Accelerating countermeasure candidate discovery for A- series chemical warfare agent exposure

• 成果类型: Article
• 署名作者: Morato, Nicolas M.; Mason, Katelyn E.; Corzett, Todd H.; Valdez, Carlos A.; Alfaro, Teneile M.; Hok, Saphon; Cooks, R. Graham; Mayer, Brian P.
• 署名单位: Purdue University System; Purdue University; United States Department of Energy (DOE); Lawrence Livermore National Laboratory; Purdue University System; Purdue University
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-9625
• DOI: 10.1073/pnas.2512471122
• 发表日期: 2025-07-22
• 关键词: ionization-mass-spectrometry; toxic organophosphorus compounds; acting oxime reactivators; human acetylcholinesterase; in-vitro; pyridinium oximes; kinetic-analysis; inhibited human; aging kinetics; electric-eel

摘要

The recent alleged use of A- series chemical warfare agents (CWAs) highlights the urgent need to better understand their inhibition of cholinesterase enzymes and the reported shortcomings of traditional oxime countermeasures. Here, using high- throughput (HT) mass spectrometry (MS) technologies, we characterized the largely unknown inhibition tion by oximes, achieving label- free quantitation at rates of up to 7,000 reactions per hour. Our findings indicate i) A- series agents exhibit inhibitory potencies similar to traditional CWAs like sarin and VX, and ii) bipyridinium- based oximes can reactivate results underscore the need for continued exploration of countermeasure candidates against A- series CWAs and demonstrate the potential of HT- MS for rapidly and safely characterizing emerging toxic chemicals.