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A comprehensive account of SARS-CoV-2 genome structure, incurred mutations, lineages and COVID-19 vaccination program

    Vijay Rani Rajpal

    *Author for correspondence: Tel.: +91 981 173 8058;

    E-mail Address: vijayrani2@gmail.com

    Hansraj College, University of Delhi, Delhi, 110007, India

    ,
    Shashi Sharma

    Virology Division, Defence Research and Development Establishment, Gwalior, Madhya Pradesh, 474002, India

    ,
    Deepmala Sehgal

    International Maize & Wheat Improvement Center (CIMMYT) Carretera México-Veracruz Km. 45, El Batán, Texcoco, 56237, México

    ,
    Apekshita Singh

    Amity Institute of Biotechnology, Amity University Uttar Pradesh, Sector 125, Noida, Uttar Pradesh, India

    ,
    Avinash Kumar

    Department of Botany, Vinoba Bhave University, Hazaribag, Jharkhand, 825319, India

    ,
    Samantha Vaishnavi

    Department of Botany, Central University of Jammu, Rahya Suchani (Bagla), Distt. Samba, Jammu and Kashmir, 181143, India

    ,
    Mugdha Tiwari

    ICMR-National Institute of Occupational Health (ICMR-NIOH), Meghaninagar, Ahmedabad, 380016, India

    ,
    Hemal Bhalla

    Department of Botany, University of Delhi, Delhi, 110007, India

    ,
    Shailendra Goel

    Department of Botany, University of Delhi, Delhi, 110007, India

    &
    Soom Nath Raina

    Amity Institute of Biotechnology, Amity University Uttar Pradesh, Sector 125, Noida, Uttar Pradesh, India

    Published Online:https://doi.org/10.2217/fvl-2021-0277

    This review collates information on the onset of COVID-19, SARS-CoV-2 genome architecture, emergence of novel viral lineages that drove multiple waves of infection around the world and standard and fast track development of vaccines. With the passage of time, the continuously evolving SARS-CoV-2 has acquired an expanded mutational landscape. The functional characterization of spike protein mutations, the primary target of diagnostics, therapeutics and vaccines has revealed increased transmission, pathogenesis and immune escape potential in the variant lineages of the virus. The incurred mutations have also resulted in substantial viral neutralization escape to vaccines, monoclonal, polyclonal and convalescent antibodies presently in use. The present situation suggests the need for development of precise next-generation vaccines and therapeutics by targeting the more conservative genomic viral regions for providing adequate protection.

    Papers of special note have been highlighted as: • of interest; •• of considerable interest

    References

    • 1. Briz-Redón Á, Serrano-Aroca Á. The effect of climate on the spread of the COVID-19 pandemic: a review of findings, and statistical and modeling techniques. Prog. Phys. Geog: Earth Environ. 44(5), 591–604 (2020).
    • 2. Briz-Redón Á, Serrano-Aroca Á. A Spatio-temporal analysis for exploring the effect of temperature on COVID-19 early evolution in Spain. Sci. Total Environ. 728 (2020).
    • 3. Lundstrom K, Barh D, Uhal BD, Takayama K, Aljabali AAA, Abd El-Aziz TM et al. COVID-19 vaccines and thrombosis-roadblock or dead-end street? Biomolecules. 11(7), 1020 (2021).
    • 4. Briz-Redón Á, Serrano-Aroca Á. On the association between COVID-19 vaccination levels and incidence and lethality rates at a regional scale in Spain. Stoch. Environ. Res. Risk Assess. 5, 1–8 (2022).
    • 5. World Health Organization. WHO Coronavirus Disease Dashboard (Accessed 9 August 2021). https://covid19.who.int/
    • 6. Hassan SS, Ghosh S, Attrish D, Choudhury PP, Aljabali AAA, Uhal BD et al. Possible transmission flow of SARS-CoV-2 based on ACE2 features. Molecules. 25(24), 5906 (2020).
    • 7. Zhu N, Zhang D, Wang W et al. A novel coronavirus from patients with pneumonia in China, 2019. N. Eng. J. Med. 382, 727–733 (2020).
    • 8. Zhou H, Chen X, Hu T et al. A novel bat coronavirus closely related to SARS-CoV-2 contains natural insertions at the S1/S2 cleavage site of the spike protein. Curr. Biol. 30, 2196–2203.e3 (2020).
    • 9. Hoffmann M, Kleine-Weber H, Schroeder S et al. SARS-CoV-2 cell entry depends on ACE2 and TMPRSS2 and is blocked by a clinically proven protease inhibitor. Cell 16, 181(2), 271–280.e8 (2020).
    • 10. Cao C, Cai Z, Xiao X et al. The architecture of the SARS-CoV-2 RNA genome inside the virion. Nat. Commun. 12, 3917 (2021).
    • 11. Chan JF, Kok KH, Zhu Z et al. Genomic characterization of the 2019 novel human-pathogenic coronavirus isolated from a patient with atypical pneumonia after visiting Wuhan. Emerg. Microbes Infect. 9(1), 221–236 (2020).
    • 12. Kim S, Lee JH, Lee S et al. The progression of SARS coronavirus 2 (SARS-CoV2): mutation in the receptor-binding domain of spike gene. Immune. Netw. 20(5), 41 (2020).
    • 13. Bianchi M, Benvenuto D, Giovanetti M et al. SARS-CoV-2 envelope and membrane proteins: structural differences linked to virus characteristics? BioMed Res. Int. 4389089, 6 (2020).
    • 14. Huang Y, Yang C, Xu XF et al. Structural and functional properties of SARS-CoV-2 spike protein: potential antivirus drug development for COVID-19. Acta Pharmacol. Sin. 41, 1141–1149 (2020).
    • 15. Ou X, Liu Y, Lei X et al. Characterization of spike glycoprotein of SARS-CoV-2 on virus entry and its immune cross-reactivity with SARS-CoV. Nat. Commun. 11(1), 1620 (2020).
    • 16. Donoghue M, Wakimoto H, Maguire CT et al. Heart block, ventricular tachycardia, and sudden death in ACE2 transgenic mice with down-regulated connexins. J. Mol. Cell. Cardiol. 35(9), 1043–1053 (2003).
    • 17. Coutard B, Valle C, de Lamballerie X, Canard B, Seidah NG, Decroly E. The spike glycoprotein of the new coronavirus 2019-nCoV contains a furin-like cleavage site absent in CoV of the same clade. Antivir. Res. 176, 104742 (2020).
    • 18. Shang J, Wan Y, Luo C et al. Cell entry mechanisms of SARS-CoV-2. Proc. Natl Acad. Sci. USA. 117(21), 11727–11734 (2020).
    • 19. Belouzard S, Chu VC, Whittaker GR. Activation of the SARS coronavirus spike protein via sequential proteolytic cleavage at two distinct sites. Proc. Natl Acad. Sci. USA. 106(14), 5871–5876 (2009).
    • 20. GISAID. (2020). https://www.gisaid.org/
    • 21. WHO. Track SARS-CoV-2 variants (2021). https://www.who.int/en/activities/tracking-SARS-CoV-2-variants/
    • 22. Centre for Disease Control and Prevention. COVID data tracker (2021). https://covid.cdc.gov/covid-data-tracker/#variant-proportions
    • 23. European Centre for Disease Prevention and Control. Data on SARS-Cov-2 variants in the EU/EEA. https://www.ecdc.europa.eu/en/publications-data/data-virus-variants-Covid-19-eueea
    • 24. Hoffmann M, Arora P, Groß R, Seidel A, Hörnich BF, Hahn AS et al. SARS-CoV-2 variants B.1.351 and P.1 escape from neutralizing antibodies. Cell 184(9), 2384–2393.e12 (2021).
    • 25. Aleem A, Akbar Samad AB, Slenker AK. Emerging variants of SARS-CoV-2 and novel therapeutics against coronavirus (COVID-19). In: StatPearls. FL, USA (2022).
    • 26. Li Q, Nie J, Wu J, Zhang L et al. SARS-CoV-2 501Y.V2 variants lack higher infectivity but do have immune escape. Cell 184(9), 2362–2371.e9 (2021).
    • 27. Johnson BA, Xie X, Bailey AL et al. Loss of furin cleavage site attenuates SARS-CoV-2 pathogenesis. Nature 591, 293–299 (2021).
    • 28. Centre for Disease Control and Prevention. A New SARS-CoV-2 variant of concern identified: the Omicron (B.1.1.529) variant
    • 29. Cascella M, Rajnik M, Cuomo A et al. Features, evaluation, and treatment of coronavirus (COVID-19). In: StatPearls FL, USA (2022).
    • 30. Michigan State University. SARS CoV-2 Mutation Tracker. https://users.math.msu.edu/users/weig/SARS-CoV-2_Mutation_Tracker.html
    • 31. Focosi D, Maggi F. Neutralising antibody escape of SARS‐CoV‐2 spike protein: risk assessment for antibody‐based COVID-19 therapeutics and vaccines. Rev. Med. Virol. 31(6), e2231 (2021).
    • 32. Jungreis I, Sealfon R, Kellis M. SARS-CoV-2 gene content and COVID-19 mutation impact by comparing 44 Sarbecovirus genomes. Nat. Commun. 12, 2642 (2021).
    • 33. Hassan SS, Attrish D, Ghosh S et al. Notable sequence homology of the ORF10 protein introspects the architecture of SARS-CoV-2. Int. J. Biol. Macromols. 181, 801–809 (2021a). • It describes the architecture of ORF10 protein of SARS-CoV-2.
    • 34. Hassan SS, Lundstrom K, Barh D et al. Implications derived from S-protein variants of SARS-CoV-2 from six continents. Int. J. Biol. Macromols. 191, 934–955 (2021b). • It describes the demography-specific evolution of S protein.
    • 35. Hassan SS, Lundstrom K, Serrano-Aroca Á et al. Emergence of unique SARS-CoV-2 ORF10 variants and their impact on protein structure and function. Int. J. Biol. Macromols. 194, 128–143 (2022a). •• It reports the emergence of dominant mutations in different countries with the incidence of highly frequent mutations.
    • 36. Hassan SS, Lundstrom K, Serrano-Aroca Á et al. Emergence of unique SARS-CoV-2 ORF10 variants and their impact on protein structure and function. Int. J. Biol. Macromols. 194, 128–143 (2022b).
    • 37. Hirabara SM, Serdan TDA, Gorjao R et al. SARSCOV-2 variants: differences and potential of immune evasion. Front. Cell. Infect. Microbiol. 11, 781429 (2022).
    • 38. Tegally H, Wilkinson E, Giovanetti M et al. Emergence and rapid spread of a new severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) lineage with multiple spike mutations in South Africa. MedRxiv. (2020). https://doi.org/10.1101/2020.12.21.20248640
    • 39. Harvey WT, Carabelli AM, Jackson B et al. SARS-CoV-2 variants, spike mutations, and immune escape. Nat. Rev. Microbiol. 19, 409–424 (2021).
    • 40. Coronavirus Antiviral and Resistance Database. SARS-Cov-2 variants. https://covdb.stanford.edu/page/mutation-viewer
    • 41. Kanekiyo M, Ellis D, King NP. New vaccine design and delivery technologies. J. Infect. Dis. 219(Suppl. 1), S88–S96 (2019).
    • 42. FDA. US Food and Drug Administration. https://www.fda.gov/vaccines-blood-biologics/development-approval-process-cber
    • 43. Pfizer Pharmaceuticals. Pfizer and BioNTech granted FDA fast-track designation for two investigational mRNA-based vaccine candidates against SARS-CoV-2. https://www.pfizer.com/news/press-release/press-release-detail
    • 44. European Pharmaceutical Review. FDA grants fast-track designation to two COVID-19 vaccines. https://www.europeanpharmaceuticalreview.com/
    • 45. European Pharmaceutical Review. EMA to fast-track development of COVID-19 vaccines and therapeutics. http://www.europeanpharmaceuticalreview.com/news
    • 46. Zhou H, Hen Y, Zhan S et al. Structural definition of a neutralization epitope on the N-terminal domain of MERS-CoV spike glycoprotein. Nat. Commun. 10, 3068 (2019).
    • 47. Yu J, Tostanoski LH, Peter L et al. DNA vaccine protection against SARS-CoV-2 in Rhesus macaques. Science 369, 806–811 (2020).
    • 48. Bloomberg. More than 10.6 billion shots given: COVID-19 tracker. https://www.bloomberg.com/graphics/covid-vaccine-tracker-global-distribution
    • 49. Robson F, Khan KS, Le TK et al. Coronavirus RNA proofreading: molecular basis and therapeutic targeting. Mol. Cell. 79(5), 710–727 (2020).
    • 50. Ju B, Jhang Q, Ge J et al. Human neutralizing antibodies elicited by SARS-CoV-2 infection. Nature 584, 115–119 (2020).
    • 51. Walls AC, Fiala B, Schäfer A et al. Elicitation of potent neutralizing antibody responses by designed protein nanoparticle vaccines for SARS-CoV-2. Cell 183(5), 1367–1382 (2020).
    • 52. Gao Q, Bao L, Mao H et al. Development of an inactivated vaccine candidate for SARS-CoV-2. Science 369, 77–81 (2020).
    • 53. Voysey M, Clemens SAC, Madhi SA, Wecks L, Folegatti PM. Safety and efficacy of the ChAdOx1 nCoV-19 vaccine (AZD1222) against SARS-CoV-2: an interim analysis of four randomized controlled trials in Brazil, South Africa, and the UK. Lancet 397(10269), 99–111 (2021).
    • 54. Yoo JH. What do we know and do not yet know about COVID-19 vaccines as of the beginning of the year 2021. Korean Med. Sci. 36, e54–e54 (2021).
    • 55. Khan KH. DNA vaccines: roles against diseases. Germs. 3, 26–35 (2013).
    • 56. Chavada VP, Pandya R, Apostolopoulos V. DNA vaccines for SARS-CoV-2: toward third-generation vaccination era. Expert Rev. Vaccines. 20(12), 1549–1560 (2021).
    • 57. Bošnjak B, Stein S C, Willenzon S et al. Low serum neutralizing anti-SARS-CoV-2 S antibody levels in mildly affected COVID-19 convalescent patients revealed by two different detection methods. Cell. Mol. Immunol. 18(4), 936–944 (2021).
    • 58. Hansen J, Baum A, Pascal KE et al. Studies in humanized mice and convalescent humans yield a SARS-CoV-2 antibody cocktail. Science 369(6506), 1010–1014 (2020).
    • 59. Planas D, Veyer D, Baidaliuk A et al. Reduced sensitivity of SARS-CoV-2 variant Delta to antibody neutralization. Nature 596, 276–280 (2021).
    • 60. Netzl A, Tureli S, LeGresley E et al. Analysis of SARS-CoV-2 omicron neutralization data up to 2021-12-22. BioRxiv. https://doi.org/10.1101/2021.12.31.474032 (2022) (Epub ahead of print). •• It describes the vaccine effectiveness and neutralization assays in the homologous or heterologous prime-boosted individuals.
    • 61. Bernal JL et al. Effectiveness of COVID-19 vaccines against the B.1.617.2 variant. N. Eng. J. Med. 385, e92 (2021).
    • 62. Dejnirattisai W, Zhou D, Supasa P et al. Antibody evasion by the P.1 strain of SARS-CoV-2. Cell 184(11), 2939–2954.e9 (2021).
    • 63. Chen X, Chen Z, Azman AS et al. Neutralizing antibodies against SARS-CoV-2 variants induced by natural infection or vaccination: a systematic review and pooled meta-analysis. Clin. Infect. Dis. 74 (4 )734 -742 (2022).
    • 64. Wang G L, Wang Z Y, Duan L J et al. Susceptibility of circulating SARS-CoV-2 variants to neutralization. N. Engl. J. Med. 384(24), 2354–2356 (2021).
    • 65. Andrews N, Tessier E, Stowe J et al. Duration of protection against mild and severe disease by COVID-19 vaccines. N. Engl. J. Med. 386, 340–350 (2022).
    • 66. Lau EH, Hui DS, Tsang OT et al. Long-term persistence of SARS-CoV-2 neutralizing antibody responses after infection and estimates of the duration of protection. eClinicalMedicine. 41, 101174 (2021).
    • 67. Schubert M, Bertoglio F, Steinke S, Heine PA et al. Human serum from SARS-CoV-2 vaccinated and COVID-19 patients show reduced binding to the RBD of SARS-CoV-2 omicron variant in comparison to the original Wuhan strain and the Beta and Delta variants. BMC Med. 20(1), 102 (2022).
    • 68. Cameroni E, Saliba C, Bowen JE et al. Broadly neutralizing antibodies overcome SARS-CoV-2 omicron antigenic shift. Nature 602, 664–670 (2021).
    • 69. Lu L, Mok B, Chen L et al. Neutralization of SARS-CoV-2 omicron variant by sera from BNT8162b2 or coronavac vaccine recipients. Clin. Infect. Dis. ciab1041 doi: 10.1093/CID/ciab1041 (2021) (Epub ahead of print).
    • 70. Liu J, Liu Y, Xia H, Zou J, Weaver SC, Swanson KA et al. BNT162b2-elicited neutralization of B.1.617 and other SARS-CoV-2 variants. Nature 596(7871), 273–27 (2021).
    • 71. Tao PL, Tzou J, Nouhin RK et al. The biological and clinical significance of emerging SARS-CoV-2 variants. Nat. Rev. Genet. 22, 757–773 (2021).
    • 72. Wu K, Werner AP, Moliva JI et al. mRNA-1273 vaccine induces neutralizing antibodies against spike mutants from global SARS-CoV-2 variants. BioRxiv. https://doi.org/10.1101/2021.01.25.427948 (2021) (Epub ahead of print).
    • 73. Klinakis A, Cournia Z, Rampias T. N-terminal domain mutations of the spike protein are structurally implicated in epitope recognition in emerging SARS-CoV-2 strains. Comput. Struct. Biotechnol. J. 4(19), 5556–5567 (2021).
    • 74. Ramesh S, Govindarajulu M, Parise RS et al. Emerging SARS-CoV-2 variants: a review of its mutations, its implications and vaccine efficacy. Vaccines. 9, 1195 (2021).
    • 75. Kimura I, Kosugi Y, Wu J et al. The genotype to phenotype Japan (G2P-Japan) consortium, Akatsuki Saito, So Nakagawa, Kei Sato. Cell Reports doi: 10.1016/j.celrep.2021.110218 (2021) (Epub ahead of print).
    • 76. Sarkar R, Lo M, Saha R, Dutta S, Sarkar MC. S glycoprotein diversity of the Omicron variant. MedRxiv. https://doi.org/10.1101/2021.12.04.21267284 (2021) (Epub ahead of print).
    • 77. Colson P, Delerce J, Burel E et al. Emergence in southern France of a new SARS-CoV-2 variant harboring both N501Y and E484K substitutions in the spike protein. Arch. Virol. 167 1185–1190 (2022).
    • 78. Tada T, Zhou H, Dcosta BM et al. High-titer neutralization of Mu and C.1.2 SARS-CoV-2 variants by vaccine-elicited antibodies of previously infected individuals. Cell Rep. 38(2), 110237 (2022).
    • 79. Stadtmüller M, Laubner A, Rost F et al. Emergence and spread of a sub-lineage of SARS-CoV-2 Alpha variant B.1.1.7 in Europe, and with further evolution of spike mutation accumulations shared with the Beta and Gamma variants. doi:10.1101/2021.11.01.21265749 (2022).
    • 80. Korber B, Fischer WM, Gnanakaran S et al. Spike mutation pipeline reveals the emergence of a more transmissible form of SARS-CoV-2. Cell. doi: 10.1016/j.cell.2020.06.043 (2020) (Epub ahead of print).
    • 81. Chaudhari AM, Kumar D, Joshi M, Patel A, Joshi C. E156G and Arg158, Phe-157/del mutation in NTD of spike protein in B.1.617.2 lineage of SARS-CoV-2 leads to immune evasion through antibody escape. doi:10.1101/2021.06.07.447321 (2021) (Epub ahead of print).
    • 82. Shen X, Tang H, McDanal C et al. C-CoV-2 variant B.1.1.7 is susceptible to neutralizing antibodies elicited by ancestral spike vaccines. Cell Host Microbe. 29, 529–539 (2021).
    • 83. Kumar S, Thambiraja TS, Karuppanan K, Subramaniam G. Omicron and Delta variant of SARS-CoV-2: a comparative computational study of the spike protein. J. Med. Virol. 94, 1641–1649 (2022).
    • 84. Sinha S, Tam B, Wang MS. Altered interaction between RBD and ACE2 receptor contributes toward the increased transmissibility of SARS CoV-2 Delta, Kappa, Beta, and Gamma strains with RBD double mutations. Viruses. doi: 10.3390/v14010001 (2021) (Epub ahead of print).
    • 85. Calcagnile M, Forgez P, Alifano M, Alifano P. The lethal triad: SARS-CoV-2 spike, ACE2 and TMPRSS2. Mutations in host and pathogen may affect the course of the pandemic. BioRxiv. https://doi.org/10.1101/2021.01.12.426365 (2021) (Epub ahead of print).
    • 86. Maaroufi H. The N764K and N856K mutations in SARS-CoV-2 Omicron BA.1 S protein generate potential cleavage sites for SKI-1/S1P protease https://doi.org/10.1101/2022.01.21.477298 (2022) (Epub ahead of print).
    • 87. Kemp SA, Collier DA, Datir RP et al. SARS-CoV-2 evolution during treatment of chronic infection. Nature 592, 277–282 (2021).
    • 88. Farkas C, Mella A, Haigh JJ. Large-scale population analysis of SARS-CoV-2 whole-genome sequences reveals host-mediated viral evolution with the emergence of mutations in the viral spike protein associated with elevated mortality rates. MedRxiv https://doi.org/10.1101/2020.10.23.20218511 (2020) (Epub ahead of print).
    • 89. Liu DX, Liang JQ, Fung TS. Human Coronavirus-229E, -OC43, -NL63, and -HKU1 (Coronaviridae). Encyclopedia Virol. 2 428–440 (2021).
    • 90. Peiris JS, Lai ST, Poon LL et al. SARS study group. Coronavirus as a possible cause of the severe acute respiratory syndrome. Lancet 361(9366), 1319–1325 (2003).
    • 91. Zaki AM, van Boheemen S, Bestebroer TM, Osterhaus AD, Fouchier RA. Isolation of a novel coronavirus from a man with pneumonia in Saudi Arabia. N. Engl. J. Med. 367(19), 1814–1820 (2012).