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SARS-CoV-2 VOCs Immune Evasion from Previously Elicited Neutralizing Antibodies Is Mainly Driven by Lower Cross-Reactivity Due to Spike RBD Electrostatic Surface Changes


 
 
 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.

 
 
