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Vol. 21, Art. 37 (pp. 452-473)    |    2020       

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Prospects for the use of scavengers as antidote therapy for acute poisoning with anticholinesterase substances (literature review)

1State Scientific-research Test Institute of the Military Medicine,
Russian Federation Defense Ministry, Saint-Petersburg, Russia
2Kirov`s Military Medical Academy, Saint-Petersburg, Russia

Brief summary

The review discusses approaches to the prevention and treatment of organophosphate (OP) poisoning associated with the use of biomolecules that bind or hydrolyze a toxicant. The current level of development in the field of creating stoichiometric scavengers is described, of which the most effective and studied are the recombinant forms of acetyl- and butyryl-cholinesterase (BuChE). Cholinesterase-based stoichiometric scavengers in animals are characterized by a level of effective doses of about 60 mg / kg, in which they provide protection against poisoning of OP in lethal doses. The prospects of the use of BuChE for the prevention of inhalation poisoning of OP are evaluated. The data on the effectiveness of chemical scavengers (based on cyclodextrins and calixarenes) are presented, which have an advantage over proteins in terms of stability and availability of production. The work pays great attention to catalytic and pseudocatalytic scavengers. As the most promising catalytic systems, enzymes human paraoxonase-1 and bacterial phosphotriesterase are justified. The data on the effectiveness of these agents in animal OP poisoning models of are presented, which indicate that catalytic scavengers, given iv in the effective dose range of about 2-5 mg / kg, provide protection for fatal poisoning. A critical analysis of the problems associated with biotechnological developments and the medical use of protein and enzyme preparations, proposed as scavengers, is presented, and directions for improving their medical, tactical and pharmaceutical characteristics are identified.


Key words

stoichiometric scavengers, catalytic bioscavengers, peptides, expression, recombinant enzymes, molecular modeling, chemical modifications

Reference list

1. John H., van der Schans M. J., Koller M, Spruit H.E. T.,Worek F., Thiermann H., Noort D. Fatal sarin poisoning in Syria 2013: forensic verification within an international laboratory network // Forensic toxicology. 2017. Vol. 36. N1. R. 61-71. doi: 10.1007/s11419-017-0376-7.


2. Tu A.T. Aum Shinrikyo's Chemical and Biological Weapons: More Than Sarin // Forensic. Sci. Rev. 2014. Vol. 26, N2. R. 115-120.


3. Konceptyalnie podhodi k razvitiu sistemi antidotnogo obespecheniya Rossiiskoi Federacii / pod red. Yiba V.V., Nazarova V.B., Gladkih V.D. M.: FGYP NPC «Farmzashita» FMBA Rossii. 2013. S. 155-156.


4. Lockridge O., Norgren R.B., Johnson R.C., Blake T.A. Naturally occurring genetic variants of human acetylcholinesterase and butyrylcholinesterase and their potential impact on the risk of toxicity from cholinesterase inhibitors // Chem. Res. Toxicol. 2016. Vol. 29, N9. R. 1381-1392. doi: 10.1021/acs.chemrestox.6b00228.


5. Rosenberg Y.J., Saxena A., Sun W., Jiang X., Chilukuri N., Luo C., Doctor B.P., Lee K.D. 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. Vol. 187, N1-3. R. 279-286. doi: 10.1016/j.cbi.2010.02.042.


6. Genovese R.F., Sun W., Johnson C.C., Ditargiani R.C., Doctor B.P., Saxena A. Safety of administration of human butyrylcholinesterase and its conjugates with soman or VX in rats // Basic Clin. Pharmacol. Toxicol. 2010. Vol. 106, N5. R. 428-434. doi: 10.1111/j.1742-7843.2009.00508.x.


7. Maxwell D.M. Brecht K.M. Carboxylesterase: specificity and spontaneous reactivation of an endogenous scavenger for organophosphorus compounds // J. Appl. Toxicol. 2001. Vol. 21. R. 103-107. doi: 10.1002/jat.833.


8. Tsai P.C., Bigley A., Li Y., Ghanem E., Cadieux C.L., Kasten S.A., Reeves T.E., Cerasoli D.M., Raushel F.M. Stereoselective hydrolysis of organophosphate nerve agents by the bacterial phosphotriesterase // Biochemistry. 2010. Vol. 49, N37. R. 7978-7987. doi: 10.1021/bi101056m.


9. Ordentlich A., Barak D., Kronman C., Benschop H.P., De Jong L.P., Ariel N., Barak R., Segall Y., Velan B., Shafferman A. Exploring the active center of human acetylcholinesterase with stereomers of an organophosphorus inhibitor with two chiral centers // Biochemistry. 1999. Vol. 38, N10. R. 3055-3066. doi.org/10.1021/bi982261f.


10. Li B., Duysen E.G., Poluektova L.Y., Murrin L.C., Lockridge O. Protection from the toxicity of diisopropylfluorophosphate by adeno-associated virus expressing acetylcholinesterase // Toxicol. Appl. Pharmacol. 2006. Vol 214, N2. R. 152-165. doi: 10.1016/j.taap.2005.12.008.


11. Pang Z., Hu C.M., Fang R.H. [at al] Detoxification of Organophosphate Poisoning Using Nanoparticle Bioscavengers. // ACS Nano. 2015 Vol. 9, N6 P.6450-6458. doi: 10.1021/acsnano.5b02132.


12. Lockridge O., David E., Schopfer L.M., Masson P., Brazzolotto X., Nachon F. Purification of recombinant human butyrylcholinesterase on Hupresin? // J. Chromatogr. B. Analyt. Technol. Biomed. Life Sci. 2018. N1102-1103. R. 109-115. doi: 10.1016/j.jchromb.2018.10.026.


13. Masson P., Nachon F. Cholinesterase reactivators and bioscavengers for pre- and post-exposure treatments of organophosphorus poisoning // J Neurochem. 2017. Vol. 142, N2. R. 26-40. doi: 10.1111/jnc.14026.


14. Goldenzweig A., Goldsmith M., Hill S.E., Gertman O., Laurino P., Ashani Y., Dym O., Unger T., Albeck S., Prilusky J., Lieberman R.L., Aharoni A., Silman I., Sussman J.L., Tawfik D.S., Fleishman S.J. Automated structure- and sequence-based design of proteins for high bacterial expression and stability // Mol. Cell. 2016. Vol. 63, N2. R. 337-346. doi: 10.1016/j.molcel.2016.06.012.


15. Terekhov S.S., Smirnov I.V., Shamborant O.G., Bobik T.V., Ilyushin D.G., Murashev A.N., Dyachenko I.A., Palikov V.A., Knorre V.D., Belogurov A.A., Ponomarenko N.A., Kuzina E.S., Genkin D.D., Masson P., Gabibov A.G. Chemical polysialylation and in vivo tetramerization improve pharmacokinetic characteristics of recombinant human butyrylcholinesterase-based bioscavengers // Acta Naturae. 2015. Vol.7, N4. R. 136-141. doi: 10.32607/20758251-2015-7-4-136-141.


16. Parikh K., Duysen E.G., Snow B., Jensen N.S., Manne V., Lockridge O., Chilukuri N. Gene-delivered butyrylcholinesterase is prophylactic against the toxicity of chemical warfare nerve agents and organophosphorus compounds // J. Pharmacol. Exp. Ther. 2011. Vol. 337, N1. R. 92-101. doi: 10.1124/jpet.110.175646.


17. Tretiakova A. Engineering AAV vector for the delivery of human bChE to protect against exposure to organophosphates // 20th Biennial USA Medical Defense Bioscience Review. 2016. R. 87.


18. Rosenberg Y.J., Adams R.J., Hernandez-Abanto S., Jiang X., Sun W., Mao L., Lee K.D. Pharmacokinetics and immunogenicity of a recombinant human butyrylcholinesterase bioscavenger in macaques following intravenous and pulmonary delivery // Chem. Biol. Interact. 2015. N242. R. 219-226. doi: 10.1016/j.cbi.2015.09.021


19. Myers T.M. Human plasma-derived butyrylcholinesterase is behaviorally safe and effective in cynomolgus macaques (Macaca fascicularis) challenged


20. Saxena A., Sun W., Fedorko J.M., Koplovitz I., Doctor B.P. Prophylaxis with human serum butyrylcholinesterase protects guinea pigs exposed to multiple lethal doses of soman or VX // Biochem. Pharmacol. 2011. Vol. 81, N1. R. 164-169. doi: 10.1016/j.bcp.2010.09.007.


21. 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. Vol. 77, N2. R. 358-367. doi: 10.1093/toxsci/kfh012.


22. Rosenberg Y.J., James B. Creation of a protective pulmonary bioshield against inhaled organophosphates using an aerosolized bioscavenger // Ann. N. Y. Acad. Sci. 2016. Vol. 1374, N1. R. 151-158. doi: 10.1111/nyas.13106.


23. Rosenberg Y.J., Laube B., Mao L., Jiang X., Hernandez-Abanto S., Lee K.D., Adams R. Pulmonary delivery of an aerosolized recombinant butyrylcholinesterase pretreatment protects against aerosolized paraoxon in macaques // Chem. Biol. Interact. 2013. Vol. 203, N1. R. 167-171. doi: 10.1016/j.cbi.2012.11.004.


24. Amitai G., Gez R., Raveh L., Bar-Ner N., Grauer E., Chapman S. Novel bifunctional hybrid small molecule scavengers for mitigating nerve agents toxicity // Chem. Biol. Interact. 2016. Vol. 259. R. 187-204. doi: 10.1016/j.cbi.2016.04.036.


25. Ashani Y., Leader H., Aggarwal N., Silman I., Worek F., Sussman J.L., Goldsmith M. In vitro evaluation of the catalytic activity of paraoxonases and phosphotriesterases predicts the enzyme circulatory levels required for in vivo protection against organophosphate intoxications // Chem. Biol. Interact. 2016. N259. R. 252-256. doi: 10.1016/j.cbi.2016.04.039.


26. Jacquet P., Daudé D., Bzdrenga J., Masson P., Elias M., Chabrière E. Current and emerging strategies for organophosphate decontamination: special focus on hyperstable enzymes // Environ. Sci. Pollut. Res. Int. 2016. Vol. 23, N9. R. 8200-8218. doi: 10.1007/s11356-016-6143-1.


27. 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. N12. R. 204-228. doi: 10.3762/bjoc.12.23.


28. Desire B., Saint-Andre S. Interaction of soman with beta-cyclodextrin // Fundam Appl Toxicol. 1986. Vol. 7, N4. P. 646-657. doi.org/10.1016/0272-0590(86)90114-4.


29. Letort S., Mathiron D, Grel T, Albaret C, Daulon S, Djedaïni-Pilard F, Gouhier G, Estour F. The first 2(IB),3(IA)-heterodifunctionalized β-cyclodextrin derivatives as artificial enzymes // Chem Commun (Camb). 2015. Vol. 51, N13. P. 2601-2604. doi: 10.1039/c4cc09189b.


30. Cabal J., Kuca K., Sevelova-Bartosova L., Dohnal V. Cyclodextrines as functional agents for decontamination of the skin contaminated by nerve agents // Acta Medica (Hradec Kralove). 2004. Vol. 47, N2. P. 115-118. doi: 10.14712/18059694.2018.75


31. Wille T., Tenberken O., Reiter G., Müller S., Le Provost R., Lafont O., Estour F., Thiermann H., Worek F. Detoxification of nerve agents by a substituted beta-cyclodextrin: application of a modified biological assay // Toxicology. 2009. Vol. 265, N3. P. 96 -100. doi: 10.1016/j.tox.2009.09.018.


32. Schneider C., Bierwisch A., Koller M., Worek F., Kubik S. Detoxification of VX and Other V-Type Nerve Agents in Water at 37 ?C and pH 7.4 by Substituted Sulfonatocalix[4]arenes // Angew Chem Int Ed Engl. 2016. Vol. 55, N 41. P. 12668-12672. doi: 10.1002/anie.201606881.


33. 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. N259. R. 148-153. doi: 10.1016/j.cbi.2016.04.023.


34. Masson P., Rochu D. Catalytic bioscavengers against toxic esters, an alternative approach for prophylaxis and treatments of poisonings // Acta Naturae. 2009. Vol. 1, N1. R. 68-79. doi: 10.32607/20758251-2009-1-1-68-78.


35. Kovarik Z., Maček Hrvat N., Katalinić M., Sit R.K., Paradyse A., Žunec S., Musilek K., Fokin V.V., Taylor P., Radić Z. Catalytic soman scavenging by the Y337A/F338A acetylcholinesterase mutant assisted with novel site-directed aldoximes // Chem. Res. Toxicol. 2015. Vol. 28, N5. R. 1036-1044. doi: 10.1021/acs.chemrestox.5b00060.


36. Hatfield M.J., Umans R.A., Hyatt J.L., Edwards C.C., Wierdl M., Tsurkan L., Taylor M.R., Potter P.M.Carboxylesterases: general detoxifying enzymes/ / Chem. Biol. Interact. 2016. N259. R. 327-331. doi: 10.1016/j.cbi.2016.02.011.


37. Huang Y.J., Lundy P.M., Lazaris A., Huang Y., Baldassarre H., Wang B., Turcotte C., Côté M., Bellemare A., Bilodeau A.S., Brouillard S., Touati M., Herskovits P., Bégin I., Neveu N., Brochu E., Pierson J., Hockley D.K., Cerasoli D.M., Lenz D.E., Wilgus H., Karatzas C.N., Langermann S. Substantially improved pharmacokinetics of recombinant human butyrylcholinesterase by fusion to human serum albumin // BMC Biotechnol. 2008. N8. R. 50. doi: 10.1186/1472-6750-8-50.


38. Razgildina N.D., Miroshnikova V.V., Fomichev A.V., Malisheva E.V., Panteleeva A.A., Pchelina S.N. Issledovanie aktivnosti paraoksonazi 1 y rabotnikov predpriyatii, dlitelno kontaktiryushih s fosfororganicheskimi soedineniyami // Ekologicheskaya genetika. 2017. T.15, N1. S. 57-63. doi: 10.17816/ecogen15157-63.


39. Valiyaveettil M., Alamneh Y., Rezk P., Biggemann L., Perkins M.W., Sciuto A.M., Doctor B.P., Nambiar M.P. Protective efficacy of catalytic bioscavenger, paraoxonase 1 against sarin and soman exposure in guinea pigs // Biochem. Pharmacol. 2011. Vol. 81, N6. R. 800-809. doi: 10.1016/j.bcp.2010.12.024.


40. Worek F., Seeger T. Goldsmith M. Ashani Y., Leader H., Sussman J.S., Tawfik D., Thiermann H., Wille T. Efficacy of the rePON1 mutant IIG1 to prevent cyclosarin toxicity in vivo and to detoxify structurally different nerve agents in vitro // Arch. Toxicol. 2014. Vol. 88, N6. R. 1257-1266. doi: 10.1007/s00204-014-1204-z.


41. Renault F., Carus T., Cléry-Barraud C., Elias M., Chabrière E., Masson P., Rochu D. Integrative analytical approach by capillary electrophoresis and kinetics under high pressure optimized for deciphering intrinsic and extrinsic cofactors that modulate activity and stability of human paraoxonase (PON1) // J. Chromatogr. B Analyt. Technol. Biomed. Life Sci. 2010. Vol. 878, N17-18. R. 1346-1355. doi: 10.1016/j.jchromb.2009.11.027.


42. Bajaj P., Tripathy R.K., Aggarwal G., Datusalia A.K., Sharma S.S., Pande A.H. Refolded recombinant human paraoxonase 1 variant exhibits prophylactic activity against organophosphate poisoning // Appl. Biochem. Biotechnol. 2016. Vol. 180, N1. R. 165-176. doi: 10.1007/s12010-016-2091-y.


43. Boado R.J., Hui E.K., Lu J.Z., Pardridge W.M. CHO cell expression, long-term stability, and primate pharmacokinetics and brain uptake of an IgG-paroxonase-1 fusion protein // Biotechnol. Bioeng. 2011. Vol. 108, N1. R. 186-196. doi: 10.1002/bit.22907.


44. Han Z.K., Liu Z.N., Yuan L., Zhang P.S., Zhao M. Preparation of paraoxonase-1 liposomes and studies on their in vivo pharmacokinetics in rats // Clin. Exp. Pharmacol. Physiol. 2014. Vol. 41, N10. R. 825-829. doi: 10.1111/1440-1681.12275.


45. Duysen E.G., Parikh K., Aleti V., Manne V., Lockridge O., Chilukuri N. Adenovirus-mediated human paraoxonase1 gene transfer to provide protection against the toxicity of the organophosphorus pesticide toxicant diazoxon // Gene Ther. 2011. Vol. 18, N3. R. 250-257. doi: 10.1038/gt.2010.136.


46. Kirby S.D., Norris J., Sweeney R., Bahnson B.J., Cerasoli D.M. A rationally designed mutant of plasma platelet-activating factor acetylhydrolase hydrolyzes the organophosphorus nerve agent soman // Biochim. Biophys. Acta. 2015. Vol. 1854, N12. R. 1809-1815. doi: 10.1016/j.bbapap.2015.09.001.


47. Ghanem E., Raushel F.M. Detoxification of organophosphate nerve agents by bacterial phosphotriesterase // Toxicol. Appl. Pharmacol. 2005. N207. R. 459-470. doi.org/10.1016/j.taap.2005.02.025.


48. Masson P. Catalytic bioscavengers: the new generation of bioscavenger-based medical countermeasure // Handbook of Toxicology of Chemical Warfare Agents. 2015. R. 1107-1123. doi: 10.1016/B978-0-12-800159-2.00075-0.


49. Bigley A.N., Mabanglo M.F., Harvey S.P., Raushel F.M. Variants of phosphotriesterase for the enhanced detoxification of the chemical warfare agent VR // Biochemistry. 2015. Vol. 54, N35. R. 5502-5512. doi: 10.1021/acs.biochem.5b00629.


50. Goldsmith M., Eckstein S., Ashani Y., Greisen P.Jr., Leader H., Sussman J.L., Aggarwal N., Ovchinnikov S., Tawfik D.S., Baker D., Thiermann H., Worek F.. Catalytic efficiencies of directly evolved phosphotriesterase variants with structurally different organophosphorus compounds in vitro // Arch. Toxicol. 2016. Vol. 90, N11. R. 2711-2724. doi: 10.1007/s00204-015-1626-2.


51. Worek F., Seeger T., Reiter G., Goldsmith M., Ashani Y., Leader H., Sussman J.L., Aggarwal N., Thiermann H., Tawfik D.S. Post-exposure treatment of VX poisoned guinea pigs with the engineered phosphotriesterase mutant C23: a proof-of-concept study // Toxicol. Lett. 2014. Vol. 231, N1. R. 45-54. doi: 10.1016/j.toxlet.2014.09.003.


52. Wille T., Neumaier K., Koller M., Ehinger C., Aggarwal N., Ashani Y., Goldsmith M., Sussman J.L., Tawfik D.S., Thiermann H., Worek F. Single treatment of VX poisoned guinea pigs with the phosphotriesterase mutant C23AL: intraosseous versus intravenous injection // Toxicol. Lett. 2016. N258. R. 198-206. doi: 10.1016/j.toxlet.2016.07.004.


53. Del Giudice I., Coppolecchia R., Merone L., Porzio E., Carusone T.M., Mandrich L., Worek F., Manco G. An efficient thermostable organophosphate hydrolase and its application in pesticide decontamination // Biotechnol. Bioeng. 2016. Vol. 113, N4. R. 724-734. doi: 10.1002/bit.25843.


54. Gotthard G., Hiblot J., Gonzalez D., Chabrière E., Elias M. Crystallization and preliminary X-ray diffraction analysis of the organophosphorus hydrolase OPHC2 from Pseudomonas pseudoalcaligenes // Acta Crystallogr. Sect. F. Struct. Biol. Cryst. Commun. 2013. N69. R. 73-76. doi: 10.1107/S174430911205049X.


55. Hiblot J., Gotthard G., Chabriere E., Elias M. Characterisation of the organophosphate hydrolase catalytic activity of SsoPox // Sci. Rep. 2012. N2. R. 779. doi: 10.1038/srep00779.


56. Hiblot J., Bzdrenga J., Champion C., Chabriere E., Elias M. Crystal structure of VmoLac, a tentative quorum quenching lactonase from the extremophilic crenarchaeon Vulcanisaeta moutnovskia // Sci. Rep. 2015. N5. R. 8372. doi: 10.1038/srep08372.


57. Pang Z., Hu C.M., Fang R.H., Luk B.T., Gao W., Wang F., Chuluun E., Angsantikul P., Thamphiwatana S., Lu W., Jiang X., Zhang L. Detoxification of organophosphate poisoning using nanoparticle bioscavengers // ACS Nano. 2015. Vol. 9, N6. R. 6450-6458. doi: 10.1021/acsnano.5b02132.


58. Szilasi M1, Budai M, Budai L, Petrikovics I. Nanoencapsulated and microencapsulated enzymes in drug antidotal therapy // Toxicol. Ind. Health. 2012. Vol. 28, N6. R. 522-531. doi: 10.1177/0748233711416946.


59. Trovaslet-Leroy M., Musilova L., Renault F., Brazzolotto X., Misik J., Novotny L., Froment M.T., Gillon E., Loiodice M., Verdier L., Masson P., Rochu D., Jun D., Nachon F. Organophosphate hydrolases as catalytic bioscavengers of organophosphorus nerve agents // Toxicol. Lett. 2011. Vol. 206, N1. R. 14-23. doi: 10.1016/j.toxlet.2011.05.1041.


60. Smirnov I., Belogurov A.Jr., Friboulet A., Masson P., Gabibov A., Renard P.Y. Strategies for the selection of catalytic antibodies against organophosphorus nerve agents // Chem. Biol. Interact. 2013. Vol. 203, N1. R. 196-201. doi: 10.1016/j.cbi.2012.10.011.


61. Braid L.R., Wood C.A., Ford B.N. Human umbilical cord perivascular cells: A novel source of the organophosphate antidote butyrylcholinesterase. // Chem Biol Interact. 2019 May 25;305:66-78. doi: 10.1016/j.cbi.2019.03.022.


62. Filatov B.N. Mediko-sanitarnie problemi ynichtojeniya himicheskogo oryjiya // Toksikologicheskii vestnik. 2007. N3. S. 2 - 6.