Advancements in bioscavenger mediated detoxification of organophosphorus poisoning

Author:

Li Hexi12ORCID,Lu Cong13ORCID,Liu Zhenmin1ORCID,Xiang Fengshun1ORCID,Liu Bo1,Wang Hongjuan1ORCID,Chang Jie1ORCID,Pan Li4ORCID,Chen Youwei1ORCID,Chen Jingfei15ORCID

Affiliation:

1. Institute of NBC Defence, PLA, ARMY , 1 North Street, Yangfang Town, Changping District, Beijing 102205 , China

2. Unit No. 31666 of PLA , 1 New City Courtyard, Jinyang Town, Liangzhou District, Wuwei, Gansu 733000 , China

3. Unit No. 94347 of PLA , 24 Wenfu Road, Shenhe District, Shenyang, Liaoning 110000 , China

4. State Key Laboratory of NBC Protection for Civilians , 30 South Central Street, Yangfang Town, Changping District, Beijing 102205 , P. R. China

5. Unit No. 32169 of PLA , 100 Shuangyong East Road, Nyingchi, Tibet 860000 , China

Abstract

Abstract Background Organophosphorus compounds, widely used in agriculture and industry, pose a serious threat to human health due to their acute neurotoxicity. Although traditional interventions for organophosphate poisoning are effective, they often come with significant side effects. Objective This paper aims to evaluate the potential of enzymes within biological organisms as organophosphorus bioclearing agents. It analyses the technical challenges in current enzyme research, such as substrate specificity, stereoselectivity, and immunogenicity, while exploring recent advancements in the field. Methods A comprehensive review of literature related to detoxifying enzymes or proteins was conducted. Existing studies on organophosphorus bioclearing agents were summarised, elucidating the biological detoxification mechanisms, with a particular focus on advancements in protein engineering and novel delivery methods. Results Current bioclearing agents can be categorised into stoichiometric and catalytic bioclearing agents, both of which have shown some success in preventing organophosphate poisoning. Technological advancements have significantly improved various properties of bioclearing agents, yet challenges remain, particularly in substrate specificity, stereoselectivity, and immunogenicity. Future research will focus on expanding the substrate spectrum, enhancing catalytic efficiency, prolonging in vivo half-life, and developing convenient administration methods. Conclusion With the progression of clinical trials, bioclearing agents are expected to become widely used as a new generation of therapeutic organophosphate detoxifiers.

Funder

Youth Independent Scientific Innovation Fund Program

Publisher

Oxford University Press (OUP)

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