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Like any unforeseen, brutal, vital event, the coronavirus crisis is causing its share of regressions: an epidemic of hoaxes, conspiracy theories and gossip of all kinds and, of course, a relentless search for culprits – from the Chinese to globalization, from neo-liberalism to climate change, from health authorities lacking in foresight to the Machiavellian government. These are so many tactics probably intended to recover a semblance of control over what escapes us. ; Check for published version during checkdate report - AC

Organophosphorus compounds are used as chemical warfare nerve agents (VX, sarin, tabun…) as well as pesticides (parathion, chlorpyrifos, glyphosate). Recent tragic events in North Korea, Russia and the United Kingdom showed that organophosphorus nerve agents (OPNA) are still a serious threat for civilians and military people. The target of OPNA are the cholinesterases, namely acetyl- and butyrylcholinesterases. Their irreversible inhibition leads to a cholinergic crisis, with convulsive seizures, and cardiorespiratory arrest and ultimately death. Pyridinium aldoximes are among the different antidotes used to treat this type of intoxication. These cholinesterase reactivators currently have serious limit. Their low passage of the blood-brain barrier translate into a poor protection of the central nervous system. Moreover, no universal oxime effective against all OPNA is known to date. It is in this context of chemical threat that this Ph. D work was carried out. The evaluation in silico, in vitro and in vivo of four oximes conjugated to a carbohydrate was carried out. These oximes initially designed to facilitate the crossing of the blood-brain barrier, proved their interest and allow to pave the way for new molecule design. In parallel, widely used pesticides such as Chlorpyrifos or Omethoate have been studied to determine their inhibitory potential, better understand the mechanisms of inhibition and to test the effectiveness of the current reactivators. Finally, in order to enhance the relevance of data acquired from in vivo studies, of candidate reactivators on porcine and zebrafish animal models, we have expressed and characterized porcine and zebrafish acetylcholinesterase. This will allow a better interpretation of the in vivo data, and a better translation to Human. ; Les neurotoxiques organophosphorés sont employés comme agents chimiques de guerre (VX, sarin, tabun…) mais également comme pesticides (parathion, chlorpyrifos, glyphosate). Les récents évènements en Corée du Nord, en Russie ou encore au ...