Dynamical changes of SARS-CoV-2 spike variants in the highly immunogenic regions impact the viral antibodies escaping.

The prolonged circulation of the SARS-CoV-2 virus resulted in the emergence of several viral variants, with different spreading features. Moreover, the increased number of recovered and/or vaccinated people introduced a selective pressure toward variants able to evade the immune system, developed against the former viral versions. This process results in reinfections. Aiming to study the latter process, we first collected a large structural dataset of antibodies in complex with the original version of SARS-CoV-2 Spike protein. We characterized the peculiarities of such antibodies population with respect to a control dataset of antibody-protein complexes, highlighting some statistically significant differences between these two sets of antibodies. Thus, moving our attention to the Spike side of the complexes, we identify the Spike region most prone to interaction with antibodies, describing in detail also the energetic mechanisms used by antibodies to recognize different epitopes. In this framework, fast protocols able to assess the effect of novel mutations on the cohort of developed antibodies would help establish the impact of the variants on the population. Performing a molecular dynamics simulation of the trimeric form of the SARS-CoV-2 Spike protein for the wild type and two variants of concern, that is, the Delta and Omicron variants, we described the physicochemical features and the conformational changes experienced locally by the variants with respect to the original version. Hence, combining the dynamical information with the structural study on the antibody-spike dataset, we quantitatively explain why the Omicron variant has a higher capability of escaping the immune system than the Delta variant, due to the higher conformational variability of the most immunogenic regions. Overall, our results shed light on the molecular mechanism behind the different responses the SARS-CoV-2 variants display against the immune response induced by either vaccines or previous infections. Moreover, our analysis proposes an approach that can be easily extended to both other SARS-CoV-2 variants or different molecular systems.