We provide a new unsupervised adaptive sampling strategy capable of producing microsecondtimescale molecular dynamics (MD) simulations using many-body polarizable force fields (PFF) on modern supercomputers. The global exploration problem is decomposed into a set of separate MD trajectories that can be restarted within an iterative/selective process to achieve sufficient phase-space sampling within large biosystems, while accurate statistical properties can be obtained through debiasing. With this pleasingly parallel setup, the Tinker-HP package can be powered by an arbitrary large number of GPUs (Graphics Processing Unit) cards available on pre-exascale supercomputers, reducing to days explorations that would have taken years. We applied the approach to the urgent problem of the modeling of the SARS–CoV–2 Main protease (Mpro) dimer. A 15.14 microsecond high-resolution all-atom simulation (AMOEBA PFF) of its apo state is provided and compared to other available long-timescale non-PFF data. Noticeable differences are found between clustering analysis of the simulations, the AMOEBA adaptive results exhibiting a richer conformational space. Overall, our high-resolution AMOEBA structural analysis captures key experimental observations concerning the stability of the oxyanion hole, a marker of activity through the stability of different stacking and salt bridge interactions. A dissymmetry is found between the enzyme protomers that exhibit different volumes. One of them appears fully inactive while the other is "activable", exhibiting some partial activity features. This activity evaluation can be further traced back to the large flexibility of the C terminal domain, fully captured by AMOEBA but not seen in X-rays due to insufficient electron densities related to the domain high mobility. The C–terminal region of the fully inactive protomer is shown to oscillate between several states, one of them interacting with the other protomer active site, therefore potentially modulating down its activity. Overall, these results reinforce the experimental hypothesis of a full inactivation of the apo state and clearly capture the asymmetric nature of protomers. Additional analysis show that the cavities volumes of the active and distal sites are found to be larger in the most active protomer with AMOEBA. To a larger extend, the PFF finds significantly larger cavities than those obtained with classical, non-polarizable simulations. The consequences on druggability are discussed as additional potential druggable cryptic pockets are found. All data produced within this research are fully accessible to the community for further analysis.