E-Volve: understanding the impact of mutations in SARS-CoV-2 variants spike protein on antibodies and ACE2 affinity through patterns of chemical interactions at protein interfaces

PeerJ. 2022 Mar 22:10:e13099. doi: 10.7717/peerj.13099. eCollection 2022.

Abstract

Background: The SARS-CoV-2 pandemic reverberated, posing health and social hygiene obstacles throughout the globe. Mutant lineages of the virus have concerned scientists because of convergent amino acid alterations, mainly on the viral spike protein. Studies have shown that mutants have diminished activity of neutralizing antibodies and enhanced affinity with its human cell receptor, the ACE2 protein.

Methods: Hence, for real-time measuring of the impacts caused by variant strains in such complexes, we implemented E-Volve, a tool designed to model a structure with a list of mutations requested by users and return analyses of the variant protein. As a proof of concept, we scrutinized the spike-antibody and spike-ACE2 complexes formed in the variants of concern, B.1.1.7 (Alpha), B.1.351 (Beta), and P.1 (Gamma), by using contact maps depicting the interactions made amid them, along with heat maps to quantify these major interactions.

Results: The results found in this study depict the highly frequent interface changes made by the entire set of mutations, mainly conducted by N501Y and E484K. In the spike-Antibody complex, we have noticed alterations concerning electrostatic surface complementarity, breaching essential sites in the P17 and BD-368-2 antibodies. Alongside, the spike-ACE2 complex has presented new hydrophobic bonds.

Discussion: Molecular dynamics simulations followed by Poisson-Boltzmann calculations corroborate the higher complementarity to the receptor and lower to the antibodies for the K417T/E484K/N501Y (Gamma) mutant compared to the wild-type strain, as pointed by E-Volve, as well as an intensification of this effect by changes at the protein conformational equilibrium in solution. A local disorder of the loop α1'/β1', as well its possible effects on the affinity to the BD-368-2 antibody were also incorporated to the final conclusions after this analysis. Moreover, E-Volve can depict the main alterations in important biological structures, as shown in the SARS-CoV-2 complexes, marking a major step in the real-time tracking of the virus mutant lineages. E-Volve is available at http://bioinfo.dcc.ufmg.br/evolve.

Keywords: ACE2; Affinity; Antibody; Chemical interactions; SARS-CoV-2; Vaccine; Variant; Web tool.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiotensin-Converting Enzyme 2 / genetics
  • Antibodies, Neutralizing
  • COVID-19* / epidemiology
  • Humans
  • Mutation
  • SARS-CoV-2* / genetics
  • Spike Glycoprotein, Coronavirus / genetics

Substances

  • Angiotensin-Converting Enzyme 2
  • spike protein, SARS-CoV-2
  • Spike Glycoprotein, Coronavirus
  • Antibodies, Neutralizing

Supplementary concepts

  • SARS-CoV-2 variants

Grants and funding

This study was financed by the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior-Brasil (CAPES)-Finance Code 001 (51/2013-23038.004007/2014-82). Physical structure and computational support were provided by the Laboratório Nacional de Computação Científica–LNCC, Petrópolis/RJ, Brazil (Project “Prospecção e testes in vitro de inibidores de proteínas associadas ao vírus SARS-Cov 2 por meio do uso conjunto de ferramentas de bioinformática, simulação molecular, química quântica e aprendizado de máquina-qcbiocovid19” Supercomputer SDumont); Centro Nacional de Processamento de Alto Desempenho em São Paulo (CENAPAD-SP); Núcleo de Processamento de Alto Desempenho of Universidade Federal do Rio Grande do Norte (NPAD/UFRN). There was no additional external funding received for this study. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.