Mechanistic insights into human carboxylesterase 2 (CES2) inhibition by the CES1 prodrug substrate remdesivir
Abhinav Pentyala, Sylvie E. Kandel, Jed Noah Lampe · Drug Metabolism and Disposition · 2025
. Through equilibrium dialysis and substrate protection experiments, we were able to further substantiate previous findings of the irreversible CES2 inhibition by remdesivir. Finally, in silico docking analysis of remdesivir to CES2 supported the proposed mechanism for covalent modification of the CES2 active site involving the catalytic triad serine via the phosphate group of remdesivir. SIGNIFICANCE STATEMENT: This study provides insights into human carboxylesterase inhibition by COVID-19 drugs and these findings demonstrate the underlying inhibition mechanism by remdesivir of recombinant human carboxylesterase 2.