Check out Galen’s latest work on the computational design of reversible covalent picomolar inhibitors of carboxylesterase αE7 – helping to overcome insecticide resistance! The manuscript ‘Overcoming insecticide resistance through computational inhibitor design’ is now available as a preprint on bioRxiv! In this work, done in collaboration with the London lab at the Weizmann Institute of Science, we use covalent computational design to produce nano/pico-molar boronic acid inhibitors of the carboxylesterase αE7 from the agricultural pest Lucilia cuprina, as well as a common Gly137Asp αE7 mutant that confers OP resistance. These inhibitors, with no intrinsic apparent toxicity, act synergistically with the OPs diazinon and malathion to reduce the amount of OP required to kill L. cuprina by up to 16-fold, and abolish resistance. These compounds represent a solution to insecticide resistance. Shoo fly!