Xanya Sofra
City University, London, New School for Social Research, New York, the United States
We traced the coronavirus classification and evolution, analyzed the Covid-19 composition and its distinguishing characteristics when compared to SARS-CoV and MERS-CoV. Despite their close kinship, SARS-CoV and Covid-19 display significant structural differences,including 380 amino acid substitutions, and variable homology between certain open reading frames that are bound to diversify the pathogenesis and virulence of the two viral compounds. A single amino acid substitution such as replacing Aspartate (D) with Glycine (G) composes the D614G mutation that is around 20% more infectious than its predecessor 614D. The B117 variant, that exhibits a 70% transmissibility rate, harbours 23 mutants,each reflecting one amino acid exchange. We examined several globally spreading mutations, 501.V2, B1351, P1, and others, with respect to the specific amino acid conversions involved. Unlike previous versions of coronavirus, where random mutations eventually precipitate extinction, the multiplicity of over 300,000 mutations appears to have rendered Covid-19 more contagious, facilitating its ability to evade detection, thus challenging the effectiveness of a large variety of emerging vaccines. Vaccination enhances immune memory and intelligence to combat or obstruct viral entry by generating antibodies that will prohibit the cellular binding and fusion with the Spike protein, restricting the virus from releasing its contents into the cell. Developing antibodies during the innate response,appears to be the most compelling solution in light of the hypothesis that Covid-19 inhibits the production of Interferon type I, compromising adaptive efficiency to recognize the virus, possibly provoking a cytokine storm that injures vital organs. With respect to that perspective, the potential safety and effectiveness of different vaccines are evaluated and compared,including the Spike protein mRNA version, the Adenovirus DNA, Spike protein subunits, the deactivated virus genres, or, finally, the live attenuated coronavirus that appears to demonstrate the greatest effectiveness, yet,encompass a relatively higher risk.
[1] Li, F., 2016. Structure, function, and evolution of coronavirus spike proteins. Annual review of virology, 3, pp.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,p.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 Aquaculture Virology (pp. 327-335).Academic Press.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., Si, H.R., Zhu, Y., Li, B., Huang,C.L.and Chen, H.D., 2020. Discovery of a novel coronavirus associated with the recent pneumonia outbreak in humans and its potential bat origin. BioRxiv.doi: 10.1038/s41586-020-2012-7. /DOI: 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 Molecular Biology of the SARS-Coronavirus (pp.129-151). Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-03683-5_9
[6] Wu, A., Peng, Y., Huang, B., Ding, X., Wang, X.,Niu, P., Meng, J., Zhu, Z., Zhang, Z., Wang, J.and Sheng, J., 2020. Genome composition and divergence of the novel coronavirus (2019-nCoV)originating in China. Cell host & microbe. https://doi.org/10.1016/j.chom.2020.02.001
[7] Ruan YJ, Wei CL, Ee AL, Vega VB, Thoreau H,Su ST, Chia JM, Ng P, Chiu, KP, Lim L, Zhang T,Peng CK, Lin EO, Lee NM, Yee SL, Ng LF, Chee RE, Stanton LW, Long PM, Liu ET. 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 ZY, Werner HC, Kong WP, Leung K, Traggiai E, Lanzavecchia A, Nabel, GJ. 2005. Evasion of antibody neutralization in emerging severe acute respiratory syndrome coronaviruses. Proc Natl Acad Sci U S A 102:797–801. https://doi.org/10.1073/pnas.0409065102.
[9] Grifoni A, Sidney J, Zhang Y, Scheuermann RH,Peters B, Sette A. 8 April 2020. A sequence homology and bioinformatic approach can predict candidate targets for immune responses to SARSCoV-2. Cell Host Microbe, https://doi.org/10.1016/j.chom.2020.03.002.
[10] 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.https://doi.org/10.1126/science.abb2507.
[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(23).m DOI: 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(6504), pp.650-655.DOI: 10.1126/science.abc6952
[13] Litman GW, Rast JP, Shamblott MJ, Haire RN, Hulst M,Roess W, Litman RT, Hinds-Frey KR,Zilch A, Amemiya CT (January 1993). “Phylogenetic diversification of immunoglobulin genes and the antibody repertoire”.Molecular Biology and Evolution. 10 (1): 60–72.DOI:10.1093/oxfordjournals.molbev.a040000
[14] Wu, F., Wang, A., Liu, M., Wang, Q., Chen, J., Xia,S., Ling, Y., Zhang, Y., Xun, J., Lu, L. and Jiang, S.,Neutralizing antibody responses to SARS-CoV-2 in a COVID-19 recovered patient cohort and their implications. medRxiv, 2020–033020047365 (2020). DOI:10.1101/2020.03. 30.20047365.Accessed 2020-04-29.https://doi.org/10.1101/2020.03.30.20047365(2020).
[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: A Journal of the Pathological Society of Great Britain and Ireland,208(2), pp.142-151. https://doi.org/10.1002/path.1897
[16] Chen, P., Nirula, A., Heller, B., Gottlieb, R.L., Boscia, J., Morris, J., Huhn, G., Cardona, J.,Mocherla,B., Stosor, V. and Shawa, I., 2020. SARS-CoV-2 neutralizing antibody LY-CoV555 in outpatients with Covid-19. New England Journal of Medicine.DOI: 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(8),pp.2940-2947.DOI: 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(4),pp.635-664.DOI: 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, pp.1-4.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(12), pp.7264-7268.DOI: 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, p.717.https://doi.org/10.3389/fimmu.2020.00717
[22] Braun, J., Loyal, L., Frentsch, M., Wendisch, D.,Georg, P., Kurth, F., Hippenstiel, S., Dingeldey,M.,Kruse, B., Fauchere, F. and Baysal, E., 2020. SARS CoV-2-reactive T cells in healthy donors and patients with COVID-19. Nature, pp.1-5. doi: https://doi.org/10.1101/2020.04.17.20061440
[23] Grifoni, A., Weiskopf, D., Ramirez, S.I., Mateus,J., Dan, J.M., Moderbacher, C.R., Rawlings,S.A.,Sutherland, A., Premkumar, L., Jadi, R.S. and Marrama, D., 2020. Targets of T cell responses to SARSCoV-2 coronavirus in humans with COVID-19 disease and unexposed individuals.Cell. 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 Pac J Allergy Immunol, 38(1),pp.1-9. http://apjai-journal.org/wp-content/uploads/2020/03/1.pdf?fbclid=IwAR1kVlFnoc-6mobqEy7FDz_93fX__AaY8ZgE4TUwtjzhh8oVqgs82rgf3QoU
[25] Faure, E., Poissy, J., Goffard, A., Fournier, C.,Kipnis, E., Titecat, M., Bortolotti, P., Martinez, L.,Dubucquoi, S., Dessein, R. and Gosset, P., 2014. Distinct immune response in two MERS-CoV-infected patients: can we go from bench to bedside?. PloS one, 9(2), p.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, pp.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(4),pp.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., 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,pp.1-4.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(2),p.12. https://doi.org/10.3390/vaccines4020012
[31] Gao, Q., Bao, L., Mao, H., Wang, L., Xu, K., Yang,M., Li, Y., Zhu, L., Wang, N., Lv, Z. and Gao,H.,2020. Development of an inactivated vaccine candidate for SARS-CoV-2. Science, 369(6499),pp.77-81.DOI: 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, pp.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. doi: 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(5), pp.515-516.DOI: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(6483), pp.1260-1263.DOI: 10.1126/science.abb2507
[36] Daniloski, Z., Guo, X. and Sanjana, N.E., 2020. The D614G mutation in SARS-CoV-2 Spike increases transduction of multiple human cell types. BioRxiv.DOI:https://doi.org/10.1101/2020.06.14.151357
[37] Korber, B., Fischer, W.M., Gnanakaran, S., Yoon, H.,Theiler, J., Abfalterer, W., Hengartner, N.,Giorgi,E.E., Bhattacharya, T., Foley, B. and Hastie, K.M.,2020. Tracking changes in SARS-CoV-2 Spike:evidence that D614G increases infectivity of the COVID-19 virus. Cell, 182(4), pp.812-827.https://doi.org/10.1016/j.cell.2020.06.043
[38] Callaway, E., 2020. Making sense of coronavirus mutations. Nature, pp.174-177. https://search.bvsalud.org/global-literature-on-novel-coronavirus-2019-ncov/resource/en/covidwho-752538, MEDLINE | ID: covidwho-752538
[39] van Dorp, L., Acman, M., Richard, D., Shaw, L.P.,Ford, C.E., Ormond, L., Owen, C.J., Pang, J.,Tan,C.C., Boshier, F.A. and Ortiz, A.T., 2020. Emergence of genomic diversity and recurrent mutations in SARS-CoV-2. Infection, Genetics and Evolution, 83, p.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(37), pp.E3900-E3909.
[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.DOI: 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(8), pp.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?.DOI: https://doi.org/10.1503/cmaj.1095915 de Alcañiz, J.G.G., Lopez-Rodas, V. and Costas, E., 2021.Sword of Damocles or choosing well. Population genetics sheds light into the future of the COVID-19 pandemic and SARS-CoV-2 new mutant strains. medRxiv. doi:https://doi.org/10.1101/2021.01.16.21249924
[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, p.2390.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 timebomb in the making? Infection Control & Hospital Epidemiology, 1-2.DOI: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.DOI: https://doi.org/10.1101/2021.01.10.426143
[48] 51Lopez-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 SARSCoV-2 Variants using Deep Learning. bioRxiv.DOI:https://doi.org/10.1101/2021.01.20.427043
Aims and Scope