Iyengar A R Satvik, Pande Abhay H
School of Biomedical Sciences and Pharmacy, The University of Newcastle, Callaghan, 2308 NSW, Australia.
Department of Biotechnology, National Institute of Pharmaceutical Education and Research (NIPER), Mohali, Punjab, India.
Protein Pept Lett. 2019;26(7):471-478. doi: 10.2174/0929866526666190403120259.
Nerve agents have been used extensively in chemical warfare in the past. However, recent use of Novichok agents have reignited the debate on the threat posed by Organophosphorus Nerve Agents (OPNAs). The currently available therapy for OPNA toxicity is only symptomatic and is potentially ineffective in neutralizing OPNAs. Hence, there is a dire need to develop a prophylactic therapy for counteracting OPNA toxicity. In this regard, human paraoxonase 1 has emerged as the enzyme of choice. In this review, we have focussed upon the recent and past events of OPNA use, their mechanism of action and toxicity. Further, we have emphasized upon the potential of enzyme based therapy and the various advances in the development of paraoxonase 1 as a countermeasure for OPNA poisoning. Finally, we have elaborated the shortcomings of paraoxonase 1 and the work that needs to be undertaken in order to develop human paraoxonase 1 as a prophylactic against OPNA poisoning.
过去，神经毒剂在化学战中被广泛使用。然而，最近诺维乔克毒剂的使用再次引发了关于有机磷神经毒剂（OPNAs）所构成威胁的辩论。目前针对OPNA中毒的治疗方法仅为对症治疗，在中和OPNAs方面可能无效。因此，迫切需要开发一种预防性疗法来对抗OPNA中毒。在这方面，人对氧磷酶1已成为首选酶。在本综述中，我们重点关注了OPNA使用的近期和过往事件、它们的作用机制和毒性。此外，我们强调了基于酶的疗法的潜力以及将对氧磷酶1开发为对抗OPNA中毒对策的各种进展。最后，我们阐述了对氧磷酶1的缺点以及为将人对氧磷酶1开发为预防OPNA中毒的药物而需要开展的工作。
