., and Guti\u00e9rrez, J.M. (2018). Delayed LY333013 (oral) and LY315920 (intravenous) reverse severe neurotoxicity and rescue juvenile pigs from lethal doses of Micrurus fulvius (eastern coral snake) venom. Toxins, 10.","DOI":"10.3390\/toxins10110479"},{"key":"ref_175","doi-asserted-by":"crossref","unstructured":"Guti\u00e9rrez, J.M., Lewin, M.R., Williams, D.J., and Lomonte, B. (2020). Varespladib (LY315920) and methyl varespladib (LY333013) abrogate or delay lethality induced by presynaptically acting neurotoxic snake venoms. Toxins, 12.","DOI":"10.3390\/toxins12020131"},{"key":"ref_176","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1016\/j.toxicon.2020.08.023","article-title":"Varespladib (LY315920) inhibits neuromuscular blockade induced by Oxyuranus scutellatus venom in a nerve-muscle preparation","volume":"187","author":"Lewin","year":"2020","journal-title":"Toxicon"},{"key":"ref_177","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.toxicon.2018.11.292","article-title":"Neutralizing properties of LY315920 toward snake venom group I and II myotoxic phospholipases A2","volume":"157","author":"Lewin","year":"2019","journal-title":"Toxicon"},{"key":"ref_178","doi-asserted-by":"crossref","unstructured":"Xiao, H., Li, H., Zhang, D., Li, Y., Sun, S., and Huang, C. (2018). Inactivation of venom PLA2 alleviates myonecrosis and facilitates muscle regeneration in envenomed mice: A time course observation. Molecules, 23.","DOI":"10.3390\/molecules23081911"},{"key":"ref_179","doi-asserted-by":"crossref","first-page":"1147","DOI":"10.1016\/j.toxicon.2005.02.018","article-title":"Structure-function relationships and mechanism of anticoagulant phospholipase A2 enzymes from snake venoms","volume":"45","author":"Kini","year":"2005","journal-title":"Toxicon"},{"key":"ref_180","doi-asserted-by":"crossref","unstructured":"Xie, C., Albulescu, L.O., Still, K.B.M., Slagboom, J., Zhao, Y., Jiang, Z., Somsen, G.W., Vonk, F.J., Casewell, N.R., and Kool, J. (2020). Varespladib inhibits the phospholipase A2 and coagulopathic activities of venom components from hemotoxic snakes. Biomedicines, 8.","DOI":"10.3390\/biomedicines8060165"},{"key":"ref_181","doi-asserted-by":"crossref","unstructured":"Youngman, N.J., Walker, A., Naude, A., Coster, K., Sundman, E., and Fry, B.G. (2020). Varespladib (LY315920) neutralises phospholipase A2 mediated prothrombinase-inhibition induced by Bitis snake venoms. Comp. Biochem. Physiol. Part C Toxicol. Pharmacol., 236.","DOI":"10.1016\/j.cbpc.2020.108818"},{"key":"ref_182","doi-asserted-by":"crossref","first-page":"176","DOI":"10.1016\/j.toxlet.2020.05.014","article-title":"Anticoagulant activity of black snake (Elapidae: Pseudechis) venoms: Mechanisms, potency, and antivenom efficacy","volume":"330","author":"Zdenek","year":"2020","journal-title":"Toxicol. Lett."},{"key":"ref_183","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1016\/j.toxlet.2020.11.010","article-title":"Anticoagulant Micrurus venoms: Targets and neutralization","volume":"337","author":"Dashevsky","year":"2021","journal-title":"Toxicol. Lett."},{"key":"ref_184","doi-asserted-by":"crossref","first-page":"725","DOI":"10.1016\/0041-0101(89)90039-1","article-title":"A new muscle damaging toxin, myotoxin II, from the venom of the snake Bothrops asper (terciopelo)","volume":"27","author":"Lomonte","year":"1989","journal-title":"Toxicon"},{"key":"ref_185","doi-asserted-by":"crossref","first-page":"667","DOI":"10.1016\/S0041-0101(03)00007-2","article-title":"Hyperalgesia induced by Asp49 and Lys49 phospholipases A2 from Bothrops asper snake venom: Pharmacological mediation and molecular determinants","volume":"41","author":"Chacur","year":"2003","journal-title":"Toxicon"},{"key":"ref_186","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1016\/j.toxicon.2004.11.004","article-title":"Inflammatory events induced by Lys-49 and Asp-49 phospholipases A 2 isolated from Bothrops asper snake venom: Role of catalytic activity","volume":"45","author":"Zuliani","year":"2005","journal-title":"Toxicon"},{"key":"ref_187","doi-asserted-by":"crossref","unstructured":"Salvador, G.H.M., Gomes, A.A.S., Bryan-Quir\u00f3s, W., Fern\u00e1ndez, J., Lewin, M.R., Guti\u00e9rrez, J.M., Lomonte, B., and Fontes, M.R.M. (2019). Structural basis for phospholipase A2-like toxin inhibition by the synthetic compound Varespladib (LY315920). Sci. Rep., 9.","DOI":"10.1038\/s41598-019-53755-5"},{"key":"ref_188","doi-asserted-by":"crossref","first-page":"29867","DOI":"10.1016\/S0021-9258(18)43961-0","article-title":"Neutralizing interaction between heparins and myotoxin II, a lysine 49 phospholipase A2 from Bothrops asper snake venom. Identification of a heparin-binding and cytolytic toxin region by the use of synthetic peptides and molecular modeling","volume":"269","author":"Lomonte","year":"1994","journal-title":"J. Biol. Chem."},{"key":"ref_189","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1016\/S0041-0101(03)00166-1","article-title":"Antagonism of myotoxic and paralyzing activities of bothropstoxin-I by suramin","volume":"42","author":"Cavalcante","year":"2003","journal-title":"Toxicon"},{"key":"ref_190","doi-asserted-by":"crossref","first-page":"416","DOI":"10.1016\/j.jmb.2005.04.072","article-title":"Inhibition of myotoxic activity of Bothrops asper myotoxin II by the anti-trypanosomal drug suramin","volume":"350","author":"Murakami","year":"2005","journal-title":"J. Mol. Biol."},{"key":"ref_191","doi-asserted-by":"crossref","unstructured":"Salvador, G.H.M., Dreyer, T.R., Gomes, A.A.S., Cavalcante, W.L.G., Dos Santos, J.I., Gandin, C.A., De Oliveira Neto, M., Gallacci, M., and Fontes, M.R.M. (2018). Structural and functional characterization of suramin-bound MjTX-I from Bothrops moojeni suggests a particular myotoxic mechanism. Sci. Rep., 8.","DOI":"10.1038\/s41598-018-28584-7"},{"key":"ref_192","first-page":"333","article-title":"Isolation and characterization of a thrombin-like enzyme from the venom of Crotalus durissus terrificus","volume":"19","author":"Raw","year":"1986","journal-title":"Braz. J. Med. Biol. Res."},{"key":"ref_193","doi-asserted-by":"crossref","first-page":"555","DOI":"10.1016\/0041-0101(95)00159-X","article-title":"Purification and partial characterization of a thrombin-like\/gyroxin enzyme from bushmaster (Lachesis muta rhombeata) venom","volume":"34","author":"Aguiar","year":"1996","journal-title":"Toxicon"},{"key":"ref_194","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1016\/j.toxicon.2013.01.019","article-title":"Alpha neurotoxins","volume":"66","author":"Barber","year":"2013","journal-title":"Toxicon"},{"key":"ref_195","doi-asserted-by":"crossref","unstructured":"Albulescu, L.O., Kazandjian, T., Slagboom, J., Bruyneel, B., Ainsworth, S., Alsolaiss, J., Wagstaff, S.C., Whiteley, G., Harrison, R.A., and Ulens, C. (2019). A decoy-receptor approach using nicotinic acetylcholine receptor mimics reveals their potential as novel therapeutics against neurotoxic snakebite. Front. Pharmacol., 10.","DOI":"10.3389\/fphar.2019.00848"},{"key":"ref_196","doi-asserted-by":"crossref","unstructured":"Zdenek, C.N., Harris, R.J., Kuruppu, S., Youngman, N.J., Dobson, J.S., Debono, J., Khan, M., Smith, I., Yarski, M., and Harrich, D. (2019). A taxon-specific and high-throughput method for measuring ligand binding to nicotinic acetylcholine receptors. Toxins, 11.","DOI":"10.3390\/toxins11100600"},{"key":"ref_197","doi-asserted-by":"crossref","unstructured":"Harris, R.J., Youngman, N.J., Zdenek, C.N., Huynh, T.M., Nouwens, A., Hodgson, W.C., Harrich, D., Dunstan, N., Portes-Junior, J.A., and Fry, B.G. (2020). Assessing the binding of venoms from aquatic elapids to the nicotinic acetylcholine receptor orthosteric site of different prey models. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21197377"},{"key":"ref_198","doi-asserted-by":"crossref","unstructured":"El-Aziz, T.M.A., Ravelet, C., Molgo, J., Fiore, E., Pale, S., Amar, M., Al-Khoury, S., Dejeu, J., Fadl, M., and Ronjat, M. (2017). Efficient functional neutralization of lethal peptide toxins in vivo by oligonucleotides. Sci. Rep., 7.","DOI":"10.1038\/s41598-017-07554-5"},{"key":"ref_199","doi-asserted-by":"crossref","unstructured":"Taiwe, G.S., Montnach, J., Nicolas, S., De Waard, S., Fiore, E., Peyrin, E., El-Aziz, T.M.A., Amar, M., Molg\u00f3, J., and Ronjat, M. (2019). Aptamer efficacies for in vitro and in vivo modulation of \u03b1C-conotoxin PrXA pharmacology. Molecules, 24.","DOI":"10.3390\/molecules24020229"},{"key":"ref_200","doi-asserted-by":"crossref","unstructured":"Lauridsen, L.H., Shamaileh, H.A., Edwards, S.L., Taran, E., and Veedu, R.N. (2012). Rapid one-step selection method for generating nucleic acid aptamers: Development of a DNA Aptamer against \u03b1-bungarotoxin. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0041702"},{"key":"ref_201","doi-asserted-by":"crossref","unstructured":"Chen, Y.J., Tsai, C.Y., Hu, W.P., and Chang, L. (2016). Sen DNA aptamers against Taiwan banded krait \u03b1-bungarotoxin recognize Taiwan cobra cardiotoxins. Toxins, 8.","DOI":"10.3390\/toxins8030066"},{"key":"ref_202","doi-asserted-by":"crossref","first-page":"13709","DOI":"10.1021\/acs.jmedchem.0c01202","article-title":"Peptide Inhibitors of the \u03b1-Cobratoxin-Nicotinic Acetylcholine Receptor Interaction","volume":"63","author":"Lynagh","year":"2020","journal-title":"J. Med. Chem."},{"key":"ref_203","doi-asserted-by":"crossref","first-page":"16604","DOI":"10.1021\/jacs.6b10950","article-title":"Engineering the Protein Corona of a Synthetic Polymer Nanoparticle for Broad-Spectrum Sequestration and Neutralization of Venomous Biomacromolecules","volume":"138","author":"Lee","year":"2016","journal-title":"J. Am. Chem. Soc."},{"key":"ref_204","doi-asserted-by":"crossref","unstructured":"O\u2019Brien, J., Lee, S.H., Guti\u00e9rrez, J.M., and Shea, K.J. (2018). Engineered nanoparticles bind elapid snake venom toxins and inhibit venom-induced dermonecrosis. PLoS Negl. Trop. Dis., 12.","DOI":"10.1371\/journal.pntd.0006736"},{"key":"ref_205","unstructured":"Mackessy, S.P. (2010). Hyaluronidases, a Neglected Class of Glycosidases from Snake Venom. Handbook of Venoms and Toxins of Reptiles, CRC Press."},{"key":"ref_206","doi-asserted-by":"crossref","first-page":"635","DOI":"10.1016\/j.toxicon.2003.09.001","article-title":"Hyaluronidase inhibitors (sodium cromoglycate and sodium auro-thiomalate) reduce the local tissue damage and prolong the survival time of mice injected with Naja kaouthia and Calloselasma rhodostoma venoms","volume":"42","author":"Yingprasertchai","year":"2003","journal-title":"Toxicon"},{"key":"ref_207","doi-asserted-by":"crossref","unstructured":"Khedrinia, M., Aryapour, H., and Mianabadi, M. (2019). Prediction of novel inhibitors for Crotalus adamanteus L-amino acid oxidase by repurposing FDA-approved drugs: A virtual screening and molecular dynamics simulation investigation. Drug Chem. Toxicol.","DOI":"10.1080\/01480545.2019.1614022"},{"key":"ref_208","doi-asserted-by":"crossref","first-page":"516","DOI":"10.1007\/s10439-011-0454-7","article-title":"The nuts and bolts of low-level laser (Light) therapy","volume":"40","author":"Chung","year":"2012","journal-title":"Ann. Biomed. Eng."},{"key":"ref_209","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1016\/j.toxicon.2018.07.006","article-title":"Photobiomodulation therapy on Bothrops snake venom-induced local pathological effects: A systematic review","volume":"152","author":"Silva","year":"2018","journal-title":"Toxicon"},{"key":"ref_210","doi-asserted-by":"crossref","first-page":"1561","DOI":"10.1039\/c4pp00111g","article-title":"Photobiostimulation reduces edema formation induced in mice by Lys-49 phospholipases A2 isolated from Bothrops moojeni venom","volume":"13","author":"Dale","year":"2014","journal-title":"Photochem. Photobiol. Sci."},{"key":"ref_211","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1016\/j.toxicon.2018.07.029","article-title":"Light emitting diode (LED) therapy reduces local pathological changes induced by Bothrops asper snake venom","volume":"152","author":"Campos","year":"2018","journal-title":"Toxicon"},{"key":"ref_212","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1111\/php.12189","article-title":"Analgesic effect of light-emitting diode (LED) therapy at wavelengths of 635 and 945 nm on Bothrops moojeni venom-induced hyperalgesia","volume":"90","author":"Zamuner","year":"2014","journal-title":"Photochem. Photobiol."},{"key":"ref_213","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1007\/s10103-011-0914-1","article-title":"Effects of photobiostimulation on edema and hemorrhage induced by Bothrops moojeni venom","volume":"27","author":"Barbosa","year":"2012","journal-title":"Lasers Med. Sci."},{"key":"ref_214","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1111\/j.1751-1097.2008.00397.x","article-title":"The ability of low level laser therapy to prevent muscle tissue damage induced by snake venom","volume":"85","author":"Baranauskas","year":"2009","journal-title":"Photochem. Photobiol."},{"key":"ref_215","doi-asserted-by":"crossref","first-page":"591","DOI":"10.1089\/pho.2008.2296","article-title":"Effect of low-level laser therapy in the myonecrosis induced by Bothrops jararacussu snake venom","volume":"27","author":"Barbosa","year":"2009","journal-title":"Photomed. Laser Surg."},{"key":"ref_216","doi-asserted-by":"crossref","unstructured":"Silva, L.M.G., Da Silva, C.A.A., Da Silva, A., Vieira, R.P., Mesquita-Ferrari, R.A., Cogo, J.C., and Zamuner, S.R. (2016). Photobiomodulation protects and promotes differentiation of C2C12 myoblast cells exposed to snake venom. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0152890"},{"key":"ref_217","doi-asserted-by":"crossref","unstructured":"Nadur-Andrade, N., Dale, C.S., da Silva Oliveira, V.R., Toniolo, E.F., Dos Santos Feliciano, R., da Silva, J.A., and Zamuner, S.R. (2016). Analgesic Effect of Photobiomodulation on Bothrops moojeni Venom-Induced Hyperalgesia: A Mechanism Dependent on Neuronal Inhibition, Cytokines and Kinin Receptors Modulation. PLoS Negl. Trop. Dis., 10.","DOI":"10.1371\/journal.pntd.0004998"},{"key":"ref_218","doi-asserted-by":"crossref","first-page":"6790","DOI":"10.1021\/jm900648x","article-title":"Hydroxamates: Relationships between structure and plasma stability","volume":"52","author":"Flipo","year":"2009","journal-title":"J. Med. Chem."}],"container-title":["Toxins"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6651\/13\/7\/451\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T06:26:39Z","timestamp":1760163999000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6651\/13\/7\/451"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,6,29]]},"references-count":218,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2021,7]]}},"alternative-id":["toxins13070451"],"URL":"https:\/\/doi.org\/10.3390\/toxins13070451","relation":{},"ISSN":["2072-6651"],"issn-type":[{"value":"2072-6651","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,6,29]]}}}