High Performance Computing on CRESCO infrastructure: research activities and results 2023

Using massively parallel equilibrium and nonequilibrium molecular dynamics simulation techniques, we examine the non-covalent association of the active principle of the Paxlovid anti-Covid-19 formulation, namely the covalent binder Nirmatrelvir, with the SARS-Cov-2 main protease as a function of the protonation of the HIS41-CYS145 catalytic dyad. The structural characterization of the complexes and the computed binding strengths provide valuable clues on the inhibition mechanism and as to how the potency of the main protease covalent inhibitors could be improved.