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: 03 dec. 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.
References
1. Cascella M, Rajnik M, Aleem A, Dulebohn SC, Di Napoli R. Features, Evaluation, and Treatment of Coronavirus (COVID-19). In: StatPearls. Treasure Island (FL): StatPearls Publishing; August 18, 2023.
2. Hu B, Guo H, Zhou P, Shi ZL. Author Correction: Characteristics of SARS-CoV-2 and COVID-19. Nat Rev Microbiol. 2022;20(5):315. doi:10.1038/s4157 9-022-00711-2
3. https://www.who.int/westernpacific/health-topics/detail/coronavirus
4. COVID-19 Epidemiological Update, Edition 166 published 12 April 2024, https://www.who.int/publications/m/item/covid-19-epidemiological-update-edition-166.
5. Boopathi S, Poma AB, Kolandaivel P. Novel 2019 coronavirus structure, mechanism of action, antiviral drug promises and rule out against its treatment. J Biomol Struct Dyn. 2021;39(9):3409-3418. doi:10.1080/07391102.2020.1758788
6. Fehr AR, Perlman S. Coronaviruses: an overview of their replication and pathogenesis. Methods Mol Biol. 2015;1282:1-23. doi:10.1007/978-1-4939-2438-7_
7. Singh D, Yi SV. On the origin and evolution of SARS-CoV-2. Exp Mol Med. 2021;53(4):537-547. doi:10.1038/s12276-021-00604-z
8. Chathappady House NN, Palissery S, Sebastian H. Corona Viruses: A Review on SARS, MERS and COVID-19. Microbiol Insights. 2021;14:117863612 11002481. Published 2021 Mar 19. doi:10.1177/11 786361211002481
9. Zhou Z, Qiu Y, Ge X. The taxonomy, host range and pathogenicity of coronaviruses and other viruses in the Nidovirales order. Anim Dis. 2021;1(1):5. doi:10.1186/s44149-021-00005-9
10. Gorkhali R, Koirala P, Rijal S, Mainali A, Baral A, Bhattarai HK. Structure and Function of Major SARS-CoV-2 and SARS-CoV Proteins. Bioinform Biol Insights. 2021;15:11779322211025876. Published 2021 Jun 22. doi:10.1177/11779322211025876
11. Naqvi AAT, Fatima K, Mohammad T, et al. Insights into SARS-CoV-2 genome, structure, evolution, pathogenesis and therapies: Structural genomics approach. Biochim Biophys Acta Mol Basis Dis. 2020;1866(10):165878. doi:10.1016/j.bb adis.2020.165878
12. Malone B, Urakova N, Snijder EJ, Campbell EA. Structures and functions of coronavirus replication-transcription complexes and their relevance for SARS-CoV-2 drug design Nat Rev Mol Cell Biol. 2022;23(1):21-39. doi:10.1038/s415 80-021-00432-z
13. Duan L, Zheng Q, Zhang H, Niu Y, Lou Y, Wang H. The SARS-CoV-2 Spike Glycoprotein Biosynthesis, Structure, Function, and Antigenicity: Implications for the Design of Spike-Based Vaccine Immunogens. Front Immunol. 2020;11:576622. Published 2020 Oct 7. doi:10.3389/fimmu.2020.576622
14. Walls AC, Park YJ, Tortorici MA, Wall A, McGuire AT, Veesler D. Structure, Function, and Antigenicity of the SARS-CoV-2 Spike Glycoprotein [published correction appears in Cell. 2020 Dec 10;183(6):1735]. Cell. 2020;181(2):281-292.e6. doi: 10.1016/j.cell.2020.02.058
15. Huang Y, Yang C, Xu XF, Xu W, Liu SW. Structural and functional properties of SARS-CoV-2 spike protein: potential antivirus drug development for COVID-19. Acta Pharmacol Sin. 2020;41(9): 1141-1149. doi:10.1038/s41401-020-0485-4
16. Qiao S, Zhang S, Ge J, Wang X. The spike glycoprotein of highly pathogenic human coronaviruses: structural insights for understanding infection, evolution and inhibition. FEBS Open Bio. 2022;12(9):1602-1622. doi:10.1002/2211-5463.13454
17. Wang MY, Zhao R, Gao LJ, Gao XF, Wang DP, Cao JM. SARS-CoV-2: Structure, Biology, and Structure-Based Therapeutics Development. Front Cell Infect Microbiol. 2020;10:587269. Published 2020 Nov 25. doi:10.3389/fcimb.2020.
18. Xia X. Domains and Functions of Spike Protein in Sars-Cov-2 in the Context of Vaccine Design. Viruses. 2021;13(1):109. Published 2021 Jan 14. doi:10.3390/v13010109.
19. Zhang J, Xiao T, Cai Y, Chen B. Structure of SARS-CoV-2 spike protein. Curr Opin Virol. 2021;5 0:173-182. doi:10.1016/j.coviro.2021.08.010.
20. Pramanick I, Sengupta N, Mishra S, et al. Conformational flexibility and structural variability of SARS-CoV2 S protein. Structure. 2021;29(8):834-845.e5. doi:10.1016/j.str.2021.04.006.
21. Carnell GW, Ciazynska KA, Wells DA, et al. SARS-CoV-2 Spike Protein Stabilized in the Closed State Induces Potent Neutralizing Responses. J Virol. 2021;95(15):e0020321. doi:10.1128/JVI.00203-21
22. Schaub JM, Chou CW, Kuo HC, et al. Expression and characterization of SARS-CoV-2 spike proteins. Nat Protoc. 2021;16(11):5339-5356. doi:10.1038/s41596-021-00623-0.
23. Chavda VP, Bezbaruah R, Deka K, Nongrang L, Kalita T. The Delta and Omicron Variants of SARS-CoV-2: What We Know So Far. Vaccines (Basel). 2022;10(11):1926. Published 2022 Nov 14. doi:10.3390/vaccines10111926.
24. Chatterjee S, Bhattacharya M, Nag S, Dhama K, Chakraborty C. A Detailed Overview of SARS-CoV-2 Omicron: Its Sub-Variants, Mutations and Pathophysiology, Clinical Characteristics, Immunological Landscape, Immune Escape, and Therapies. Viruses. 2023;15(1):167. Published 2023 Jan 5. doi:10.3390/v15010167.
25. https://data.who.int/dashboards/covid19/variants
26. https:// www.ncbi.nlm.nih.gov/activ
27. Cosar B, Karagulleoglu ZY, Unal S, et al. SARS-CoV-2 Mutations and their Viral Variants. Cytokine Growth Factor Rev. 2022;63:10-22. doi:10.1016/j.c ytogfr.2021.06.001.
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.
41. Liu J, Chandrashekar A, Sellers D, et al. Vaccines elicit highly conserved cellular immunity to SARS-CoV-2 Omicron. Nature. 2022;603(7901) :493-496. doi:10.1038/s41586-022-04465-y.
42. Min L, Sun Q. Antibodies and Vaccines Target RBD of SARS-CoV-2. Front Mol Biosci. 2021;8:6716 33. Published 2021 Apr 22. doi:10.3389/fmolb. 2021.671633.
43. Addala S, Vissapragada M, Aggunna M, et al. Success of Current COVID-19 Vaccine Strategies vs. the Epitope Topology of SARS-CoV-2 Spike Protein-Receptor Binding Domain (RBD): A Computational Study of RBD Topology to Guide Future Vaccine Design. Vaccines (Basel). 2022;10(6):841. Published 2022 May 25. doi:10. 3390/vaccines10060841
44. Kabsch W. Acta. Cryst. A32 922-923 (1976).
45. Agirre J, Atanasova M, Bagdonas H, et al. The CCP4 suite: integrative software for macromolecular crystallography. Acta Crystallogr D Struct Biol. 2023;79(Pt 6):449-461. doi:10.1107/S2059798323003595
46. Vissapragada, M, et al. (2021). Major structural deviations in the receptor binding domain of SARS-CoV-2 spike protein may pose threat to the existing vaccines. TCABSE-J, Vol. 1, Issue 1:12-14. Epub: Apr 13th , 2021.
47. Vissapragada et al. (2023). In silico analysis of molnupiravir usage vs. efficacy of COVID-19 vaccines. TCABSE-J, Vol. 1, Issue 5:1-11. Mar 22 nd , 2023. Epub: Oct 20th, 2022.
48. Benton DJ, Wrobel AG, Xu P, et al. Receptor binding and priming of the spike protein of SARS-CoV-2 for membrane fusion. Nature. 2020;588 (7837):327-330. doi:10.1038/s41586-020-2772-0.
49. Aggunna, M., Grandhi, A.V.K.S. and Yedidi, R.S. (2023). Molecular dynamics simulations of cytotoxin-associated gene A coded protein from Helicobacter pylori to probe the flexibility of p53 binding pocket for inhibitor design. TCABSE-J, Vol. 1, Issue 6:9-14. Oct 24th, 2023. Epub: Aug 10th, 2023.
50. Shaw DE, Maragakis P, Lindorff-Larsen K, et al. Atomic-level characterization of the structural dynamics of proteins. Science. 2010;330(6002) :341-346. doi:10.1126/science.1187409.
51. Alkhatib M, Svicher V, Salpini R, et al. SARS-CoV-2 Variants and Their Relevant Mutational Profiles: Update Summer 2021. Microbiol Spectr. 2021;9(3):e0109621. doi:10.1128/Spectrum.01096-21.
52. Farhud DD, Mojahed N. SARS-COV-2 Notable Mutations and Variants: A Review Article. Iran J Public Health. 2022;51(7):1494-1501. doi:10.18502 /ijph.v51i7.10083.
53. Chakraborti S, Gill J, Goswami R, Kumar S, Chandele A, Sharma A. Structural Profiles of SARS-CoV-2 Variants in India. Curr Microbiol. 2022;80 (1):1. Published 2022 Nov 22. doi:10.1007/s00284-022-03094-y.
54. Tamura T, Ito J, Uriu K, et al. Virological characteristics of the SARS-CoV-2 XBB variant derived from recombination of two Omicron subvariants. Nat Commun. 2023;14(1):2800. Published 2023 May 16. doi:10.1038/s41467-023-38435-3.
55. Parums DV. Editorial: The XBB.1.5 ('Kraken') Subvariant of Omicron SARS-CoV-2 and its Rapid Global Spread. Med Sci Monit. 2023;29:e939580. Published 2023 Feb 1. doi:10.12659/MSM.939580.
56. Dudas G, Hong SL, Potter BI, et al. Emergence and spread of SARS-CoV-2 lineage B.1.620 with variant of concern-like mutations and deletions. Nat Commun. 2021;12(1):5769. Published 2021 Oct 1. doi:10.1038/s41467-021-26055-8.
57. Olia AS, Tsybovsky Y, Chen SJ, et al. SARS-CoV-2 S2P spike ages through distinct states with altered immunogenicity. J Biol Chem. 2021;297(4) :101127. doi:10.1016/j.jbc.2021.101127.
58. Xu J, Xu K, Jung S, et al. Nanobodies from camelid mice and llamas neutralize SARS-CoV-2 variants. Nature. 2021;595(7866):278-282. doi:10. 1038/s41586-021-03676-z.
59. Zhou T, Wang L, Misasi J, et al. Structural basis for potent antibody neutralization of SARS-CoV-2 variants including B.1.1.529. Science. 2022;376(65 91):eabn8897. doi:10.1126/science.abn8897.
60. López-Cortés GI, Palacios-Pérez M, Veledíaz HF, et al. The Spike Protein of SARS-CoV-2 Is Adapting Because of Selective Pressures. Vaccines (Basel). 2022;10(6):864. Published 2022 May 28. doi:10.3390/vaccines10060864
61. Pinho SS, Alves I, Gaifem J, Rabinovich GA. Immune regulatory networks coordinated by glycans and glycan-binding proteins in autoimmunity and infection. Cell Mol Immunol. 2023;20(10) :1101-1113. doi:10.1038/s41423-023-01074-1
62. Sirohi PR, Gupta J, Somvanshi P, Prajapati VK, Grover A. Multiple epitope-based vaccine prediction against SARS-CoV-2 spike glycoprotein. J Biomol Struct Dyn. 2022;40(8):3347-3358. doi:10 .1080/07391102.2020.1846626
63. Surti M, Patel M, Adnan M, et al. Ilimaquinone (marine sponge metabolite) as a novel inhibitor of SARS-CoV-2 key target proteins in comparison with suggested COVID-19 drugs: designing, docking and molecular dynamics simulation study. RSC Adv. 2020;10(62):37707-37720. Published 2020 Oct 13. doi:10.1039/d0ra06379g
2. Hu B, Guo H, Zhou P, Shi ZL. Author Correction: Characteristics of SARS-CoV-2 and COVID-19. Nat Rev Microbiol. 2022;20(5):315. doi:10.1038/s4157 9-022-00711-2
3. https://www.who.int/westernpacific/health-topics/detail/coronavirus
4. COVID-19 Epidemiological Update, Edition 166 published 12 April 2024, https://www.who.int/publications/m/item/covid-19-epidemiological-update-edition-166.
5. Boopathi S, Poma AB, Kolandaivel P. Novel 2019 coronavirus structure, mechanism of action, antiviral drug promises and rule out against its treatment. J Biomol Struct Dyn. 2021;39(9):3409-3418. doi:10.1080/07391102.2020.1758788
6. Fehr AR, Perlman S. Coronaviruses: an overview of their replication and pathogenesis. Methods Mol Biol. 2015;1282:1-23. doi:10.1007/978-1-4939-2438-7_
7. Singh D, Yi SV. On the origin and evolution of SARS-CoV-2. Exp Mol Med. 2021;53(4):537-547. doi:10.1038/s12276-021-00604-z
8. Chathappady House NN, Palissery S, Sebastian H. Corona Viruses: A Review on SARS, MERS and COVID-19. Microbiol Insights. 2021;14:117863612 11002481. Published 2021 Mar 19. doi:10.1177/11 786361211002481
9. Zhou Z, Qiu Y, Ge X. The taxonomy, host range and pathogenicity of coronaviruses and other viruses in the Nidovirales order. Anim Dis. 2021;1(1):5. doi:10.1186/s44149-021-00005-9
10. Gorkhali R, Koirala P, Rijal S, Mainali A, Baral A, Bhattarai HK. Structure and Function of Major SARS-CoV-2 and SARS-CoV Proteins. Bioinform Biol Insights. 2021;15:11779322211025876. Published 2021 Jun 22. doi:10.1177/11779322211025876
11. Naqvi AAT, Fatima K, Mohammad T, et al. Insights into SARS-CoV-2 genome, structure, evolution, pathogenesis and therapies: Structural genomics approach. Biochim Biophys Acta Mol Basis Dis. 2020;1866(10):165878. doi:10.1016/j.bb adis.2020.165878
12. Malone B, Urakova N, Snijder EJ, Campbell EA. Structures and functions of coronavirus replication-transcription complexes and their relevance for SARS-CoV-2 drug design Nat Rev Mol Cell Biol. 2022;23(1):21-39. doi:10.1038/s415 80-021-00432-z
13. Duan L, Zheng Q, Zhang H, Niu Y, Lou Y, Wang H. The SARS-CoV-2 Spike Glycoprotein Biosynthesis, Structure, Function, and Antigenicity: Implications for the Design of Spike-Based Vaccine Immunogens. Front Immunol. 2020;11:576622. Published 2020 Oct 7. doi:10.3389/fimmu.2020.576622
14. Walls AC, Park YJ, Tortorici MA, Wall A, McGuire AT, Veesler D. Structure, Function, and Antigenicity of the SARS-CoV-2 Spike Glycoprotein [published correction appears in Cell. 2020 Dec 10;183(6):1735]. Cell. 2020;181(2):281-292.e6. doi: 10.1016/j.cell.2020.02.058
15. Huang Y, Yang C, Xu XF, Xu W, Liu SW. Structural and functional properties of SARS-CoV-2 spike protein: potential antivirus drug development for COVID-19. Acta Pharmacol Sin. 2020;41(9): 1141-1149. doi:10.1038/s41401-020-0485-4
16. Qiao S, Zhang S, Ge J, Wang X. The spike glycoprotein of highly pathogenic human coronaviruses: structural insights for understanding infection, evolution and inhibition. FEBS Open Bio. 2022;12(9):1602-1622. doi:10.1002/2211-5463.13454
17. Wang MY, Zhao R, Gao LJ, Gao XF, Wang DP, Cao JM. SARS-CoV-2: Structure, Biology, and Structure-Based Therapeutics Development. Front Cell Infect Microbiol. 2020;10:587269. Published 2020 Nov 25. doi:10.3389/fcimb.2020.
18. Xia X. Domains and Functions of Spike Protein in Sars-Cov-2 in the Context of Vaccine Design. Viruses. 2021;13(1):109. Published 2021 Jan 14. doi:10.3390/v13010109.
19. Zhang J, Xiao T, Cai Y, Chen B. Structure of SARS-CoV-2 spike protein. Curr Opin Virol. 2021;5 0:173-182. doi:10.1016/j.coviro.2021.08.010.
20. Pramanick I, Sengupta N, Mishra S, et al. Conformational flexibility and structural variability of SARS-CoV2 S protein. Structure. 2021;29(8):834-845.e5. doi:10.1016/j.str.2021.04.006.
21. Carnell GW, Ciazynska KA, Wells DA, et al. SARS-CoV-2 Spike Protein Stabilized in the Closed State Induces Potent Neutralizing Responses. J Virol. 2021;95(15):e0020321. doi:10.1128/JVI.00203-21
22. Schaub JM, Chou CW, Kuo HC, et al. Expression and characterization of SARS-CoV-2 spike proteins. Nat Protoc. 2021;16(11):5339-5356. doi:10.1038/s41596-021-00623-0.
23. Chavda VP, Bezbaruah R, Deka K, Nongrang L, Kalita T. The Delta and Omicron Variants of SARS-CoV-2: What We Know So Far. Vaccines (Basel). 2022;10(11):1926. Published 2022 Nov 14. doi:10.3390/vaccines10111926.
24. Chatterjee S, Bhattacharya M, Nag S, Dhama K, Chakraborty C. A Detailed Overview of SARS-CoV-2 Omicron: Its Sub-Variants, Mutations and Pathophysiology, Clinical Characteristics, Immunological Landscape, Immune Escape, and Therapies. Viruses. 2023;15(1):167. Published 2023 Jan 5. doi:10.3390/v15010167.
25. https://data.who.int/dashboards/covid19/variants
26. https:// www.ncbi.nlm.nih.gov/activ
27. Cosar B, Karagulleoglu ZY, Unal S, et al. SARS-CoV-2 Mutations and their Viral Variants. Cytokine Growth Factor Rev. 2022;63:10-22. doi:10.1016/j.c ytogfr.2021.06.001.
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.
41. Liu J, Chandrashekar A, Sellers D, et al. Vaccines elicit highly conserved cellular immunity to SARS-CoV-2 Omicron. Nature. 2022;603(7901) :493-496. doi:10.1038/s41586-022-04465-y.
42. Min L, Sun Q. Antibodies and Vaccines Target RBD of SARS-CoV-2. Front Mol Biosci. 2021;8:6716 33. Published 2021 Apr 22. doi:10.3389/fmolb. 2021.671633.
43. Addala S, Vissapragada M, Aggunna M, et al. Success of Current COVID-19 Vaccine Strategies vs. the Epitope Topology of SARS-CoV-2 Spike Protein-Receptor Binding Domain (RBD): A Computational Study of RBD Topology to Guide Future Vaccine Design. Vaccines (Basel). 2022;10(6):841. Published 2022 May 25. doi:10. 3390/vaccines10060841
44. Kabsch W. Acta. Cryst. A32 922-923 (1976).
45. Agirre J, Atanasova M, Bagdonas H, et al. The CCP4 suite: integrative software for macromolecular crystallography. Acta Crystallogr D Struct Biol. 2023;79(Pt 6):449-461. doi:10.1107/S2059798323003595
46. Vissapragada, M, et al. (2021). Major structural deviations in the receptor binding domain of SARS-CoV-2 spike protein may pose threat to the existing vaccines. TCABSE-J, Vol. 1, Issue 1:12-14. Epub: Apr 13th , 2021.
47. Vissapragada et al. (2023). In silico analysis of molnupiravir usage vs. efficacy of COVID-19 vaccines. TCABSE-J, Vol. 1, Issue 5:1-11. Mar 22 nd , 2023. Epub: Oct 20th, 2022.
48. Benton DJ, Wrobel AG, Xu P, et al. Receptor binding and priming of the spike protein of SARS-CoV-2 for membrane fusion. Nature. 2020;588 (7837):327-330. doi:10.1038/s41586-020-2772-0.
49. Aggunna, M., Grandhi, A.V.K.S. and Yedidi, R.S. (2023). Molecular dynamics simulations of cytotoxin-associated gene A coded protein from Helicobacter pylori to probe the flexibility of p53 binding pocket for inhibitor design. TCABSE-J, Vol. 1, Issue 6:9-14. Oct 24th, 2023. Epub: Aug 10th, 2023.
50. Shaw DE, Maragakis P, Lindorff-Larsen K, et al. Atomic-level characterization of the structural dynamics of proteins. Science. 2010;330(6002) :341-346. doi:10.1126/science.1187409.
51. Alkhatib M, Svicher V, Salpini R, et al. SARS-CoV-2 Variants and Their Relevant Mutational Profiles: Update Summer 2021. Microbiol Spectr. 2021;9(3):e0109621. doi:10.1128/Spectrum.01096-21.
52. Farhud DD, Mojahed N. SARS-COV-2 Notable Mutations and Variants: A Review Article. Iran J Public Health. 2022;51(7):1494-1501. doi:10.18502 /ijph.v51i7.10083.
53. Chakraborti S, Gill J, Goswami R, Kumar S, Chandele A, Sharma A. Structural Profiles of SARS-CoV-2 Variants in India. Curr Microbiol. 2022;80 (1):1. Published 2022 Nov 22. doi:10.1007/s00284-022-03094-y.
54. Tamura T, Ito J, Uriu K, et al. Virological characteristics of the SARS-CoV-2 XBB variant derived from recombination of two Omicron subvariants. Nat Commun. 2023;14(1):2800. Published 2023 May 16. doi:10.1038/s41467-023-38435-3.
55. Parums DV. Editorial: The XBB.1.5 ('Kraken') Subvariant of Omicron SARS-CoV-2 and its Rapid Global Spread. Med Sci Monit. 2023;29:e939580. Published 2023 Feb 1. doi:10.12659/MSM.939580.
56. Dudas G, Hong SL, Potter BI, et al. Emergence and spread of SARS-CoV-2 lineage B.1.620 with variant of concern-like mutations and deletions. Nat Commun. 2021;12(1):5769. Published 2021 Oct 1. doi:10.1038/s41467-021-26055-8.
57. Olia AS, Tsybovsky Y, Chen SJ, et al. SARS-CoV-2 S2P spike ages through distinct states with altered immunogenicity. J Biol Chem. 2021;297(4) :101127. doi:10.1016/j.jbc.2021.101127.
58. Xu J, Xu K, Jung S, et al. Nanobodies from camelid mice and llamas neutralize SARS-CoV-2 variants. Nature. 2021;595(7866):278-282. doi:10. 1038/s41586-021-03676-z.
59. Zhou T, Wang L, Misasi J, et al. Structural basis for potent antibody neutralization of SARS-CoV-2 variants including B.1.1.529. Science. 2022;376(65 91):eabn8897. doi:10.1126/science.abn8897.
60. López-Cortés GI, Palacios-Pérez M, Veledíaz HF, et al. The Spike Protein of SARS-CoV-2 Is Adapting Because of Selective Pressures. Vaccines (Basel). 2022;10(6):864. Published 2022 May 28. doi:10.3390/vaccines10060864
61. Pinho SS, Alves I, Gaifem J, Rabinovich GA. Immune regulatory networks coordinated by glycans and glycan-binding proteins in autoimmunity and infection. Cell Mol Immunol. 2023;20(10) :1101-1113. doi:10.1038/s41423-023-01074-1
62. Sirohi PR, Gupta J, Somvanshi P, Prajapati VK, Grover A. Multiple epitope-based vaccine prediction against SARS-CoV-2 spike glycoprotein. J Biomol Struct Dyn. 2022;40(8):3347-3358. doi:10 .1080/07391102.2020.1846626
63. Surti M, Patel M, Adnan M, et al. Ilimaquinone (marine sponge metabolite) as a novel inhibitor of SARS-CoV-2 key target proteins in comparison with suggested COVID-19 drugs: designing, docking and molecular dynamics simulation study. RSC Adv. 2020;10(62):37707-37720. Published 2020 Oct 13. doi:10.1039/d0ra06379g