In silico prediction of COVID-19 vaccine efficacy based on the strain-specific structural deviations in the SARS CoV-2 spike protein receptor binding domain
Main Article Content
Abstract
Coronavirus disease-2019 (COVID-19) pandemic gave the opportunity for various vaccine design strategies and their evaluation. However, the emergence of variants severely challenged the efficacy of the COVID-19 vaccines. The changes in the amino acid sequences and corresponding changes in the epitope topology of the variants could be the primary reasons for the loss of antibody binding affinity. The structural deviations in the epitopes may not be the same for all the variants resulting in differential efficacy of the same vaccine against different variants. In this study we performed an in silico evaluation of the strain-specific structural deviations in 15 variants of coronavirus in order to predict the antibody binding affinity and in turn estimate the success/failure of the current vaccines. The spike protein trimer homology models of 15 variants along with the wild type were prepared in close, open and semi-open conformations. The variant models were superposed onto the wild type model to calculate the C α root mean square deviations (RMSD) in their epitopes and ACE2 binding sites. Our results show that both the epitopes and the ACE2 binding sites of variants have RMSDs >35 Å suggesting that such large structural deviations in the epitopes are potentially responsible for the loss of binding affinities of the neutralizing antibodies that are generated in response to the current vaccine shots. Based on our analysis, we further prepared two hand-drawn clover leaf plots one for the main variants and the other for the omicron sub-variants summarizing all the structural deviations in the epitopes and ACE2 binding sites in open, closed and semi-open conformations. These plots serve as quick reference charts to predict the efficacy of current vaccines. For example, large structural deviations that are >20 Å can certainly lead to total loss of the antibody binding. Based on our findings in this study we propose alternative and improved strategies of future vaccine design for COVID-19.
Keywords:
COVID-19 vaccine efficacy, SARS-CoV-2 variants, Spike protein, In silico study, Antibody binding affinity, Structural deviations, Receptor-binding domain (RBD)
Article Details
How to Cite
VISSAPRAGADA, Madhuri et al.
In silico prediction of COVID-19 vaccine efficacy based on the strain-specific structural deviations in the SARS CoV-2 spike protein receptor binding domain.
Medical Research Archives, [S.l.], v. 12, n. 9, sep. 2024.
ISSN 2375-1924.
Available at: <https://esmed.org/MRA/mra/article/view/5718>. Date accessed: 04 oct. 2024.
doi: https://doi.org/10.18103/mra.v12i9.5718.
Section
Research Articles
The Medical Research Archives grants authors the right to publish and reproduce the unrevised contribution in whole or in part at any time and in any form for any scholarly non-commercial purpose with the condition that all publications of the contribution include a full citation to the journal as published by the Medical Research Archives.
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28. RCSB PDB - 7XNR: SARS-CoV-2 Omicron BA. 2.13 variant spike
29. Farahat RA, Abdelaal A, Umar TP, et al. The emergence of SARS-CoV-2 Omicron subvariants: current situation and future trends. Infez Med. 2022;30(4):480-494. Published 2022 Dec 1. doi:10.53854/liim-3004-2.
30. Samieefar N, Rashedi R, Akhlaghdoust M, Mashhadi M, Darzi P, Rezaei N. Delta Variant: The New Challenge of COVID-19 Pandemic, an Overview of Epidemiological, Clinical, and Immune Characteristics. Acta Biomed. 2022;93(1):e202217 9. Published 2022 Mar 14. doi:10.23750/abm.v93i 1.12210.
31. Subbaraman N. How do vaccinated people spread Delta? What the science says. Nature. 2021;596(7872):327-328. doi:10.1038/d41586-021 -02187-1.
32. Ahmad A, Fawaz MAM, Aisha A. A comparative overview of SARS-CoV-2 and its variants of concern. Infez Med. 2022;30(3):328-343. Published 2022 Sep 1. doi:10.53854/liim-3003-2
33. Galloway SE, Paul P, MacCannell DR, et al. Emergence of SARS-CoV-2 B.1.1.7 Lineage - United States, December 29, 2020-January 12, 2021. MMWR Morb Mortal Wkly Rep. 2021;70(3):9 5-99. Published 2021 Jan 22. doi:10.15585/mmwr .mm7003e2.
34. Shirbhate E, Pandey J, Patel VK, et al. Understanding the role of ACE-2 receptor in pathogenesis of COVID-19 disease: a potential approach for therapeutic intervention. Pharmacol Rep. 2021;73(6):1539-1550. doi:10.1007/s43440-021-00303-6
35. Piplani S, Singh PK, Winkler DA, Petrovsky N. In silico comparison of SARS-CoV-2 spike protein-ACE2 binding affinities across species and implications for virus origin [published correction appears in Sci Rep. 2021 Sep 14;11(1):18610]. Sci Rep. 2021;11(1):13063. Published 2021 Jun 24. doi:10.1038/s41598-021-92388-5.
36. Lan J, Ge J, Yu J, et al. Structure of the SARS-CoV-2 spike receptor-binding domain bound to the ACE2 receptor. Nature. 2020;581(7807):215-220. doi:10.1038/s41586-020-2180-5
37. Jawad B, Adhikari P, Podgornik R, Ching WY. Key Interacting Residues between RBD of SARS-CoV-2 and ACE2 Receptor: Combination of Molecular Dynamics Simulation and Density Functional Calculation. J Chem Inf Model. 2021;61(9):4425-4441. doi:10.1021/acs.jcim.
38. Chen Y, Guo Y, Pan Y, Zhao ZJ. Structure analysis of the receptor binding of 2019-nCoV. Biochem Biophys Res Commun. Published online February 17, 2020. doi:10.1016/j.bbrc.2020.02.071.
39. Khatri I, Staal FJT, van Dongen JJM. Blocking of the High-Affinity Interaction-Synapse Between SARS-CoV-2 Spike and Human ACE2 Proteins Likely Requires Multiple High-Affinity Antibodies: An Immune Perspective [published correction appears in Front Immunol. 2021 Apr 14;12:659375] . Front Immunol. 2020;11:570018. Published 2020 Sep 17. doi:10.3389/fimmu.2020.570018.
40. Ghazy RM, Ashmawy R, Hamdy NA, et al. Efficacy and Effectiveness of SARS-CoV-2 Vaccines: A Systematic Review and Meta-Analysis. Vaccines (Basel). 2022;10(3):350. Published 2022 Feb 23. doi:10.3390/vaccines10030350.
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