In the MD-based alchemical approach for drug design, an alternative way of overcoming the formidable stumbling blocks in the sampling of complex conformational landscapes of hosts or ligand receptor systems is that of limiting the enhanced sampling simulations to the sampling of the endstates only, and then, in lieu of the FEP λ stratification, connecting these end-states by a swarm of fast (few ns at most) non-equilibrium (NE) alchemical simulations, recovering the free energy change from the resulting NE work distribution using the Jarzynski 62 or the Crooks theorems. This approach, by forcing the occurrence of fast rare events exploiting the replica diffusion in the scaling ladder or the sampling efficiency of many short and independent MD replicates on parallel platforms, in some sense restores the thermodynamics, hence avoiding to rely on an often unattainable ergodicity on each intermediate alchemical state in a single extended simulation of a single molecular systems characterized by a rugged free energy landscape.