{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T12:35:06Z","timestamp":1780490106485,"version":"3.54.1"},"reference-count":66,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2023,5,30]],"date-time":"2023-05-30T00:00:00Z","timestamp":1685404800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Wellcome Trust DBT India Alliance Fellowship","award":["IA\/I\/19\/2\/504647"],"award-info":[{"award-number":["IA\/I\/19\/2\/504647"]}]},{"name":"Hamish Ogston Foundation, United Kingdom","award":["IA\/I\/19\/2\/504647"],"award-info":[{"award-number":["IA\/I\/19\/2\/504647"]}]},{"name":"Ministry of Human Resource Development (MHRD)","award":["IA\/I\/19\/2\/504647"],"award-info":[{"award-number":["IA\/I\/19\/2\/504647"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The socioeconomic impact of snakebites in India is largely attributed to a subset of snake species commonly known as the \u2018big four\u2019. However, envenoming by a range of other clinically important yet neglected snakes, a.k.a. the \u2018neglected many\u2019, also adds to this burden. The current approach of treating bites from these snakes with the \u2018big four\u2019 polyvalent antivenom is ineffective. While the medical significance of various species of cobras, saw-scaled vipers, and kraits is well-established, the clinical impact of pit vipers from regions such as the Western Ghats, northeastern India, and the Andaman and Nicobar Islands remains poorly understood. Amongst the many species of snakes found in the Western Ghats, the hump-nosed (Hypnale hypnale), Malabar (Craspedocephalus malabaricus), and bamboo (Craspedocephalus gramineus) pit vipers can potentially inflict severe envenoming. To evaluate the severity of toxicity inflicted by these snakes, we characterised their venom composition, biochemical and pharmacological activities, and toxicity- and morbidity-inducing potentials, including their ability to damage kidneys. Our findings highlight the therapeutic inadequacies of the Indian and Sri Lankan polyvalent antivenoms in neutralising the local and systemic toxicity resulting from pit viper envenomings.<\/jats:p>","DOI":"10.3390\/ijms24119516","type":"journal-article","created":{"date-parts":[[2023,5,31]],"date-time":"2023-05-31T03:59:35Z","timestamp":1685505575000},"page":"9516","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Fangs in the Ghats: Preclinical Insights into the Medical Importance of Pit Vipers from the Western Ghats"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1166-0234","authenticated-orcid":false,"given":"Suyog","family":"Khochare","sequence":"first","affiliation":[{"name":"Evolutionary Venomics Lab, Centre for Ecological Sciences, Indian Institute of Science, Bangalore 560012, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9151-7771","authenticated-orcid":false,"given":"R. R.","family":"Senji Laxme","sequence":"additional","affiliation":[{"name":"Evolutionary Venomics Lab, Centre for Ecological Sciences, Indian Institute of Science, Bangalore 560012, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Priyanka","family":"Jaikumar","sequence":"additional","affiliation":[{"name":"Evolutionary Venomics Lab, Centre for Ecological Sciences, Indian Institute of Science, Bangalore 560012, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Navneet","family":"Kaur","sequence":"additional","affiliation":[{"name":"Evolutionary Venomics Lab, Centre for Ecological Sciences, Indian Institute of Science, Bangalore 560012, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2632-6837","authenticated-orcid":false,"given":"Saurabh","family":"Attarde","sequence":"additional","affiliation":[{"name":"Evolutionary Venomics Lab, Centre for Ecological Sciences, Indian Institute of Science, Bangalore 560012, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerard","family":"Martin","sequence":"additional","affiliation":[{"name":"The Liana Trust, Survey #1418\/1419, Rathnapuri, Hunsur 571189, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0998-1581","authenticated-orcid":false,"given":"Kartik","family":"Sunagar","sequence":"additional","affiliation":[{"name":"Evolutionary Venomics Lab, Centre for Ecological Sciences, Indian Institute of Science, Bangalore 560012, India"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,5,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e54076","DOI":"10.7554\/eLife.54076","article-title":"Trends in snakebite deaths in India from 2000 to 2019 in a nationally representative mortality study","volume":"9","author":"Suraweera","year":"2020","journal-title":"eLife"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Laxme, R.S., Khochare, S., de Souza, H.F., Ahuja, B., Suranse, V., Martin, G., Whitaker, R., and Sunagar, K. (2019). Beyond the \u2018big four\u2019: Venom profiling of the medically important yet neglected Indian snakes reveals disturbing antivenom deficiencies. PLoS Negl. Trop. Dis., 13.","DOI":"10.1371\/journal.pntd.0007899"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1016\/j.jprot.2016.12.018","article-title":"Proteomic analysis to unravel the complex venom proteome of eastern India Naja naja: Correlation of venom composition with its biochemical and pharmacological properties","volume":"156","author":"Dutta","year":"2017","journal-title":"J. Proteom."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1080\/14789450.2020.1778471","article-title":"Mass spectrometric analysis to unravel the venom proteome composition of Indian snakes: Opening new avenues in clinical research","volume":"17","author":"Chanda","year":"2020","journal-title":"Expert Rev. Proteom."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"129561","DOI":"10.1016\/j.bbagen.2020.129561","article-title":"The action of Echis carinatus and Naja naja venoms on human neutrophils; an emphasis on NETosis","volume":"1864","author":"Swethakumar","year":"2020","journal-title":"Biochim. Biophys. Acta Gen. Subj."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"837","DOI":"10.1080\/14789450.2018.1528150","article-title":"Proteomic analysis reveals geographic variation in venom composition of Russell\u2019s Viper in the Indian subcontinent: Implications for clinical manifestations post-envenomation and antivenom treatment","volume":"15","author":"Kalita","year":"2018","journal-title":"Expert Rev. Proteom."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"583","DOI":"10.1021\/acs.jproteome.6b00693","article-title":"Unraveling the Proteome Composition and Immuno-profiling of Western India Russell\u2019s Viper Venom for In-Depth Understanding of Its Pharmacological Properties, Clinical Manifestations, and Effective Antivenom Treatment","volume":"16","author":"Kalita","year":"2017","journal-title":"J. Proteome Res."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"104256","DOI":"10.1016\/j.jprot.2021.104256","article-title":"Remarkable intrapopulation venom variability in the monocellate cobra (Naja kaouthia) unveils neglected aspects of India\u2019s snakebite problem","volume":"242","author":"Rashmi","year":"2021","journal-title":"J. Proteom."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Senji Laxme, R., Khochare, S., Attarde, S., Suranse, V., Iyer, A., Casewell, N.R., Whitaker, R., Martin, G., and Sunagar, K. (2021). Biogeographic venom variation in Russell\u2019s viper (Daboia russelii) and the preclinical inefficacy of antivenom therapy in snakebite hotspots. PLoS Negl. Trop. Dis., 15.","DOI":"10.1371\/journal.pntd.0009247"},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Senji Laxme, R.R., Attarde, S., Khochare, S., Suranse, V., Martin, G., Casewell, N.R., Whitaker, R., and Sunagar, K. (2021). Biogeographical venom variation in the Indian spectacled cobra (Naja naja) underscores the pressing need for pan-India efficacious snakebite therapy. PLoS Negl. Trop. Dis., 15.","DOI":"10.1371\/journal.pntd.0009150"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Sunagar, K., Khochare, S., Senji Laxme, R., Attarde, S., Dam, P., Suranse, V., Khaire, A., Martin, G., and Captain, A. (2021). A wolf in another wolf\u2019s clothing: Post-genomic regulation dictates venom profiles of medically-important cryptic kraits in India. Toxins, 13.","DOI":"10.7934\/P3897"},{"key":"ref_12","unstructured":"Whitaker, R., Captain, A., and Ahmed, F. (2004). Snakes of India, Draco Books."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1016\/j.trstmh.2006.03.008","article-title":"First authenticated cases of life-threatening envenoming by the hump-nosed pit viper (Hypnale hypnale) in India","volume":"101","author":"Joseph","year":"2007","journal-title":"Trans. R Soc. Trop. Med. Hyg."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Silva, A., Gunawardena, P., Weilgama, D., Maduwage, K., and Gawarammana, I. (2012). Comparative in-vivo toxicity of venoms from South Asian hump-nosed pit vipers (Viperidae: Crotalinae: Hypnale). BMC Res. Notes, 5.","DOI":"10.1186\/1756-0500-5-471"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1120","DOI":"10.1016\/j.trstmh.2008.03.023","article-title":"Frequent and potentially fatal envenoming by hump-nosed pit vipers (Hypnale hypnale and H. nepa) in Sri Lanka: Lack of effective antivenom","volume":"102","author":"Ariaratnam","year":"2008","journal-title":"Trans. R Soc. Trop. Med. Hyg."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"725","DOI":"10.4269\/ajtmh.2009.09-0225","article-title":"Syndromic approach to treatment of snake bite in Sri Lanka based on results of a prospective national hospital-based survey of patients envenomed by identified snakes","volume":"81","author":"Ariaratnam","year":"2009","journal-title":"Am. J. Trop. Med. Hyg."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"527","DOI":"10.3109\/15563650.2013.811589","article-title":"Hump-nosed pit viper (Hypnale hypnale) envenoming causes mild coagulopathy with incomplete clotting factor consumption","volume":"51","author":"Maduwage","year":"2013","journal-title":"Clin. Toxicol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1016\/j.toxicon.2020.10.026","article-title":"Hump-nosed pit viper (Hypnale hypnale and Hypnale zara) envenoming in Deniyaya, Sri Lanka: Epidemiological and clinical features from a prospective observational study","volume":"189","author":"Witharana","year":"2021","journal-title":"Toxicon"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1186\/1678-9199-20-24","article-title":"Hump-nosed viper bite: An important but under-recognized cause of systemic envenoming","volume":"20","author":"Shivanthan","year":"2014","journal-title":"J. Venom. Anim. Toxins Incl. Trop. Dis."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1093\/trstmh\/try120","article-title":"Kidney injury following envenoming by hump-nosed pit viper (Genus: Hypnale) in Sri Lanka: Proven and probable cases","volume":"113","author":"Rathnayaka","year":"2019","journal-title":"Trans. R Soc. Trop. Med. Hyg."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"2050313X20944308","DOI":"10.1177\/2050313X20944308","article-title":"Thrombotic microangiopathy following hump-nosed viper \u2018Hypnale\u2019 envenomation","volume":"8","author":"Puthra","year":"2020","journal-title":"SAGE Open Med. Case Rep."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"25","DOI":"10.4269\/ajtmh.1995.52.25","article-title":"Electroencephalographic abnormalities in patients with snake bites","volume":"52","author":"Ramachandran","year":"1995","journal-title":"Am. J. Trop. Med. Hyg."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1186\/1477-9560-10-21","article-title":"Acute ischemic stroke following Hump-nosed viper envenoming; first authenticated case","volume":"10","author":"Jeevagan","year":"2012","journal-title":"Thromb. J."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Thillainathan, S., Priyangika, D., Marasinghe, I., Kanapathippillai, K., and Premawansa, G. (2015). Rare cardiac sequelae of a hump-nosed viper bite. BMC Res. Notes, 8.","DOI":"10.1186\/s13104-015-1426-z"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"209","DOI":"10.2147\/IJGM.S136153","article-title":"Clinical and epidemiologic profile and predictors of outcome of poisonous snake bites\u2014An analysis of 1500 cases from a tertiary care center in Malabar, North Kerala, India","volume":"11","author":"Kumar","year":"2018","journal-title":"Int. J. Gen. Med."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1007\/s11010-006-1738-3","article-title":"Strong myotoxic activity of Trimeresurus malabaricus venom: Role of metalloproteases","volume":"282","author":"Gowda","year":"2006","journal-title":"Mol. Cell Biochem."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1177\/00494755211066680","article-title":"Rare snake bite\u2014A case report","volume":"52","author":"Rathod","year":"2022","journal-title":"Trop. Doct."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1016\/j.wem.2021.10.001","article-title":"A Tropical Kiss by a Malabar Pit Viper","volume":"33","author":"Sirur","year":"2022","journal-title":"Wilderness Env. Med."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"167","DOI":"10.4103\/JETS.JETS_3_20","article-title":"Trimeresurus Malabaricus Bites: Need of Species-specific Management for Snakebites","volume":"13","author":"Harikrishnan","year":"2020","journal-title":"J. Emerg. Trauma Shock"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1016\/j.toxicon.2014.11.231","article-title":"Proteomic investigation of Sri Lankan hump-nosed pit viper (Hypnale hypnale) venom","volume":"93","author":"Tan","year":"2015","journal-title":"Toxicon"},{"key":"ref_31","first-page":"17","article-title":"The in vitro toxicity of venoms from South Asian hump-nosed pit vipers (Viperidae: Hypnale)","volume":"2","author":"Maduwage","year":"2011","journal-title":"J. Venom Res."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"338","DOI":"10.1016\/j.jprot.2013.07.020","article-title":"Proteomic comparison of Hypnale hypnale (hump-nosed pit-viper) and Calloselasma rhodostoma (Malayan pit-viper) venoms","volume":"91","author":"Ali","year":"2013","journal-title":"J. Proteom."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1736","DOI":"10.1016\/j.ijbiomac.2018.07.016","article-title":"Mass spectrometry-assisted venom profiling of Hypnale hypnale found in the Western Ghats of India incorporating de novo sequencing approaches","volume":"118","author":"Vanuopadath","year":"2018","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1029","DOI":"10.1016\/j.ijbiomac.2020.01.226","article-title":"Delineating the venom toxin arsenal of Malabar pit viper (Trimeresurus malabaricus) from the Western Ghats of India and evaluating its immunological cross-reactivity and in vitro cytotoxicity","volume":"148","author":"Vanuopadath","year":"2020","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"332","DOI":"10.3389\/fevo.2019.00332","article-title":"Snake Venom in Context: Neglected Clades and Concepts","volume":"7","author":"Jackson","year":"2019","journal-title":"Front. Ecol. Evol."},{"key":"ref_36","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 Pharm. Sci."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1016\/0035-9203(94)90301-8","article-title":"Haemostatic dysfunction and acute renal failure following envenoming by Merrem\u2019s hump-nosed viper (Hypnale hypnale) in Sri Lanka: First authenticated case","volume":"88","author":"Wijekoon","year":"1994","journal-title":"Trans. R Soc. Trop. Med. Hyg."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"205","DOI":"10.5853\/jos.2014.16.3.205","article-title":"A case of bilateral occipital lobe infarcts following Indian tree viper bite","volume":"16","author":"Mahale","year":"2014","journal-title":"J. Stroke"},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Attarde, S., Iyer, A., Khochare, S., Shaligram, U., Vikharankar, M., and Sunagar, K. (2022). The Preclinical Evaluation of a Second-Generation Antivenom for Treating Snake Envenoming in India. Toxins, 14.","DOI":"10.3390\/toxins14030168"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1016\/j.actatropica.2010.11.001","article-title":"Cross neutralization of Hypnale hypnale (hump-nosed pit viper) venom by polyvalent and monovalent Malayan pit viper antivenoms in vitro and in a rodent model","volume":"117","author":"Tan","year":"2011","journal-title":"Acta Trop."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1016\/j.actatropica.2012.01.016","article-title":"Immunological properties of Hypnale hypnale (hump-nosed pit viper) venom: Antibody production with diagnostic and therapeutic potentials","volume":"122","author":"Tan","year":"2012","journal-title":"Acta Trop."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"150","DOI":"10.5527\/wjn.v6.i3.150","article-title":"Clinicopathological spectrum of snake bite-induced acute kidney injury from India","volume":"6","author":"Vikrant","year":"2017","journal-title":"World J. Nephrol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"3829","DOI":"10.1007\/s00467-020-04911-x","article-title":"Snake bite associated with acute kidney injury","volume":"36","author":"Sarkar","year":"2021","journal-title":"Pediatr. Nephrol."},{"key":"ref_44","first-page":"853","article-title":"A study on the acute kidney injury in snake bite victims in a tertiary care centre","volume":"7","author":"Harshavardhan","year":"2013","journal-title":"J. Clin. Diagn. Res."},{"key":"ref_45","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_46","doi-asserted-by":"crossref","first-page":"442","DOI":"10.1111\/j.1440-1797.2006.00599.x","article-title":"Snakebite nephropathy","volume":"11","author":"Sitprija","year":"2006","journal-title":"Nephrology"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1007\/s13312-021-2158-x","article-title":"Evolution Bites\u2014Timeworn Inefficacious Snakebite Therapy in the Era of Recombinant Vaccines","volume":"58","author":"Kaur","year":"2021","journal-title":"Indian Pediatr."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1016\/0003-2697(76)90527-3","article-title":"A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding","volume":"72","author":"Bradford","year":"1976","journal-title":"Anal. Biochem."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1385\/0-89603-062-8:41","article-title":"SDS Polyacrylamide Gel Electrophoresis of Proteins","volume":"Volume 1","author":"Walker","year":"1984","journal-title":"Proteins"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"671","DOI":"10.1038\/nmeth.2089","article-title":"NIH Image to ImageJ: 25 years of image analysis","volume":"9","author":"Schneider","year":"2012","journal-title":"Nat. Methods"},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Senji Laxme, R.R., Khochare, S., Attarde, S., Kaur, N., Jaikumar, P., Shaikh, N.Y., Aharoni, R., Primor, N., Hawlena, D., and Moran, Y. (2022). The Middle Eastern Cousin: Comparative Venomics of Daboia palaestinae and Daboia russelii. Toxins, 14.","DOI":"10.3390\/toxins14110725"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"D442","DOI":"10.1093\/nar\/gky1106","article-title":"The PRIDE database and related tools and resources in 2019: Improving support for quantification data","volume":"47","author":"Csordas","year":"2019","journal-title":"Nucleic Acids Res."},{"key":"ref_53","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_54","doi-asserted-by":"crossref","unstructured":"Freitas-de-Sousa, L.A., Nachtigall, P.G., Portes-Junior, J.A., Holding, M.L., Nystrom, G.S., Ellsworth, S.A., Guimar\u00e3es, N.C., Tioyama, E., Ortiz, F., and Silva, B.R. (2020). Size matters: An evaluation of the molecular basis of ontogenetic modifications in the composition of Bothrops jararacussu snake venom. Toxins, 12.","DOI":"10.3390\/toxins12120791"},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Tasoulis, T., Lee, M.S., Ziajko, M., Dunstan, N., Sumner, J., and Isbister, G.K. (2020). Activity of two key toxin groups in Australian elapid venoms show a strong correlation to phylogeny but not to diet. BMC Evol. Biol., 20.","DOI":"10.1186\/s12862-020-1578-x"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1006\/abio.2001.5381","article-title":"A spectrophotometric microplate assay for L-amino acid oxidase","volume":"298","author":"Kishimoto","year":"2001","journal-title":"Anal. Biochem."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"4159","DOI":"10.1128\/iai.58.12.4159-4162.1990","article-title":"Purification and characterization of a protease produced by Vibrio mimicus","volume":"58","author":"Chowdhury","year":"1990","journal-title":"Infect. Immun."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"777","DOI":"10.1016\/0041-0101(85)90008-X","article-title":"Species difference in the fibrinogenolytic effects of \u03b1-and \u03b2-fibrinogenases from Trimeresurus mucrosquamatus snake venom","volume":"23","author":"Teng","year":"1985","journal-title":"Toxicon"},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"op den Brouw, B., Ghezellou, P., Casewell, N.R., Ali, S.A., Fathinia, B., Fry, B.G., Bos, M.H., and Ikonomopoulou, M.P. (2021). Pharmacological characterisation of Pseudocerastes and Eristicophis viper venoms reveal anticancer (Melanoma) properties and a potentially novel mode of fibrinogenolysis. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22136896"},{"key":"ref_60","doi-asserted-by":"crossref","unstructured":"Casewell, N.R., Cook, D.A., Wagstaff, S.C., Nasidi, A., Durfa, N., Wuster, W., and Harrison, R.A. (2010). Pre-clinical assays predict pan-African Echis viper efficacy for a species-specific antivenom. PLoS Negl. Trop. Dis., 4.","DOI":"10.1371\/journal.pntd.0000851"},{"key":"ref_61","unstructured":"Finney, D.J. (1971). Probit Analysis, Cambridge University Press. [3rd ed.]."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"43","DOI":"10.7883\/yoken1952.13.43","article-title":"Studies on the quantitative method for determination of hemorrhagic activity of Habu snake venom","volume":"13","author":"Kondo","year":"1960","journal-title":"Jpn. J. Med. Sci. Biol."},{"key":"ref_63","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_64","unstructured":"WHO (2018). World Health Organisation Guidelines for the Production, Control and Regulation of Snake Antivenom Immunoglobulins, World Health Organisation."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1038\/ki.1984.147","article-title":"Mesangial immune injury, hypertension, and progressive glomerular damage in Dahl rats","volume":"26","author":"Raij","year":"1984","journal-title":"Kidney Int."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1161\/01.HYP.25.2.207","article-title":"Glomerular dynamics and morphology of aged spontaneously hypertensive rats. Effects of angiotensin-converting enzyme inhibition","volume":"25","author":"Komatsu","year":"1995","journal-title":"Hypertension"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/11\/9516\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T19:45:34Z","timestamp":1760125534000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/11\/9516"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,5,30]]},"references-count":66,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2023,6]]}},"alternative-id":["ijms24119516"],"URL":"https:\/\/doi.org\/10.3390\/ijms24119516","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,5,30]]}}}