SARS-CoV-2 remains a health threat with the continuous emergence of new variants. This work aims to expand the knowledge about the SARS-CoV-2 receptor-binding domain (RBD) interactions with cell receptors and monoclonal antibodies (mAbs). By using constant-pH Monte Carlo simulations, the free energy of interactions between the RBD from different variants and several partners (Angiotensin-Converting Enzyme-2 (ACE2) polymorphisms and various mAbs) were predicted. Computed RBD-ACE2-binding affinities were higher for two ACE2 polymorphisms (rs142984500 and rs4646116) typically found in Europeans which indicates a genetic susceptibility. This is amplified for Omicron (BA.1) and its sublineages BA.2 and BA.3. The antibody landscape was computationally investigated with the largest set of mAbs so far in the literature. From the 32 studied binders, groups of mAbs were identified from weak to strong binding affinities (e.g. S2K146). These mAbs with strong binding capacity and especially their combination are amenable to experimentation and clinical trials because of their high predicted binding affinities and possible neutralization potential for current known virus mutations and a universal coronavirus.