Ligand RQN binds to the active binding site of the 3CLPro target protein whereas LZE binds to the allosteric binding site II. In this study, we have performed simulations that contain both RQN and LZE ligands binding to the 3CLPro target at the same time. Therefore, we discuss the observed effect of the presence of LZE on the binding of RQN ligand by comparing the results from this system with those from the system containing only RQN. First of all, the presence of LZE does not affect the value of ∆G direct for RQN binding with 3CLPro.