Leveraging structural data and computer modelling techniques, we investigated the variation in the binding free-energy (𝛥𝛥𝐺) profile of VOCs and VOIs SARS-CoV-2 lineages with hACE2 and with a dataset of known human nAbs. In agreement with the available experimental data, our results show only a marginal impact of VOC RBD amino acid changes to hACE2 affinity. On the other hand, we found that VOCs RBDs have a significant unfavorable 𝛥𝛥𝐺 to nAbs that can be related to changes in the electrostatic potential surface profiles, hence identifying the molecular and thermodynamical components behind SARS-CoV-2 antibody evasion. In addition, our data suggests that a close attention should be given to lineage P.3, as it likely holds a high spreading potential in a human population with rising immunity. In summary, the current observed higher transmission of SARS-CoV-2 VOCs is likely associated with a partial or complete failure of the antibody recognition and neutralization in individuals previously exposed to SARS-CoV-2 non-VOC variants. These results have key implications on i. the basic understanding of VOCs emergence and maintenance; ii. on the rational design of antibody-based therapeutics; iii. vaccine efficacy and updates; and iv. may be exploited to rapidly screen immune scape worrisome lineages.