Pomotrelvir and Nirmatrelvir Binding and Reactivity with SARS-CoV-2 Main Protease: Implications for Resistance Mechanisms from Computations.

We investigate the inhibition mechanism between pomotrelvir and the SARS-CoV-2 main protease using molecular mechanics and quantum mechanics/molecular mechanics simulations. Alchemical transformations where each Pi group of pomotrelvir was transformed into its counterpart in nirmatrelvir were performed to unravel the individual contribution of each group to the binding and reaction processes. We have shown that while a γ-lactam ring is preferred at position P1, a δ-lactam ring is a good alternative for the design of inhibitors for variants presenting mutations at position 166.

Interstitial or interstitialcy: effect of the cation size on the migration mechanism in NaSICON materials.

Sodium superionic conductors (NaSICONs) with general formula NaMAO have attracted significant attention as solid electrolytes for all solid-state batteries owing to their remarkable room temperature ionic conductivity in the order of 10 S cm. Their flexible structural framework, which allows the incorporation of various aliovalent cations, affects the Na ion transport. However, establishing a straightforward correlation between Na mobility and NaSICON composition proves challenging due to competing influences such as framework alteration and stoichiometric changes of the cation substituents and thus the mobile Na ions.