Nerve agents are a class of lethal neurotoxic chemicals used in chemical warfare. In
this review, we have briefly discussed a brief history of chemical warfare, followed by an exploration
of the historical context surrounding nerve agents. The article explores the classification of these
agents, their contemporary uses, their toxicity mechanisms, and the disadvantages of the current
treatment options for nerve agent poisoning. It then discusses the possible application of enzymes
as prophylactics against nerve agent poisoning, outlining the benefits and drawbacks of
paraoxonase-1. Finally, the current studies on paraoxonase-1 are reviewed, highlighting that several
challenges need to be addressed in the use of paraoxonase-1 in the actual field and that its potential
as a prophylactic antidote against nerve agent poisoning needs to be evaluated. The literature
used in this manuscript was searched using various electronic databases, such as PubMed, Google
Scholar, Web of Science, Elsevier, Springer, ACS, Google Patent, and books using the keywords
chemical warfare agent, Butyrylcholinesterase, enzyme, nerve agent, prophylactic, and paraoxonase-
1, with the time scale for the analysis of articles between 1960 to 2023, respectively. The
study has suggested that concerted efforts by researchers and agencies must be made to develop effective
countermeasures against NA poisoning and that PON1 has suitable properties for the development
of efficient prophylaxis against NA poisoning.