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A therapeutic combination of two small molecule toxin inhibitors provides broad preclinical efficacy against viper snakebite
  1. 1.

    Gutiérrez, J. M. et al. Snakebite envenoming. Nat. Rev. Dis. Prim. 3, 17063 (2017).

    PubMed  Google Scholar 

  2. 2.

    Harrison, R. A., Casewell, N. R., Ainsworth, S. A. & Lalloo, D. G. The time is now: a call for action to translate recent momentum on tackling tropical snakebite into sustained benefit for victims. Trans. R. Soc. Trop. Med. Hyg. 113, 835–838 (2019).

    PubMed  PubMed Central  Google Scholar 

  3. 3.

    Williams, D. J. et al. Strategy for a globally coordinated response to a priority neglected tropical disease: Snakebite envenoming. PLoS Negl. Trop. Dis. 13, e0007059 (2019).

    PubMed  PubMed Central  Google Scholar 

  4. 4.

    Casewell, N. R. et al. Medically important differences in snake venom composition are dictated by distinct postgenomic mechanisms. Proc. Natl Acad. Sci. USA 111, 9205–9210 (2014).

    ADS  CAS  PubMed  Google Scholar 

  5. 5.

    Tasoulis, T. & Isbister, G. K. A review and database of snake venom proteomes. Toxins 9, 290 (2017).

    PubMed Central  Google Scholar 

  6. 6.

    Williams, D. J. et al. Ending the drought: New strategies for improving the flow of affordable, effective antivenoms in Asia and Africa. J. Proteom. 74, 1735–1767 (2011).

    CAS  Google Scholar 

  7. 7.

    Arnold, C. Vipers, mambas and taipans: the escalating health crisis over snakebites. Nature 537, 26–28 (2016).

    ADS  CAS  PubMed  Google Scholar 

  8. 8.

    Gutiérrez, J. M. Global availability of antivenoms: The relevance of public manufacturing laboratories. Toxins 11, 5 (2019).

    Google Scholar 

  9. 9.

    Casewell, N. R. et al. Pre-clinical assays predict pan-African Echis viper efficacy for a species-specific antivenom. PLoS Negl. Trop. Dis. 4, e851 (2010).

    PubMed  PubMed Central  Google Scholar 

  10. 10.

    de Silva, H. A. et al. Low-dose adrenaline, promethazine, and hydrocortisone in the prevention of acute adverse reactions to antivenom following snakebite: A randomised, double-blind, placebo-controlled trial. PLoS Med. 8, e1000435 (2011).

    PubMed  PubMed Central  Google Scholar 

  11. 11.

    Mohapatra, B. et al. Snakebite mortality in India: a nationally representative mortality survey. PLoS Negl. Trop. Dis. 5, e1018 (2011).

    PubMed  PubMed Central  Google Scholar 

  12. 12.

    Bulfone, T. C., Samuel, S. P., Bickler, P. E. & Lewin, M. R. Developing small molecule therapeutics for the initial and adjunctive treatment of snakebite. J. Trop. Med. 2018, 1–14 (2018).

    Google Scholar 

  13. 13.

    Knudsen, C. & Laustsen, A. H. Recent advances in next generation snakebite antivenoms. Trop. Med. Infect. Dis 3, 42 (2018).

    PubMed Central  Google Scholar 

  14. 14.

    Habib, A. G., Gebi, U. I. & Onyemelukwe, G. C. Snake bite in Nigeria. Afr. J. Med. &. Med. Sci. 30, 171–178 (2001).

    CAS  Google Scholar 

  15. 15.

    Otero-Patiño, R. Epidemiological, clinical and therapeutic aspects of Bothrops asper bites. Toxicon 54, 998–1011 (2009).

    PubMed  Google Scholar 

  16. 16.

    Kumar, K. G. S., Narayanan, S., Udayabhaskaran, V. & Thulaseedharan, N. K. Clinical and epidemiologic profile and predictors of outcome of poisonous snake bites – an analysis of 1,500 cases from a tertiary care center in Malabar, North Kerala, India. Int. J. Gen. Med. 11, 209–216 (2018).

    PubMed  PubMed Central  Google Scholar 

  17. 17.

    Slagboom, J., Kool, J., Harrison, R. A. & Casewell, N. R. Haemotoxic snake venoms: their functional activity, impact on snakebite victims and pharmaceutical promise. Br. J. Haematol. 177, 947–959 (2017).

    PubMed  PubMed Central  Google Scholar 

  18. 18.

    Gutiérrez, J. M. & Rucavado, A. Snake venom metalloproteinases: their role in the pathogenesis of local tissue damage. Biochimie 82, 841–850 (2000).

    PubMed  Google Scholar 

  19. 19.

    Gutiérrez, J. M., Escalante, T., Rucavado, A. & Herrera, C. Hemorrhage caused by snake venom metalloproteinases: a journey of discovery and understanding. Toxins (Basel). 8, 93 (2016).

    PubMed  PubMed Central  Google Scholar 

  20. 20.

    Ferraz, C. R. et al. Multifunctional toxins in snake venoms and therapeutic implications: from pain to hemorrhage and necrosis. Front. Ecol. Evol. 7, 1–19 (2019).

    Google Scholar 

  21. 21.

    Howes, J.-M., Theakston, R. D. G. & Laing, G. D. Neutralization of the haemorrhagic activities of viperine snake venoms and venom metalloproteinases using synthetic peptide inhibitors and chelators. Toxicon 49, 734–739 (2007).

    CAS  PubMed  Google Scholar 

  22. 22.

    Lewin, M., Samuel, S., Merkel, J. & Bickler, P. Varespladib (LY315920) appears to be a potent, broad-spectrum, inhibitor of snake venom phospholipase A2 and a possible pre-referral treatment for envenomation. Toxins 8, 248 (2016).

    PubMed Central  Google Scholar 

  23. 23.

    Arias, A. S., Rucavado, A. & Gutiérrez, J. M. Peptidomimetic hydroxamate metalloproteinase inhibitors abrogate local and systemic toxicity induced by Echis ocellatus (saw-scaled) snake venom. Toxicon 132, 40–49 (2017).

    CAS  PubMed  Google Scholar 

  24. 24.

    Rucavado, A. et al. Inhibition of local hemorrhage and dermonecrosis induced by Bothrops asper snake venom: effectiveness of early in situ administration of the peptidomimetic metalloproteinase inhibitor batimastat and the chelating agent CaNa2EDTA. Am. J. Trop. Med. Hyg. 63, 313–319 (2000).

    CAS  PubMed  Google Scholar 

  25. 25.

    Ainsworth, S. et al. The paraspecific neutralisation of snake venom induced coagulopathy by antivenoms. Commun. Biol. 1, 34 (2018).

    PubMed  PubMed Central  Google Scholar 

  26. 26.

    Lewin, M. et al. Delayed LY333013 (Oral) and LY315920 (Intravenous) reverse severe neurotoxicity and rescue juvenile pigs from lethal doses of Micrurus fulvius (Eastern coral snake) venom. Toxins 10, 479 (2018).

    CAS  PubMed Central  Google Scholar 

  27. 27.

    Lewin, M. et al. Delayed oral LY333013 rescues mice from highly neurotoxic, lethal doses of Papuan taipan (Oxyuranus scutellatus) venom. Toxins 10, 380 (2018).

    CAS  PubMed Central  Google Scholar 

  28. 28.

    Albulescu, L.-O. et al. Preclinical validation of a repurposed metal chelator as an early-intervention therapeutic for hemotoxic snakebite. Sci. Trans. Med. 12, eaay8314 (2020).

    CAS  Google Scholar 

  29. 29.

    Wang, Y. et al. Exploration of the inhibitory potential of varespladib for snakebite envenomation. Molecules 23, 391 (2018).

    PubMed Central  Google Scholar 

  30. 30.

    Layfield, H. J. et al. Repurposing cancer drugs batimastat and marimastat to inhibit the activity of a group I metalloprotease from the venom of the Western diamondback rattlesnake, Crotalus atrox. Toxins 12, 309 (2020).

    CAS  PubMed Central  Google Scholar 

  31. 31.

    Rowsell, S. et al. Crystal structure of human MMP9 in complex with a reverse hydroxamate inhibitor. J. Mol. Biol. 319, 173–181 (2002).

    CAS  PubMed  Google Scholar 

  32. 32.

    Warrell, D. A. & Arnett, C. The importance of bites by the saw scaled or carpet viper (Echis carinatus): Epidemiological studies in Nigeria and a review of the world. Acta Trop. 33, 307–341 (1976).

    CAS  PubMed  Google Scholar 

  33. 33.

    Warrell, D. in Handbook of Clinical Toxicology of Animal Venoms and Poisons (eds White, J. & Meier, J.) pp 534–594 (CRC Press, 1995).

  34. 34.

    Warrell, D. in Handbook of Clinical Toxicology of Animal Venoms and Poisons (eds. White, J. & Meier, J.) pp 455–492 (CRC Press, 1995).

  35. 35.

    Still, K. et al. Multipurpose HTS Coagulation Analysis: Assay Development and Assessment of Coagulopathic Snake Venoms. Toxins 9, 382 (2017).

    MathSciNet  PubMed Central  Google Scholar 

  36. 36.

    Rogalski, A. et al. Differential procoagulant effects of saw-scaled viper (Serpentes: Viperidae: Echis) snake venoms on human plasma and the narrow taxonomic ranges of antivenom efficacies. Toxicol. Lett. 280, 159–170 (2017).

    CAS  PubMed  Google Scholar 

  37. 37.

    Slagboom, J. et al. High throughput screening and identification of coagulopathic snake venom proteins and peptides using nanofractionation and proteomics approaches. PLoS Negl. Trop. Dis. 14, e0007802 (2020).

    PubMed  PubMed Central  Google Scholar 

  38. 38.

    Winer, A., Adams, S. & Mignatti, P. Matrix metalloproteinase inhibitors in cancer therapy: turning past failures into future successes. Mol. Cancer Ther. 17, 1147–1155 (2018).

    CAS  PubMed  PubMed Central  Google Scholar 

  39. 39.

    Kim, E. Y. et al. Low-dose nafamostat mesilate in hemodialysis patients at high bleeding risk. Kidney Res. Clin. Pract. 30, 61–66 (2011).

    Google Scholar 

  40. 40.

    Kim, H. S. et al. Cardiac arrest caused by nafamostat mesilate. Kidney Res. Clin. Pract. 35, 187–189 (2016).

    PubMed  Google Scholar 

  41. 41.

    Theakston, R. D. & Reid, H. A. Development of simple standard assay procedures for the characterization of snake venom. Bull. World Health Organ. 61, 949–956 (1983).

    CAS  PubMed  PubMed Central  Google Scholar 

  42. 42.

    Harrison, R. A. et al. Preclinical antivenom-efficacy testing reveals potentially disturbing deficiencies of snakebite treatment capability in East Africa. PLoS Negl. Trop. Dis. 11, e0005969 (2017).

    PubMed  PubMed Central  Google Scholar 

  43. 43.

    WHO, WHO Guidelines for the Production, Control and Regulation of Snake Antivenom Immunoglobulins (WHO, (2018).

  44. 44.

    Bolaños, R. Toxicity of Costa Rican snake venoms for the white mouse. Am. J. Trop. Med. Hyg. 21, 360–363 (1972).

    PubMed  Google Scholar 

  45. 45.

    Villalta, M. et al. Development of a new polyspecific antivenom for snakebite envenoming in Sri Lanka: Analysis of its preclinical efficacy as compared to a currently available antivenom. Toxicon 122, 152–159 (2016).

    CAS  PubMed  Google Scholar 

  46. 46.

    Mora-Obando, D. et al. Proteomic and functional profiling of the venom of Bothrops ayerbei from Cauca, Colombia, reveals striking interspecific variation with Bothrops asper venom. J. Proteom. 96, 159–172 (2014).

    CAS  Google Scholar 

  47. 47.

    Harrison, R. A. & Gutiérrez, J. M. Priority actions and progress to substantially and sustainably reduce the mortality, morbidity and socioeconomic burden of tropical snakebite. Toxins 8, 351 (2016).

    PubMed Central  Google Scholar 

  48. 48.

    de la Rosa, G. et al. Horse immunization with short-chain consensus α-neurotoxin generates antibodies against broad spectrum of elapid venomous species. Nat. Commun. 10, 3642 (2019).

    ADS  PubMed  PubMed Central  Google Scholar 

  49. 49.

    Kini, R. M., Sidhu, S. S. & Laustsen, A. H. Biosynthetic oligoclonal antivenom (BOA) for snakebite and next-generation treatments for snakebite victims. Toxins 10, 534 (2018).

    CAS  PubMed Central  Google Scholar 

  50. 50.

    Laustsen, A. H. et al. In vivo neutralization of dendrotoxin-mediated neurotoxicity of black mamba venom by oligoclonal human IgG antibodies. Nat. Commun. 9, 3928 (2018).

    ADS  PubMed  PubMed Central  Google Scholar 

  51. 51.

    Peterson, J. The importance of estimating the therapeutic index in the development of matrix metalloproteinase inhibitors. Cardiovasc. Res. 69, 677–687 (2006).

    ADS  CAS  PubMed  Google Scholar 

  52. 52.

    Millar, A. W. et al. Results of single and repeat dose studies of the oral matrix metalloproteinase inhibitor marimastat in healthy male volunteers. Br. J. Clin. Pharmacol. 45, 21–26 (1998).

    CAS  PubMed  PubMed Central  Google Scholar 

  53. 53.

    Rosemurgy, A. et al. Marimastat in patients with advanced pancreatic cancer: a dose-finding study. Am. J. Clin. Oncol. 22, 247–252 (1999).

    CAS  PubMed  Google Scholar 

  54. 54.

    Nair, A. & Jacob, S. A simple practice guide for dose conversion between animals and human. J. Basic Clin. Pharm. 7, 27 (2016).

    PubMed  PubMed Central  Google Scholar 

  55. 55.

    Adis R&D Profile. Varespladib. Am. J. Cardiovasc. Drugs 11, 137–143 (2011).

    Google Scholar 

  56. 56.

    Rosenson, R. S. et al. Effects of varespladib methyl on biomarkers and major cardiovascular events in acute coronary syndrome patients. J. Am. Coll. Cardiol. 56, 1079–1088 (2010).

    CAS  PubMed  Google Scholar 

  57. 57.

    Abraham, E. et al. Efficacy and safety of LY315920Na/S-5920, a selective inhibitor of 14-kDa group IIA secretory phospholipase A2, in patients with suspected sepsis and organ failure. Crit. Care Med. 31, 718–728 (2003).

    CAS  PubMed  Google Scholar 

  58. 58.

    Nicholls, S. J. et al. Varespladib and cardiovascular events in patients with an acute coronary syndrome: The VISTA-16 randomized clinical trial. JAMA - J. Am. Med. Assoc. 311, 252–262 (2014).

    CAS  Google Scholar 

  59. 59.

    Gutiérrez, J. M., Lewin, M. R., Williams, D. J. & Lomonte, B. Varespladib (LY315920) and methyl varespladib (LY333013) abrogate or delay lethality induced by presynaptically acting neurotoxic snake venoms. Toxins 12, 131 (2020).

    PubMed Central  Google Scholar 

  60. 60.

    Ohtake, Y. et al. Nafamostat mesylate as anticoagulant in continuous hemofiltration and continuous hemodiafiltration. Contrib. Nephrol. 93, 215–217 (1991).

    CAS  PubMed  Google Scholar 

  61. 61.

    Maiorino, R. M., Xu, Z. F. & Aposhian, H. V. Determination and metabolism of dithiol chelating agents. XVII. In humans, sodium 2,3-dimercapto-1-propanesulfonate is bound to plasma albumin via mixed disulfide formation and is found in the urine as cyclic polymeric disulfides. J. Pharmacol. Exp. Ther. 277, 375–384 (1996).

    CAS  PubMed  Google Scholar 

  62. 62.

    Kosnett, M. J. The role of chelation in the treatment of arsenic and mercury poisoning. J. Med. Toxicol. 9, 347–354 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  63. 63.

    Wagstaff, S. C., Sanz, L., Juárez, P., Harrison, R. A. & Calvete, J. J. Combined snake venomics and venom gland transcriptomic analysis of the ocellated carpet viper, Echis ocellatus. J. Proteom. 71, 609–623 (2009).

    CAS  Google Scholar 

  64. 64.

    Tan, N. H. et al. Functional venomics of the Sri Lankan Russell’s viper (Daboia russelii) and its toxinological correlations. J. Proteom. 128, 403–423 (2015).

    CAS  Google Scholar 

  65. 65.

    Pla, D. et al. Phylovenomics of Daboia russelii across the Indian subcontinent. Bioactivities and comparative in vivo neutralization and in vitro third-generation antivenomics of antivenoms against venoms from India, Bangladesh and Sri Lanka. J. Proteom. 207, 103443 (2019).

    CAS  Google Scholar 

  66. 66.

    Bradley, J. D. et al. A randomized, double-blinded, placebo-controlled clinical trial of LY333013, a selective inhibitor of group II secretory phospholipase A2, in the treatment of rheumatoid arthritis. J. Rheumatol. 32, 417–423 (2005).

    CAS  PubMed  Google Scholar 

  67. 67.

    Sevenet, P. O. & Depasse, F. Clot waveform analysis: Where do we stand in 2017? Int. J. Lab. Hematol. 39, 561–568 (2017).

    CAS  PubMed  Google Scholar 

  68. 68.

    Patra, A., Kalita, B., Chanda, A. & Mukherjee, A. K. Proteomics and antivenomics of Echis carinatus carinatus venom: Correlation with pharmacological properties and pathophysiology of envenomation. Sci. Rep. 7, 17119 (2017).

    ADS  PubMed  PubMed Central  Google Scholar 

  69. 69.

    Alape-Girón, A. et al. Studies on the venom proteome of Bothrops asper: perspectives and applications. Toxicon 54, 938–948 (2009).

    PubMed  Google Scholar 

  70. 70.

    Calvete, J. J., Escolano, J. & Sanz, L. Snake venomics of Bitis species reveals large intragenus venom toxin composition variation: application to taxonomy of congeneric taxa. J. Proteome Res. 6, 2732–2745 (2007).

    CAS  PubMed  Google Scholar 

Original Text (This is the original text for your reference.)

  1. 1.

    Gutiérrez, J. M. et al. Snakebite envenoming. Nat. Rev. Dis. Prim. 3, 17063 (2017).

    PubMed  Google Scholar 

  2. 2.

    Harrison, R. A., Casewell, N. R., Ainsworth, S. A. & Lalloo, D. G. The time is now: a call for action to translate recent momentum on tackling tropical snakebite into sustained benefit for victims. Trans. R. Soc. Trop. Med. Hyg. 113, 835–838 (2019).

    PubMed  PubMed Central  Google Scholar 

  3. 3.

    Williams, D. J. et al. Strategy for a globally coordinated response to a priority neglected tropical disease: Snakebite envenoming. PLoS Negl. Trop. Dis. 13, e0007059 (2019).

    PubMed  PubMed Central  Google Scholar 

  4. 4.

    Casewell, N. R. et al. Medically important differences in snake venom composition are dictated by distinct postgenomic mechanisms. Proc. Natl Acad. Sci. USA 111, 9205–9210 (2014).

    ADS  CAS  PubMed  Google Scholar 

  5. 5.

    Tasoulis, T. & Isbister, G. K. A review and database of snake venom proteomes. Toxins 9, 290 (2017).

    PubMed Central  Google Scholar 

  6. 6.

    Williams, D. J. et al. Ending the drought: New strategies for improving the flow of affordable, effective antivenoms in Asia and Africa. J. Proteom. 74, 1735–1767 (2011).

    CAS  Google Scholar 

  7. 7.

    Arnold, C. Vipers, mambas and taipans: the escalating health crisis over snakebites. Nature 537, 26–28 (2016).

    ADS  CAS  PubMed  Google Scholar 

  8. 8.

    Gutiérrez, J. M. Global availability of antivenoms: The relevance of public manufacturing laboratories. Toxins 11, 5 (2019).

    Google Scholar 

  9. 9.

    Casewell, N. R. et al. Pre-clinical assays predict pan-African Echis viper efficacy for a species-specific antivenom. PLoS Negl. Trop. Dis. 4, e851 (2010).

    PubMed  PubMed Central  Google Scholar 

  10. 10.

    de Silva, H. A. et al. Low-dose adrenaline, promethazine, and hydrocortisone in the prevention of acute adverse reactions to antivenom following snakebite: A randomised, double-blind, placebo-controlled trial. PLoS Med. 8, e1000435 (2011).

    PubMed  PubMed Central  Google Scholar 

  11. 11.

    Mohapatra, B. et al. Snakebite mortality in India: a nationally representative mortality survey. PLoS Negl. Trop. Dis. 5, e1018 (2011).

    PubMed  PubMed Central  Google Scholar 

  12. 12.

    Bulfone, T. C., Samuel, S. P., Bickler, P. E. & Lewin, M. R. Developing small molecule therapeutics for the initial and adjunctive treatment of snakebite. J. Trop. Med. 2018, 1–14 (2018).

    Google Scholar 

  13. 13.

    Knudsen, C. & Laustsen, A. H. Recent advances in next generation snakebite antivenoms. Trop. Med. Infect. Dis 3, 42 (2018).

    PubMed Central  Google Scholar 

  14. 14.

    Habib, A. G., Gebi, U. I. & Onyemelukwe, G. C. Snake bite in Nigeria. Afr. J. Med. &. Med. Sci. 30, 171–178 (2001).

    CAS  Google Scholar 

  15. 15.

    Otero-Patiño, R. Epidemiological, clinical and therapeutic aspects of Bothrops asper bites. Toxicon 54, 998–1011 (2009).

    PubMed  Google Scholar 

  16. 16.

    Kumar, K. G. S., Narayanan, S., Udayabhaskaran, V. & Thulaseedharan, N. K. Clinical and epidemiologic profile and predictors of outcome of poisonous snake bites – an analysis of 1,500 cases from a tertiary care center in Malabar, North Kerala, India. Int. J. Gen. Med. 11, 209–216 (2018).

    PubMed  PubMed Central  Google Scholar 

  17. 17.

    Slagboom, J., Kool, J., Harrison, R. A. & Casewell, N. R. Haemotoxic snake venoms: their functional activity, impact on snakebite victims and pharmaceutical promise. Br. J. Haematol. 177, 947–959 (2017).

    PubMed  PubMed Central  Google Scholar 

  18. 18.

    Gutiérrez, J. M. & Rucavado, A. Snake venom metalloproteinases: their role in the pathogenesis of local tissue damage. Biochimie 82, 841–850 (2000).

    PubMed  Google Scholar 

  19. 19.

    Gutiérrez, J. M., Escalante, T., Rucavado, A. & Herrera, C. Hemorrhage caused by snake venom metalloproteinases: a journey of discovery and understanding. Toxins (Basel). 8, 93 (2016).

    PubMed  PubMed Central  Google Scholar 

  20. 20.

    Ferraz, C. R. et al. Multifunctional toxins in snake venoms and therapeutic implications: from pain to hemorrhage and necrosis. Front. Ecol. Evol. 7, 1–19 (2019).

    Google Scholar 

  21. 21.

    Howes, J.-M., Theakston, R. D. G. & Laing, G. D. Neutralization of the haemorrhagic activities of viperine snake venoms and venom metalloproteinases using synthetic peptide inhibitors and chelators. Toxicon 49, 734–739 (2007).

    CAS  PubMed  Google Scholar 

  22. 22.

    Lewin, M., Samuel, S., Merkel, J. & Bickler, P. Varespladib (LY315920) appears to be a potent, broad-spectrum, inhibitor of snake venom phospholipase A2 and a possible pre-referral treatment for envenomation. Toxins 8, 248 (2016).

    PubMed Central  Google Scholar 

  23. 23.

    Arias, A. S., Rucavado, A. & Gutiérrez, J. M. Peptidomimetic hydroxamate metalloproteinase inhibitors abrogate local and systemic toxicity induced by Echis ocellatus (saw-scaled) snake venom. Toxicon 132, 40–49 (2017).

    CAS  PubMed  Google Scholar 

  24. 24.

    Rucavado, A. et al. Inhibition of local hemorrhage and dermonecrosis induced by Bothrops asper snake venom: effectiveness of early in situ administration of the peptidomimetic metalloproteinase inhibitor batimastat and the chelating agent CaNa2EDTA. Am. J. Trop. Med. Hyg. 63, 313–319 (2000).

    CAS  PubMed  Google Scholar 

  25. 25.

    Ainsworth, S. et al. The paraspecific neutralisation of snake venom induced coagulopathy by antivenoms. Commun. Biol. 1, 34 (2018).

    PubMed  PubMed Central  Google Scholar 

  26. 26.

    Lewin, M. et al. Delayed LY333013 (Oral) and LY315920 (Intravenous) reverse severe neurotoxicity and rescue juvenile pigs from lethal doses of Micrurus fulvius (Eastern coral snake) venom. Toxins 10, 479 (2018).

    CAS  PubMed Central  Google Scholar 

  27. 27.

    Lewin, M. et al. Delayed oral LY333013 rescues mice from highly neurotoxic, lethal doses of Papuan taipan (Oxyuranus scutellatus) venom. Toxins 10, 380 (2018).

    CAS  PubMed Central  Google Scholar 

  28. 28.

    Albulescu, L.-O. et al. Preclinical validation of a repurposed metal chelator as an early-intervention therapeutic for hemotoxic snakebite. Sci. Trans. Med. 12, eaay8314 (2020).

    CAS  Google Scholar 

  29. 29.

    Wang, Y. et al. Exploration of the inhibitory potential of varespladib for snakebite envenomation. Molecules 23, 391 (2018).

    PubMed Central  Google Scholar 

  30. 30.

    Layfield, H. J. et al. Repurposing cancer drugs batimastat and marimastat to inhibit the activity of a group I metalloprotease from the venom of the Western diamondback rattlesnake, Crotalus atrox. Toxins 12, 309 (2020).

    CAS  PubMed Central  Google Scholar 

  31. 31.

    Rowsell, S. et al. Crystal structure of human MMP9 in complex with a reverse hydroxamate inhibitor. J. Mol. Biol. 319, 173–181 (2002).

    CAS  PubMed  Google Scholar 

  32. 32.

    Warrell, D. A. & Arnett, C. The importance of bites by the saw scaled or carpet viper (Echis carinatus): Epidemiological studies in Nigeria and a review of the world. Acta Trop. 33, 307–341 (1976).

    CAS  PubMed  Google Scholar 

  33. 33.

    Warrell, D. in Handbook of Clinical Toxicology of Animal Venoms and Poisons (eds White, J. & Meier, J.) pp 534–594 (CRC Press, 1995).

  34. 34.

    Warrell, D. in Handbook of Clinical Toxicology of Animal Venoms and Poisons (eds. White, J. & Meier, J.) pp 455–492 (CRC Press, 1995).

  35. 35.

    Still, K. et al. Multipurpose HTS Coagulation Analysis: Assay Development and Assessment of Coagulopathic Snake Venoms. Toxins 9, 382 (2017).

    MathSciNet  PubMed Central  Google Scholar 

  36. 36.

    Rogalski, A. et al. Differential procoagulant effects of saw-scaled viper (Serpentes: Viperidae: Echis) snake venoms on human plasma and the narrow taxonomic ranges of antivenom efficacies. Toxicol. Lett. 280, 159–170 (2017).

    CAS  PubMed  Google Scholar 

  37. 37.

    Slagboom, J. et al. High throughput screening and identification of coagulopathic snake venom proteins and peptides using nanofractionation and proteomics approaches. PLoS Negl. Trop. Dis. 14, e0007802 (2020).

    PubMed  PubMed Central  Google Scholar 

  38. 38.

    Winer, A., Adams, S. & Mignatti, P. Matrix metalloproteinase inhibitors in cancer therapy: turning past failures into future successes. Mol. Cancer Ther. 17, 1147–1155 (2018).

    CAS  PubMed  PubMed Central  Google Scholar 

  39. 39.

    Kim, E. Y. et al. Low-dose nafamostat mesilate in hemodialysis patients at high bleeding risk. Kidney Res. Clin. Pract. 30, 61–66 (2011).

    Google Scholar 

  40. 40.

    Kim, H. S. et al. Cardiac arrest caused by nafamostat mesilate. Kidney Res. Clin. Pract. 35, 187–189 (2016).

    PubMed  Google Scholar 

  41. 41.

    Theakston, R. D. & Reid, H. A. Development of simple standard assay procedures for the characterization of snake venom. Bull. World Health Organ. 61, 949–956 (1983).

    CAS  PubMed  PubMed Central  Google Scholar 

  42. 42.

    Harrison, R. A. et al. Preclinical antivenom-efficacy testing reveals potentially disturbing deficiencies of snakebite treatment capability in East Africa. PLoS Negl. Trop. Dis. 11, e0005969 (2017).

    PubMed  PubMed Central  Google Scholar 

  43. 43.

    WHO, WHO Guidelines for the Production, Control and Regulation of Snake Antivenom Immunoglobulins (WHO, (2018).

  44. 44.

    Bolaños, R. Toxicity of Costa Rican snake venoms for the white mouse. Am. J. Trop. Med. Hyg. 21, 360–363 (1972).

    PubMed  Google Scholar 

  45. 45.

    Villalta, M. et al. Development of a new polyspecific antivenom for snakebite envenoming in Sri Lanka: Analysis of its preclinical efficacy as compared to a currently available antivenom. Toxicon 122, 152–159 (2016).

    CAS  PubMed  Google Scholar 

  46. 46.

    Mora-Obando, D. et al. Proteomic and functional profiling of the venom of Bothrops ayerbei from Cauca, Colombia, reveals striking interspecific variation with Bothrops asper venom. J. Proteom. 96, 159–172 (2014).

    CAS  Google Scholar 

  47. 47.

    Harrison, R. A. & Gutiérrez, J. M. Priority actions and progress to substantially and sustainably reduce the mortality, morbidity and socioeconomic burden of tropical snakebite. Toxins 8, 351 (2016).

    PubMed Central  Google Scholar 

  48. 48.

    de la Rosa, G. et al. Horse immunization with short-chain consensus α-neurotoxin generates antibodies against broad spectrum of elapid venomous species. Nat. Commun. 10, 3642 (2019).

    ADS  PubMed  PubMed Central  Google Scholar 

  49. 49.

    Kini, R. M., Sidhu, S. S. & Laustsen, A. H. Biosynthetic oligoclonal antivenom (BOA) for snakebite and next-generation treatments for snakebite victims. Toxins 10, 534 (2018).

    CAS  PubMed Central  Google Scholar 

  50. 50.

    Laustsen, A. H. et al. In vivo neutralization of dendrotoxin-mediated neurotoxicity of black mamba venom by oligoclonal human IgG antibodies. Nat. Commun. 9, 3928 (2018).

    ADS  PubMed  PubMed Central  Google Scholar 

  51. 51.

    Peterson, J. The importance of estimating the therapeutic index in the development of matrix metalloproteinase inhibitors. Cardiovasc. Res. 69, 677–687 (2006).

    ADS  CAS  PubMed  Google Scholar 

  52. 52.

    Millar, A. W. et al. Results of single and repeat dose studies of the oral matrix metalloproteinase inhibitor marimastat in healthy male volunteers. Br. J. Clin. Pharmacol. 45, 21–26 (1998).

    CAS  PubMed  PubMed Central  Google Scholar 

  53. 53.

    Rosemurgy, A. et al. Marimastat in patients with advanced pancreatic cancer: a dose-finding study. Am. J. Clin. Oncol. 22, 247–252 (1999).

    CAS  PubMed  Google Scholar 

  54. 54.

    Nair, A. & Jacob, S. A simple practice guide for dose conversion between animals and human. J. Basic Clin. Pharm. 7, 27 (2016).

    PubMed  PubMed Central  Google Scholar 

  55. 55.

    Adis R&D Profile. Varespladib. Am. J. Cardiovasc. Drugs 11, 137–143 (2011).

    Google Scholar 

  56. 56.

    Rosenson, R. S. et al. Effects of varespladib methyl on biomarkers and major cardiovascular events in acute coronary syndrome patients. J. Am. Coll. Cardiol. 56, 1079–1088 (2010).

    CAS  PubMed  Google Scholar 

  57. 57.

    Abraham, E. et al. Efficacy and safety of LY315920Na/S-5920, a selective inhibitor of 14-kDa group IIA secretory phospholipase A2, in patients with suspected sepsis and organ failure. Crit. Care Med. 31, 718–728 (2003).

    CAS  PubMed  Google Scholar 

  58. 58.

    Nicholls, S. J. et al. Varespladib and cardiovascular events in patients with an acute coronary syndrome: The VISTA-16 randomized clinical trial. JAMA - J. Am. Med. Assoc. 311, 252–262 (2014).

    CAS  Google Scholar 

  59. 59.

    Gutiérrez, J. M., Lewin, M. R., Williams, D. J. & Lomonte, B. Varespladib (LY315920) and methyl varespladib (LY333013) abrogate or delay lethality induced by presynaptically acting neurotoxic snake venoms. Toxins 12, 131 (2020).

    PubMed Central  Google Scholar 

  60. 60.

    Ohtake, Y. et al. Nafamostat mesylate as anticoagulant in continuous hemofiltration and continuous hemodiafiltration. Contrib. Nephrol. 93, 215–217 (1991).

    CAS  PubMed  Google Scholar 

  61. 61.

    Maiorino, R. M., Xu, Z. F. & Aposhian, H. V. Determination and metabolism of dithiol chelating agents. XVII. In humans, sodium 2,3-dimercapto-1-propanesulfonate is bound to plasma albumin via mixed disulfide formation and is found in the urine as cyclic polymeric disulfides. J. Pharmacol. Exp. Ther. 277, 375–384 (1996).

    CAS  PubMed  Google Scholar 

  62. 62.

    Kosnett, M. J. The role of chelation in the treatment of arsenic and mercury poisoning. J. Med. Toxicol. 9, 347–354 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  63. 63.

    Wagstaff, S. C., Sanz, L., Juárez, P., Harrison, R. A. & Calvete, J. J. Combined snake venomics and venom gland transcriptomic analysis of the ocellated carpet viper, Echis ocellatus. J. Proteom. 71, 609–623 (2009).

    CAS  Google Scholar 

  64. 64.

    Tan, N. H. et al. Functional venomics of the Sri Lankan Russell’s viper (Daboia russelii) and its toxinological correlations. J. Proteom. 128, 403–423 (2015).

    CAS  Google Scholar 

  65. 65.

    Pla, D. et al. Phylovenomics of Daboia russelii across the Indian subcontinent. Bioactivities and comparative in vivo neutralization and in vitro third-generation antivenomics of antivenoms against venoms from India, Bangladesh and Sri Lanka. J. Proteom. 207, 103443 (2019).

    CAS  Google Scholar 

  66. 66.

    Bradley, J. D. et al. A randomized, double-blinded, placebo-controlled clinical trial of LY333013, a selective inhibitor of group II secretory phospholipase A2, in the treatment of rheumatoid arthritis. J. Rheumatol. 32, 417–423 (2005).

    CAS  PubMed  Google Scholar 

  67. 67.

    Sevenet, P. O. & Depasse, F. Clot waveform analysis: Where do we stand in 2017? Int. J. Lab. Hematol. 39, 561–568 (2017).

    CAS  PubMed  Google Scholar 

  68. 68.

    Patra, A., Kalita, B., Chanda, A. & Mukherjee, A. K. Proteomics and antivenomics of Echis carinatus carinatus venom: Correlation with pharmacological properties and pathophysiology of envenomation. Sci. Rep. 7, 17119 (2017).

    ADS  PubMed  PubMed Central  Google Scholar 

  69. 69.

    Alape-Girón, A. et al. Studies on the venom proteome of Bothrops asper: perspectives and applications. Toxicon 54, 938–948 (2009).

    PubMed  Google Scholar 

  70. 70.

    Calvete, J. J., Escolano, J. & Sanz, L. Snake venomics of Bitis species reveals large intragenus venom toxin composition variation: application to taxonomy of congeneric taxa. J. Proteome Res. 6, 2732–2745 (2007).

    CAS  PubMed  Google Scholar 

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