Dataset Information

Thermodynamics and kinetics in antibody resistance of the 501Y.V2 SARS-CoV-2 variant.

ABSTRACT: Understanding the thermodynamics and kinetics of the binding process of an antibody to the SARS-CoV-2 receptor-binding domain (RBD) of the spike protein is very important for the development of COVID-19 vaccines. In particular, it is essential to understand how the binding mechanism may change under the effects of RBD mutations. In this context, we have demonstrated that the South African variant (B1.351 or 501Y.V2) can resist the neutralizing antibody (NAb). Three substitutions in the RBD including K417N, E484K, and N501Y alter the free energy landscape, binding pose, binding free energy, binding kinetics, hydrogen bonding, nonbonded contacts, and unbinding pathway of RBD + NAb complexes. The low binding affinity of NAb to 501Y.V2 RBD confirms the antibody resistance of the South African variant. Moreover, the fragment of NAb + RBD can be used as an affordable model to investigate changes in the binding process between the mutated RBD and antibodies.

SUBMITTER: Ngo ST

PROVIDER: S-EPMC9042284 | biostudies-literature | 2021 Oct

REPOSITORIES: biostudies-literature

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Thermodynamics and kinetics in antibody resistance of the 501Y.V2 SARS-CoV-2 variant.

Ngo Son Tung ST Nguyen Trung Hai TH Pham Duc-Hung DH Tung Nguyen Thanh NT Nam Pham Cam PC

RSC advances 20211013 53

Understanding the thermodynamics and kinetics of the binding process of an antibody to the SARS-CoV-2 receptor-binding domain (RBD) of the spike protein is very important for the development of COVID-19 vaccines. In particular, it is essential to understand how the binding mechanism may change under the effects of RBD mutations. In this context, we have demonstrated that the South African variant (B1.351 or 501Y.V2) can resist the neutralizing antibody (NAb). Three substitutions in the RBD inclu ...[more]

PMID: 35497518

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Project description:BackgroundThe existence of mutated Delta (B.1.617.2) variants of SARS-CoV-2 causes rapid transmissibility, increase in virulence, and decrease in the effectiveness of public health. Majority of mutations are seen in the surface spike, and they are considered as antigenicity and immunogenicity of the virus. Hence, finding suitable cross antibody or natural antibody and understanding its biomolecular recognition for neutralizing surface spike are crucial for developing many clinically approved COVID-19 vaccines. Here, we aim to design SARS-CoV-2 variant and hence, to understand its mechanism, binding affinity and neutralization potential with several antibodies.ResultsIn this study, we modelled six feasible spike protein (S1) configurations for Delta SARS-CoV-2 (B.1.617.2) and identified the best structure to interact with human antibodies. Initially, the impact of mutations at the receptor-binding domain (RBD) of B.1.617.2 was tested, and it is found that all mutations increase the stability of proteins (ΔΔG) and decrease the entropies. An exceptional case is noted for the mutation of G614D variant for which the vibration entropy change is found to be within the range of 0.133-0.004 kcal/mol/K. Temperature-dependent free energy change values (ΔG) for wild type is found to be - 0.1 kcal/mol, whereas all other cases exhibit values within the range of - 5.1 to - 5.5 kcal/mol. Mutation on spike increases the interaction with the glycoprotein antibody CR3022 and the binding affinity (CLUSpro energy = - 99.7 kcal/mol). The docked Delta variant with the following antibodies, etesevimab, bebtelovimab, BD-368-2, imdevimab, bamlanivimab, and casirivimab, exhibit a substantially decreased docking score (- 61.7 to - 112.0 kcal/mol) and the disappearance of several hydrogen bond interactions.ConclusionCharacterization of antibody resistance for Delta variant with respect to the wild type gives understanding regarding why Delta variant endures the resistance boosted through several trademark vaccines. Several interactions with CR3022 have appeared compared to Wild for Delta variant, and hence, it is suggested that modification on the CR3022 antibody could further improve for the prevention of viral spread. Antibody resistance decreased significantly due to numerous hydrogen bond interactions which clearly indicate that these marketed/launched vaccines (etesevimab) will be effective for Delta variants.

Dataset Information

Thermodynamics and kinetics in antibody resistance of the 501Y.V2 SARS-CoV-2 variant.

Publications

Thermodynamics and kinetics in antibody resistance of the 501Y.V2 SARS-CoV-2 variant.

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