Counteracting poisoning with chemical warfare nerve agents
References
- Holmstedt B. Structure-activity relationships of the organophosphorus anticholinesterase agents. In: Koelle GB, editor. Cholinesterases and anticholinesterase agents. Berlin: Springer-Verlag; 1963. p. 428–85.
- Chambers HW. Organophosphorus compounds: an overview. In: Chambers JE, Levi PE, editors. Organophosphates: chemistry, fate, and effects. San Diego: Academic Press; 1992. p. 3-17.
- Eddleston M, Buckley NA, Eyer P, Dawson AH. Management of acute organophosphorus pesticide poisoning. Lancet 2008;371:597–607. doi: 10.1016/S0140-6736(07)61202-1
- Kaur HG, Garg H. Pesticides: environmental impacts and management strategies. In: Larramendy ML, Soloneski S, editors. Pesticides - toxic aspects. London: IntechOpen; 2014. p. 187–229. doi: 10.5772/57399
- Dolgin E. Syrian gas attack reinforces need for better anti-sarin drugs. Nat Med 2013;19:1194–5. doi: 10.1038/nm1013-1194
- Stone R. U.K. attack puts nerve agent in the spotlight. Science 2018;359:1314–5. doi: 10.1126/science.359.6382.1314
- Bakry NM, el-Rashidy AH, Eldefrawi AT, Eldefrawi ME. Direct actions of organophosphate anticholinesterases on nicotinic and muscarinic acetylcholine receptors. J Biochem Toxicol 1988;3:235–59. doi: 10.1002/jbt.2570030404
- Wiener SW, Hoffman RS. Nerve agents: a comprehensive review. J Intensive Care Med 2004;19:22–37. doi: 10.1177/0885066603258659
- Costa LG. Toxicology of pesticides: a brief history. In: Costa LG, Galli CL, Murphy SD, editors. Toxicology of pesticides: experimental, clinical, and regulatory perspectives, NATO ASI Series. Vol. 13. Berlin-Heidelberg: Springer; 1987. p. 1–10.
- Tucker JB. War of Nerves: Chemical Warfare from World War I to Al-Qaeda. New York: Anchor; 2007.
- Delfino RT, Ribeiro TS, Figueroa-Villar JD. Organophosphorus compounds as chemical warfare agents: a review. J Braz Chem Soc 2009;20:407–28. doi: 10.1590/S0103-50532009000300003
- Sidell FR. Nerve agents. In: Sidell FR, Takafuji ET, Franz DR, editors. Medical aspects of chemical and biological warfare. Textbook of military medicine. Washington (DC): Office of the Surgeon General, Department of the Army USA; 1997. p. 129–79.
- Hoenig SL. Nerve agents. In: Compendium of chemical warfare agents. New York (NY): Springer; 2007. p. 77–128. doi: 10.1007/978-0-387-69260-9_5
- Pitschmann V. Overall view of chemical and biochemical weapons. Toxins (Basel) 2014;6:1761–84. doi: 10.3390/toxins6061761
- Vásárhelyi G, Földi L. History of Russia’s chemical weapons. AARMS 2007;6:135–46.
- Carlsen L. After Salisbury nerve agents revised. Mol Inform 2019;38(8–9):e1800106. doi: 10.1002/minf.201800106
- Pita R, Domingo J. The use of chemical weapons in the Syrian conflict. Toxics 2014;2:391–402. doi: 10.3390/toxics2030391
- Balali-Mood M, Saber H. Recent advances in the treatment of organophosphorous poisonings. Iran J Med Sci 2012;37:74–91. PMCID: PMC3470074
- Timperley C, Forman J, Aas P, Abdollahi M, Benachour D, Al-Amri A, Baulig A, Becker-Arnold R, Borrett V, Carino FA, Curty C, Gonzalez D, Geist M, Kane W, Kovarik Z, Martínez-Alvarez R, Mikulak R, Mourao N, Neffe S, Izzati F. Advice from the Scientific Advisory Board of the Organisation for the Prohibition of Chemical Weapons on riot control agents in connection to the Chemical Weapons Convention. RSC Advances 2018;8:41731–9. doi: 10.1039/C8RA08273A
- John H, van der Schans MJ, Koller M, Spruit HET, Worek F, Thiermann H, Noort D. Fatal sarin poisoning in Syria 2013: forensic verification within an international laboratory network. Forensic Toxicol 2018;36:61–71. doi: 10.1007/s11419-017-0376-7
- Shwirtz M. Nerve agent was used to poison Navalny, chemical weapons body confirms.
The New York Times online [displayed 22 November 2020]. Available athttps://www.nytimes.com/2020/10/06/world/europe/navalny-opcw-russia-novichok.html - Organisation for the Prohibition of Chemical Weapons (OPCW). OPCW issues report on technical assistance requested by Germany [displayed 22 November 2020]. Available at
https://www.opcw.org/media-centre/news/2020/10/opcw-issues-report-technical-assistance-requested-germany - Jokanović M, Stojiljković MP. Current understanding of the application of pyridinium oximes as cholinesterase reactivators in treatment of organophosphate poisoning. Eur J Pharmacol 2006;553:10–17. doi: 10.1016/j. ejphar.2006.09.054
- Bucht G, Puu G. Aging and reactivatability of plaice cholinesterase inhibited by soman and its stereoisomers. Biochem Pharmacol 1984;33:3573–7. doi: 10.1016/0006-2952(84)90139-4
- Benschop HP, De Jong, LPA. Nerve agent stereoisomers: analysis isolation and toxicology. Acc Chem Res 1988;21:368–74. doi: 10.1021/ar00154a003
- Worek F, Koller M, Thiermann H, Szinicz L. Diagnostic aspects of organophosphate poisoning. Toxicology 2005;214:182–9. doi: 10.1016/j.tox.2005.06.012
- Quin DM. Acetylcholinesterase: enzyme structure, reaction dynamics, and virtual transitions states. Chem Rev 1987;78:955–79. doi: 10.1021/cr00081a005
- Taylor P, Radić Z. The cholinesterases: from genes to proteins. Annu Rev Pharmacol Toxicol 1994;34:281–320. doi: 10.1146/annurev.pa.34.040194.001433
- Bourne Y, Taylor P, Bougis PE, Marchot P. Crystal structure of mouse acetylcholinesterase. A peripheral site-occluding loop in a tetrameric assembly. J Biol Chem 1999;274:2963–70. doi: 10.1074/jbc.274.5.2963
- Silman I, Sussman JL. Acetylcholinesterase: how is structure related to function? Chem Biol Interact 2008;175:3–10. doi: 10.1016/j.cbi.2008.05.035
- Sanson B, Colletier JP, Xu Y, Lang PT, Jiang H, Silman I, Sussman JL, Weik M. Backdoor opening mechanism in acetylcholinesterase based on X-ray crystallography and molecular dynamics simulations. Protein Sci 2011;20:1114–8. doi: 10.1002/pro.661
- Çokuğras AN. Butyrylcholinesterase: structure and physiological importance. Turk J Biochem 2003;28:54–61.
- Nicolet Y, Lockridge O, Masson P, Fontecilla-Camps JC, Nachon F. Crystal structure of human butyrylcholinesterase and of its complexes with substrate and products. J Biol Chem 2003;278:41141–7. doi: 10.1074/jbc.M210241200
- Chatonnet A, Lockridge O. Comparison of butyrylcholinesterase and acetylcholinesterase. Biochem J 1989;260:625–34. doi: 10.1042/bj2600625
- Darvesh S, Hopkins DA, Geula C. Neurobiology of butyrylcholinesterase. Nat Rev Neurosci 2003;4:131–8. doi: 10.1038/nrn1035
- Grisaru D, Sternfeld M, Eldor A, Glick D, Soreq H. Structural roles of acetylcholinesterase variants in biology and pathology. Eur J Biochem 1999;264:672–86. doi: 10.1046/j.1432-1327.1999.00693.x
- Soreq H, Seidman S. Acetylcholinesterase-new roles for an old actor. Nat Rev Neurosci 2001;2:294–302. doi: 10.1038/35067589
- Bosak A, Gazić I, Vinković V, Kovarik Z. Stereoselective inhibition of human, mouse, and horse cholinesterases by bambuterol enantiomers. Chem Biol Interact 2008;175:192–5. doi: 10.1016/j.cbi.2008.04.050
- Xie W, Stribley JA, Chatonnet A, Wilder PJ, Rizzino A, McComb RD, Taylor P, Hinrichs SH, Lockridge O. Postnatal developmental delay and supersensitivity to organophosphate in gene-targeted mice lacking acetylcholinesterase. J Pharmacol Exp Ther 2000;293:896–902. PMID: 10869390
- Bajgar J. Prophylaxis against organophosphorus poisoning. J Med Chem Def 2004;1:1–16.
- Newmark J. Therapy for nerve agent poisoning. Arch Neurol 2004;61:649–52. doi: 10.1001/archneur.61.5.649
- Hobbiger F. Reactivation of phosphorylated acetylcholinesterase. In: Koelle GB, editor. Cholinesterases and anticholinesterase agents. Handbook of experimental pharmacology. Vol. 15. Berlin, Heidelberg: Springer; 1963. p. 921–88.
- Holmstedt B. Cholinesterase inhibitors: an introduction. In: Giacobini E, editor. Cholinesterases and cholinesterase inhibitors. London: Martin Dunitz Ltd; 2000. p. 1–8.
- Benschop HP, Konings CA, Van Genderen J, De Jong LP. Isolation, anticholinesterase properties, and acute toxicity in mice of the four stereoisomers of the nerve agent soman. Toxicol Appl Pharmacol 1984;72:61–74. doi: 10.1016/0041-008x(84)90249-7
- Reiner E, Radić Z. Mechanism of action of cholinesterase inhibitor. In: Giacobini E, editor. Cholinesterases and cholinesterase inhibitors. London: Martin Dunitz Ltd; 2000. p. 103–19.
- Bosak A, Katalinić M, Kovarik Z. Kolinesteraze: struktura, uloga, inhibicija [Cholinesterases: structure, role, and inhibition, in Croatian]. Arh Hig Rada Toksikol 2011;62:175–90. doi: 10.2478/10004-1254-62-2011-2107
- Millard CB, Koellner G, Ordentlich A, Shafferman A, Silman I, Sussman JL. Reaction products of acetylcholinesterase and VX reveal a mobile histidine in the catalytic triad. J Am Chem Soc 1999;121:9883–4. doi: 10.1021/ja992704i
- Ekström F, Akfur C, Tunemalm AK, Lundberg S. Structural changes of phenylalanine 338 and histidine 447 revealed by the crystal structures of tabun-inhibited murine acetylcholinesterase. Biochemistry 2006;45:74–81. doi: 10.1021/bi051286t
- Masson P, Nachon F, Lockridge O. Structural approach to the aging of phosphylated cholinesterases. Chem Biol Interact 2010;187:157–62. doi: 10.1016/j.cbi.2010.03.027
- Chandar NB, Ganguly B. A first principles investigation of aging processes in soman conjugated AChE. Chem Biol Interact 2013;204:185–90. doi: 10.1016/j.cbi.2013.05.013
- de Jong LP, Wolring GZ. Stereospecific reactivation by some Hagedorn-oximes of acetylcholinesterases from various species including man, inhibited by soman. Biochem Pharmacol 1984;33:1119–25. doi: 10.1016/0006-2952(84)90523-9
- Worek F, Thiermann H, Szinicz L, Eyer P. Kinetic analysis of interactions between human acetylcholinesterase, structurally different organophosphorus compounds and oximes. Biochem Pharmacol 2004;68:2237–48. doi: 10.1016/j.bcp.2004.07.038
- Zhuang Q, Franjesevic AJ, Corrigan TS, Coldren WH, Dicken R, Sillart S, DeYong A, Yoshino N, Smith J, Fabry S, Fitzpatrick K, Blanton TG, Joseph J, Yoder RJ, McElroy CA, Ekici ÖD, Callam CS, Hadad CM. Demonstration of
in vitro resurrection of aged acetylcholinesterase after exposure to organophosphorus chemical nerve agents. J Med Chem 2018;61:7034–42. doi: 10.1021/acs.jmedchem.7b01620 - Shih TM, Rowland TC, McDonough JH. Anticonvulsants for nerve agentinduced seizures: the influence of the therapeutic dose of atropine. J Pharmacol Exp Ther 2007;320:154–61. doi: 10.1124/jpet.106.111252
- Thiermann H, Steinritz D, Worek F, Radtke B, Eyer P, Eyer F, Felgenhauer N, Zilker T. Atropine maintenance dosage in patients with severe organophosphate pesticide poisoning. Toxicol Lett 2011;206:77–83. doi: 10.1016/j. toxlet.2011.07.006
- Sidell FR, Newmark J, McDonough JH. Nerve agents. In: Lenhart MK, Tuorinsky SD, editors. Textbooks of military medicine, medical aspects of chemical warfare. Washington (DC): Department of the Army USA; 2008. p. 155–219.
- Childs AF, Davies DR, Green AL, Rutland JP. The reactivation by oximes and hydroxamic acids of cholinesterase inhibited by organo-phosphorus compounds. Br J Pharmacol Chemother 1955;10:462–5. doi: 10.1111/j.1476-5381.1955. tb00106.x
- Wilson IB, Ginsburg S. Reactivation of acetylcholinesterase inhibited by alkylphosphates. Arch Biochem Biophys 1955;54:569–71. doi: 10.1016/0003-9861(55)90075-8
- Rousseaux CG, Dua AK. Pharmacology of HI-6, an H-series oxime. Can J Physiol Pharmacol 1989;67:1183–9. doi: 10.1139/y89-188
- Eyer P. In memory of Ilse Hagedorn. Toxicology 2007;233:3–7. doi: 10.1016/j.tox.2006.09.014
- Worek F, Thiermann H, Wille T. Oximes in organophosphate poisoning: 60 years of hope and despair. Chem Biol Interact 2016;259(Pt B):93–8. doi: 10.1016/j.cbi.2016.04.032
- Dawson RM. Review of oximes available for treatment of nerve agent poisoning. J Appl Toxicol 1994;14:317–31. doi: 10.1002/jat.2550140502
- Antonijević B, Stojiljković MP. Unequal efficacy of pyridinium oximes in acute organophosphate poisoning. Clin Med Res 2007;5:71–82. doi: 10.3121/cmr.2007.701
- Thiermann H, Worek F, Kehe K. Limitations and challenges in treatment of acute chemical warfare agent poisoning. Chem Biol Interact 2013;206:435–43. doi: 10.1016/j. cbi.2013.09.015
- Thiermann H, Szinicz L, Eyer F, Worek F, Eyer P, Felgenhauer N, Zilker T. Modern strategies in therapy of organophosphate poisoning. Toxicol Lett 1999;107:233–9. doi: 10.1016/s0378-4274(99)00052-1
- Worek F, Szinicz L, Eyer P, Thiermann H. Evaluation of oxime efficacy in nerve agent poisoning: development of a kinetic-based dynamic model. Toxicol Appl Pharmacol 2005;209:193–202. doi: 10.1016/j.taap.2005.04.006
- Lorke DE, Kalasz H, Petroianu GA, Tekes K. Entry of oximes into the brain: a review. Curr Med Chem 2008;15:743–53. doi: 10.2174/092986708783955563
- Kovarik Z, Radić Z, Berman HA, Simeon-Rudolf V, Reiner E, Taylor P. Mutant cholinesterases possessing enhanced capacity for reactivation of their phosphonylated conjugates. Biochemistry 2004;43:3222–9. doi: 10.1021/bi036191a
- Kovarik Z, Čalić M, Šinko G, Bosak A, Berend S, Lucić Vrdoljak A, Radić B. Oximes: Reactivators of phosphorylated acetylcholinesterase and antidotes in therapy against tabun poisoning. Chem Biol Interact 2008;175:173–9. doi: 10.1016/j.cbi.2008.04.011
- Kovarik Z, Katalinić M, Šinko G, Binder J, Holas O, Jung YS, Musilova L, Jun D, Kuča K. Pseudo-catalytic scavenging: Searching for a suitable reactivator of phosphorylated butyrylcholinesterase. Chem Biol Interact 2010;187:167–71. doi: 10.1016/j.cbi.2010.02.023
- Kovarik Z, Maček Hrvat N, Katalinić M, Sit RK, Paradyse A, Žunec S, Musilek K, Fokin VV, Taylor P, Radić Z. Catalytic soman scavenging by the Y337A/F338A acetylcholinesterase mutant assisted with novel site-directed aldoximes. Chem Res Toxicol 2015;28:1036–44. doi: 10.1021/acs.chemrestox.5b00060
- Worek F, Reiter G, Eyer P, Szinicz L. Reactivation kinetics of acetylcholinesterase from different species inhibited by highly toxic organophosphates. Arch Toxicol 2002;76:523–9. doi: 10.1007/s00204-002-0375-1
- Ekström F, Pang YP, Boman M, Artursson E, Akfur C, Börjegren S. Crystal structures of acetylcholinesterase in complex with HI-6, Ortho-7 and obidoxime: structural basis for differences in the ability to reactivate tabun conjugates. Biochem Pharmacol 2006;72:597–607. doi: 10.1016/j. bcp.2006.05.027
- Kovarik Z, Kalisiak J, Maček Hrvat N, Katalinić M, Zorbaz T, Žunec S, Green C, Radić Z, Fokin VV, Sharpless KB, Taylor P. Reversal of tabun toxicity enabled by a triazole annulated oxime library-reactivators of acetylcholinesterase. Chem Eur J 2019;25:4100–14. doi: 10.1002/chem.201805051
- Kovarik Z, Ciban N, Radić Z, Simeon-Rudolf V, Taylor P. Active site mutant acetylcholinesterase interactions with 2-PAM, HI-6, and DDVP. Biochem Biophys Res Commun 2006;342(3):973–8. doi: 10.1016/j.bbrc.2006.02.056
- de Koning MC, Joosen MJ, Noort D, van Zuylen A, Tromp MC. Peripheral site ligand-oxime conjugates: A novel concept towards reactivation of nerve agent-inhibited human acetylcholinesterase. Bioorg Med Chem 2011;19:588–94. doi: 10.1016/j.bmc.2010.10.059
- Maraković N, Knežević A, Vinković V, Kovarik Z, Šinko G. Design and synthesis of
N -substituted-2-hydroxyiminoacetamides and interactions with cholinesterases. Chem Biol Interact 2016;259:122–32. doi: 10.1016/j.cbi.2016.05.035 - Kovarik Z, Maček Hrvat N, Kalisiak J, Katalinić M, Sit RK, Zorbaz T, Radić Z, Fokin VV, Sharpless KB, Taylor P. Counteracting tabun inhibition by reactivation by pyridinium aldoximes interacting with active center gorge mutations of acetylcholinesterase. Toxicol Appl Pharmacol 2019;372:40–6. doi: 10.1016/j.taap.2019.04.007
- Maček Hrvat N, Kalisiak J, Šinko G, Radić Z, Sharpless KB, Taylor P, Kovarik Z. Evaluation of high-affinity phenyltetrahydroisoquinoline aldoximes, linked through
anti -triazoles, as reactivators of phosphylated cholinesterases. Toxicol Lett 2020;321:83–9. doi: 10.1016/j.toxlet.2019.12.016 - Primožič I, Odžak R, Tomić S, Simeon-Rudolf V, Reiner E. Pyridinium, imidazolium, and quinucludinium oximes: synthesis, interaction with native and phosphylated cholinesterases, and antidotes against organophosphorus compounds. J Med Chem Def 2004;2:1–30.
- Oh KA, Yang GY, Jun D, Kuca K, Jung YS. Bispyridiumaldoxime reactivators connected with CH2O(CH2 n OCH2 linkers between pyridinium rings and their reactivity against VX. Bioorg Med Chem Lett 2006;16:4852–5. doi: 10.1016/j.bmcl.2006.06.063
- Musilek K, Holas O, Jun D, Dohnal V, Gunn-Moore F, Opletalova V, Dolezal M, Kuca K. Monooxime reactivators of acetylcholinesterase with
E -but-2-ene linker: preparation and reactivation of tabun- and paraoxon-inhibited acetylcholinesterase. Bioorg Med Chem 2007;15:6733–41. doi: 10.1016/j.bmc.2007.08.002 - Acharya J, Dubey DK, Srivastava AK, Raza SK.
In vitr o reactivation of sarin-inhibited human acetylcholinesterase (AChE) by bis-pyridinium oximes connected by xylene linkers. Toxicol In Vitro 2011;25:251–6. doi: 10.1016/j. tiv.2010.07.024 - Čalić M, Bosak A, Šinko G, Jelić D. In vitro evaluation of aldoxime interactions with human acetylcholinesterase. Croat Chem Acta 2008;81:47–57.
- Kryger G, Silman I, Sussman JL. Structure of acetylcholinesterase complexed with E2020 (Aricept): implications for the design of new anti-Alzheimer drugs. Structure 1999;7:297–307. doi: 10.1016/s0969-2126(99)80040-9
- McHardy SF, Bohmann JA, Corbett MR, Campos B, Tidwell MW, Thompson PM, Bemben CJ, Menchaca TA, Reeves TE, Cantrell WRJr, Bauta WE, Lopez A, Maxwell DM, Brecht KM, Sweeney RE, McDonough J. Design, synthesis, and characterization of novel, nonquaternary reactivators of GF-inhibited human acetylcholinesterase. Bioorg Med Chem Lett 2014;24:1711–4. doi: 10.1016/j.bmcl.2014.02.049
- Renou J, Dias J, Mercey G, Verdelet T, Rousseau C, Gastellier A-J, Arboleas M, Touvrey-Loiodice M, Baati R, Jean L, Nachon F, Renard P-Y. Synthesis and
in vitro evaluation of donepezil- based reactivators and analogues for nerve agent-inhibited human acetylcholinesterase. RSC Adv 2016;6:17929–40. doi: 10.1039/C5RA25477A - de Koning MC, van Grol M, Noort D. Peripheral site ligand conjugation to a non-quaternary oxime enhances reactivation of nerve agent-inhibited human acetylcholinesterase. Toxicol Lett 2011;206:54–9. doi: 10.1016/j.toxlet.2011.04.004
- Kliachyna M, Santoni G, Nussbaum V, Renou J, Sanson B, Colletier J-P, Arboléas M, Loiodice M, Weik M, Jean L, Renard P-Y, Nachon F, Baati R. Design, synthesis and biological evaluation of novel tetrahydroacridine pyridinealdoxime and -amidoxime hybrids as efficient uncharged reactivators of nerve agent-inhibited human acetylcholinesterase. Eur J Med Chem 2014;78:455–67. doi: 10.1016/j.ejmech.2014.03.044
- Renou J, Loiodice M, Arboléas M, Baati R, Jean L, Nachon F, Renard P-Y. Tryptoline-3-hydroxypyridinaldoxime conjugates as efficient reactivators of phosphylated human acetyl and butyrylcholinesterases. Chem Commun 2014;50:3947–50. doi: 10.1039/C4CC00561A
- Zorbaz T, Braïki A, Maraković N, Renou J, de la Mora E, Maček Hrvat N, Katalinić M, Silman I, Sussman JL, Mercey G, Gomez C, Mougeot R, Pérez B, Baati R, Nachon F, Weik M, Jean L, Kovarik Z, Renard P-Y. Potent 3-hydroxy-2-pyridine aldoxime reactivators of organophosphate-inhibited cholinesterases with predicted blood-brain barrier penetration. Chem Eur J 2018;24:9675–91. doi: 10.1002/chem.201801394
- Mercey G, Verdelet T, Saint-André G, Gillon E, Wagner A, Baati R, Jean L, Nachon F, Renard P-Y. First efficient uncharged reactivators for the dephosphylation of poisoned human acetylcholinesterase. Chem Commun 2011;47:5295–7. doi: 10.1039/C1CC10787A
- Mercey G, Renou J, Verdelet T, Kliachyna M, Baati R, Gillon E, Arboléas M, Loiodice M, Nachon F, Jean L, Renard P-Y. Phenyltetrahydroisoquinoline-pyridinaldoxime conjugates as efficient uncharged reactivators for the dephosphylation of inhibited human acetylcholinesterase. J Med Chem 2012;55:10791–5. doi: 10.1021/jm3015519
- Kalisiak J, Ralph EC, Zhang J, Cashman JR. Amidineoximes: reactivators for organophosphate exposure. J Med Chem 2011;54:3319–30. doi: 10.1021/jm200054r
- Sit RK, Radić Z, Gerardi V, Zhang L, Garcia E, Katalinić M, Amitai G, Kovarik Z, Fokin VV, Sharpless KB, Taylor P. New structural scaffolds for centrally acting oxime reactivators of phosphylated cholinesterases. J Biol Chem 2011;286:19422–30. doi: 10.1074/jbc.M111.230656
- Kalisiak J, Ralph EC, Cashman JR. Nonquaternary reactivators for organophosphate-inhibited cholinesterases. J Med Chem 2012;55:465–74. doi: 10.1021/jm201364d
- Radić Z, Sit RK, Kovarik Z, Berend S, Garcia E, Zhang L, Amitai G, Green C, Radić B, Fokin VV, Sharpless KB, Taylor P. Refinement of structural leads for centrally acting oxime reactivators of phosphylated cholinesterases. J Biol Chem 2012;287:11798–809. doi: 10.1074/jbc.M111.333732
- Chambers JE, Chambers HW, Meek EC, Pringle RB. Testing of novel brain-penetrating oxime reactivators of acetylcholinesterase inhibited by nerve agent surrogates. Chem Biol Interact 2013;203:135–8. doi: 10.1016/j. cbi.2012.10.017
- Kovarik Z, Maček N, Sit RK, Radić Z, Fokin VV, Barry Sharpless K, Taylor P. Centrally acting oximes in reactivation of tabun-phosphoramidated AChE. Chem Biol Interact 2013;203:77–80. doi: 10.1016/j.cbi.2012.08.019
- Sit RK, Kovarik Z, Maček Hrvat N, Žunec S, Green C, Fokin VV, Sharpless KB, Radić Z, Taylor P. Pharmacology, pharmacokinetics, and tissue disposition of zwitterionic hydroxyiminoacetamido alkylamines as reactivating antidotes for organophosphate exposure. J Pharmacol Exp Ther 2018;367:363–72. doi: 10.1124/jpet.118.249383
- Taylor P, Yan-Jye S, Momper J, Hou W, Camacho-Hernandez GA, Radić Z, Rosenberg Y, Kovarik Z, Sit R, Sharpless KB. Assessment of ionizable, zwitterionic oximes as reactivating antidotal agents for organophosphate exposure. Chem Biol Interact 2019;308:194–7. doi: 10.1016/j.cbi.2019.05.015
- Rosenberg YJ, Mao L, Jiang X, Lees J, Zhang L, Radić Z, Taylor P. Post-exposure treatment with the oxime RS194B rapidly reverses early and advanced symptoms in macaques exposed to sarin vapor. Chem Biol Interact 2017;274:50–7. doi: 10.1016/j.cbi.2017.07.003
- Rosenberg YJ, Wang J, Ooms T, Rajendran N, Mao L, Jiang X, Lees J, Urban L, Momper JD, Sepulveda Y, Shyong YJ, Taylor P. Post-exposure treatment with the oxime RS194B rapidly reactivates and reverses advanced symptoms of lethal inhaled paraoxon in macaques. Toxicol Lett 2018;293:229–34. doi: 10.1016/j.toxlet.2017.10.025
- Kreuter J, Alyautdin RN, Kharkevich DA, Ivanov AA. Passage of peptides through the blood-brain barrier with colloidal polymer particles (nanoparticles). Brain Res 1995;674:171–4. doi: 10.1016/0006-8993(95)00023-j
- Wagner S, Kufleitner J, Zensi A, Dadparvar M, Wien S, Bungert J, Vogel T, Worek F, Kreuter J, Briesen HV. Nanoparticulate transport of oximes over an
in vitro blood-brain barrier model. PLoS One 2010;5(12):e14213. doi: 10.1371/journal.pone.0014213 - Demar JC, Clarkson ED, Ratcliffe RH, Campbell AJ, Thangavelu SG, Herdman CA, Leader H, Schulz SM, Marek E, Medynets MA, Ku TC, Evans SA, Khan FA, Owens RR, Nambiar MP, Gordon RK. Pro-2-PAM therapy for central and peripheral cholinesterases. Chem Biol Interact 2010;187:191–8. doi: 10.1016/j.cbi.2010.02.015
- Jeong HC, Park NJ, Chae CH, Musilek K, Kassa J, Kuča K, Jung Y-S. Fluorinated pyridinium oximes as potential reactivators for acetylcholinesterases inhibited by paraoxon organophosphorus agent. Bioorg Med Chem 2009;17:6213–7. doi: 10.1016/j.bmc.2009.07.043
- Zorbaz T, Malinak D, Maraković N, Maček Hrvat N, Zandona A, Novotny M, Skarka A, Andrys R, Benkova M, Soukup O, Katalinić M, Kuca K, Kovarik Z, Musilek K. Pyridinium oximes with ortho-positioned chlorine moiety exhibit improved physicochemical properties and efficient reactivation of human acetylcholinesterase inhibited by several nerve agents. J Med Chem 2018;61:10753–66. doi: 10.1021/acs.jmedchem.8b01398
- Joosen MJ, van der Schans MJ, van Dijk CG, Kuijpers WC, Wortelboer HM, van Helden HP. Increasing oxime efficacy by blood-brain barrier modulation. Toxicol Lett 2011;206:67–71. doi: 10.1016/j.toxlet.2011.05.231
- Heldman E, Ashani Y, Raveh L, Rachaman ES. Sugar conjugates of pyridinium aldoximes as antidotes against organophosphate poisoning. Carbohydr Res 1986;151:337–47. doi: 10.1016/s0008-6215(00)90353–7
- Garcia GE, Campbell AJ, Olson J, Moorad-Doctor D, Morthole VI. Novel oximes as blood-brain barrier penetrating cholinesterase reactivators. Chem Biol Interact 2010;187:199–206. doi: 10.1016/j.cbi.2010.02.033
- Eto M. Organic and biological chemistry. In: Zweig G, editor. The organophosphorus pesticides. Cleveland: CRC Press Inc; 1976. p. 142.
- Cabal J, Kuca K, Kassa J. Specification of the structure of oximes able to reactivate tabun-inhibited acetylcholinesterase. Basic Clin Pharmacol Toxicol 2004;95:81–6. doi: 10.1111/j.1742-7843.2004.950207.x
- Čalić M, Bosak A, Kuca K, Kovarik Z. Interactions of butane, but-2-ene or xylene-like linked bispyridinium
para aldoximes with native and tabun-inhibited human cholinesterases. Chem Biol Interact 2008;175:305–8. doi: 10.1016/j.cbi.2008.04.010 - Artursson E, Akfur C, Hörnberg A, Worek F, Ekström F. Reactivation of tabun-hAChE investigated by structurally analogous oximes and mutagenesis. Toxicology 2009;265:108–14. doi: 10.1016/j.tox.2009.09.002
- Kovarik Z, Čalić M, Šinko G, Bosak A. Structure-activity approach in the reactivation of tabun-phosphorylated human acetylcholinesterase with bispyridinium
para -aldoximes. Arh Hig Rada Toksikol 2007;58:201–9. doi: 10.2478/v10004-007-0013-7 - Berend S, Katalinić M, Lucić Vrdoljak A, Kovarik Z, Kuca K, Radić B.
In vivo experimental approach to treatment against tabun poisoning. J Enzyme Inhib Med Chem 2010;25:531–6. doi: 10.3109/14756360903357593 - Kovarik Z, Lucić Vrdoljak A, Berend S, Katalinić M, Kuča K, Musilek K, Radić B. Evaluation of oxime K203 as antidote in tabun poisoning. Arh Hig Rada Toksikol 2009;60:19–26. doi: 10.2478/10004-1254-60-2009-1890
- Elsinghorst PW, Worek F, Thiermann H, Wille T. Drug development for the management of organophosphorus poisoning. Expert Opin Drug Discov 2013;8:1467–77. doi: 10.1517/17460441.2013.847920
- Seeger T, Eichhorn M, Lindner M, Niessen KV, Tattersall JEH, Timperley CM, Bird M, Green AC, Thiermann H, Worek F. Restoration of soman-blocked neuromuscular transmission in human and rat muscle by the bispyridinium non-oxime MB327
in vitro . Toxicology 2012:294:80–4. doi: 10.1016/j.tox.2012.02.002 - Turner SR, Chad JE, Price M, Timperley CM, Bird M, Green AC, Tattersall JEH. Protection against nerve agent poisoning by a noncompetitive nicotinic antagonist. Toxicol Lett 2011;206:105–11. doi: 10.1016/j.toxlet.2011.05.1035
- Price ME, Whitmore CL, Tattersall JEH, Green AC, Rice H. Efficacy of the antinicotinic compound MB327 against soman poisoning - Importance of experimental end point. Toxicol Lett 2018;293:167–71. doi: 10.1016/j.toxlet.2017.11.006
- Katz FS, Pecic S, Tran TH, Trakht I, Schneider L, Zhu Z, Ton-That L, Luzac M, Zlatanic V, Damera S, Macdonald J, Landry DW, Tong L, Stojanovic MN. Discovery of new classes of compounds that reactivate acetylcholinesterase inhibited by organophosphates. Chembiochem 2015;16:2205–15. doi: 10.1002/cbic.201500348
- de Koning MC, Horn G, Worek F, van Grol M. Discovery of a potent non-oxime reactivator of nerve agent inhibited human acetylcholinesterase. Eur J Med Chem 2018;157:151–60. doi: 10.1016/j.ejmech.2018.08.016
- Horn G, de Koning MC, van Grol M, Thiermann H, Worek F. Interactions between acetylcholinesterase, toxic organophosphorus compounds and a short series of structurally related non-oxime reactivators: Analysis of reactivation and inhibition kinetics
in vitro . Toxicol Lett 2018;299:218–25. doi: 10.1016/j.toxlet.2018.10.004 - McDonough JH Jr, Shih TM. Neuropharmacological mechanisms of nerve agent-induced seizure and neuropathology. Neurosci Biobehav Rev 1997;21:559–79. doi: 10.1016/s0149-7634(96)00050-4
- Rump S. Convulsions in organophosphate intoxications: their mechanism and treatment. In: Sohns T, Voicu A, Szinicz L, Finke E-J, Mircioiu C, Lundy P, Brain KR, Kempf H, editors. NBC risks current capabilities and future perspectives for protection. NATO science series (Series 1: disarmament technologies). Vol 25. Dordrecht: Springer; 1999. p. 189–95.
- Guignet M, Lein PJ. Neuroinflammation in organophosphate-induced neurotoxicity. In: Aschner M, Costa LG, editors. Advances in neurotoxicology. Vol 3. Massachusetts: Academic Press; 2019. p. 35–79.
- Chen Z, Duan RS, Quezada HC, Mix E, Nennesmo I, Adem A, Winblad B, Zhu J. Increased microglial activation and astrogliosis after intranasal administration of kainic acid in C57BL/6 mice. J Neurobiol 2005;62:207–18. doi: 10.1002/neu.20099
- Banks CN, Lein PJ. A review of experimental evidence linking neurotoxic organophosphorus compounds and inflammation. Neurotoxicology 2012;33:575–84. doi: 10.1016/j.neuro.2012.02.002
- Turtzo LC, Lescher J, Janes L, Dean DD, Budde MD, Frank JA. Macrophagic and microglial responses after focal traumatic brain injury in the female rat. J Neuroinflammation 2014;11:82. doi: 10.1186/1742-2094-11-82
- Becher B, Spath S, Goverman J. Cytokine networks in neuroinflammation. Nat Rev Immunol 2017;17:49–59. doi: 10.1038/nri.2016.123
- Marrs TC. Diazepam in the treatment of organophosphorus ester pesticide poisoning. Toxicol Rev 2003;22:75–81. doi: 10.2165/00139709-200322020-00002
- Tattersall J. Seizure activity post organophosphate exposure. Front Biosci (Landmark Ed) 2009;14:3688–711. doi: 10.2741/3481
- Timperley CM, Abdollahi M, Al-Amri AS, Baulig A, Benachour D, Borrett V, Cariño FA, Geist M, Gonzalez D, Kane W, Kovarik Z, Martínez-Álvarez R, Fusaro Mourão NM, Neffe S, Raza SK, Rubaylo V, Suárez AG, Takeuchi K, Tang C, Trifirò F, van Straten FM, Vanninen PS, Vučinić S, Zaitsev V, Zafar-Uz-Zaman M, Zina MS, Holen S, Forman JE, Alwan WS, Suri V. Advice on assistance and protection from the Scientific Advisory Board of the Organisation for the Prohibition of Chemical Weapons: Part 2. On preventing and treating health effects from acute, prolonged, and repeated nerve agent exposure, and the identification of medical countermeasures able to reduce or eliminate the longer term health effects of nerve agents. Toxicology 2019;413:13–23. doi: 10.1016/j.tox.2018.11.009
- Aroniadou-Anderjaska V, Apland JP, Figueiredo TH, De Araujo Furtado M, Braga MF. Acetylcholinesterase inhibitors (nerve agents) as weapons of mass destruction: History, mechanisms of action, and medical countermeasures. Neuropharmacology 2020;181:108298. doi: 10.1016/j. neuropharm.2020.108298
- North Atlantic Treaty Organization (NATO). Handbook on the medical aspects of NBC defensive operations [displayed 22 November 2020]. Available at
https://fas.org/nuke/guide/usa/doctrine/dod/fm8-9/3ch2.htm - Myhrer T, Aas P. Pretreatment and prophylaxis against nerve agent poisoning: Are undesirable behavioral side effects unavoidable? Neurosci Biobehav Rev 2016;71:657–70. doi: 10.1016/j.neubiorev.2016.10.017
- Layish I, Krivoy A, Rotman E, Finkelstein A, Tashma Z, Yehezkelli Y. Pharmacologic prophylaxis against nerve agent poisoning. Isr Med Assoc J 2005;7:182–7. PMID: 15792266
- Bajgar J, Fusek J, Kassa J, Kuca K, Jun D. Pharmacological prophylaxis against nerve agent poisoning: experimental studies and practical implications. In: Gupta RC, editor. Handbook of toxicology of chemical warfare agents. 2nd ed. Cambridge, MA: Academic Press; 2015. p. 979–87. doi: 10.1016/B978-0-12-800159-2.00066-X
- Bajgar J, Fusek J, Kassa J, Kuca K, Jun D. Chemical aspects of pharmacological prophylaxis against nerve agent poisoning. Curr Med Chem 2009;16:2977–86. doi: 10.2174/092986709788803088
- Masson P. Evolution of and perspectives on therapeutic approaches to nerve agent poisoning. Toxicol Lett 2011;206:5–13. doi: 10.1016/j.toxlet.2011.04.006
- Lenz DE, Yeung D, Smith JR, Sweeney RE, Lumley LA, Cerasoli DM. Stoichiometric and catalytic scavengers as protection against nerve agent toxicity: a mini review. Toxicology 2007;233:31–9. doi: 10.1016/j.tox.2006.11.066
- Nachon F, Brazzolotto X, Trovaslet M, Masson P. Progress in the development of enzyme-based nerve agent bioscavengers. Chem Biol Interact 2013;206:536–44. doi: 10.1016/j.cbi.2013.06.012
- Eckert S, Eyer P, Mückter H, Worek F. Kinetic analysis of the protection afforded by reversible inhibitors against irreversible inhibition of acetylcholinesterase by highly toxic organophosphorus compounds. Biochem Pharmacol 2006;72:344–57. doi: 10.1016/j.bcp.2006.04.015
- Gordon JJ, Leadbeater L, Maidment MP. The protection of animals against organophosphate poisoning by pretreatment with a carbamate. Toxicol Appl Pharmacol 1978;43:207–16. doi: 10.1016/s0041-008x(78)80045-3
- Keeler JR, Hurst CG, Dunn MA. Pyridostigmine used as a nerve agent pretreatment under wartime conditions. JAMA 1991;266:693–5. doi: 10.1001/jama.1991.03470050093029
- Kassa J. Therapeutic and neuroprotective efficacy of pharmacological pretreatment and antidotal treatment of acute tabun or soman poisoning with the emphasis on pretreatment drug PANPAL. Arh Hig Rada Toksikol 2006;57:427–34.
- Golomb BA. Acetylcholinesterase inhibitors and Gulf War illnesses. Proc Natl Acad Sci U S A 2008;105:4295–300. doi: 10.1073/pnas.0711986105
- Leader H, Wolfe AD, Chiang PK, Gordon RK. Pyridophens: binary pyridostigmine-aprophen prodrugs with differential inhibition of acetylcholinesterase, butyrylcholinesterase, and muscarinic receptors. J Med Chem 2002;45:902–10. doi: 10.1021/jm010196t
- Philippens IH, Joosen MJ, Vanwersch RA. Stress adversely affects efficacy of physostigmine-scopolamine pretreatment against soman in guinea pigs. Pharmacol Biochem Behav 2005;82:125–32. doi: 10.1016/j.pbb.2005.07.018
- Aracava Y, Pereira EF, Akkerman M, Adler M, Albuquerque EX. Effectiveness of donepezil, rivastigmine, and (+/-) huperzine A in counteracting the acute toxicity of organophosphorus nerve agents: comparison with galantamine. J Pharmacol Exp Ther 2009;331:1014–24. doi: 10.1124/jpet.109.160028
- Pereira EF, Aracava Y, Alkondon M, Akkerman M, Merchenthaler I, Albuquerque EX. Molecular and cellular actions of galantamine: clinical implications for treatment of organophosphorus poisoning. J Mol Neurosci 2010;40:196–203. doi: 10.1007/s12031-009-9234-3
- Alexandrova EA, Aracava Y, Pereira EF, Albuquerque EX. Pretreatment of Guinea pigs with galantamine prevents immediate and delayed effects of soman on inhibitory synaptic transmission in the hippocampus. J Pharmacol Exp Ther 2010;334:1051–8. doi: 10.1124/jpet.110.167700
- Lucić Vrdoljak A, Čalić M, Radić B, Berend S, Jun D, Kuča K, Kovarik Z. Pretreatment with pyridinium oximes improves antidotal therapy against tabun poisoning. Toxicology 2006;228:41–50. doi: 10.1016/j.tox.2006.08.012
- Bajgar J. Complex view on poisoning with nerve agents and organophosphates. Acta Medica (Hradec Kralove) 2005;48:3–21. doi: 10.14712/18059694.2018.23
- Maxwell DM, Brecht KM. Carboxylesterase: specificity and spontaneous reactivation of an endogenous scavenger for organophosphorus compounds. J Appl Toxicol 2001;21(Suppl 1):S103–7. doi: 10.1002/jat.833
- Sogorb MA, Vilanova E. Serum albumins and detoxication of anti-cholinesterase agents. Chem Biol Interact 2010;187:325–9. doi: 10.1016/j.cbi.2010.03.001
- Lockridge O. Review of human butyrylcholinesterase structure, function, genetic variants, history of use in the clinic, and potential therapeutic uses. Pharmacol Ther 2015;148:34–46. doi: 10.1016/j.pharmthera.2014.11.011
- Doctor BP, Saxena A. Bioscavengers for the protection of humans against organophosphate toxicity. Chem Biol Interact 2005;157–158:167–71. doi: 10.1016/j.cbi.2005.10.024
- Kovarik Z, Maček Hrvat N. Efficient detoxification of nerve agents by oxime-assisted reactivation of acetylcholinesterase mutants. Neuropharmacology 2020;171:108111. doi: 10.1016/j.neuropharm.2020.108111
- Liu Y, Li J, Lu Y. Enzyme therapeutics for systemic detoxification. Adv Drug Deliv Rev 2015;90:24–39. doi: 10.1016/j.addr.2015.05.005
- Zhang P, Jain P, Tsao C, Sinclair A, Sun F, Hung H-C, Bai T, Wu K, Jiang S. Butyrylcholinesterase nanocapsule as a long circulating bioscavenger with reduced immune response. J Control Release 2016;230:73–8. doi: 10.1016/j. jconrel.2016.04.008
- Ashani Y, Pistinner S. Estimation of the upper limit of human butyrylcholinesterase dose required for protection against organophosphates toxicity: a mathematically based toxicokinetic model. Toxicol Sci 2004;77:358–67. doi: 10.1093/toxsci/kfh012
- Saxena A, Sun W, Fedorko JM, Koplovitz I, Doctor BP. Prophylaxis with human serum butyrylcholinesterase protects guinea pigs exposed to multiple lethal doses of soman or VX. Biochem Pharmacol 2011;81:164–9. doi: 10.1016/j. bcp.2010.09.007
- Saxena A, Tipparaju P, Luo C, Doctor BP. Pilot-scale production of human serum butyrylcholinesterase suitable for use as a bioscavenger against nerve agent toxicity. Process Biochem 2010;45:1313–8. doi: 10.1016/j. procbio.2010.04.021
- Genovese RF, Sun W, Johnson CC, Ditargiani RC, Doctor BP, Saxena A. Safety of administration of human butyrylcholinesterase and its conjugates with soman or VX in rats. Basic Clin Pharmacol Toxicol 2010;106:428–34. doi: 10.1111/j.1742-7843.2009.00508.x
- Čadež T, Kovarik Z. Advancements in recombinant technology for production of butyrylcholinesterase, a bioscavenger of nerve agents. Period Biol. 2020;121–122:55–63. doi: 10.18054/pb.v121i1-2.10867
- Nachon F, Nicolet Y, Viguiea N, Masson P, Fontecilla-Camps JC, Lockridge O. Engineering of a monomeric and lowglycosylated form of human butyrylcholinesterase: expression, purifcation, characterization and crystallization. Eur J Biochem 2002;269:630–7. doi: 10.1046/j.0014-2956.2001.02692.x
- Terekhov S, Smirnov I, Bobik T, Shamborant O, Zenkova M, Chernolovskaya E, Gladkikh D, Murashev A, Dyachenko I, Paliko V, Palikova Y, Knorre V, Belogurov A Jr, Ponomarenko N, Blackburn GM, Masson P, Gabibov A. A novel expression cassette delivers efficient production of exclusively tetrameric human butyrylcholinesterase with improved pharmacokinetics for protection against organophosphate poisoning. Biochimie 2015;118:51–9. doi: 10.1016/j.biochi.2015.07.028
- Brazzolotto X, Wandhammer M, Ronco C, Trovaslet M, Jean L, Lockridge O, Renard PY, Nachon F. Human butyrylcholinesterase produced in insect cells: huprine-based affinity purification and crystal structure. FEBS J 2012;279:2905–16. doi: 10.1111/j.1742-4658.2012.08672.x
- Li S, Ip DT, Lin HQ, Liu JM, Miao YG, Ke LJ, Wan DC. High-level expression of functional recombinant human butyrylcholinesterase in silkworm larvae by Bac-to-Bac system. Chem Biol Interact 2010;187:101–5. doi: 10.1016/j. cbi.2010.03.055
- Geyer BC, Kannan L, Garnaud PE, Broomfield CA, Cadieux CL, Cherni I, Hodgins SM, Kasten SA, Kelley K, Kilbourne J, Oliver ZP, Otto TC, Puffenberger I, Reeves TE, Robbins N 2nd, Woods RR, Soreq H, Lenz DE, Cerasoli DM, Mor TS. Plant-derived human butyrylcholinesterase, but not an organophosphorous-compound hydrolyzing variant thereof, protects rodents against nerve agents. Proc Natl Acad Sci U S A 2010;107:20251–6. doi: 10.1073/pnas.1009021107
- Egelkrout E, Hayden CA, Wales M, Walker J, Novikov B, Grimsley J, Howard J. Production of the bioscavenger butyrylcholinesterase in maize. Mol Breeding 2017;37:136. doi: 10.1007/s11032-017-0731-8
- Corbin JM, Hashimoto BI, Karuppanan K, Kyser ZR, Wu L, Roberts BA, Noe AR, Rodriguez RL, McDonald KA, Nandi S. Semicontinuous bioreactor production of recombinant butyrylcholinesterase in transgenic rice cell suspension cultures. Front Plant Sci 2016;7:412. doi: 10.3389/fpls.2016.00412
- Huang YJ, Huang Y, Baldassarre H, Wang B, Lazaris A, Leduc M, Bilodeau AS, Bellemare A, Côté M, Herskovits P, Touati M, Turcotte C, Valeanu L, Lemée N, Wilgus H, Bégin I, Bhatia B, Rao K, Neveu N, Brochu E, Pierson J, Hockley DK, Cerasoli DM, Lenz DE, Karatzas CN, Langermann S. Recombinant human butyrylcholinesterase from milk of transgenic animals to protect against organophosphate poisoning. Proc Natl Acad Sci U S A 2007;104:13603–8. doi: 10.1073/pnas.0702756104
- Terekhov SS, Smirnov IV, Stepanova AV, Bobik TV, Mokrushina YA, Ponomarenko NA, Belogurov AA Jr, Rubtsova MP, Kartseva OV, Gomzikova MO, Moskovtsev AA, Bukatin AS, Dubina MV, Kostryukova ES, Babenko VV, Vakhitova MT, Manolov AI, Malakhova MV, Kornienko MA, Tyakht AV, Vanyushkina AA, Ilina EN, Masson P, Gabibov AG, Altman S. Microfluidic droplet platform for ultrahigh-throughput single-cell screening of biodiversity. Proc Natl Acad Sci U S A 2017;114:2550–5. doi: 10.1073/pnas.1621226114
- Brazzolotto X, Igert A, Guillon V, Santoni G, Nachon F. Bacterial expression of human butyrylcholinesterase as a tool for nerve agent bioscavengers development. Molecules 2017;22:1828. doi: 10.3390/molecules22111828
- Gupta V, Cadieux LC, Mcmenamin D, Medina-Jaszek CA, Arif M, Ahonkhai O, Wielechowski E, Taheri M, Che Y, Goode T, Limberis MP, Li M, Cerasoli DM, Tretiakova AP, Wilson JM. Adeno-associated virus-mediated expression of human butyrylcholinesterase to treat organophosphate poisoning. PLoS One 2019;14(11):e0225188. doi: 10.1371/journal.pone.0225188
- Lockridge O, David E, Schopfer LM, Masson P, Brazzolotto X, Nachon F. Purification of recombinant human butyrylcholinesterase on Hupresin® J Chromatogr B 2018;1102–1103:109–15. doi: 10.1016/j. jchromb.2018.10.026
- Larson MA, Lockridge O, Hinrichs SH. Polyproline promotes tetramerization of recombinant human butyrylcholinesterase. Biochem J 2014;462:329–35. doi: 10.1042/BJ20140421
- Rosenberg YJ, Saxena A, Sun W, Jiang X, Chilukuri N, Luo C, Doctor BP, Lee KD. Demonstration of
in vivo stability and lack of immunogenicity of a polyethyleneglycolconjugated recombinant CHO-derived butyrylcholinesterase bioscavenger using a homologous macaque model. Chem Biol Interact 2010;187:279–86. doi: 10.1016/j.cbi.2010.02.042 - Terekhov SS, Smirnov IV, Shamborant OG, Bobik TV, Ilyushin DG, Murashev AN, Dyachenko IA, Palikov VA, Knorre VD, Belogurov AA, Ponomarenko NA, Kuzina ES, Genkin DD, Masson P, Gabibov AG. Chemical polysialylation and
in vivo tetramerization improve pharmacokinetic characteristics of recombinant human butyrylcholinesterase-based bioscavengers. Acta Naturae 2015;7:136–41. doi: 10.32607/20758251-2015-7-4-136-141 - Huang YJ, Lundy PM, Lazaris A, Huang Y, Baldassarre H, Wang B, Turcotte C, Côté M, Bellemare A, Bilodeau AS, Brouillard S, Touati M, Herskovits P, Bégin I, Neveu N, Brochu E, Pierson J, Hockley DK, Cerasoli DM, Lenz DE, Wilgus H, Karatzas CN, Langermann S. Substantially improved pharmacokinetics of recombinant human butyrylcholinesterase by fusion to human serum albumin. BMC Biotechnol 2008;8:50. doi: 10.1186/1472-6750-8-50
- Ilyushin DG, Smirnov IV, Belogurov AA Jr, Dyachenko IA, Zharmukhamedova TIu, Novozhilova TI, Bychikhin EA, Serebryakova MV, Kharybin ON, Murashev AN, Anikienko KA, Nikolaev EN, Ponomarenko NA, Genkin DD, Blackburn GM, Masson P, Gabibov AG. Chemical polysialylation of human recombinant butyrylcholinesterase delivers a long-acting bioscavenger for nerve agents
in vivo . Proc Natl Acad Sci U S A 2013;110:1243–8. doi: 10.1073/pnas.1211118110 - Atsmon J, Brill-Almon E, Nadri-Shay C, Chertkoff R, Alon S, Shaikevich D, Volokhov I, Haim KY, Bartfeld D, Shulman A, Ruderfer I, Ben-Moshe T, Shilovitzky O, Soreq H, Shaaltiel Y. Preclinical and first-in-human evaluation of PRX-105, a PEGylated, plant-derived, recombinant human acetylcholinesterase-R. Toxicol Appl Pharmacol 2015;287:202–9. doi: 10.1016/j.taap.2015.06.004
- Pascual L, Sayed SE, Martínez-Máñez R, Costero AM, Gil S, Gavina P, Sancenon F. Acetylcholinesterase-capped mesoporous silica nanoparticles that open in the presence of Maček Hrvat N, Kovarik Z. Counteracting poisoning with chemical warfare nerve agents Arh Hig Rada Toksikol 2020;71:266-284 diisopropylfluorophosphate (a sarin or soman simulant). Org Lett 2016;18:5548–51. doi: 10.1021/acs.orglett.6b02793
- Cohen O, Kronman C, Raveh L, Mazor O, Ordentlich A, Shafferman A. Comparison of polyethylene glycolconjugated recombinant human acetylcholinesterase and serum human butyrylcholinesterase as bioscavengers of organophosphate compounds. Mol Pharmacol 2006;70:1121–31. doi: 10.1124/mol.106.026179
- Masson P, Nachon F, Broomfield CA, Lenz DE, Verdier L, Schopfer LM, Lockridge O. A collaborative endeavor to design cholinesterase-based catalytic scavengers against toxic organophosphorus esters. Chem Biol Interact 2008;175:273–80. doi: 10.1016/j.cbi.2008.04.005
- Cochran R, Kalisiak J, Küçükkilinç, T, Radić Z, Garcia E, Zhang L, Ho KY, Amitai G, Kovarik Z, Fokin VV, Sharpless KB, Taylor P. Oxime-assisted acetylcholinesterase catalytic scavengers of organophosphates that resist aging. J Biol Chem 2011;286:29718–24. doi: 10.1074/jbc.M111.264739
- Horn G, Wille T, Musilek K, Kuca K, Thiermann H, Worek F. Reactivation kinetics of 31 structurally different bispyridinium oximes with organophosphate-inhibited human butyrylcholinesterase. Arch Toxicol 2015;89:405–14. doi: 10.1007/s00204-014-1288-5
- Radić Z, Dale T, Kovarik Z, Berend S, Garcia E, Zhang L, Amitai G, Green C, Radić B, Duggan BM, Ajami D, Rebek J, Taylor P. Catalytic detoxification of nerve agent and pesticide organophosphates by butyrylcholinesterase assisted with non-pyridinium oximes. Biochem J 2013;450:231–42. doi: 10.1042/BJ20121612
- Sit RK, Fokin VV, Amitai G, Sharpless KB, Taylor P, Radić Z. Imidazole aldoximes effective in assisting butyrylcholinesterase catalysis of organophosphate detoxification. J Med Chem 2014;57:1378–89. doi: 10.1021/jm401650z
- Bušić V, Katalinić M, Šinko G, Kovarik Z, Gašo-Sokač D. Pyridoxal oxime derivative potency to reactivate cholinesterases inhibited by organophosphorus compounds. Toxicol Lett 2016;262:114–22. doi: 10.1016/j. toxlet.2016.09.015
- Katalinić M, Maček Hrvat N, Baumann K, Morasi Piperčić S, Makarić S, Tomić S, Jović O, Hrenar T, Miličević A, Jelić D, Žunec S, Primožič I, Kovarik Z. A comprehensive evaluation of novel oximes in creation of butyrylcholinesterase-based nerve agent bioscavengers. Toxicol Appl Pharmacol 2016;310:195–204. doi: 10.1016/j.taap.2016.09.015
- Katalinić M, Zandona A, Ramić A, Zorbaz T, Primožič I, Kovarik Z. New cinchona oximes evaluated as reactivators of acetylcholinesterase and butyrylcholinesterase inhibited by organophosphorus compounds. Molecules 2017;22(7):1234. doi: 10.3390/molecules22071234
- Zorbaz T, Malinak D, Kuca K, Musilek K, Kovarik Z. Butyrylcholinesterase inhibited by nerve agents is efficiently reactivated with chlorinated pyridinium oximes. Chem Biol Interact 2019;307:16–20. doi: 10.1016/j.cbi.2019.04.020
- Kovarik Z, Radić Z, Berman HA, Simeon-Rudolf V, Reiner E, Taylor P. Acetylcholinesterase active centre and gorge conformations analysed by combinatorial mutations and enantiomeric phosphonates. Biochem J 2003;373:33–40. doi: 10.1042/BJ20021862
- Katalinić M, Šinko G, Maček Hrvat N, Zorbaz T, Bosak A, Kovarik Z. Oxime-assisted reactivation of tabun-inhibited acetylcholinesterase analysed by active site mutations. Toxicology 2018;406–407:104–13. doi: 10.1016/j. tox.2018.05.008
- Kovarik Z, Radić Z, Berman HA, Taylor P. Mutation of acetylcholinesterase to enhance oxime-assisted catalytic turnover of methylphosphonates. Toxicology 2007;233:79–84. doi: 10.1016/j.tox.2006.08.032
- Taylor P, Kovarik Z, Reiner E, Radić Z. Acetylcholinesterase: converting a vulnerable target to a template for antidotes and detection of inhibitor exposure. Toxicology 2007;233:70–8. doi: 10.1016/j.tox.2006.11.061
- Katalinić M, Kovarik Z. Reactivation of tabun-inhibited acetylcholinesterase investigated by two oximes and mutagenesis. Croat Chem Acta 2012;85:209–12. doi: 10.5562/cca1815
- Kovarik Z, Maček Hrvat N, Žunec S, Katalinić M. Detoxification of tabun-exposed mice by an acetylcholinesterase mutant assisted with a novel pyridinium aldoxime. BiIol Serb 2019;41:4–8. doi: 10.5281/zenodo.3532038
- Mazor O, Cohen O, Kronman C, Raveh L, Stein D, Ordentlich A, Shafferman A. Aging-resistant organophosphate bioscavenger based on polyethylene glycol-conjugated F338A human acetylcholinesterase. Mol Pharmacol 2008;74:755–63. doi: 10.1124/mol.108.047449
- Kronman C, Cohen O, Mazor O, Ordentlich A, Raveh L, Velan B, Shafferman A. Next generation OP-bioscavengers: a circulatory long-lived 4-PEG hypolysine mutant of F338AHuAChE with optimal pharmacokinetics and pseudo-catalytic characteristics. Chem Biol Interact 2010;187:253–8. doi: 10.1016/j.cbi.2009.12.004
- Maček Hrvat N, Žunec S, Taylor P, Radić Z, Kovarik Z. HI-6 assisted catalytic scavenging of VX by acetylcholinesterase choline binding site mutants. Chem Biol Interact 2016;259:148–53. doi: 10.1016/j.cbi.2016.04.023
- Sweeney RE, Maxwell DM. A theoretical expression for the protection associated with stoichiometric and catalytic scavengers in a single compartment model of organophosphorus poisoning. Math Biosci 2003;181:133–43. doi: 10.1016/s0025-5564(02)00154-2
- Ashani Y, Leader H, Aggarwal N, Silman I, Worek F, Sussman JL, Goldsmith M.
In vitro evaluation of the catalytic activity of paraoxonases and phosphotriesterases predicts the enzyme circulatory levels required forin vivo protection against organophosphate intoxications. Chem Biol Interact 2016;259:252–6. doi: 10.1016/j.cbi.2016.04.039 - Rochu D, Chabrière E, Masson P. Human paraoxonase: a promising approach for pre-treatment and therapy of organophosphorus poisoning. Toxicology 2007;233:47–59. doi: 10.1016/j.tox.2006.08.037
- Bosak A, Bavec A, Konte T, Šinko G, Kovarik Z, Goličnik M. Interactions of paraoxonase-1 with pharmacologically relevant carbamates. Molecules 2020;25:1–15. doi: 10.3390/molecules25010211
- Kirby SD, Norris J, Sweeney R, Bahnson BJ, Cerasoli DM. A rationally designed mutant of plasma platelet-activating factor acetylhydrolase hydrolyzes the organophosphorus nerve agent soman. Biochim Biophys Acta 2015;1854:1809–15. doi: 10.1016/j.bbapap.2015.09.001
- Hemmert AC, Otto TC, Wierdl M, Edwards CC, Fleming CD, MacDonald M, Cashman JR, Potter PM, Cerasoli DM, Redinbo MR. Human carboxylesterase 1 stereoselectively binds the nerve agent cyclosarin and spontaneously hydrolyzes the nerve agent sarin. Mol Pharmacol 2010;77:508–16. doi: 10.1124/mol.109.062356
- Yeung DT, Smith JR, Sweeney RE, Lenz DE, Cerasoli DM. A gas chromatographic-mass spectrometric approach to examining stereoselective interaction of human plasma proteins with soman. J Anal Toxicol 2008;32:86–91. doi: 10.1093/jat/32.1.86
- Valiyaveettil M, Alamneh Y, Biggemann L, Soojhawon I, Doctor BP, Nambiar MP. Efficient hydrolysis of the chemical warfare nerve agent tabun by recombinant and purified human and rabbit serum paraoxonase 1. Biochem Biophys Res Commun 2010;403:97–102. doi: 10.1016/j.bbrc.2010.10.125
- Worek F, Seeger T, Goldsmith M, Ashani Y, Leader H, Sussman JS, Tawfik D, Thiermann H, Wille T. Efficacy of the rePON1 mutant IIG1 to prevent cyclosarin toxicity
in vivo and to detoxify structurally different nerve agentsin vitro . Arch Toxicol 2014;88:1257–66. doi: 10.1007/s00204-014-1204-z - Masson P, Rochu D. Catalytic bioscavengers against toxic esters, an alternative approach for prophylaxis and treatments of poisonings. Acta Naturae 2009;1:68–79. PMCID: PMC3347506
- Bigley AN, Xu C, Henderson TJ, Harvey SP, Raushel FM. Enzymatic neutralization of the chemical warfare agent VX: evolution of phosphotriesterase for phosphorothiolate hydrolysis. J Am Chem Soc 2013;135:10426–32. doi: 10.1021/ja402832z
- Goldsmith M, Eckstein S, Ashani Y, Greisen P Jr, Leader H, Sussman JL, Aggarwal N, Ovchinnikov S, Tawfik DS, Baker D, Thiermann H, Worek F. Catalytic efficiencies of directly evolved phosphotriesterase variants with structurally different organophosphorus compounds
in vitro . Arch Toxicol 2016;90:2711–24. doi: 10.1007/s00204-015-1626-2 - Smirnov I, Belogurov A Jr, Friboulet A, Masson P, Gabibov A, Renard PY. Strategies for the selection of catalytic antibodies against organophosphorus nerve agents. Chem Biol Interact 2013;203:196–201. doi: 10.1016/j. cbi.2012.10.011
- Letort S, Balieu S, Erb W, Gouhier G, Estour F. Interactions of cyclodextrins and their derivatives with toxic organophosphorus compounds. Beilstein J Org Chem 2016;12:204–28. doi: 10.3762/bjoc.12.23
- Taylor PW, Lukey BJ, Clark CR, Lee RB, Roussel RR. Field verification of Test-mate ChE. Mil Med 2003;168:314–9. PMID: 12733677
- Worek F, Baumann M, Pfeiffer B, Aurbek N, Balszuweit F, Thiermann H. Cholinesterase kit for field diagnosis of organophosphate exposure. CBRN Medical Defense International 2013 [displayed 13 November 2020]. Available at
https://www.securetec.net/wp-content/uploads/2018/08/Challenge_ChE_check_mobile_Special_2013.pdf - Moshiri M, Darchini-Maragheh E, Balali-Mood M. Advances in toxicology and medical treatment of chemical warfare nerve agents. Daru 2012;20(1):81. doi: 10.1186/2008-2231-20-81
- Timperley CM, Forman JE, Abdollahi M, Al-Amri AS, Baulig A, Benachour D, Borrett V, Cariño FA, Geist M, Gonzalez D, Kane W, Kovarik Z, Martínez-Álvarez R, Mourão NMF, Neffe S, Raza SK, Rubaylo V, Suárez AG, Takeuchi K, Tang C, Trifirò F, van Straten FM, Vanninen PS, Vučinić S, Zaitsev V, Zafar-Uz-Zaman M, Zina MS, Holen S. Advice on assistance and protection provided by the Scientific Advisory Board of the Organisation for the Prohibition of Chemical Weapons: Part 1. On medical care and treatment of injuries from nerve agents. Toxicology 2019;415:56–69. doi: 10.1016/j.tox.2019.01.004
- Thiermann H, Aurbek N, Worek F. Treatment of nerve agent poisoning. In: Worek F, Jenner J, Thiermann H, editors. Chemical warfare toxicology: Volume 2: Management of poisoning. London: The Royal Society of Chemistry; 2016. p. 1–42.
- Bentur Y, Layish I, Krivoy A, Berkovitch M, Rotman E, Bar Haim S, Yehezkelli Y, Kozer E. Civilian adult self injections of atropine-trimedoxime (TMB4) auto-injectors. Clin Toxicol (Phila) 2006;44:301–6. doi: 10.1080/15563650600584519
- Marrs TC, Rice P, Vale JA. The role of oximes in the treatment of nerve agent poisoning in civilian casualties. Toxicol Rev 2006;25:297–323. doi: 10.2165/00139709-200625040-00009
- Koller M, Becker C, Thiermann H, Worek F. GC-MS and LC-MS analysis of nerve agents in body fluids: intra-laboratory verification test using spiked plasma and urine samples. J Chromatogr B 2010;878:1226–33. doi: 10.1016/j. jchromb.2009.12.023
Language: English, Croatian, Slovenian
Page range: 266 - 284
Submitted on: Jul 1, 2020
Accepted on: Nov 1, 2020
Published on: Dec 31, 2020
Published by: Institute for Medical Research and Occupational Health
In partnership with: Paradigm Publishing Services
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© 2020 Nikolina Maček Hrvat, Zrinka Kovarik, published by Institute for Medical Research and Occupational Health
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