Accelerating drug discovery using Free Energy Perturbation Identification of potential inhibitors for SARS-Cov-2 cysteine proteases

Sílvia Illa Tuset, Sofia Bariami, Giorgia Zaetta, and Mark Mackey

Cresset Discovery experts in Free Energy Perturbation (FEP) methods investigated the binding affinity of compounds with known experimental activity to the Mpro protein, a potential target for SARS-CoV2. Using FEP calculations and applying de novo design expertise to optimize bioisosteric replacement, we generated new designs predicted to be more active than the starting point.