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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

preprint
submitted on 31.03.2021, 00:33 and posted on 31.03.2021, 13:02 by Matheus Ferraz, EMERSON MOREIRA, Danilo F. Coêlho, Gabriel Wallau, Roberto Lins

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.

Funding

CNPq

CAPES

FIOCRUZ, INOVA Program

FIOCRUZ COVID-19 Genomic Surveillance Network

FACEPE

INCT-FCx

History

Email Address of Submitting Author

roberto.lins@cpqam.fiocruz.br

Institution

Aggeu Magalhães Institute, Oswaldo Cruz Foundation

Country

Brazil

ORCID For Submitting Author

0000-0002-3983-8025

Declaration of Conflict of Interest

The authors have declared no competing interests.

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