{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T21:16:16Z","timestamp":1792790176742,"version":"4.5.0"},"reference-count":129,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T00:00:00Z","timestamp":1789948800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado de S\u00e3o Paulo","award":["2025\/17976-8"],"award-info":[{"award-number":["2025\/17976-8"]}],"id":[{"id":"https:\/\/ror.org\/02ddkpn78","id-type":"ROR","asserted-by":"crossref"}]},{"name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado de S\u00e3o Paulo","award":["2025\/22164-2"],"award-info":[{"award-number":["2025\/22164-2"]}],"id":[{"id":"https:\/\/ror.org\/02ddkpn78","id-type":"ROR","asserted-by":"crossref"}]},{"name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado de S\u00e3o Paulo","award":["2024\/01801-1"],"award-info":[{"award-number":["2024\/01801-1"]}],"id":[{"id":"https:\/\/ror.org\/02ddkpn78","id-type":"ROR","asserted-by":"crossref"}]},{"name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado de S\u00e3o Paulo","award":["2025\/11949-9"],"award-info":[{"award-number":["2025\/11949-9"]}],"id":[{"id":"https:\/\/ror.org\/02ddkpn78","id-type":"ROR","asserted-by":"crossref"}]},{"name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado de S\u00e3o Paulo","award":["2026\/04159-4"],"award-info":[{"award-number":["2026\/04159-4"]}],"id":[{"id":"https:\/\/ror.org\/02ddkpn78","id-type":"ROR","asserted-by":"crossref"}]},{"name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado de S\u00e3o Paulo","award":["2024\/13258-0"],"award-info":[{"award-number":["2024\/13258-0"]}],"id":[{"id":"https:\/\/ror.org\/02ddkpn78","id-type":"ROR","asserted-by":"crossref"}]},{"name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado de S\u00e3o Paulo","award":["2025\/01407-4"],"award-info":[{"award-number":["2025\/01407-4"]}],"id":[{"id":"https:\/\/ror.org\/02ddkpn78","id-type":"ROR","asserted-by":"crossref"}]},{"award":["2025\/17976-8"],"award-info":[{"award-number":["2025\/17976-8"]}],"id":[{"id":"https:\/\/ror.org\/02ddkpn78","id-type":"ROR","asserted-by":"publisher"}]},{"award":["2025\/22164-2"],"award-info":[{"award-number":["2025\/22164-2"]}],"id":[{"id":"https:\/\/ror.org\/02ddkpn78","id-type":"ROR","asserted-by":"publisher"}]},{"award":["2024\/01801-1"],"award-info":[{"award-number":["2024\/01801-1"]}],"id":[{"id":"https:\/\/ror.org\/02ddkpn78","id-type":"ROR","asserted-by":"publisher"}]},{"award":["2025\/11949-9"],"award-info":[{"award-number":["2025\/11949-9"]}],"id":[{"id":"https:\/\/ror.org\/02ddkpn78","id-type":"ROR","asserted-by":"publisher"}]},{"award":["2026\/04159-4"],"award-info":[{"award-number":["2026\/04159-4"]}],"id":[{"id":"https:\/\/ror.org\/02ddkpn78","id-type":"ROR","asserted-by":"publisher"}]},{"award":["2024\/13258-0"],"award-info":[{"award-number":["2024\/13258-0"]}],"id":[{"id":"https:\/\/ror.org\/02ddkpn78","id-type":"ROR","asserted-by":"publisher"}]},{"award":["2025\/01407-4"],"award-info":[{"award-number":["2025\/01407-4"]}],"id":[{"id":"https:\/\/ror.org\/02ddkpn78","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004809","name":"Financiadora de Estudos e Projetos","doi-asserted-by":"publisher","award":["01.23.0034.00 (0419\/22)"],"award-info":[{"award-number":["01.23.0034.00 (0419\/22)"]}],"id":[{"id":"10.13039\/501100004809","id-type":"DOI","asserted-by":"publisher"}]},{"award":["01.23.0034.00 (0419\/22)"],"award-info":[{"award-number":["01.23.0034.00 (0419\/22)"]}],"id":[{"id":"https:\/\/ror.org\/030w99567","id-type":"ROR","asserted-by":"publisher"}]},{"name":"Coordena\u00e7\u00e3o de Aperfei\u00e7oamento de Pessoal de N\u0131vel Superior","award":["001"],"award-info":[{"award-number":["001"]}],"id":[{"id":"https:\/\/ror.org\/00x0ma614","id-type":"ROR","asserted-by":"crossref"}]},{"award":["001"],"award-info":[{"award-number":["001"]}],"id":[{"id":"https:\/\/ror.org\/00x0ma614","id-type":"ROR","asserted-by":"publisher"}]},{"name":"Center for Translational Science and Biopharmaceutical Development","award":["2021\/11936-3"],"award-info":[{"award-number":["2021\/11936-3"]}]},{"name":"Lyofilizaion multi-user equipment","award":["2023\/16514-5"],"award-info":[{"award-number":["2023\/16514-5"]}]},{"name":"National Council for Scientific and Technological Development","award":["301608\/2022-9"],"award-info":[{"award-number":["301608\/2022-9"]}],"id":[{"id":"https:\/\/ror.org\/03swz6y49","id-type":"ROR","asserted-by":"crossref"}]},{"name":"National Council for Scientific and Technological Development","award":["305778\/2023-4"],"award-info":[{"award-number":["305778\/2023-4"]}],"id":[{"id":"https:\/\/ror.org\/03swz6y49","id-type":"ROR","asserted-by":"crossref"}]},{"award":["301608\/2022-9"],"award-info":[{"award-number":["301608\/2022-9"]}],"id":[{"id":"https:\/\/ror.org\/03swz6y49","id-type":"ROR","asserted-by":"publisher"}]},{"award":["305778\/2023-4"],"award-info":[{"award-number":["305778\/2023-4"]}],"id":[{"id":"https:\/\/ror.org\/03swz6y49","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Toxins"],"abstract":"<jats:p>Leishmaniasis and Chagas disease are neglected tropical diseases that continue to pose significant public health challenges, highlighting the need for new therapeutic strategies. Brazilian snake venoms represent a valuable and underexplored source of bioactive molecules with diverse pharmacological activities and promising therapeutic potential. In this context, the present study aimed to investigate the in vitro antiprotozoal potential of venoms from Bothrops and Crotalus species, including Bothrops jararacussu, Bothrops pauloensis, Bothrops alternatus, Bothrops leucurus, Bothrops atrox, Bothrops jararaca, Crotalus durissus terrificus, and Crotalus durissus ruruima, metalloprotease (MTL)- and crotoxin (CTX)-enriched, against Leishmania spp. and Trypanosoma cruzi. Crude venom protein profiles were analyzed by SDS-PAGE, and cytotoxicity was assessed in differentiated C2C12 myotubes and murine peritoneal macrophages. Antiprotozoal activity was evaluated against extracellular parasite forms, including promastigotes of Leishmania amazonensis and Leishmania infantum and epimastigotes of T. cruzi. Venoms exhibiting the highest selectivity indices (SIs), calculated using murine macrophage cytotoxicity data, were further tested against intracellular amastigotes of L. amazonensis. Among the tested samples, B. jararacussu venom showed activity against promastigotes of both L. amazonensis (IC50 = 2.9 \u00b5g mL\u22121) and L. infantum (IC50 = 2.8 \u00b5g mL\u22121), as well as in epimastigotes of T. cruzi (IC50 = 15.5 \u00b5g mL\u22121). The MTLand CTX pools from C. d. ruruima venom exhibited the highest activity against promastigotes of L. amazonensis, with IC50 values of 1.6 and 3.8 \u00b5g mL\u22121, respectively. Against intracellular amastigotes, MTL and CTX showed IC50 values of 4.1 and 2.5 \u00b5g mL\u22121, respectively, with selectivity indices (SIs) of 73.1 and 120, respectively. Overall, these findings provide preliminary evidence for the antiparasitic potential of snake venom-derived molecules, supporting further characterization and in vivo evaluation.<\/jats:p>","DOI":"10.3390\/toxins18090405","type":"journal-article","created":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T17:23:17Z","timestamp":1790011397000},"page":"405","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Brazilian Bothrops and Crotalus Snake Venoms as a Source of Antiprotozoal Agents: Unlocking Toxins for Therapeutic Development"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1827-9102","authenticated-orcid":false,"given":"Tulio Cust\u00f3dio","family":"Reis","sequence":"first","affiliation":[{"name":"Graduate Program in Bioscience and Biotechnology Applied to Pharmacy, School of Pharmaceutical Sciences, S\u00e3o Paulo State University (UNESP), Araraquara 19060-900, S\u00e3o Paulo, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"validation","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"}]},{"given":"Ana Clara Lunardi","family":"Yagi","sequence":"additional","affiliation":[{"name":"Graduate Program in Bioscience and Biotechnology Applied to Pharmacy, School of Pharmaceutical Sciences, S\u00e3o Paulo State University (UNESP), Araraquara 19060-900, S\u00e3o Paulo, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"methodology","vocabulary":"credit"},{"role":"validation","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"},{"role":"software","vocabulary":"credit"},{"role":"conceptualization","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1566-1867","authenticated-orcid":false,"given":"Eloise T.","family":"Filardi","sequence":"additional","affiliation":[{"name":"Graduate Program in Bioscience and Biotechnology Applied to Pharmacy, School of Pharmaceutical Sciences, S\u00e3o Paulo State University (UNESP), Araraquara 19060-900, S\u00e3o Paulo, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"methodology","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"}]},{"given":"Marcela","family":"Romanazzi","sequence":"additional","affiliation":[{"name":"Graduate Program in Bioscience and Biotechnology Applied to Pharmacy, School of Pharmaceutical Sciences, S\u00e3o Paulo State University (UNESP), Araraquara 19060-900, S\u00e3o Paulo, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"methodology","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3587-351X","authenticated-orcid":false,"given":"Michele Ferreira da Silva","family":"Mela","sequence":"additional","affiliation":[{"name":"Graduate Program in Bioscience and Biotechnology Applied to Pharmacy, School of Pharmaceutical Sciences, S\u00e3o Paulo State University (UNESP), Araraquara 19060-900, S\u00e3o Paulo, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"methodology","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6952-0512","authenticated-orcid":false,"given":"Rui S.","family":"Ferreira J\u00fanior","sequence":"additional","affiliation":[{"name":"Center for the Study of Venoms and Venomous Animals (CEVAP), S\u00e3o Paulo State University (UNESP), Botucatu 18619-002, S\u00e3o Paulo, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Felipe A.","family":"Cerni","sequence":"additional","affiliation":[{"name":"Medical School, Federal University of Roraima (UFRR), Boa Vista 69310-000, Roraima, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"resources","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"validation","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7280-3775","authenticated-orcid":false,"given":"M\u00e1rcia A. S.","family":"Graminha","sequence":"additional","affiliation":[{"name":"Graduate Program in Bioscience and Biotechnology Applied to Pharmacy, School of Pharmaceutical Sciences, S\u00e3o Paulo State University (UNESP), Araraquara 19060-900, S\u00e3o Paulo, Brazil"},{"name":"Department of Clinical Analysis, School of Pharmaceutical Sciences, S\u00e3o Paulo State University (UNESP), Araraquara 19060-900, S\u00e3o Paulo, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"resources","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"},{"role":"project-administration","vocabulary":"credit"},{"role":"funding-acquisition","vocabulary":"credit"},{"role":"visualization","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2594-7068","authenticated-orcid":false,"given":"Manuela B.","family":"Pucca","sequence":"additional","affiliation":[{"name":"Graduate Program in Bioscience and Biotechnology Applied to Pharmacy, School of Pharmaceutical Sciences, S\u00e3o Paulo State University (UNESP), Araraquara 19060-900, S\u00e3o Paulo, Brazil"},{"name":"Center for the Study of Venoms and Venomous Animals (CEVAP), S\u00e3o Paulo State University (UNESP), Botucatu 18619-002, S\u00e3o Paulo, Brazil"},{"name":"Department of Clinical Analysis, School of Pharmaceutical Sciences, S\u00e3o Paulo State University (UNESP), Araraquara 19060-900, S\u00e3o Paulo, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"9141","DOI":"10.1038\/s41598-017-08707-2","article-title":"Biodiversity Conservation Gaps in the Brazilian Protected Areas","volume":"7","author":"Oliveira","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Lepsch-Cunha, N., Muraro, V., Nascimento, H.E.M., Mazoni, A., Nunez, C.V., and Bonacelli, M.B.M. (2024). Technical-Scientific Production and Knowledge Networks about Medicinal Plants and Herbal Medicines in the Amazon. Front. Res. Metr. Anal., 9.","DOI":"10.3389\/frma.2024.1396472"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1186\/s40409-015-0011-1","article-title":"Epidemiology of Envenomations by Terrestrial Venomous Animals in Brazil Based on Case Reporting: From Obvious Facts to Contingencies","volume":"21","author":"Chippaux","year":"2015","journal-title":"J. Venom. Anim. Toxins Incl. Trop. Dis."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"e2022666","DOI":"10.1590\/s2237-96222023000100002","article-title":"Completeness of Notifications of Accidents Involving Venomous Animals in the Information System for Notifiable Diseases: A Descriptive Study, Brazil, 2007\u20132019","volume":"32","author":"Brito","year":"2023","journal-title":"Epidemiol. Servi\u00e7os Sa\u00fade"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1","DOI":"10.21680\/2446-7286.2023v9n2ID32538","article-title":"Trends in Occurrences of Accidents by Venomous Animals in Brazil: Analysis of Notifications from 2007 to 2021","volume":"9","author":"Santos","year":"2023","journal-title":"Rev. Ci\u00eancia Plur."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"54","DOI":"10.7322\/jhgd.96768","article-title":"Accidents with Poisonous Animals in Brazil by Age and Sex","volume":"25","author":"Bernarde","year":"2015","journal-title":"J. Hum. Growth Dev."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"e37262","DOI":"10.1016\/j.heliyon.2024.e37262","article-title":"Analysis of the Genus Bothrops Snake Venom: An Inter and Intraspecific Comparative Study","volume":"10","author":"Silveira","year":"2024","journal-title":"Heliyon"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Pucca, M.B., Bernarde, P.S., Rocha, A.M., Viana, P.F., Farias, R.E.S., Cerni, F.A., Oliveira, I.S., Ferreira, I.G., Sandri, E.A., and Sachett, J. (2021). Crotalus durissus ruruima: Current Knowledge on Natural History, Medical Importance, and Clinical Toxinology. Front. Immunol., 12.","DOI":"10.3389\/fimmu.2021.659515"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"719","DOI":"10.1042\/BST20200110","article-title":"Cytotoxicity of Snake Venom Enzymatic Toxins: Phospholipase A2 and L-Amino Acid Oxidase","volume":"48","author":"Hiu","year":"2020","journal-title":"Biochem. Soc. Trans."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Zona Rubio, D.C., Arag\u00f3n, D.M., and Almeida Alves, I. (2025). Innovations in Snake Venom-Derived Therapeutics: A Systematic Review of Global Patents and Their Pharmacological Applications. Toxins, 17.","DOI":"10.3390\/toxins17030136"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"100175","DOI":"10.1016\/j.medidd.2023.100175","article-title":"Therapeutic Potential of Snake Venom: Toxin Distribution and Opportunities in Deep Learning for Novel Drug Discovery","volume":"21","author":"Bedraoui","year":"2024","journal-title":"Med. Drug Discov."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"124745","DOI":"10.1016\/j.ijbiomac.2023.124745","article-title":"Unlocking the Potential of Snake Venom-Based Molecules against the Malaria, Chagas Disease, and Leishmaniasis Triad","volume":"242","author":"Almeida","year":"2023","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"31010","DOI":"10.1074\/jbc.M403959200","article-title":"Drug Uptake and Modulation of Drug Resistance in Leishmania by an Aquaglyceroporin","volume":"279","author":"Gourbal","year":"2004","journal-title":"J. Biol. Chem."},{"key":"ref_14","unstructured":"World Health Organization (2026, July 23). Leishmaniasis. Available online: https:\/\/www.who.int\/news-room\/fact-sheets\/detail\/leishmaniasis."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Knight, C.A., Harris, D.R., Alshammari, S.O., Gugssa, A., Young, T., and Lee, C.M. (2023). Leishmaniasis: Recent Epidemiological Studies in the Middle East. Front. Microbiol., 13.","DOI":"10.3389\/fmicb.2022.1052478"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1261","DOI":"10.1111\/tmi.70035","article-title":"Mapping the Burden of Tegumentary Leishmaniasis in South America: A Systematic Review and Meta-Analysis","volume":"30","author":"Caldas","year":"2025","journal-title":"Trop. Med. Int. Health"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Vilas-Boas, D.F., Nakasone, E.K.N., Gon\u00e7alves, A.A.M., Lair, D.F., de Oliveira, D.S., Pereira, D.F.S., Silva, G.G., Conrado, I.d.S.S., Resende, L.A., and Zald\u00edvar, M.F. (2024). Global Distribution of Canine Visceral Leishmaniasis and the Role of the Dog in the Epidemiology of the Disease. Pathogens, 13.","DOI":"10.3390\/pathogens13060455"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"426","DOI":"10.4269\/ajtmh.2012.11-0378","article-title":"Epidemiological and Clinical Changes in American Tegumentary Leishmaniasis in an Area of Leishmania (Viannia) braziliensis Transmission over a 20-Year Period","volume":"86","author":"Jirmanus","year":"2012","journal-title":"Am. J. Trop. Med. Hyg."},{"key":"ref_19","first-page":"100881","article-title":"The Epidemiology of Chagas Disease in the Americas","volume":"37","author":"Ceccarelli","year":"2024","journal-title":"Lancet Reg. Health Am."},{"key":"ref_20","unstructured":"World Health Organization (2026, July 18). Chagas Disease (Also Known as American Trypanosomiasis). Available online: https:\/\/www.who.int\/news-room\/fact-sheets\/detail\/chagas-disease-(american-trypanosomiasis)."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"da Gama, A.N.S., and Soeiro, M.d.N.C. (2025). Trypanosoma cruzi Transmission Through Blood Samples and Derivatives: Main Routes, Control Strategies, and Recent Advancements in Blood Banks. Pathogens, 14.","DOI":"10.3390\/pathogens14020133"},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Kemmerling, U., Osuna, A., Schijman, A.G., and Truyens, C. (2019). Congenital Transmission of Trypanosoma cruzi: A Review about the Interactions between the Parasite, the Placenta, the Maternal and the Fetal\/Neonatal Immune Responses. Front. Microbiol., 10.","DOI":"10.3389\/fmicb.2019.01854"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"565","DOI":"10.1002\/clc.22421","article-title":"The Epidemiology, Clinical Manifestations, and Management of Chagas Heart Disease","volume":"38","author":"Malik","year":"2015","journal-title":"Clin. Cardiol."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Zhang, H., Yan, R., Liu, Y., Yu, M., He, Z., Xiao, J., Li, K., Liu, G., Ning, Q., and Li, Y. (2025). Progress in Antileishmanial Drugs: Mechanisms, Challenges, and Prospects. PLoS Negl. Trop. Dis., 19.","DOI":"10.1371\/journal.pntd.0012735"},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Bhusal, C.K., Sinha, S., Kaur, D., and Sehgal, R. (2025). Unravelling Drug Resistance in Leishmaniasis: Genomic Adaptations and Emerging Therapies. Front. Mol. Biosci., 12.","DOI":"10.3389\/fmolb.2025.1573618"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1358\/dot.2021.57.4.3251712","article-title":"Update on Nifurtimox for Treatment of Chagas Disease","volume":"57","author":"Thakare","year":"2021","journal-title":"Drugs Today"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"111702","DOI":"10.1016\/j.molbiopara.2025.111702","article-title":"Surface Molecules of Leishmania: From Virulence Determinants to Therapeutic and Vaccine Targets","volume":"264","author":"Reis","year":"2025","journal-title":"Mol. Biochem. Parasitol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1289","DOI":"10.4269\/ajtmh.16-0761","article-title":"Experimental and Clinical Treatment of Chagas Disease: A Review","volume":"97","author":"Sales","year":"2017","journal-title":"Am. J. Trop. Med. Hyg."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"598","DOI":"10.1007\/s00436-002-0626-3","article-title":"Ultrastructural Alterations and Growth Inhibition of Trypanosoma cruzi and Leishmania Major Induced by Bothrops jararaca Venom","volume":"88","author":"Soares","year":"2002","journal-title":"Parasitol. Res."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"e00688-17","DOI":"10.1128\/AAC.00688-17","article-title":"Efficacy of a Binuclear Cyclopalladated Compound Therapy for Cutaneous Leishmaniasis in the Murine Model of Infection with Leishmania amazonensis and Its Inhibitory Effect on Topoisomerase 1B","volume":"61","author":"Ribeiro","year":"2017","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"751","DOI":"10.1038\/nrd4683","article-title":"Hit and Lead Criteria in Drug Discovery for Infectious Diseases of the Developing World","volume":"14","author":"Katsuno","year":"2015","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Colombini, M., Rocha, A.M., Freitas-De-sousa, L.A., Chaves, A.F.A., Serrano, S.M.T., Souza, V.C., Viala, V.L., Junqueira-Azevedo, I.L.M., Cerni, F.A., and Sartim, M.A. (2025). Phenotypic Dichotomy in Crotalus durissus ruruima Venom and Potential Consequences for Clinical Management of Snakebite Envenomations. PLoS Negl. Trop. Dis., 19.","DOI":"10.1371\/journal.pntd.0013296"},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Abdullahi, Z.U., Musa, S.S., He, D., and Bello, U.M. (2021). Antiprotozoal Effect of Snake Venoms and Their Fractions: A Systematic Review. Pathogens, 10.","DOI":"10.3390\/pathogens10121632"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"616","DOI":"10.1016\/j.ijbiomac.2020.07.178","article-title":"Insights into the Antiviral Activity of Phospholipases A2 (PLA2s) from Snake Venoms","volume":"164","author":"Teixeira","year":"2020","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_35","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_36","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1016\/j.ijbiomac.2017.05.025","article-title":"A New L-Amino Acid Oxidase from Bothrops jararacussu Snake Venom: Isolation, Partial Characterization, and Assessment of pro-Apoptotic and Antiprotozoal Activities","volume":"103","author":"Carone","year":"2017","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_37","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_38","doi-asserted-by":"crossref","unstructured":"Romanazzi, M., Filardi, E.T.M., Pires, G.M.M., Cerveja, M.F., Melo-dos-Santos, G., Oliveira, I.S., Ferreira, I.G., Cerni, F.A., Santos-Filho, N.A., and Monteiro, W.M. (2025). The Versatility of Serine Proteases from Brazilian Bothrops Venom: Their Roles in Snakebites and Drug Discovery. Biomolecules, 15.","DOI":"10.3390\/biom15020154"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1016\/S0003-9861(03)00028-6","article-title":"Wide Distribution of Cysteine-Rich Secretory Proteins in Snake Venoms: Isolation and Cloning of Novel Snake Venom Cysteine-Rich Secretory Proteins","volume":"412","author":"Yamazaki","year":"2003","journal-title":"Arch. Biochem. Biophys."},{"key":"ref_40","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_41","doi-asserted-by":"crossref","unstructured":"Adade, C.M., Carvalho, A.L.O., Tomaz, M.A., Costa, T.F.R., Godinho, J.L., Melo, P.A., Lima, A.P.C.A., Rodrigues, J.C.F., Zingali, R.B., and Souto-Padr\u00f3n, T. (2014). Crovirin, a Snake Venom Cysteine-Rich Secretory Protein (CRISP) with Promising Activity against Trypanosomes and Leishmania. PLoS Negl. Trop. Dis., 8.","DOI":"10.1371\/journal.pntd.0003252"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1016\/j.toxicon.2014.10.020","article-title":"Toxins and Drug Discovery","volume":"92","author":"Harvey","year":"2014","journal-title":"Toxicon"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1059","DOI":"10.1017\/S0031182017001846","article-title":"Antichagasic Effect of Crotalicidin, a Cathelicidin-like Vipericidin, Found in Crotalus durissus terrificus Rattlesnake\u2019s Venom Gland","volume":"145","author":"Bandeira","year":"2018","journal-title":"Parasitology"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1038\/s41573-020-00135-8","article-title":"Trends in Peptide Drug Discovery","volume":"20","author":"Muttenthaler","year":"2021","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1787","DOI":"10.1021\/acs.jnatprod.1c00153","article-title":"Mechanistic Insights into the Leishmanicidal and Bactericidal Activities of Batroxicidin, a Cathelicidin-Related Peptide from a South American Viper (Bothrops atrox)","volume":"84","author":"Dematei","year":"2021","journal-title":"J. Nat. Prod."},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Rodr\u00edguez-Vargas, A., Vega, N., Reyes-Monta\u00f1o, E., Corzo, G., Neri-Castro, E., Clement, H., and Ruiz-G\u00f3mez, F. (2022). Intraspecific Differences in the Venom of Crotalus durissus cumanensis from Colombia. Toxins, 14.","DOI":"10.3390\/toxins14080532"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1016\/j.jprot.2009.01.018","article-title":"Venomics: Digging into the Evolution of Venomous Systems and Learning to Twist Nature to Fight Pathology","volume":"72","author":"Calvete","year":"2009","journal-title":"J. Proteom."},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Moreira, V.P., da Silva Mela, M.F., dos Anjos, L.R., Saraiva, L.F., Arenas Vel\u00e1squez, A.M., Kalaba, P., Fabisikov\u00e1, A., Clementino, L.d.C., Aufy, M., and Studenik, C. (2022). Novel Selective and Low-Toxic Inhibitor of LmCPB2.8\u0394CTE (CPB) One Important Cysteine Protease for Leishmania Virulence. Biomolecules, 12.","DOI":"10.3390\/biom12121903"},{"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":"80","DOI":"10.1590\/S0104-79301998000100008","article-title":"Epidemiological Clinical Study of Envenoming by Bothrops leucurus Wagler, 1824 (Serpentes; Viperidae) in the Metropolitan Area of Salvador, Bahia, Brazil","volume":"4","year":"1998","journal-title":"J. Venom. Anim. Toxins"},{"key":"ref_51","first-page":"328","article-title":"Ecological and Phylogenetic Correlates of Feeding Habits in Neotropical Pitvipers of the Genus Bothrops","volume":"307","author":"Martins","year":"2002","journal-title":"Biol. Vipers"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1016\/j.toxicon.2020.05.028","article-title":"Sexual and Ontogenetic Variation of Bothrops leucurus Venom","volume":"184","author":"Pereira","year":"2020","journal-title":"Toxicon"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1590\/S0101-81752005000200012","article-title":"Caracteriza\u00e7\u00e3o Individual Do Veneno de Bothrops alternatus Dum\u00e9ril, Bibron & Dum\u00e9ril Em Fun\u00e7\u00e3o Da Distribui\u00e7\u00e3o Geogr\u00e1fica No Brasil (Serpentes, Viperidae)","volume":"22","author":"Furtado","year":"2005","journal-title":"Rev. Bras. Zool."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"2278","DOI":"10.1021\/pr901027r","article-title":"Analysis of the Ontogenetic Variation in the Venom Proteome\/Peptidome of Bothrops jararaca Reveals Different Strategies to Deal with Prey","volume":"9","author":"Zelanis","year":"2010","journal-title":"J. Proteome Res."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1081","DOI":"10.1080\/15287394.2012.697839","article-title":"Intraspecific Variation of Biological Activities in Venoms from Wild and Captive Bothrops jararaca","volume":"75","author":"Saad","year":"2012","journal-title":"J. Toxicol. Environ. Health Part A"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1016\/j.toxicon.2006.06.005","article-title":"Sexual Dimorphism in Venom of Bothrops jararaca(Serpentes: Viperidae)","volume":"48","author":"Furtado","year":"2006","journal-title":"Toxicon"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1016\/j.toxicon.2020.07.030","article-title":"Ontogenetic Study of Bothrops jararacussu Venom Composition Reveals Distinct Profiles","volume":"186","author":"Silveira","year":"2020","journal-title":"Toxicon"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1186\/1477-5956-4-11","article-title":"Ontogenetic Variations in the Venom Proteome of the Amazonian Snake Bothrops atrox","volume":"4","author":"Shevchenko","year":"2006","journal-title":"Proteome Sci."},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"Sousa, L.F., Holding, M.L., Del-Rei, T.H.M., Rocha, M.M.T., Mour\u00e3o, R.H.V., Chalkidis, H.M., Prezoto, B., Gibbs, H.L., and Moura-Da-silva, A.M. (2021). Individual Variability in Bothrops atrox Snakes Collected from Different Habitats in the Brazilian Amazon: New Findings on Venom Composition and Functionality. Toxins, 13.","DOI":"10.3390\/toxins13110814"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"958","DOI":"10.1016\/j.toxicon.2005.06.008","article-title":"Individual Venom Variability in Crotalus durissus ruruima Snakes, a Subspecies of Crotalus Durissus from the Amazonian Region","volume":"46","author":"Assis","year":"2005","journal-title":"Toxicon"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"e20200016","DOI":"10.1590\/1678-9199-jvatitd-2020-0016","article-title":"Geographic Variation of Individual Venom Profile of Crotalus Durissus Snakes","volume":"26","author":"Rodrigues","year":"2020","journal-title":"J. Venom. Anim. Toxins Incl. Trop. Dis."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1016\/j.toxicon.2013.01.006","article-title":"Individual Venom Profiling of Crotalus durissus terrificus Specimens from a Geographically Limited Region: Crotamine Assessment and Captivity Evaluation on the Biological Activities","volume":"69","author":"Pimenta","year":"2013","journal-title":"Toxicon"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"844","DOI":"10.1017\/S0031182013000012","article-title":"BnSP-7 Toxin, a Basic Phospholipase A2 from Bothrops pauloensis Snake Venom, Interferes with Proliferation, Ultrastructure and Infectivity of Leishmania (Leishmania) amazonensis","volume":"140","author":"Nunes","year":"2013","journal-title":"Parasitology"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"490","DOI":"10.1016\/j.biochi.2008.12.004","article-title":"Structural and Functional Properties of Bp-LAAO, a New l-Amino Acid Oxidase Isolated from Bothrops pauloensis Snake Venom","volume":"91","author":"Rodrigues","year":"2009","journal-title":"Biochimie"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"595","DOI":"10.1016\/S0041-0101(03)00002-3","article-title":"Effect of Bothrops leucurus Venom in Chick Biventer Cervicis Preparations","volume":"41","author":"Prianti","year":"2003","journal-title":"Toxicon"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1016\/j.biochi.2006.10.010","article-title":"Purification and Partial Characterization of Two Phospholipases A2 from Bothrops leucurus (White-Tailed-Jararaca) Snake Venom","volume":"89","author":"Higuchi","year":"2007","journal-title":"Biochimie"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"941467","DOI":"10.1155\/2013\/941467","article-title":"Unmasking Snake Venom of Bothrops leucurus: Purification and Pharmacological and Structural Characterization of New PLA2 Bleu TX-III","volume":"2013","author":"Marangoni","year":"2013","journal-title":"BioMed Res. Int."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/j.toxicon.2022.04.002","article-title":"Bothrops leucurus Snake Venom Protein Profile, Isolation and Biological Characterization of Its Major Toxin PLA2s-Like","volume":"213","author":"Dias","year":"2022","journal-title":"Toxicon"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"1095","DOI":"10.1021\/acs.jproteome.5c00933","article-title":"Venomics across the Bothrops neuwiedi Species Complex Revealed a P-III Snake Venom Metalloproteases\/K49-PLA2 Dichotomy and a Remarkable Paraspecific Neutralization of the Brazilian Pentabothropic Antivenom","volume":"25","author":"Galizio","year":"2026","journal-title":"J. Proteome Res."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1016\/j.biochi.2004.02.002","article-title":"Analysis of Bothrops jararacussu Venomous Gland Transcriptome Focusing on Structural and Functional Aspects: I\u2014Gene Expression Profile of Highly Expressed Phospholipases A2","volume":"86","author":"Kashima","year":"2004","journal-title":"Biochimie"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"2422","DOI":"10.1021\/pr901128x","article-title":"The Venomics of Bothrops alternatus Is a Pool of Acidic Proteins with Predominant Hemorrhagic and Coagulopathic Activities","volume":"9","author":"Georgieva","year":"2010","journal-title":"J. Proteome Res."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"169","DOI":"10.3109\/15569543.2014.922581","article-title":"The Proteinase-Rich Proteome of Bothrops jararaca Venom","volume":"33","author":"Serrano","year":"2014","journal-title":"Toxin Rev."},{"key":"ref_73","doi-asserted-by":"crossref","unstructured":"Sousa, L.F., Nicolau, C.A., Peixoto, P.S., Bernardoni, J.L., Oliveira, S.S., Portes-Junior, J.A., Mour\u00e3o, R.H.V., Lima-dos-Santos, I., Sano-Martins, I.S., and Chalkidis, H.M. (2013). Comparison of Phylogeny, Venom Composition and Neutralization by Antivenom in Diverse Species of Bothrops Complex. PLoS Negl. Trop. Dis., 7.","DOI":"10.1371\/journal.pntd.0002442"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1016\/j.toxicon.2013.01.023","article-title":"Dexamethasone Antagonizes the in Vivo Myotoxic and Inflammatory Effects of Bothrops Venoms","volume":"69","author":"Tomaz","year":"2013","journal-title":"Toxicon"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"488","DOI":"10.1590\/S0100-879X2012007500033","article-title":"Pulsed Ultrasound Therapy Accelerates the Recovery of Skeletal Muscle Damage Induced by Bothrops jararacussu Venom","volume":"45","author":"Tomaz","year":"2012","journal-title":"Braz. J. Med. Biol. Res."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"997","DOI":"10.1016\/j.toxicon.2005.02.029","article-title":"Hemorrhage Induced by Snake Venom Metalloproteinases: Biochemical and Biophysical Mechanisms Involved in Microvessel Damage","volume":"45","author":"Rucavado","year":"2005","journal-title":"Toxicon"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"546","DOI":"10.1016\/j.toxicon.2005.06.019","article-title":"Proteolytic, Edematogenic and Myotoxic Activities of a Hemorrhagic Metalloproteinase Isolated from Bothrops alternatus Venom","volume":"46","author":"Gay","year":"2005","journal-title":"Toxicon"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"280","DOI":"10.1016\/j.toxicon.2012.03.026","article-title":"Jararhagin, a Hemorrhagic Snake Venom Metalloproteinase from Bothrops jararaca","volume":"60","author":"Baldo","year":"2012","journal-title":"Toxicon"},{"key":"ref_79","doi-asserted-by":"crossref","unstructured":"Santos Barreto, G.N.L., de Oliveira, S.S., dos Anjos, I.V., Chalkidis, H.d.M., Mour\u00e3o, R.H.V., Moura-da-Silva, A.M., Sano-Martins, I.S., and Gon\u00e7alves, L.R.d.C. (2017). Experimental Bothrops atrox Envenomation: Efficacy of Antivenom Therapy and the Combination of Bothrops Antivenom with Dexamethasone. PLoS Negl. Trop. Dis., 11.","DOI":"10.1371\/journal.pntd.0005458"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"1345923","DOI":"10.1155\/2019\/1345923","article-title":"Clinical, Laboratory, and Therapeutic Aspects of Crotalus Durissus (South American Rattlesnake) Victims: A Literature Review","volume":"2019","author":"Frare","year":"2019","journal-title":"BioMed Res. Int."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"603","DOI":"10.1016\/j.ijbiomac.2021.07.121","article-title":"Catalytically Active Phospholipase A2 Myotoxin from Crotalus durissus terrificus Induces Proliferation and Differentiation of Myoblasts Dependent on Prostaglandins Produced by Both COX-1 and COX-2 Pathways","volume":"187","author":"Silva","year":"2021","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"352","DOI":"10.2174\/0113892037317894240926081324","article-title":"Myotoxicity of Crotoxin on C2C12 Myoblasts and Its Inhibition by Crotalus Neutralizing Factor versus Enhanced Resistance in Myotubes: Exploring Toxicity and Membrane Potential","volume":"26","author":"Tavares","year":"2024","journal-title":"Curr. Protein Pept. Sci."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"1141","DOI":"10.1016\/S0041-0101(00)00245-2","article-title":"Systemic Skeletal Muscle Necrosis Induced by Crotoxin","volume":"39","author":"Salvini","year":"2001","journal-title":"Toxicon"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"1045","DOI":"10.1016\/j.toxicon.2010.01.011","article-title":"Crotoxin: Novel Activities for a Classic \u03b2-Neurotoxin","volume":"55","author":"Sampaio","year":"2010","journal-title":"Toxicon"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"915","DOI":"10.1016\/j.toxicon.2003.11.005","article-title":"Skeletal Muscle Degeneration Induced by Venom Phospholipases A2: Insights into the Mechanisms of Local and Systemic Myotoxicity","volume":"42","author":"Ownby","year":"2003","journal-title":"Toxicon"},{"key":"ref_86","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. Primers"},{"key":"ref_87","doi-asserted-by":"crossref","unstructured":"Guti\u00e9rrez, J.M., Solano, G., Pla, D., Herrera, M., Segura, \u00c1., Vargas, M., Villalta, M., S\u00e1nchez, A., Sanz, L., and Lomonte, B. (2017). Preclinical Evaluation of the Efficacy of Antivenoms for Snakebite Envenoming: State-of-the-Art and Challenges Ahead. Toxins, 9.","DOI":"10.3390\/toxins9050163"},{"key":"ref_88","doi-asserted-by":"crossref","unstructured":"Guti\u00e9rrez, J.M., Vargas, M., Segura, \u00c1., Herrera, M., Villalta, M., Solano, G., S\u00e1nchez, A., Herrera, C., and Le\u00f3n, G. (2021). In Vitro Tests for Assessing the Neutralizing Ability of Snake Antivenoms: Toward the 3Rs Principles. Front. Immunol., 11.","DOI":"10.3389\/fimmu.2020.617429"},{"key":"ref_89","doi-asserted-by":"crossref","unstructured":"Weekers, D.J.C., Alonso, L.L., Verstegen, A.X., Slagboom, J., and Kool, J. (2024). Qualitative Profiling of Venom Toxins in the Venoms of Several Bothrops Species Using High-Throughput Venomics and Coagulation Bioassaying. Toxins, 16.","DOI":"10.3390\/toxins16070300"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1016\/j.toxicon.2015.01.006","article-title":"Neuromuscular Effects of Venoms and Crotoxin-like Proteins from Crotalus durissus ruruima and Crotalus durissus cumanensis","volume":"96","author":"Cavalcante","year":"2015","journal-title":"Toxicon"},{"key":"ref_91","doi-asserted-by":"crossref","unstructured":"Demico, P.J., Oliveira, I.N., Proen\u00e7a-Hirata, V.S., Dias, S.R., Ghirotti, H.A., Silva, E.O., Giometti, I.C., Pacagnelli, F.L., Torres-Bonilla, K.A., and Hyslop, S. (2025). Comparative Analysis of the Enzymatic, Coagulant, and Neuromuscular Activities of Two Variants of Crotalus durissus ruruima Venom and Antivenom Efficacy. Pharmaceuticals, 18.","DOI":"10.3390\/ph18010054"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"e20180526","DOI":"10.1590\/0037-8682-0526-2018","article-title":"Local and Systemic Effects Caused by Crotalus durissus terrificus, Crotalus durissus collilineatus, and Crotalus durissus cascavella Snake Venoms in Swiss Mice","volume":"52","author":"Teixeira","year":"2019","journal-title":"Rev. Soc. Bras. Med. Trop."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"941","DOI":"10.1016\/j.biochi.2011.01.009","article-title":"Cell Cycle Arrest Evidence, Parasiticidal and Bactericidal Properties Induced by l-Amino Acid Oxidase from Bothrops atrox Snake Venom","volume":"93","author":"Antonucci","year":"2011","journal-title":"Biochimie"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1016\/j.toxicon.2017.02.031","article-title":"Evaluation of the Antichagasic Activity of Batroxicidin, a Cathelicidin-Related Antimicrobial Peptide Found in Bothrops atrox Venom Gland","volume":"130","author":"Mello","year":"2017","journal-title":"Toxicon"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"2561","DOI":"10.1007\/s00726-014-1801-4","article-title":"Vipericidins: A Novel Family of Cathelicidin-Related Peptides from the Venom Gland of South American Pit Vipers","volume":"46","author":"Falcao","year":"2014","journal-title":"Amino Acids"},{"key":"ref_96","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_97","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1016\/0041-0101(74)90241-4","article-title":"Fractionation of Vipera ammodytes Venom and Seasonal Variation of Its Composition","volume":"12","author":"Sket","year":"1974","journal-title":"Toxicon"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"100246","DOI":"10.1016\/j.toxcx.2026.100246","article-title":"Venom Variation and the Future of Antivenom Design: Integrating Population Venomics, Evolutionary Toxinology, and Precision Therapeutics","volume":"30","author":"Dingwoke","year":"2026","journal-title":"Toxicon X"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1159\/000371391","article-title":"Biodegradable Microparticles Containing Crotamine Isolated from Crotalus durissus terrificus Display Antileishmanial Activity in Vitro","volume":"95","author":"Macedo","year":"2015","journal-title":"Pharmacology"},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1186\/s40409-015-0049-0","article-title":"In Vitro Activity of Phospholipase A2 and of Peptides from Crotalus durissus terrificus Venom against Amastigote and Promastigote Forms of Leishmania (L.) infantum Chagasi","volume":"21","author":"Barros","year":"2015","journal-title":"J. Venom. Anim. Toxins Incl. Trop. Dis."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"1458","DOI":"10.1017\/S0031182017000944","article-title":"Crotoxin Stimulates an M1 Activation Profile in Murine Macrophages during Leishmania amazonensis Infection","volume":"144","author":"Farias","year":"2017","journal-title":"Parasitology"},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1016\/j.biochi.2019.05.009","article-title":"Insights into the Structure, Function and Stability of Bordonein-L, the First L-Amino Acid Oxidase from Crotalus durissus terrificus Snake Venom","volume":"163","author":"Wiezel","year":"2019","journal-title":"Biochimie"},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"107934","DOI":"10.1016\/j.exppara.2020.107934","article-title":"A Natural Cell-Penetrating Nanopeptide Combined with Pentavalent Antimonial as Experimental Therapy against Cutaneous Leishmaniasis","volume":"217","author":"Ferreira","year":"2020","journal-title":"Exp. Parasitol."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1016\/j.toxicon.2022.08.009","article-title":"Antileishmanial Activity, Cytotoxicity and Cellular Response of Amphotericin B in Combination with Crotamine Derived from Crotalus durissus terrificus Venom Using in Vitro and in Silico Approaches","volume":"217","author":"Macedo","year":"2022","journal-title":"Toxicon"},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"e20240049","DOI":"10.1590\/1678-9199-jvatitd-2024-0049","article-title":"Molecular Interaction Assays in Silico of Crotapotin from Crotalus durissus terrificus against the Molecular Target Trypanothione Reductase from Leishmania braziliensis","volume":"31","author":"Macedo","year":"2025","journal-title":"J. Venom. Anim. Toxins Incl. Trop. Dis."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1016\/0041-0101(87)90246-7","article-title":"Several Isoforms of Crotoxin Are Present in Individual Venoms from the South American Rattlesnake Crotalus durissus terrificus","volume":"25","author":"Faure","year":"1987","journal-title":"Toxicon"},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"105123","DOI":"10.1016\/j.micinf.2023.105123","article-title":"BjussuLAAO-II, an L-Amino Acid Oxidase from Bothrops jararacussu Snake Venom, Impairs Toxoplasma gondii Infection in Human Trophoblast Cells and Villous Explants from the Third Trimester of Pregnancy","volume":"25","author":"Teixeira","year":"2023","journal-title":"Microbes Infect."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1016\/j.ijbiomac.2020.11.146","article-title":"A Comparative Study on the Leishmanicidal Activity of the L-Amino Acid Oxidases BjussuLAAO-II and BmooLAAO-II Isolated from Brazilian Bothrops Snake Venoms","volume":"167","author":"Barbosa","year":"2021","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1016\/j.intimp.2016.04.025","article-title":"Liposomes Containing an ASP49-Phospholipase A2 from Bothrops jararacussu Snake Venom as Experimental Therapy against Cutaneous Leishmaniasis","volume":"36","author":"Macedo","year":"2016","journal-title":"Int. Immunopharmacol."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1016\/j.intimp.2017.12.012","article-title":"ASP49-Phospholipase A2-Loaded Liposomes as Experimental Therapy in Cutaneous Leishmaniasis Model","volume":"55","author":"Ferreira","year":"2018","journal-title":"Int. Immunopharmacol."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"614","DOI":"10.1590\/S1678-91992010000400012","article-title":"Antimicrobial Activity of an L-Amino Acid Oxidase Isolated from Bothrops leucurus Snake Venom","volume":"16","author":"Torres","year":"2010","journal-title":"J. Venom. Anim. Toxins Incl. Trop. Dis."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1016\/j.ijbiomac.2018.08.064","article-title":"In Vitro Effect of Bothrops leucurus Lectin (BLL) against Leishmania amazonensis and Leishmania braziliensis Infection","volume":"120","year":"2018","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1590\/S0074-02762005000100006","article-title":"Programmed Cell Death in Trypanosoma cruzi Induced by Bothrops jararaca Venom","volume":"100","author":"Deolindo","year":"2005","journal-title":"Mem. Inst. Oswaldo Cruz"},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"944","DOI":"10.1016\/j.toxicon.2010.06.019","article-title":"L-Amino Acid Oxidase Activity Present in Fractions of Bothrops jararaca Venom Is Responsible for the Induction of Programmed Cell Death in Trypanosoma cruzi","volume":"56","author":"Deolindo","year":"2010","journal-title":"Toxicon"},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"330","DOI":"10.1016\/j.toxicon.2008.12.004","article-title":"Antigenic, Microbicidal and Antiparasitic Properties of an l-Amino Acid Oxidase Isolated from Bothrops jararaca Snake Venom","volume":"53","author":"Ciscotto","year":"2009","journal-title":"Toxicon"},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1016\/j.toxicon.2021.05.009","article-title":"Photobiomodulation Induces Murine Macrophages Polarization toward M2 Phenotype","volume":"198","author":"Reis","year":"2021","journal-title":"Toxicon"},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1016\/j.tiv.2016.02.023","article-title":"Bjcul, a Snake Venom Lectin, Modulates Monocyte-Derived Macrophages to a pro-Inflammatory Profile in Vitro","volume":"33","author":"Trindade","year":"2016","journal-title":"Toxicol. Vitr."},{"key":"ref_118","first-page":"2745286","article-title":"Crotalus durissus ruruima Snake Venom and a Phospholipase A2 Isolated from This Venom Elicit Macrophages to Form Lipid Droplets and Synthesize Inflammatory Lipid Mediators","volume":"2019","author":"Giannotti","year":"2019","journal-title":"J. Immunol. Res."},{"key":"ref_119","doi-asserted-by":"crossref","unstructured":"Boeno, C.N., Paloschi, M.V., Lopes, J.A., Pires, W.L., da Silva Set\u00fabal, S., Evangelista, J.R., Soares, A.M., and Zuliani, J.P. (2020). Inflammasome Activation Induced by a Snake Venom Lys49-Phospholipase A2 Homologue. Toxins, 12.","DOI":"10.3390\/toxins12010022"},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1016\/j.toxicon.2020.07.017","article-title":"Bothrops erythromelas Venom and Its Action on Isolated Murine Macrophages","volume":"185","author":"Nery","year":"2020","journal-title":"Toxicon"},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"33619","DOI":"10.1021\/acsomega.5c04319","article-title":"Crotoxin Elicits Differential Increases in Macrophage Lipid Droplet Formation In Vitro Modulated during Leishmania (Leishmania) amazonensis Infection","volume":"10","author":"Moraes","year":"2025","journal-title":"ACS Omega"},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1128\/CMR.19.1.111-126.2006","article-title":"Drug Resistance in Leishmaniasis","volume":"19","author":"Croft","year":"2006","journal-title":"Clin. Microbiol. Rev."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"16164","DOI":"10.1021\/acsomega.5c11292","article-title":"Functional Effects of Cyclization on Li1 Peptide Activity against Metacyclic Leishmania amazonensis Internalization","volume":"11","author":"Reis","year":"2026","journal-title":"ACS Omega"},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1016\/0014-4894(66)90016-6","article-title":"Growth Characteristics and Chemical Composition of Trypanosoma cruzi","volume":"18","author":"Fernandes","year":"1966","journal-title":"Exp. Parasitol."},{"key":"ref_125","doi-asserted-by":"crossref","unstructured":"Verga, J.B.M., Graminha, M.A.S., Jacobs-Lorena, M., and Cha, S.J. (2024). Peptide Selection via Phage Display to Inhibit Leishmania-Macrophage Interactions. Front. Microbiol., 15.","DOI":"10.3389\/fmicb.2024.1362252"},{"key":"ref_126","first-page":"47","article-title":"Morphology-Based Analysis of Myoblasts for Prediction of Myotube Formation","volume":"24","author":"Ishikawa","year":"2019","journal-title":"SLAS Discov. Adv. Life Sci. R D"},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"e649","DOI":"10.1002\/mco2.649","article-title":"Skeletal Muscle: Molecular Structure, Myogenesis, Biological Functions, and Diseases","volume":"5","author":"Feng","year":"2024","journal-title":"MedComm"},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"108554","DOI":"10.1016\/j.exppara.2023.108554","article-title":"Promising Natural Products for the Treatment of Cutaneous Leishmaniasis: A Review of in Vitro and in Vivo Studies","volume":"251","author":"Afonso","year":"2023","journal-title":"Exp. Parasitol."},{"key":"ref_129","doi-asserted-by":"crossref","unstructured":"Perdomo, C., Aguilera, E., Corvo, I., Faral-Tello, P., Serna, E., Robello, C., Wilkinson, S.R., Yaluff, G., and Alvarez, G. (2021). Preclinical Studies in Anti-Trypanosomatidae Drug Development. Pharmaceuticals, 14.","DOI":"10.3390\/ph14070644"}],"container-title":["Toxins"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6651\/18\/9\/405\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T04:21:39Z","timestamp":1790137299000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6651\/18\/9\/405"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,21]]},"references-count":129,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2026,9]]}},"alternative-id":["toxins18090405"],"URL":"https:\/\/doi.org\/10.3390\/toxins18090405","relation":{},"ISSN":["2072-6651"],"issn-type":[{"value":"2072-6651","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,21]]}}}