In the most comprehensive, structure-based approach to date, a team of scientists may have discovered a new family of antidotes for certain poisons that can mitigate their effects more efficiently compared with existing remedies.
Poisons such as organophosphorus nerve agents and pesticides wreak havoc by blocking an enzyme essential for proper brain and nerve function. Fast-acting drugs, called reactivators, are required to reach the central nervous system and counteract damage that could lead to death.
“To enhance the antidote’s effectiveness, we need to improve the reactivator’s ability to cross the blood-brain barrier, bind loosely to the enzyme, chemically snatch the poison and then leave quickly,” said Oak Ridge National Laboratory’s Andrey Kovalevsky, co-author of a study led by Zoran Radić of UC San Diego.
The team designed and tested reactivators on three different nerve agents and one pesticide with positive initial results. Their next step is to use neutron crystallography to better understand antidote designs.
