Research Article
BibTex RIS Cite

Mutations in the SARS CoV2 Spike Gene and Their Reflections on the Spike Protein

Year 2022, , 472 - 478, 30.06.2022

Elif Çağlayan , Kadir Turan

https://doi.org/10.33808/clinexphealthsci.981816

Abstract

Objective: In this study, it was aimed to determine the mutation frequency in spike (S) genes of SARS CoV2 from six different regions of the world, their distribution on the gene and reflections of these mutations to the S protein.
Materials and methods: SARS CoV2 S gene sequences originating from Asia, Africa, Europe, South America, Oceania and North America were obtained from NCBI virus database. The sequences were analyzed with Geneious and BioEdit multiple sequence alignment programs.
Results and Conclusion: 865 distinct mutations on the S genes were detected in the virus samples. Among these, 59 variants with numbers of 10 and above in the virus population were detected. The D614G(A1841G) substitution was found to be the most common with an average of 88.6%. Furthermore, it was determined that S477N(G1430A) substitution in theviruses of Oceania differed from other regions with a rate of 86.7%. The average mutation frequency of the S genes from different regions was calculated as 4x10-5. The amino acid substitutions particularly in the RBD (receptor binding domain) have great importance for the virus adsorption to the cells via ACE2 (angiotensin converting enzyme 2) receptor and transmission. However, the importance of these mutations needs to be demonstrated both in silico and experimental studies.

Keywords

SARS CoV2 Coronavirus Covid-19 Spike protein Mutation

Supporting Institution

Health Institutes of Turkey (TUSEB)

Project Number

8608

References

  • [1] Rota PA, Oberste MS, Monroe SS, Nix WA, Campagnoli R, Icenogle JP, Penaranda S, Bankamp B, Maher K, Chen MH, Tong S, Tamin A, Lowe L, Frace M, DeRisi JL, Chen Q, Wang D, Erdman DD, Peret TC, Burns C, Ksiazek TG, Rollin PE, Sanchez A, Liffick S, Holloway B, Limor J, McCaustland K, OlsenRasmussen M, Fouchier R, Gunther S, Osterhaus AD, Drosten C, Pallansch MA, Anderson LJ, Bellini WJ. Characterization of a novel coronavirus associated with severe acute respiratory syndrome. Science 2003; 300: 1394-1399.
  • [2] Azhar EI, El-Kafrawy SA, Farraj SA, Hassan AM, Al-Saeed MS, Hashem AM, Madani TA. Evidence for camel-to-human transmission of MERS coronavirus. N Engl J Med 2014; 370: 2499-505.
  • [3] 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 2012; 367: 1814- 1820.
  • [4] Zhang X, Tan Y, Ling Y, Lu G, Liu F, Yi Z, Jia X, Wu M, Shi B, Xu S, Chen J, Wang W, Chen B, Jiang L, Yu S, Lu J, Wang J, Xu M, Yuan Z, Zhang Q, Zhang X, Zhao G, Wang S, Chen S, Lu H. Viral and host factors related to the clinical outcome of COVID-19. Nature 2020; 583: 437-440.
  • [5] Bertram S, Dijkman R, Habjan M, Heurich A, Gierer S, Glowacka I, Welsch K, Winkler M, Schneider H, HofmannWinkler H, Thiel V, Pohlmann S. TMPRSS2 activates the human coronavirus 229E for cathepsin-independent host cell entry and is expressed in viral target cells in the respiratory epithelium. J Virol 2013; 87: 6150-6160.
  • [6] Fehr AR, Perlman S. Coronaviruses: an overview of their replication and pathogenesis. Methods Mol Biol 2015; 1282: 1-23.
  • [7] Chan JF, Kok KH, Zhu Z, Chu H, To KK, Yuan S, Yuen KY. Genomic characterization of the 2019 novel human-pathogenic coronavirus isolated from a patient with atypical pneumonia after visiting Wuhan. Emerg Microbes Infect 2020; 9: 221-236.
  • [8] Duffy S. Why are RNA virus mutation rates so damn high? PLoS Biol 2018; 16: e3000003.
  • [9] Lauring AS, Andino R. Quasispecies theory and the behavior of RNA viruses. PLoS Pathog 2010; 6: e1001005.
  • [10] Boni MF, Gog JR, Andreasen V, Feldman MW. Epidemic dynamics and antigenic evolution in a single season of influenza A. Proc Biol Sci 2006; 273: 1307-1316.
  • [11] Taubenberger JK, Kash JC. Influenza virus evolution, host adaptation, and pandemic formation. Cell Host Microbe 2010; 7: 440-451.
  • [12] O’Donnell CD, Subbarao K. The contribution of animal models to the understanding of the host range and virulence of influenza A viruses. Microbes Infect 2011; 13: 502-515.
  • [13] Minskaia E, Hertzig T, Gorbalenya AE, Campanacci V, Cambillau C, Canard B, Ziebuhr J. Discovery of an RNA virus 3’->5’ exoribonuclease that is critically involved in coronavirus RNA synthesis. Proc Natl Acad Sci U S A 2006; 103: 5108-5113.
  • [14] Gorbalenya AE, Enjuanes L, Ziebuhr J, Snijder EJ. Nidovirales: evolving the largest RNA virus genome. Virus Res 2006; 117: 17-37.
  • [15] Walls AC, Park YJ, Tortorici MA, Wall A, McGuire AT, Veesler D. Structure, Function, and Antigenicity of the SARS-CoV-2 Spike Glycoprotein. Cell 2020; 181: 281-92 e6.
  • [16] Xia S, Zhu Y, Liu M, Lan Q, Xu W, Wu Y, Ying T, Liu S, Shi Z, Jiang S, Lu L. Fusion mechanism of 2019-nCoV and fusion inhibitors targeting HR1 domain in spike protein. Cell Mol Immunol 2020; 17: 765-767.
  • [17] Letko M, Marzi A, Munster V. Functional assessment of cell entry and receptor usage for SARS-CoV-2 and other lineage B betacoronaviruses. Nat Microbiol 2020; 5: 562-569.
  • [18] Pauly MD, Procario MC, Lauring AS. A novel twelve class fluctuation test reveals higher than expected mutation rates for influenza A viruses. Elife 2017; 6.
  • [19] Ogando NS, Ferron F, Decroly E, Canard B, Posthuma CC, Snijder EJ. The curious case of the nidovirus exoribonuclease: Its role in RNA synthesis and replication fidelity. Front Microbiol 2019; 10: 1813.
  • [20] Romano M, Ruggiero A, Squeglia F, Maga G, Berisio R. A Structural view of SARS-CoV-2 RNA replication machinery:

Year 2022, , 472 - 478, 30.06.2022

Elif Çağlayan , Kadir Turan

https://doi.org/10.33808/clinexphealthsci.981816

Abstract

Project Number

8608

References

  • [1] Rota PA, Oberste MS, Monroe SS, Nix WA, Campagnoli R, Icenogle JP, Penaranda S, Bankamp B, Maher K, Chen MH, Tong S, Tamin A, Lowe L, Frace M, DeRisi JL, Chen Q, Wang D, Erdman DD, Peret TC, Burns C, Ksiazek TG, Rollin PE, Sanchez A, Liffick S, Holloway B, Limor J, McCaustland K, OlsenRasmussen M, Fouchier R, Gunther S, Osterhaus AD, Drosten C, Pallansch MA, Anderson LJ, Bellini WJ. Characterization of a novel coronavirus associated with severe acute respiratory syndrome. Science 2003; 300: 1394-1399.
  • [2] Azhar EI, El-Kafrawy SA, Farraj SA, Hassan AM, Al-Saeed MS, Hashem AM, Madani TA. Evidence for camel-to-human transmission of MERS coronavirus. N Engl J Med 2014; 370: 2499-505.
  • [3] 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 2012; 367: 1814- 1820.
  • [4] Zhang X, Tan Y, Ling Y, Lu G, Liu F, Yi Z, Jia X, Wu M, Shi B, Xu S, Chen J, Wang W, Chen B, Jiang L, Yu S, Lu J, Wang J, Xu M, Yuan Z, Zhang Q, Zhang X, Zhao G, Wang S, Chen S, Lu H. Viral and host factors related to the clinical outcome of COVID-19. Nature 2020; 583: 437-440.
  • [5] Bertram S, Dijkman R, Habjan M, Heurich A, Gierer S, Glowacka I, Welsch K, Winkler M, Schneider H, HofmannWinkler H, Thiel V, Pohlmann S. TMPRSS2 activates the human coronavirus 229E for cathepsin-independent host cell entry and is expressed in viral target cells in the respiratory epithelium. J Virol 2013; 87: 6150-6160.
  • [6] Fehr AR, Perlman S. Coronaviruses: an overview of their replication and pathogenesis. Methods Mol Biol 2015; 1282: 1-23.
  • [7] Chan JF, Kok KH, Zhu Z, Chu H, To KK, Yuan S, Yuen KY. Genomic characterization of the 2019 novel human-pathogenic coronavirus isolated from a patient with atypical pneumonia after visiting Wuhan. Emerg Microbes Infect 2020; 9: 221-236.
  • [8] Duffy S. Why are RNA virus mutation rates so damn high? PLoS Biol 2018; 16: e3000003.
  • [9] Lauring AS, Andino R. Quasispecies theory and the behavior of RNA viruses. PLoS Pathog 2010; 6: e1001005.
  • [10] Boni MF, Gog JR, Andreasen V, Feldman MW. Epidemic dynamics and antigenic evolution in a single season of influenza A. Proc Biol Sci 2006; 273: 1307-1316.
  • [11] Taubenberger JK, Kash JC. Influenza virus evolution, host adaptation, and pandemic formation. Cell Host Microbe 2010; 7: 440-451.
  • [12] O’Donnell CD, Subbarao K. The contribution of animal models to the understanding of the host range and virulence of influenza A viruses. Microbes Infect 2011; 13: 502-515.
  • [13] Minskaia E, Hertzig T, Gorbalenya AE, Campanacci V, Cambillau C, Canard B, Ziebuhr J. Discovery of an RNA virus 3’->5’ exoribonuclease that is critically involved in coronavirus RNA synthesis. Proc Natl Acad Sci U S A 2006; 103: 5108-5113.
  • [14] Gorbalenya AE, Enjuanes L, Ziebuhr J, Snijder EJ. Nidovirales: evolving the largest RNA virus genome. Virus Res 2006; 117: 17-37.
  • [15] Walls AC, Park YJ, Tortorici MA, Wall A, McGuire AT, Veesler D. Structure, Function, and Antigenicity of the SARS-CoV-2 Spike Glycoprotein. Cell 2020; 181: 281-92 e6.
  • [16] Xia S, Zhu Y, Liu M, Lan Q, Xu W, Wu Y, Ying T, Liu S, Shi Z, Jiang S, Lu L. Fusion mechanism of 2019-nCoV and fusion inhibitors targeting HR1 domain in spike protein. Cell Mol Immunol 2020; 17: 765-767.
  • [17] Letko M, Marzi A, Munster V. Functional assessment of cell entry and receptor usage for SARS-CoV-2 and other lineage B betacoronaviruses. Nat Microbiol 2020; 5: 562-569.
  • [18] Pauly MD, Procario MC, Lauring AS. A novel twelve class fluctuation test reveals higher than expected mutation rates for influenza A viruses. Elife 2017; 6.
  • [19] Ogando NS, Ferron F, Decroly E, Canard B, Posthuma CC, Snijder EJ. The curious case of the nidovirus exoribonuclease: Its role in RNA synthesis and replication fidelity. Front Microbiol 2019; 10: 1813.
  • [20] Romano M, Ruggiero A, Squeglia F, Maga G, Berisio R. A Structural view of SARS-CoV-2 RNA replication machinery:
There are 20 citations in total.

Details

Primary Language English
Subjects Health Care Administration
Journal Section Articles
Authors

Elif Çağlayan 0000-0002-4249-0824

Kadir Turan 0000-0003-4175-3423

Project Number 8608
Publication Date June 30, 2022
Submission Date August 12, 2021
Published in Issue Year 2022

Cite

APA Çağlayan, E., & Turan, K. (2022). Mutations in the SARS CoV2 Spike Gene and Their Reflections on the Spike Protein. Clinical and Experimental Health Sciences, 12(2), 472-478. https://doi.org/10.33808/clinexphealthsci.981816
AMA Çağlayan E, Turan K. Mutations in the SARS CoV2 Spike Gene and Their Reflections on the Spike Protein. Clinical and Experimental Health Sciences. June 2022;12(2):472-478. doi:10.33808/clinexphealthsci.981816
Chicago Çağlayan, Elif, and Kadir Turan. “Mutations in the SARS CoV2 Spike Gene and Their Reflections on the Spike Protein”. Clinical and Experimental Health Sciences 12, no. 2 (June 2022): 472-78. https://doi.org/10.33808/clinexphealthsci.981816.
EndNote Çağlayan E, Turan K (June 1, 2022) Mutations in the SARS CoV2 Spike Gene and Their Reflections on the Spike Protein. Clinical and Experimental Health Sciences 12 2 472–478.
IEEE E. Çağlayan and K. Turan, “Mutations in the SARS CoV2 Spike Gene and Their Reflections on the Spike Protein”, Clinical and Experimental Health Sciences, vol. 12, no. 2, pp. 472–478, 2022, doi: 10.33808/clinexphealthsci.981816.
ISNAD Çağlayan, Elif - Turan, Kadir. “Mutations in the SARS CoV2 Spike Gene and Their Reflections on the Spike Protein”. Clinical and Experimental Health Sciences 12/2 (June 2022), 472-478. https://doi.org/10.33808/clinexphealthsci.981816.
JAMA Çağlayan E, Turan K. Mutations in the SARS CoV2 Spike Gene and Their Reflections on the Spike Protein. Clinical and Experimental Health Sciences. 2022;12:472–478.
MLA Çağlayan, Elif and Kadir Turan. “Mutations in the SARS CoV2 Spike Gene and Their Reflections on the Spike Protein”. Clinical and Experimental Health Sciences, vol. 12, no. 2, 2022, pp. 472-8, doi:10.33808/clinexphealthsci.981816.
Vancouver Çağlayan E, Turan K. Mutations in the SARS CoV2 Spike Gene and Their Reflections on the Spike Protein. Clinical and Experimental Health Sciences. 2022;12(2):472-8.

14639   14640