We examined the coronavirus classification and evolution through its multiple mutations that have increased its transmissibility rate up to 70% globally, threatening to undermine the promise of a number of emerging vaccines that primarily focus on the immune detection of the Spike trimer. The safety and effectiveness of different vaccination methods are evaluated and compared, including the mRNA version, the Adenovirus DNA, Spike protein subunits, the deactivated virus genres, and the live attenuated coronavirus. Mutations have been long considered as random events, or mistakes during the viral RNA replication. Usually, what can go wrong will go wrong; therefore, repeated transformations lead to the extinction of a virus. On the contrary, the aggregate result of over 300,000 Covid-19 variants has expanded its transmissibility and infectiousness. Covid-19 mutations do not degrade the virus; they empower and facilitate its disguise to evade detection. Unlike other coronaviruses, Covid-19 amino acid switches do not reflect the random unfolding of errors that eventually eradicate the virus. Covid-19 appears to use mutations adaptively in the service of its survival and expansion. We cite evidence that Covid-19 inhibits the interferon type I production, compromising adaptive immunity from recognizing the virus. The deleterious consequences of the cytokine storm where the CD8+ killer cells injure the vital organs of the host may well be a Covid-19 manoeuvring to escape exposure. It is probable that evolution has programmed Covid-19 with an adeptness designed to debilitate key systemic defences to secure its subsistence. To date the infectiousness of the Covid-19 pandemic is exponentially increasing, denoting the possibility of an even more dangerously elusive, inconspicuous, and sophisticated version of the disease.
References
[1]
Li, F. (2016) Structure, Function, and Evolution of Coronavirus Spike Proteins. Annual Review of Virology, 3, 237-261.
https://doi.org/10.1146/annurev-virology-110615-042301
[2]
Decaro, N. and Lorusso, A. (2020) Novel Human Coronavirus (SARS-CoV-2): A Lesson from Animal Coronaviruses. Veterinary Microbiology, 244, Article ID: 108693. https://doi.org/10.1016/j.vetmic.2020.108693
http://www.sciencedirect.com/science/article/pii/S0378113520302935
[3]
Schütze, H. (2016) Coronaviruses in Aquatic Organisms. In: Kibenge, F.S.B. and Godoy, M.G., Eds., Aquaculture Virology, Academic Press, Cambridge, 327-335.
https://doi.org/10.1016/B978-0-12-801573-5.00020-6
https://www.sciencedirect.com/topics/agricultural-and-biological-sciences/deltacoronavirus
[4]
Zhou, P., Yang, X.L., Wang, X.G., Hu, B., Zhang, L., Zhang, W., et al. (2020) Discovery of a Novel Coronavirus Associated with the Recent Pneumonia Outbreak in Humans and Its Potential Bat Origin. bioRxiv.
https://doi.org/10.1101/2020.01.22.914952
[5]
Surjit, M. and Lal, S.K. (2010) The Nucleocapsid Protein of the SARS Coronavirus: Structure, Function and Therapeutic Potential. In: Lal, S., Ed., Molecular Biology of the SARS-Coronavirus, Springer, Berlin, Heidelberg, 129-151.
https://doi.org/10.1007/978-3-642-03683-5_9
[6]
Wu, A., Peng, Y., Huang, B., Ding, X., Wang, X., Niu, P., et al. (2020) Genome Composition and Divergence of the Novel Coronavirus (2019-nCoV) Originating in China. Cell Host & Microbe, 27, 325-328.
https://doi.org/10.1016/j.chom.2020.02.001
[7]
Ruan, Y.J., Wei, C.L., Ee, A.L., Vega, V.B., Thoreau, H., Su, S.T., et al. (2003) Comparative Full-Length Genome Sequence Analysis of 14 SARS Coronavirus Isolates and Common Mutations Associated with Putative Origins of Infection. Lancet, 361, 1779-1785. https://doi.org/10.1016/S0140-6736(03)13414-9
[8]
Yang, Z.Y., Werner, H.C., Kong, W.P., Leung, K., Traggiai, E., Lanzavecchia, A. and Nabel, G.J. (2005) Evasion of Antibody Neutralization in Emerging Severe Acute Respiratory Syndrome Coronaviruses. Proceedings of the National Academy of Sciences of the United States of America, 102, 797-801.
https://doi.org/10.1073/pnas.0409065102
[9]
Grifoni, A., Sidney, J., Zhang, Y., Scheuermann, R.H., Peters, B. and Sette, A. (2020) A Sequence Homology and Bioinformatic Approach Can Predict Candidate Targets for Immune Responses to SARS-CoV-2. Cell Host Microbe, 27, 670-680.E2.
https://doi.org/10.1016/j.chom.2020.03.002
[10]
Wu, F., Zhao, S., Yu, B., Chen, Y.M., Wang, W., Song, Z.G., Zhang, Y.Z., et al. (2020) A New Coronavirus Associated with Human Respiratory Disease in China. Nature, 579, 265-269. https://doi.org/10.1038/s41586-020-2008-3
[11]
Wrapp, D. and McLellan, J.S. (2019) The 3.1-Angstrom Cryo-Electron Microscopy Structure of the Porcine Epidemic Diarrhea Virus Spike Protein in the Prefusion Conformation. Journal of Virology, 93, e00923-19.
https://doi.org/10.1128/JVI.00923-19
[12]
Chi, X., Yan, R., Zhang, J., Zhang, G., Zhang, Y., Hao, M., Zhang, Z., Fan, P., Dong, Y., Yang, Y. and Chen, Z. (2020) A Neutralizing Human Antibody Binds to the N-Terminal Domain of the Spike Protein of SARS-CoV-2. Science, 369, 650-655.
https://doi.org/10.1126/science.abc6952
[13]
Litman, G.W., Rast, J.P., Shamblott, M.J., Haire, R.N., Hulst, M., Roess, W., Litman, R.T., Hinds-Frey, K.R., Zilch, A. and Amemiya, C.T. (1993) Phylogenetic Diversification of Immunoglobulin Genes and the Antibody Repertoire. Molecular Biology and Evolution, 10, 60-72. https://doi.org/10.1093/oxfordjournals.molbev.a040000
[14]
Wu, F., Wang, A., Liu, M., Wang, Q., Chen, J., Xia, S., et al. (2020) Neutralizing Antibody Responses to SARS-CoV-2 in a COVID-19 Recovered Patient Cohort and Their Implications. medRxiv, 2020–033020047365.
https://dx.doi.org/10.2139/ssrn.3566211
[15]
Lo, A.W., Tang, N.L. and To, K.F. (2006) How the SARS Coronavirus Causes Disease: Host or Organism? The Journal of Pathology, 208, 142-151.
https://doi.org/10.1002/path.1897
[16]
Chen, P., Nirula, A., Heller, B., Gottlieb, R.L., Boscia, J., Morris, J., et al. (2020) SARS-CoV-2 Neutralizing Antibody LY-CoV555 in Outpatients with Covid-19. New England Journal of Medicine, 384, 229-237.
https://doi.org/10.1056/NEJMoa2029849
[17]
Gaunt, E.R., Hardie, A., Claas, E.C., Simmonds, P. and Templeton, K.E. (2010) Epidemiology and Clinical Presentations of the Four Human Coronaviruses 229E, HKU1, NL63, and OC43 Detected over 3 Years Using a Novel Multiplex Real-Time PCR Method. Journal of Clinical Microbiology, 48, 2940-2947.
https://doi.org/10.1128/JCM.00636-10
[18]
Weiss, S.R. and Navas-Martin, S. (2005) Coronavirus Pathogenesis and the Emerging Pathogen Severe Acute Respiratory Syndrome Coronavirus. Microbiology and Molecular Biology Reviews, 69, 635-664.
https://doi.org/10.1128/MMBR.69.4.635-664.2005
[19]
Amanat, F., Stadlbauer, D., Strohmeier, S., Nguyen, T.H., Chromikova, V., McMahon, M., Jiang, K., Arunkumar, G.A., Jurczyszak, D., Polanco, J. and Bermudez-Gonzalez, M. (2020) A Serological Assay to Detect SARS-CoV-2 Seroconversion in Humans. Nature Medicine, 26, 1033-1036.
https://doi.org/10.1038/s41591-020-0913-5
[20]
Tang, F., Quan, Y., Xin, Z.T., Wrammert, J., Ma, M.J., Lv, H., Wang, T.B., Yang, H., Richardus, J.H., Liu, W. and Cao, W.C. (2011) Lack of Peripheral Memory B Cell Responses in Recovered Patients with Severe Acute Respiratory Syndrome: A Six-Year Follow-Up Study. The Journal of Immunology, 186, 7264-7268.
https://doi.org/10.4049/jimmunol.0903490
[21]
Wagner, A. and Weinberger, B. (2020) Vaccines to Prevent Infectious Diseases in the Older Population: Immunological Challenges and Future Perspectives. Frontiers in Immunology, 11, Article No. 717. https://doi.org/10.3389/fimmu.2020.00717
[22]
Braun, J., Loyal, L., Frentsch, M., Wendisch, D., Georg, P., Kurth, F., et al. (2020) SARS-CoV-2-Reactive T Cells in Healthy Donors and Patients with COVID-19. Nature, 587, 270-274. https://doi.org/10.1038/s41586-020-2598-9
[23]
Grifoni, A., Weiskopf, D., Ramirez, S.I., Mateus, J., Dan, J.M., Moderbacher, C.R., et al. (2020) Targets of T Cell Responses to SARS-CoV-2 Coronavirus in Humans with COVID-19 Disease and Unexposed Individuals. Cell, 181, 1489-1501.E15.
https://doi.org/10.1016/j.cell.2020.05.015
[24]
Prompetchara, E., Ketloy, C. and Palaga, T. (2020) Immune Responses in COVID-19 and Potential Vaccines: Lessons Learned from SARS and MERS Epidemic. Asian Pacific Journal of Allergy and Immunology, 38, 1-9.
http://apjai-journal.org/wp-content/uploads/2020/03/1.pdf?fbclid=IwAR1kVlFnoc6mobqEy7FDz_93fX__AaY8ZgE4TUwtjzhh8oVqgs82rgf3QoU
[25]
Faure, E., Poissy, J., Goffard, A., Fournier, C., Kipnis, E., Titecat, M., et al. (2014) Distinct Immune Response in two MERS-CoV-Infected Patients: Can We Go from Bench to Bedside? PLoS ONE, 9, e88716.
https://doi.org/10.1371/journal.pone.0088716
[26]
Killerby, M.E., Biggs, H.M., Haynes, A., Dahl, R.M., Mustaquim, D., Gerber, S.I. and Watson, J.T. (2018) Human Coronavirus Circulation in the United States 2014-2017. Journal of Clinical Virology, 101, 52-56.
https://doi.org/10.1016/j.jcv.2018.01.019
[27]
Maruggi, G., Zhang, C., Li, J., Ulmer, J.B. and Yu, D. (2019) mRNA as a Transformative Technology for Vaccine Development to Control Infectious Diseases. Molecular Therapy, 27, 757-772. https://doi.org/10.1016/j.ymthe.2019.01.020
[28]
Connors, M., Graham, B.S., Lane, H.C. and Fauci, A.S. (2021) SARS-CoV-2 Vaccines: Much Accomplished, Much to Learn. Annals of Internal Medicine.
https://doi.org/10.7326/M21-0111
[29]
Chen, W.H., Strych, U., Hotez, P.J. and Bottazzi, M.E. (2020) The SARS-CoV-2 Vaccine Pipeline: An Overview. Current Tropical Medicine Reports, 7, 61-64.
https://doi.org/10.1007/s40475-020-00201-6
[30]
Vartak, A. and Sucheck, S.J. (2016) Recent Advances in Subunit Vaccine Carriers. Vaccines, 4, 12. https://doi.org/10.3390/vaccines4020012
[31]
Gao, Q., Bao, L., Mao, H., Wang, L., Xu, K., Yang, M., et al. (2020) Development of an Inactivated Vaccine Candidate for SARS-CoV-2. Science, 369, 77-81.
https://doi.org/10.1126/science.abc1932
[32]
Li, L., Guo, P., Zhang, X., Yu, Z., Zhang, W. and Sun, H. (2020) SARS-CoV-2 Vaccine Candidates in Rapid Development. Human Vaccines & Immunotherapeutics, 1-10. https://doi.org/10.1080/21645515.2020.1804777
[33]
Ng, W.H., Liu, X. and Mahalingam, S. (2020) Development of Vaccines for SARS-CoV-2. F1000Research, 9. https://doi.org/10.12688/f1000research.25998.1
[34]
Chen, Y. and Li, L. (2020) SARS-CoV-2: Virus Dynamics and Host Response. The Lancet Infectious Diseases, 20, 515-516.
https://doi.org/10.1016/S1473-3099(20)30235-8
[35]
Wrapp, D., Wang, N., Corbett, K.S., Goldsmith, J.A., Hsieh, C.L., Abiona, O., Graham, B.S. and McLellan, J.S. (2020) Cryo-EM Structure of the 2019-nCoV Spike in the Prefusion Conformation. Science, 367, 1260-1263.
https://doi.org/10.1126/science.abb2507
[36]
Daniloski, Z., Jordan, T.X., Ilmain, J.K., Guo, X., Bhabha, G., tenOever, B.R. and Sanjana, N.E. (2020) The D614G Mutation in SARS-CoV-2 Spike Increases Transduction of Multiple Human Cell Types. bioRxiv.
https://doi.org/10.1101/2020.06.14.151357
[37]
Korber, B., Fischer, W.M., Gnanakaran, S., Yoon, H., Theiler, J., Abfalterer, W., et al. (2020) Tracking Changes in SARS-CoV-2 Spike: Evidence That D614G Increases Infectivity of the COVID-19 Virus. Cell, 182, 812-827.E19.
https://doi.org/10.1016/j.cell.2020.06.043
[38]
Callaway, E. (2020) Making Sense of Coronavirus Mutations. Nature, 585, 174-177.
https://search.bvsalud.org/global-literature-on-novel-coronavirus-2019-ncov/resource/en/covidwho-752538
[39]
van Dorp, L., Acman, M., Richard, D., Shaw, L.P., Ford, C.E., Ormond, L., et al. (2020) Emergence of Genomic Diversity and Recurrent Mutations in SARS-CoV-2. Infection, Genetics and Evolution, 83, Article ID: 104351.
https://doi.org/10.1016/j.meegid.2020.104351
[40]
Subissi, L., Posthuma, C.C., Collet, A., Zevenhoven-Dobbe, J.C., Gorbalenya, A.E., Decroly, E., Snijder, E.J., Canard, B. and Imbert, I. (2014) One Severe Acute Respiratory Syndrome Coronavirus Protein Complex Integrates Processive RNA Polymerase and Exonuclease Activities. Proceedings of the National Academy of Sciences, 111, E3900-E3909. https://doi.org/10.1073/pnas.1323705111
[41]
Bartolini, B., Rueca, M., Gruber, C.E.M., Messina, F., Giombini, E., Ippolito, G., Capobianchi, M.R. and Di Caro, A. (2020) The Newly Introduced SARS-CoV-2 Variant A222V is Rapidly Spreading in Lazio Region, Italy. medRxiv.
https://doi.org/10.1101/2020.11.28.20237016
[42]
Zhang, B.Z., Hu, Y.F., Chen, L.L., Yau, T., Tong, Y.G., Hu, J.C., Cai, J.P., Chan, K.H., Dou, Y., Deng, J. and Wang, X.L. (2020) Mining of Epitopes on Spike Protein of SARS-CoV-2 from COVID-19 Patients. Cell Research, 30, 702-704.
https://doi.org/10.1038/s41422-020-0366-x
[43]
He, S. and Wong, S.W. (2021) Statistical Challenges in The analysis of Sequence and Structure Data for the COVID-19 Spike Protein. arXiv Preprint arXiv:2101.02304.
https://arxiv.org/abs/2101.02304
[44]
Duong, D. (2021) What’s Important to Know about the New COVID-19 Variants? Canadian Medical Association Journal, 193, E141-E142.
https://doi.org/10.1503/cmaj.1095915
[45]
Liu, S., Shen, J., Fang, S., Li, K., Liu, J., Yang, L., Hu, C.D. and Wan, J. (2020) Genetic Spectrum and Distinct Evolution Patterns of SARS-CoV-2. Frontiers in Microbiology, 11, Article ID: 593548. https://doi.org/10.3389/fmicb.2020.593548
[46]
Arif, T. (2021) The 501.V2 and B.1.1.7 Variants of Coronavirus Disease 2019 (COVID-19): A New Time-Bomb in the Making? Infection Control & Hospital Epidemiology, 1-2. https://doi.org/10.1017/ice.2020.1434
[47]
Cheng, M.H., Krieger, J.M., Kaynak, B., Arditi, M.A. and Bahar, I. (2021) Impact of South African 501. V2 Variant on SARS-CoV-2 Spike Infectivity and Neutralization: A Structure-Based Computational Assessment. bioRxiv.
https://doi.org/10.1101/2021.01.10.426143
[48]
Lopez-Rincon, A., Perez-Romero, C., Tonda, A., Mendoza-Maldonado, L., Claassen, E., Garssen, J. and Kraneveld, A.D. (2021) Design of Specific Primer Sets for the Detection of B. 1.1. 7, B. 1.351 and P. 1 SARS-CoV-2 Variants Using Deep Learning. bioRxiv. https://doi.org/10.1101/2021.01.20.427043
