Novichok is an organophosphate compound found as a nerve agent chemical weapon. However, the information about its chemical properties, biological activities, and molecular interactions in the body are still protected under the “top secret” security clearance. Novichok, with the codes A230, A232 and A234, is a compound whose structure has been successfully determined. The compound is synthesized from a precursor through a nucleophilic substitution reaction. Novichok agents are considered more potent than VX gas and can be applied in unitary and binary forms. This compound has ability for the binding with acetylcholinesterase (AChE) due to inability of acetylcholine metabolism. AChE catalyzes the rapid hydrolysis of acetylcholine to acetate and choline. The treatment of Novichok agent poisoning is similar to management of other nerve agents, such as atropine and pralidoxime administered intravenously. In this paper, we reviewed the Novichok component from chemical and biological perspective. Moreover, we discussed the potential molecular interaction and treatment of this compound.
An, Y., Zhu, Y., Yao, Y., & Liu, J. (2016). Is it possible to reverse aged acetylcholinesterase inhibited by organophosphorus compounds? Insight from the theoretical study. Physical Chemistry Chemical Physics : PCCP, 18(14), 9838–9846. https://doi.org/10.1039/c5cp07991h
Bajracharya, S. R., Prasad, P. N., & Ghimire, R. (2016). Management of Organophosphorus Poisoning. Journal of Nepal Health Research Council, 14(34), 131–138.
Bajgar, J., Bartosova, L., Kuca, K., Jun, D., & Fusek, J. (2007). Changes of cholinesterase activities in the rat blood and brain after sarin intoxication pretreated with butyrylcholinesterase. Drug and Chemical Toxicology, 30(4), 351–359. https://doi.org/10.1080/01480540701522395
Bhakhoa, H., Rhyman, L., & Ramasami, P. (2019). Theoretical study of the molecular aspect of the suspected novichok agent A234 of the Skripal poisoning. Royal Society Open Science, 6(2), 181831. https://doi.org/10.1098/rsos.181831
Bird, S. B., Gaspari, R. J., Lee, W. J., & Dickson, E. W. (2002). Diphenhydramine as a protective agent in a rat model of acute, lethal organophosphate poisoning. Academic Emergency Medicine, 9(12), 1369–1372. https://doi.org/10.1111/j.1553-2712.2002.tb01604.x
Broomfield, C. A., & Kirby, S. D. (2001). Progress on the road to new nerve agent treatments. Journal of Applied Toxicology, 21 Suppl 1, S43–S46. https://doi.org/10.1002/jat.804
Brooks, J., Erickson, T. B., Kayden, S., Ruiz, R., Wilkinson, S., & Burkle, F. M., Jr (2018). Responding to chemical weapons violations in Syria: legal, health, and humanitarian recommendations. Conflict and Health, 12, 12. https://doi.org/10.1186/s13031-018-0143-3
Carlsen L. (2019). After Salisbury Nerve Agents Revisited. Molecular Informatics, 38(8-9), e1800106. https://doi.org/10.1002/minf.201800106
Cerasoli, D. M., Armstrong, S. J., Reeves, T. E., Hodgins, S. M., Kasten, S. A., Lee-Stubbs, R. B., Cadieux, C. L., Otto, T. C., Capacio, B. R., & Lenz, D. E. (2020). Butyrylcholinesterase, a stereospecific in vivo bioscavenger against nerve agent intoxication. Biochemical Pharmacology, 171, 113670. https://doi.org/10.1016/j.bcp.2019.113670
Chai, P. R., Hayes, B. D., Erickson, T. B., & Boyer, E. W. (2018). Novichok agents: a historical, current, and toxicological perspective. Toxicology Communications, 2(1), 45–48. https://doi.org/10.1080/24734306.2018.1475151
Colović, M. B., Krstić, D. Z., Lazarević-Pašti, T. D., Bondžić, A. M., & Vasić, V. M. (2013). Acetylcholinesterase inhibitors: pharmacology and toxicology. Current Neuropharmacology, 11(3), 315–335. https://doi.org/10.2174/1570159X11311030006
DeClementi, C. (2007). Veterinary Toxicology: Basic and Clinical. 1st Edition. Academic Press
Eisenkraft, A., & Falk, A. (2016). The possible role of intravenous lipid emulsion in the treatment of chemical warfare agent poisoning. Toxicology Reports, 3, 202–210. https://doi.org/10.1016/j.toxrep.2015.12.007
Ellison, D.H. (2016). Emergency Action for Chemical and Biological Warfare Agents. 2nd Edition. CRC Press.
Eyer, P. (2003). The role of oximes in the management of organophosphorus pesticide poisoning. Toxicological Reviews, 22(3), 165–190. https://doi.org/10.2165/00139709-200322030-00004
Franca, T., Kitagawa, D., Cavalcante, S., da Silva, J., Nepovimova, E., & Kuca, K. (2019). Novichoks: The dangerous fourth generation of chemical weapons. International Journal of Molecular Sciences, 20(5), 1222. https://doi.org/10.3390/ijms20051222
Gupta, R.C. (2015). Handbook of Toxicology of Chemical Warfare Agents. Academic Press.
Halámek, E., Kobliha, Z. (2011). Potential Chemical Warfare Agents. Chemicke Listy. 105, 323–333.
Hamachi. A., Imasaka, T., Imasaka, T. (2016). Femtosecond ionization mass spectrometry: an advanced tool for the analysis of pollutants, explosives, and nerve agents. 13th Asian Conference on Analytical Sciences. (pp46) Chiang Mai, Thailand
Hoenig, S.L. (2007). Compendium of Chemical Warfare Agents. New York: Springer-Verlag.
Jeong, K., Choi, J. (2019). Theoretical study on the toxicity of ‘Novichok’ agent candidates. Royal Society Open Science , 6: 190414.
Khan, M. A., Lo, R., Bandyopadhyay, T., & Ganguly, B. (2011). Probing the reactivation process of sarin-inhibited acetylcholinesterase with α-nucleophiles: hydroxylamine anion is predicted to be a better antidote with DFT calculations. Journal of Molecular Graphics & Modelling, 29(8), 1039–1046. https://doi.org/10.1016/j.jmgm.2011.04.009
Korabecny, J., Soukup, O., Dolezal, R., Spilovska, K., Nepovimova, E., Andrs, M., Nguyen, T. D., Jun, D., Musilek, K., Kucerova-Chlupacova, M., & Kuca, K. (2014). From pyridinium-based to centrally active acetylcholinesterase reactivators. Mini Reviews in Medicinal Chemistry, 14(3), 215–221. https://doi.org/10.2174/1389557514666140219103138
Masson, P., & Nachon, F. (2017). Cholinesterase reactivators and bioscavengers for pre- and post-exposure treatments of organophosphorus poisoning. Journal of Neurochemistry, 142 Suppl 2, 26–40. https://doi.org/10.1111/jnc.14026
Mirzayanov, V.S. (2009). State Secrets: An Insider’s Chronicle of the Russian Chemical Weapons Program. Outskirts Press, Incorporated.
Myers T. M. (2019). Human plasma-derived butyrylcholinesterase is behaviorally safe and effective in cynomolgus macaques (Macaca fascicularis) challenged with soman. Chemico-Biological Interactions, 308, 170–178. https://doi.org/10.1016/j.cbi.2019.05.021
Nepovimova, E., & Kuca, K. (2018). Chemical warfare agent NOVICHOK - mini-review of available data. Food and Chemical Toxicology, 121, 343–350. https://doi.org/10.1016/j.fct.2018.09.015
Raveh, L., Grauer, E., Grunwald, J., Cohen, E., & Ashani, Y. (1997). The stoichiometry of protection against soman and VX toxicity in monkeys pretreated with human butyrylcholinesterase. Toxicology and Applied Pharmacology, 145(1), 43–53. https://doi.org/10.1006/taap.1997.8160
Smithson, A.E., Mirzayanov, V.S., Lajoie, R., et al. (1995). Chemical weapons disarmament in Russia: Problems and prospects. Washington, DC: The Stimson Center. 1–83.
Szinicz, L. (2005). History of chemical and biological warfare agents. Toxicology, 214(3), 167–181
Vale, J. A., Marrs, T. C., OBE, & Maynard, R. L., CBE (2018). Novichok: a murderous nerve agent attack in the UK. Clinical Toxicology, 56(11), 1093–1097. https://doi.org/10.1080/15563650.2018.1469759
Wang, J., Gu, J., Leszczynski, J. (2006). Phosphonylation mechanisms of sarin and acetylcholinesterase: a model DFT study. The Journal of Physical Chemistry B, 110, 7567 – 7573.
Wang, J., Pumera, M., Chatrathi, M. P., Escarpa, A., Musameh, M., Collins, G., Mulchandani, A., Lin, Y., & Olsen, K. (2002). Single-channel microchip for fast screening and detailed identification of nitroaromatic explosives or organophosphate nerve agents. Analytical Chemistry, 74(5), 1187–1191.
Zhang, L., Murata, H., Amitai, G., Smith, P. N., Matyjaszewski, K., & Russell, A. J. (2020). Catalytic Detoxification of Organophosphorus Nerve Agents by Butyrylcholinesterase-Polymer-Oxime Bioscavengers. Biomacromolecules, 21(9), 3867–3877. https://doi.org/10.1021/acs.biomac.0c00959
Rahmania, Tesia Aisyah; Wardhani, Bantari Wisynu Kusuma; Renesteen, Editha; and Harahap, Yahdiana
"Chemical Properties, Biological Activities and Poisoning Treatment of Novichok: A Review,"
Pharmaceutical Sciences and Research: Vol. 8
, Article 2.
Available at: https://scholarhub.ui.ac.id/psr/vol8/iss2/2