Happy to share that our paper on pomotrelvir and nirmatrelvir binding and reactivity with SARS-CoV-2 main protease in @angew_chem has just been anounced as a paper of the month by the Spanish Biophysical Society @SBEsp (https://sbe.es/paperhighlights-oct2024-1/). 馃憦馃帀
In this work, we studied the inhibition mechanism of pomotrelvir against SARS-CoV-2 main protease, using MM and QM/MM simulations and free energy calculations. Transforming pomotrelvir’s groups to those in nirmatrelvir revealed that tertiary amines are favored at P2, while flexible side chains at this position may disrupt active site organization. These insights may aid in designing improved inhibitors for current and future SARS-CoV-2 variants.