Evidence map›Paper›PMID 40752825›Full record

ArticleChemico-biological interactions2025

A cocaine hydrolase engineered from human butyrylcholinesterase as a medical countermeasure for aldicarb poisoning.

Johnathan E LeSaint, Nellore Bhanu Chandar, Annet Kyomuhangi, Huimei Wei, Fang Zheng, Chang-Guo Zhan

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Chemico-biological interactions, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

6 authors.

Johnathan E LeSaintMolecular Modeling and Biopharmaceutical Center, College of Pharmacy, University of Kentucky, 789 South Limestone Street, Lexington, KY, 40536, USA; Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, 789 South Limestone Street, Lexington, KY, 40536, USA.
Nellore Bhanu ChandarMolecular Modeling and Biopharmaceutical Center, College of Pharmacy, University of Kentucky, 789 South Limestone Street, Lexington, KY, 40536, USA; Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, 789 South Limestone Street, Lexington, KY, 40536, USA.
Annet KyomuhangiMolecular Modeling and Biopharmaceutical Center, College of Pharmacy, University of Kentucky, 789 South Limestone Street, Lexington, KY, 40536, USA; Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, 789 South Limestone Street, Lexington, KY, 40536, USA.
Huimei WeiMolecular Modeling and Biopharmaceutical Center, College of Pharmacy, University of Kentucky, 789 South Limestone Street, Lexington, KY, 40536, USA; Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, 789 South Limestone Street, Lexington, KY, 40536, USA.
Fang ZhengMolecular Modeling and Biopharmaceutical Center, College of Pharmacy, University of Kentucky, 789 South Limestone Street, Lexington, KY, 40536, USA; Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, 789 South Limestone Street, Lexington, KY, 40536, USA. Electronic address: fzhen2@uky.edu.
Chang-Guo ZhanMolecular Modeling and Biopharmaceutical Center, College of Pharmacy, University of Kentucky, 789 South Limestone Street, Lexington, KY, 40536, USA; Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, 789 South Limestone Street, Lexington, KY, 40536, USA. Electronic address: zhan@uky.edu.

Funding

Development of a Long-acting Enzyme Therapy for Treatment of Cocaine AbuseU01DA051079 · NIDA · UNIVERSITY OF KENTUCKY · PI ZHAN, CHANG-GUO · 2020 to 2022
$11.8M
Development of Long-acting Cocaine Hydrolase as a Treatment for Cocaine AbuseUH3DA041115 · NIDA · UNIVERSITY OF KENTUCKY · PI ZHAN, CHANG-GUO · 2017 to 2019
$3.8M
Long-lasting cocaine-metabolizing enzyme for cocaine addiction treatmentR01DA035552 · NIDA · UNIVERSITY OF KENTUCKY · PI ZHAN, CHANG-GUO · 2013 to 2015
$3.4M
Redesign of Butyrylcholinesterase for Cocaine MetabolismR01DA013930 · NIDA · UNIVERSITY OF KENTUCKY · PI ZHAN, CHANG-GUO · 2003 to 2010
$2.4M
Ghrelin Deacylase as a Treatment for Opioid Polysubstance AbuseR01DA056646 · NIDA · UNIVERSITY OF KENTUCKY · PI ZHAN, CHANG-GUO, ZHENG, FANG · 2022 to 2025
$2.2M
Development of Long-acting Cocaine Hydrolase as a Treatment for Cocaine AbuseUH2DA041115 · NIDA · UNIVERSITY OF KENTUCKY · PI ZHAN, CHANG-GUO · 2015 to 2016
$2.2M
Development of a Cocaine-Metabolizing Enzyme for Drug Overdose TreatmentR01DA032910 · NIDA · UNIVERSITY OF KENTUCKY · PI ZHAN, CHANG-GUO · 2012 to 2015
$1.8M
Long-acting aldicarb hydrolase as a medical countermeasure for aldicarb poisoningUH3NS134920 · NINDS · UNIVERSITY OF KENTUCKY · PI CHANG-GUO ZHAN, Fang Zheng · 2025 to 2026
$1.3M
Long-acting aldicarb hydrolase as a medical countermeasure for aldicarb poisoningUG3NS134920 · NINDS · UNIVERSITY OF KENTUCKY · PI ZHAN, CHANG-GUO, ZHENG, FANG · 2023 to 2024
$1.1M
Validation of ghrelin hydrolysis as an effective approach to treatment of substance use disordersU18DA052319 · NIDA · UNIVERSITY OF KENTUCKY · PI ZHENG, FANG · 2020 to 2020
$230k
NIDA NIH HHS R01 DA013930NIDA NIH HHS R01 DA032910NIDA NIH HHS R01 DA035552NIDA NIH HHS R01 DA056646NIDA NIH HHS U01 DA051079NIDA NIH HHS U18 DA052319NIDA NIH HHS UH2 DA041115NIDA NIH HHS UH3 DA041115NINDS NIH HHS UG3 NS134920NINDS NIH HHS UH3 NS134920
6 · The paper itself

Abstract

Aldicarb is known to be the most toxic carbamate pesticide and could be used easily by terrorists to cause a mass casualty incident. It is highly desired to discover a medical countermeasure for aldicarb poisoning. Based on structural insights from molecular modeling and in vitro experimental validation, CocH3-Fc(M3), a potent cocaine hydrolase engineered from human butyrylcholinesterase (BChE), has a ∼4-fold improved binding affinity with aldicarb compared to wild-type human acetylcholinesterase (AChE) and BChE and a 9-28-fold improved bimolecular rate constant for the carbamylation with aldicarb compared to AChE. CocH3-Fc(M3) also has significant catalytic activity for aldicarb hydrolysis and, hence, is identified as an aldicarb hydrolase. To the best of our knowledge, this is the first aldicarb hydrolase identified so far. Due to significant catalytic activity against aldicarb, CocH3-Fc(M3) effectively and dose-dependently rescued all mice that had been injected with a lethal dose of aldicarb, demonstrating the promise of CocH3-Fc(M3) as a potential medical countermeasure for aldicarb poisoning.

Indexed as

AldicarbButyrylcholinesteraseAcetylcholinesteraseAnimalsHumansHydrolysisKineticsMedical CountermeasuresMiceMolecular Docking SimulationProtein EngineeringAcetylcholinesteraseAldicarbButyrylcholinesteraseCarbamateCholinergic warfareCocaine hydrolaseEsteraseHydrolysisPesticide

Identifiers

PMID40752825
PMCPMC12374750

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.