{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,10]],"date-time":"2026-03-10T07:55:27Z","timestamp":1773129327967,"version":"3.50.1"},"update-to":[{"DOI":"10.1371\/journal.pntd.0010292","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2022,4,25]],"date-time":"2022-04-25T00:00:00Z","timestamp":1650844800000}}],"reference-count":88,"publisher":"Public Library of Science (PLoS)","issue":"3","license":[{"start":{"date-parts":[[2022,3,28]],"date-time":"2022-03-28T00:00:00Z","timestamp":1648425600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosntds.org"],"crossmark-restriction":false},"short-container-title":["PLoS Negl Trop Dis"],"abstract":"<jats:p>Envenoming by the hump-nosed pit viper (<jats:italic>Hypnale hypnale<\/jats:italic>) raises concern as it inflicts significant debilitation and death in the Western Ghats of India and in the adjacent island nation of Sri Lanka. In India, its medical significance was realized only during 2007 due to its misidentification as <jats:italic>Echis carinatus<\/jats:italic> and sometimes as <jats:italic>Daboia russelii<\/jats:italic>. Of late, several case reports have underlined the ineptness of the existing polyvalent anti-venom therapy against <jats:italic>H<\/jats:italic>. <jats:italic>hypnale<\/jats:italic> envenoming. Currently, <jats:italic>H<\/jats:italic>. <jats:italic>hypnale<\/jats:italic> bite has remained dreadful in India due to the lack of neutralizing anti-venom therapy. Hence, this study was undertaken to establish a systematic comparative, biochemical, pathological, and immunological properties of Sri Lankan <jats:italic>H<\/jats:italic>. <jats:italic>hypnale<\/jats:italic> venom alongside Indian <jats:italic>E<\/jats:italic>. <jats:italic>carinatus<\/jats:italic>, and <jats:italic>D<\/jats:italic>. <jats:italic>russelii<\/jats:italic> venoms. All three venoms differed markedly in the extent of biochemical activities including proteolytic, deoxyribonuclease, L-amino acid oxidase, 5\u2019-nucleotidase, hyaluronidase, and indirect hemolytic activities. The venoms also differed markedly in their pathological properties such as edema, hemorrhage, myotoxic, cardiotoxic, and coagulant activities. The venoms showed stark differences in their protein banding pattern. Strikingly, the affinity-purified rabbit monovalent anti-venoms prepared against <jats:italic>H<\/jats:italic>. <jats:italic>hypnale<\/jats:italic>, <jats:italic>E<\/jats:italic>. <jats:italic>carinatus<\/jats:italic>, and <jats:italic>D<\/jats:italic>. <jats:italic>russelii<\/jats:italic> venoms readily reacted and neutralized the biochemical and pathological properties of their respective venoms, but they insignificantly cross-reacted with, and thus failed to show paraspecific neutralization of any of the effects of the other two venoms, demonstrating the large degree of variations between these venoms. Further, the Indian therapeutic polyvalent anti-venoms from VINS Bioproducts, and Bharath Serums and Vaccines failed to protect <jats:italic>H<\/jats:italic>. <jats:italic>hypnale<\/jats:italic> venom-induced lethal effects in mice.<\/jats:p>","DOI":"10.1371\/journal.pntd.0010292","type":"journal-article","created":{"date-parts":[[2022,3,28]],"date-time":"2022-03-28T17:31:16Z","timestamp":1648488676000},"page":"e0010292","update-policy":"https:\/\/doi.org\/10.1371\/journal.pntd.corrections_policy","source":"Crossref","is-referenced-by-count":18,"title":["A comparative cross-reactivity and paraspecific neutralization study on Hypnale hypnale, Echis carinatus, and Daboia russelii monovalent and therapeutic polyvalent anti-venoms"],"prefix":"10.1371","volume":"16","author":[{"given":"Vaddaragudisalu D.","family":"Sandesha","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bhaskar","family":"Darshan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chandrashekar","family":"Tejas","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kesturu S.","family":"Girish","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3204-0907","authenticated-orcid":true,"given":"Kemparaju","family":"Kempaiah","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2022,3,28]]},"reference":[{"key":"pntd.0010292.ref001","doi-asserted-by":"crossref","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":"W Suraweera","year":"2020","journal-title":"Elife"},{"issue":"4","key":"pntd.0010292.ref002","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":"JP Chippaux","year":"2011","journal-title":"Toxicon"},{"issue":"12","key":"pntd.0010292.ref003","doi-asserted-by":"crossref","first-page":"e569","DOI":"10.1371\/journal.pntd.0000569","article-title":"Snake envenoming: a disease of poverty","volume":"3","author":"RA Harrison","year":"2009","journal-title":"PLoS Negl Trop Dis"},{"issue":"12","key":"pntd.0010292.ref004","doi-asserted-by":"crossref","first-page":"e0007899","DOI":"10.1371\/journal.pntd.0007899","article-title":"Beyond the \u2019big four\u2019: Venom profiling of the medically important yet neglected Indian snakes reveals disturbing antivenom deficiencies","volume":"13","author":"RR Senji Laxme","year":"2019","journal-title":"PLoS Negl Trop Dis"},{"issue":"1","key":"pntd.0010292.ref005","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":"JK Joseph","year":"2007","journal-title":"Trans R Soc Trop Med Hyg"},{"issue":"3","key":"pntd.0010292.ref006","first-page":"733","article-title":"Estimates of disease burden due to land-snake bite in Sri Lankan hospitals","volume":"36","author":"A Kasturiratne","year":"2005","journal-title":"Southeast Asian J Trop Med Public Health"},{"issue":"4","key":"pntd.0010292.ref007","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":"CA Ariaratnam","year":"2009","journal-title":"Am J Trop Med Hyg"},{"issue":"3","key":"pntd.0010292.ref008","doi-asserted-by":"crossref","first-page":"458","DOI":"10.4269\/ajtmh.2008.79.458","article-title":"Distinctive epidemiologic and clinical features of common krait (Bungarus caeruleus) bites in Sri Lanka","volume":"79","author":"CA Ariaratnam","year":"2008","journal-title":"Am J Trop Med Hyg"},{"issue":"2","key":"pntd.0010292.ref009","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":"CH Tan","year":"2011","journal-title":"Acta Trop"},{"key":"pntd.0010292.ref010","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 1,500 cases from a tertiary care center in Malabar, North Kerala, India","volume":"11","author":"KS Kumar","year":"2018","journal-title":"Int J Gen Med"},{"issue":"10","key":"pntd.0010292.ref011","doi-asserted-by":"crossref","first-page":"1225","DOI":"10.1007\/s12098-011-0396-y","article-title":"Inadequacy of present polyspecific anti snakevenom\u2014a study from central Kerala","volume":"78","author":"V Kumar","year":"2011","journal-title":"Indian J Pediatr"},{"key":"pntd.0010292.ref012","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1016\/j.toxicon.2016.10.007","article-title":"Development of a new polyspecific antivenom for snakebite envenoming in Sri Lanka: Analysis of its preclinical efficacy as compared to a currently available antivenom","volume":"122","author":"M Villalta","year":"2016","journal-title":"Toxicon"},{"issue":"1","key":"pntd.0010292.ref013","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1016\/S0021-9258(19)52451-6","article-title":"Protein measurement with the Folin phenol reagent","volume":"193","author":"OH Lowry","year":"1951","journal-title":"J Biol Chem"},{"issue":"5259","key":"pntd.0010292.ref014","doi-asserted-by":"crossref","first-page":"680","DOI":"10.1038\/227680a0","article-title":"Cleavage of structural proteins during the assembly of the head of bacteriophage T4","volume":"227","author":"UK Laemmli","year":"1970","journal-title":"Nature"},{"issue":"1","key":"pntd.0010292.ref015","doi-asserted-by":"crossref","first-page":"196","DOI":"10.1016\/0003-2697(80)90338-3","article-title":"Electrophoretic analysis of plasminogen activators in polyacrylamide gels containing sodium dodecyl sulfate and copolymerized substrates","volume":"102","author":"C Heussen","year":"1980","journal-title":"Anal Biochem"},{"issue":"1","key":"pntd.0010292.ref016","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1006\/abio.1994.1560","article-title":"A microplate assay for hyaluronidase and hyaluronidase inhibitors","volume":"223","author":"JS Tung","year":"1994","journal-title":"Anal Biochem"},{"key":"pntd.0010292.ref017","first-page":"438","article-title":"Studies on snake venom. XIII. Chromatographic separation and properties of three proteinases from Agkistrodon halys blomhoffii venom","volume":"53","author":"M Satake","year":"1963","journal-title":"J Biochem"},{"key":"pntd.0010292.ref018","doi-asserted-by":"crossref","first-page":"11361","DOI":"10.1038\/ncomms11361","article-title":"NETosis and lack of DNase activity are key factors in Echis carinatus venom-induced tissue destruction","volume":"7","author":"GD Katkar","year":"2016","journal-title":"Nat Commun."},{"issue":"3","key":"pntd.0010292.ref019","doi-asserted-by":"crossref","first-page":"619","DOI":"10.1016\/0006-3002(57)90256-1","article-title":"Chromatography of rattlesnake venom; a separation of three phosphodiesterases","volume":"24","author":"HG Boman","year":"1957","journal-title":"Biochim Biophys Acta"},{"issue":"4","key":"pntd.0010292.ref020","doi-asserted-by":"crossref","first-page":"745","DOI":"10.1016\/0305-0491(88)90329-X","article-title":"A comparative study of cobra (Naja) venom enzymes","volume":"90","author":"NH Tan","year":"1988","journal-title":"Comp Biochem Physiol B"},{"issue":"2","key":"pntd.0010292.ref021","doi-asserted-by":"crossref","first-page":"334","DOI":"10.1016\/0005-2736(71)90331-2","article-title":"Preparation and properties of plasma membrane and endoplasmic reticulum fragments from isolated rat fat cells","volume":"233","author":"J Avruch","year":"1971","journal-title":"Biochim Biophys Acta"},{"issue":"4","key":"pntd.0010292.ref022","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1016\/j.toxicon.2006.06.017","article-title":"Anticoagulant effect of Naja naja venom 5\u2019nucleotidase: demonstration through the use of novel specific inhibitor, vanillic acid","volume":"48","author":"BL Dhananjaya","year":"2006","journal-title":"Toxicon"},{"issue":"2","key":"pntd.0010292.ref023","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1055\/s-0038-1657347","article-title":"Anticoagulant activity and plasma phosphatidylserine hydrolysis by snake venom phospholipases A2","volume":"49","author":"E Condrea","year":"1983","journal-title":"Thromb Haemost"},{"issue":"3","key":"pntd.0010292.ref024","doi-asserted-by":"crossref","first-page":"340","DOI":"10.1007\/s11239-009-0379-2","article-title":"Anti-coagulant activity of a metalloprotease: further characterization from the Indian cobra (Naja naja) venom","volume":"29","author":"MS Kumar","year":"2010","journal-title":"J Thromb Thrombolysis"},{"issue":"1","key":"pntd.0010292.ref025","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1016\/0041-0101(69)90154-8","article-title":"Coagulant and anticoagulant action of snake venoms","volume":"7","author":"KW Denson","year":"1969","journal-title":"Toxicon"},{"issue":"2","key":"pntd.0010292.ref026","doi-asserted-by":"crossref","first-page":"298","DOI":"10.1016\/0005-2795(76)90321-4","article-title":"Fibrinogenolytic enzymes of Trimeresurus mucrosquamatus venom","volume":"420","author":"C Ouyang","year":"1976","journal-title":"Biochim Biophys Acta"},{"issue":"1","key":"pntd.0010292.ref027","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1007\/s11239-009-0341-3","article-title":"Factor Xa-like and fibrin(ogen)olytic activities of a serine protease from Hippasa agelenoides spider venom gland extract","volume":"29","author":"S Devaraja","year":"2010","journal-title":"J Thromb Thrombolysis"},{"key":"pntd.0010292.ref028","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1007\/978-1-4684-0886-7_10","article-title":"Fractionation of sakishimahabu (Trimeresurus elegans) venom and lethal, hemorrhagic and edema-forming activities of the fractions","volume":"1","author":"M Yamakawa","year":"1976","journal-title":"Animal, plant and microbial toxins"},{"key":"pntd.0010292.ref029","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":"H Kondo","year":"1960","journal-title":"Jpn J Med Sci Biol"},{"issue":"4","key":"pntd.0010292.ref030","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1016\/0041-0101(86)90199-6","article-title":"Approximate LD50 determinations of snake venoms using eight to ten experimental animals","volume":"24","author":"J Meier","year":"1986","journal-title":"Toxicon"},{"issue":"1","key":"pntd.0010292.ref031","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1016\/0014-4800(90)90055-I","article-title":"Changes in myofibrillar components after skeletal muscle necrosis induced by a myotoxin isolated from the venom of the snake Bothrops asper","volume":"52","author":"JM Gutierrez","year":"1990","journal-title":"Exp Mol Pathol"},{"issue":"1\u20132","key":"pntd.0010292.ref032","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1023\/A:1017972511272","article-title":"Variations in biochemical and pharmacological properties of Indian cobra (Naja naja naja) venom due to geographical distribution","volume":"229","author":"R Shashidharamurthy","year":"2002","journal-title":"Mol Cell Biochem"},{"issue":"10","key":"pntd.0010292.ref033","doi-asserted-by":"crossref","first-page":"e851","DOI":"10.1371\/journal.pntd.0000851","article-title":"Pre-clinical assays predict pan-African Echis viper efficacy for a species-specific antivenom","volume":"4","author":"NR Casewell","year":"2010","journal-title":"PLoS Negl Trop Dis"},{"issue":"2","key":"pntd.0010292.ref034","doi-asserted-by":"crossref","first-page":"e0009073","DOI":"10.1371\/journal.pntd.0009073","article-title":"Antivenomics and in vivo preclinical efficacy of six Latin American antivenoms towards south-western Colombian Bothrops asper lineage venoms","volume":"15","author":"D Mora-Obando","year":"2021","journal-title":"PLoS Neglected Tropical Diseases"},{"issue":"7","key":"pntd.0010292.ref035","doi-asserted-by":"crossref","first-page":"713","DOI":"10.1016\/0041-0101(87)90121-8","article-title":"Ability of a polyvalent antivenom to neutralize the venom of Lachesis muta melanocephala, a new Costa Rican subspecies of the bushmaster","volume":"25","author":"JM Guti\u00e9rrez","year":"1987","journal-title":"Toxicon"},{"key":"pntd.0010292.ref036","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1016\/j.actatropica.2017.01.004","article-title":"Melatonin inhibits snake venom and antivenom induced oxidative stress and augments treatment efficacy","volume":"169","author":"RD Sharma","year":"2017","journal-title":"Acta Trop"},{"issue":"1","key":"pntd.0010292.ref037","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1580\/06-WEME-CO-023R1.1","article-title":"Snakes of medical importance in India: is the concept of the \"Big 4\" still relevant and useful?","volume":"18","author":"ID Simpson","year":"2007","journal-title":"Wilderness Environ Med"},{"key":"pntd.0010292.ref038","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":"MC Shivanthan","year":"2014","journal-title":"J Venom Anim Toxins Incl Trop Dis"},{"issue":"11","key":"pntd.0010292.ref039","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":"CA Ariaratnam","year":"2008","journal-title":"Trans R Soc Trop Med Hyg"},{"issue":"1","key":"pntd.0010292.ref040","doi-asserted-by":"crossref","first-page":"17119","DOI":"10.1038\/s41598-017-17227-y","article-title":"Proteomics and antivenomics of Echis carinatus carinatus venom: Correlation with pharmacological properties and pathophysiology of envenomation","volume":"7","author":"A Patra","year":"2017","journal-title":"Scientific Reports"},{"issue":"8","key":"pntd.0010292.ref041","doi-asserted-by":"crossref","first-page":"2819","DOI":"10.1021\/acs.jproteome.8b00291","article-title":"Proteomic Analysis and Immuno-Profiling of Eastern India Russell\u2019s Viper (Daboia russelii) Venom: Correlation between RVV Composition and Clinical Manifestations Post RV Bite","volume":"17","author":"B Kalita","year":"2018","journal-title":"Journal of Proteome Research"},{"issue":"10","key":"pntd.0010292.ref042","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":"B Kalita","year":"2018","journal-title":"Expert Review of Proteomics"},{"issue":"2","key":"pntd.0010292.ref043","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":"B Kalita","year":"2017","journal-title":"Journal of Proteome Research"},{"issue":"6","key":"pntd.0010292.ref044","doi-asserted-by":"crossref","first-page":"532","DOI":"10.2174\/1389203716666150515125002","article-title":"Disintegrins from snake venoms and their applications in cancer research and therapy","volume":"16","author":"JK Arruda Mac\u00eado","year":"2015","journal-title":"Curr Protein Pept Sci"},{"issue":"Pt B","key":"pntd.0010292.ref045","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":"M Vanuopadath","year":"2018","journal-title":"Int J Biol Macromol"},{"key":"pntd.0010292.ref046","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":"SA Ali","year":"2013","journal-title":"J Proteomics"},{"issue":"3","key":"pntd.0010292.ref047","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":"CH Tan","year":"2012","journal-title":"Acta Trop"},{"key":"pntd.0010292.ref048","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":"CH Tan","year":"2015","journal-title":"Toxicon"},{"issue":"3","key":"pntd.0010292.ref049","doi-asserted-by":"crossref","DOI":"10.3390\/toxins11030170","article-title":"Protease Activity Profiling of Snake Venoms Using High-Throughput Peptide Screening","volume":"11","author":"K Kalogeropoulos","year":"2019","journal-title":"Toxins (Basel)"},{"issue":"2","key":"pntd.0010292.ref050","first-page":"154","article-title":"Inhibition of local effects of Indian Daboia\/Vipera russelli venom by the methanolic extract of grape (Vitis vinifera L.) seeds","volume":"46","author":"YH Mahadeswaraswamy","year":"2009","journal-title":"Indian J Biochem Biophys"},{"issue":"1\u20132","key":"pntd.0010292.ref051","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1023\/A:1020651607164","article-title":"Snake venom hyaluronidase: an evidence for isoforms and extracellular matrix degradation","volume":"240","author":"KS Girish","year":"2002","journal-title":"Mol Cell Biochem"},{"issue":"8","key":"pntd.0010292.ref052","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":"RM Kini","year":"2003","journal-title":"Toxicon"},{"key":"pntd.0010292.ref053","doi-asserted-by":"crossref","first-page":"6592820","DOI":"10.1155\/2017\/6592820","article-title":"Snake Venom PLA(2), a Promising Target for Broad-Spectrum Antivenom Drug Development","volume":"2017","author":"H Xiao","year":"2017","journal-title":"Biomed Res Int"},{"issue":"6","key":"pntd.0010292.ref054","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":"RM Kini","year":"2010","journal-title":"Toxicon"},{"issue":"2","key":"pntd.0010292.ref055","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1016\/0041-0101(89)90136-0","article-title":"Purification and characterization of a major phospholipase A2 from Russell\u2019s viper (Vipera russelli) venom","volume":"27","author":"S Kasturi","year":"1989","journal-title":"Toxicon"},{"issue":"10","key":"pntd.0010292.ref056","doi-asserted-by":"crossref","first-page":"1187","DOI":"10.1016\/0041-0101(94)90348-4","article-title":"Purification of a basic phospholipase A2 from Indian saw-scaled viper (Echis carinatus) venom: characterization of antigenic, catalytic and pharmacological properties","volume":"32","author":"K Kemparaju","year":"1994","journal-title":"Toxicon"},{"issue":"3","key":"pntd.0010292.ref057","first-page":"331","article-title":"Purification and characterization of the venom phospholipases A2 from Asian monotypic crotalinae snakes","volume":"8","author":"YM Wang","year":"1999","journal-title":"J Nat Toxins"},{"key":"pntd.0010292.ref058","doi-asserted-by":"crossref","first-page":"951561","DOI":"10.1155\/2014\/951561","article-title":"Animal toxins and their advantages in biotechnology and pharmacology","volume":"2014","author":"SL Da Silva","year":"2014","journal-title":"Biomed Res Int"},{"issue":"3","key":"pntd.0010292.ref059","doi-asserted-by":"crossref","first-page":"e0009247","DOI":"10.1371\/journal.pntd.0009247","article-title":"Biogeographic venom variation in Russell\u2019s viper (Daboia russelii) and the preclinical inefficacy of antivenom therapy in snakebite hotspots","volume":"15","author":"RR Senji Laxme","year":"2021","journal-title":"PLoS Negl Trop Dis"},{"issue":"9","key":"pntd.0010292.ref060","doi-asserted-by":"crossref","DOI":"10.3390\/toxins9090290","article-title":"A Review and Database of Snake Venom Proteomes","volume":"9","author":"T Tasoulis","year":"2017","journal-title":"Toxins (Basel)"},{"issue":"7","key":"pntd.0010292.ref061","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":"K Maduwage","year":"2013","journal-title":"Clin Toxicol (Phila)"},{"key":"pntd.0010292.ref062","first-page":"17","article-title":"The in vitro toxicity of venoms from South Asian hump-nosed pit vipers (Viperidae: Hypnale)","volume":"2","author":"K Maduwage","year":"2011","journal-title":"J Venom Res"},{"issue":"6","key":"pntd.0010292.ref063","doi-asserted-by":"crossref","first-page":"821","DOI":"10.4269\/ajtmh.1998.58.821","article-title":"Excessive fibrinolysis: the coagulopathy following Merrem\u2019s hump-nosed viper (Hypnale hypnale) bites","volume":"58","author":"AP Premawardena","year":"1998","journal-title":"Am J Trop Med Hyg"},{"issue":"218","key":"pntd.0010292.ref064","article-title":"Multifunctional Toxins in Snake Venoms and Therapeutic Implications: From Pain to Hemorrhage and Necrosis","volume":"7","author":"CR Ferraz","year":"2019","journal-title":"Frontiers in Ecology and Evolution"},{"issue":"8","key":"pntd.0010292.ref065","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":"JM Guti\u00e9rrez","year":"2005","journal-title":"Toxicon"},{"issue":"5","key":"pntd.0010292.ref066","doi-asserted-by":"crossref","first-page":"8319","DOI":"10.1002\/jcb.28115","article-title":"Plant DNases are potent therapeutic agents against Echis carinatus venom-induced tissue necrosis in mice","volume":"120","author":"GV Rudresha","year":"2019","journal-title":"J Cell Biochem"},{"issue":"3\u20136","key":"pntd.0010292.ref067","first-page":"234","article-title":"Snake venom prothrombin activators homologous to blood coagulation factor Xa","volume":"31","author":"JS Joseph","year":"2001","journal-title":"Haemostasis"},{"issue":"12","key":"pntd.0010292.ref068","doi-asserted-by":"crossref","first-page":"1515","DOI":"10.1016\/0041-0101(92)90023-X","article-title":"Structural and functional properties of snake venom prothrombin activators","volume":"30","author":"J Rosing","year":"1992","journal-title":"Toxicon"},{"issue":"11","key":"pntd.0010292.ref069","doi-asserted-by":"crossref","first-page":"1581","DOI":"10.1016\/S0041-0101(97)00043-3","article-title":"Prothrombin and factor X activator activities in the venoms of Viperidae snakes","volume":"35","author":"D Yamada","year":"1997","journal-title":"Toxicon"},{"issue":"6","key":"pntd.0010292.ref070","doi-asserted-by":"crossref","first-page":"3476","DOI":"10.1016\/j.bbagen.2013.02.007","article-title":"Biochemical and pharmacological properties of a new thrombin-like serine protease (Russelobin) from the venom of Russell\u2019s Viper (Daboia russelii russelii) and assessment of its therapeutic potential","volume":"1830","author":"AK Mukherjee","year":"2013","journal-title":"Biochim Biophys Acta"},{"key":"pntd.0010292.ref071","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1042\/bj0840052","article-title":"The fractionation of Russell\u2019s-viper (Vipera russellii) venom with special reference to the coagulant protein","volume":"84","author":"WJ Williams","year":"1962","journal-title":"Biochem J"},{"key":"pntd.0010292.ref072","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.toxicon.2015.03.019","article-title":"Elucidation of procoagulant mechanism and pathophysiological significance of a new prothrombin activating metalloprotease purified from Daboia russelii russelii venom","volume":"100","author":"R Thakur","year":"2015","journal-title":"Toxicon"},{"issue":"2","key":"pntd.0010292.ref073","doi-asserted-by":"crossref","first-page":"246","DOI":"10.1016\/j.gene.2005.12.002","article-title":"Ohanin, a novel protein from king cobra venom: its cDNA and genomic organization","volume":"371","author":"YF Pung","year":"2006","journal-title":"Gene"},{"issue":"7\u20138","key":"pntd.0010292.ref074","doi-asserted-by":"crossref","first-page":"843","DOI":"10.1007\/s00018-003-3325-z","article-title":"Snake venom thrombin-like enzymes: from reptilase to now","volume":"61","author":"HC Castro","year":"2004","journal-title":"Cell Mol Life Sci"},{"issue":"12","key":"pntd.0010292.ref075","doi-asserted-by":"crossref","DOI":"10.3390\/toxins9120392","article-title":"Direct Fibrinolytic Snake Venom Metalloproteinases Affecting Hemostasis: Structural, Biochemical Features and Therapeutic Potential","volume":"9","author":"EF Sanchez","year":"2017","journal-title":"Toxins (Basel)"},{"issue":"1\u20132","key":"pntd.0010292.ref076","doi-asserted-by":"crossref","first-page":"16","DOI":"10.3109\/15569543.2013.852109","article-title":"Snake venom thrombin-like enzymes","volume":"33","author":"P Pradniwat","year":"2014","journal-title":"Toxin Reviews"},{"issue":"8","key":"pntd.0010292.ref077","doi-asserted-by":"crossref","first-page":"841","DOI":"10.1016\/0041-0101(89)90096-2","article-title":"Comparative study on coagulant, defibrinating, fibrinolytic and fibrinogenolytic activities of Costa Rican crotaline snake venoms and their neutralization by a polyvalent antivenom","volume":"27","author":"J Gen\u00e9","year":"1989","journal-title":"Toxicon"},{"issue":"12","key":"pntd.0010292.ref078","doi-asserted-by":"crossref","first-page":"e0005172","DOI":"10.1371\/journal.pntd.0005172","article-title":"Clinical and Pharmacological Investigation of Myotoxicity in Sri Lankan Russell\u2019s Viper (Daboia russelii) Envenoming","volume":"10","author":"A Silva","year":"2016","journal-title":"PLoS Negl Trop Dis"},{"issue":"8","key":"pntd.0010292.ref079","doi-asserted-by":"crossref","first-page":"e0135843","DOI":"10.1371\/journal.pone.0135843","article-title":"Progressive Hemorrhage and Myotoxicity Induced by Echis carinatus Venom in Murine Model: Neutralization by Inhibitor Cocktail of N,N,N\u2019,N\u2019-Tetrakis (2-Pyridylmethyl) Ethane-1,2-Diamine and Silymarin","volume":"10","author":"AN Nanjaraj Urs","year":"2015","journal-title":"PLoS One"},{"issue":"8","key":"pntd.0010292.ref080","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":"JM Guti\u00e9rrez","year":"2003","journal-title":"Toxicon"},{"key":"pntd.0010292.ref081","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1590\/S1678-91992011000400015","article-title":"Enzymatic and toxinological activities of Hypnale hypnale (hump-nosed pit viper) venom and its fractionation by ion exchange high performance liquid chromatography","volume":"17","author":"C Tan","year":"2011","journal-title":"Journal of Venomous Animals and Toxins including Tropical Diseases"},{"issue":"1","key":"pntd.0010292.ref082","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1080\/24734306.2018.1560991","article-title":"Sub-clinical neuromuscular dysfunction after envenoming by Merrem\u2019s hump-nosed pit viper (Hypnale hypnale)","volume":"3","author":"A Silva","year":"2019","journal-title":"Toxicology Communications"},{"issue":"3","key":"pntd.0010292.ref083","doi-asserted-by":"crossref","first-page":"260","DOI":"10.4269\/ajtmh.1995.53.260","article-title":"Efficacy of antivenom in the treatment of severe local envenomation by the hump-nosed viper (Hypnale hypnale)","volume":"53","author":"KH Sellahewa","year":"1995","journal-title":"Am J Trop Med Hyg"},{"key":"pntd.0010292.ref084","first-page":"63","article-title":"Phylogenetic relationships of the \"Agkistrodon complex\" based on mitochondrial sequence data","volume":"1997","author":"S. Moody","year":"1997","journal-title":"Symposia zoological society London"},{"issue":"3","key":"pntd.0010292.ref085","doi-asserted-by":"crossref","first-page":"366","DOI":"10.1006\/mpev.1998.0509","article-title":"Weighting and congruence: a case study based on three mitochondrial genes in pitvipers","volume":"9","author":"N Vidal","year":"1998","journal-title":"Mol Phylogenet Evol"},{"issue":"2","key":"pntd.0010292.ref086","doi-asserted-by":"crossref","first-page":"445","DOI":"10.1016\/j.ympev.2008.08.019","article-title":"A nesting of vipers: Phylogeny and historical biogeography of the Viperidae (Squamata: Serpentes)","volume":"49","author":"W W\u00fcster","year":"2008","journal-title":"Mol Phylogenet Evol"},{"issue":"6","key":"pntd.0010292.ref087","doi-asserted-by":"crossref","first-page":"427","DOI":"10.4103\/0971-4065.175987","article-title":"Snakebite mediated acute kidney injury, prognostic predictors, oxidative and carbonyl stress: A prospective study","volume":"26","author":"P Mukhopadhyay","year":"2016","journal-title":"Indian J Nephrol"},{"key":"pntd.0010292.ref088","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1016\/j.toxicon.2013.01.022","article-title":"Antivenom for snakebite envenoming in Sri Lanka: the need for geographically specific antivenom and improved efficacy","volume":"69","author":"D Keyler","year":"2013","journal-title":"Toxicon"}],"updated-by":[{"DOI":"10.1371\/journal.pntd.0010292","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2022,4,25]],"date-time":"2022-04-25T00:00:00Z","timestamp":1650844800000}}],"container-title":["PLOS Neglected Tropical Diseases"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pntd.0010292","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,4,25]],"date-time":"2022-04-25T17:41:08Z","timestamp":1650908468000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pntd.0010292"}},"subtitle":[],"editor":[{"given":"Nicholas R.","family":"Casewell","sequence":"first","affiliation":[],"role":[{"role":"editor","vocabulary":"crossref"}]}],"short-title":[],"issued":{"date-parts":[[2022,3,28]]},"references-count":88,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2022,3,28]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pntd.0010292","relation":{"new_version":[{"id-type":"doi","id":"10.1371\/journal.pntd.0010292","asserted-by":"object"}]},"ISSN":["1935-2735"],"issn-type":[{"value":"1935-2735","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,3,28]]}}}