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SARS CoV-2’nin Karşılaştırmalı Genomik ve Proteomik Analizi – İlaç Hedefleme ve Potansiyel Mutasyon Olasılıkları

Year 2020, Volume: 13 Issue: 3, 1187 - 1197, 31.12.2020
https://doi.org/10.18185/erzifbed.758406

Abstract

Yüksek oranda patojenik SARS-CoV-2’nin neden olduğu COVID-19 dünya genelinde 470 binden fazla insanın ölümüne neden oldu. RNA virüslerinin yüksek mutasyon potansiyelleri tedavi için en doğru yapının tanımlanmasını gerektirir. Bu çalışmada COVID19’un aynı alt sınıfta yer alan SARS ve MERS ile karşılaştırmalı genomik, proteomik analizleri ve rezidülerin mutasyon potansiyelleri biyoinformatik araçlar ile analiz edildi. COVID19’un nükleotid düzeyinde SARS ile 80.08% ve MERS ile 58.79% benzer olduğu bulundu. GC% oranları COVID19, SARS ve MERS sırası ile 38%, 40.8% ve 41.2%’dir. 5’UTR GC içeriği COVID19 (44.6%), MERS (43.5%) ve SARS (44.7%)’dir. Aminoasit düzeyinde COVID19, SARS ile 83.3%, MERS ile 42.5% benzerlik gösterdi. Temel yapısal proteinler kıyaslandığında COVID19/SARS’ın E, M, N ve S-proteinleri sırasıyla 94.7, 90.1, 90.6 and 76,1% oranında aynıdır. COVID19 için 14 yüksek mutasyon riski olan rezidü ve genomda tekrar sayıları belirlendi. Sonuç olarak; COVID19 ve SARS’ın yüksek yapısal benzerlikleri proteinlerin fonksiyonel benzerliklerine işaret edebilir. Bu çalışmanın verileri, düşük mutasyon riski ile ORF6 ve ORF7b gibi fonksiyonel olmayan korunmuş proteinlerin fonksiyonel özellikleri ile tedavi için uygun hedefler olabileceğini işaret etmektedir.

References

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  • Carroll, H., Beckstead, W., O’Connor, T., Ebbert, M., Clement, M., Snell, Q. and Mcclellan, D. 2007. “DNA reference alignment benchmarks based on tertiary structure of encoded proteins”. Bioinformatics, 23(19), 2648–2649.
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  • Kumar, S., Stecher, G., Li, M., Knyaz, C. and Tamura, K. 2018. “MEGA X: Molecular evolutionary genetics analysis across computing platforms”. Molecular Biology and Evolution, 35(6), 1547–1549.
  • Lam, T. T. Y., Shum, M. H. H., Zhu, H. C., Tong, Y. G., Ni, X. B., Liao, Y. S., Wei, W., Cheung, W. Y. M., Li, W. J., Li, L. F., Leung, G. M., Holmes, E. C., Hu, Y. L. and Guan, Y. 2020. “Identification of 2019-nCoV related coronaviruses in Malayan pangolins in southern China”. bioRxiv, 945485, 1-22.
  • Li, C., Yang, Y. and Ren, L. 2020. “Genetic evolution analysis of 2019 novel coronavirus and coronavirus from other species”. Infection Genetics and Evolution, 82(104285), 1-3.
  • Lin, R. W., Chen, G. W., Sung, H. H., Lin, R. J., Yen, L. C., Tseng, Y. L., Chang, Y. K., Lien, S. P., Shih, S. R. and Liao, C. L. 2019. “Naturally occurring mutations in PB1 affect influenza A virus replication fidelity, virulence, and adaptability”. Journal of Biomedical Science, 26(55), 1-14.
  • Liu, C., Zhou, Q., Li, Y., Garner, L. V., Watkins, S. P., Carter, L. J., Smoot, J., Gregg, A. C., Daniels, A. D., Jervey, S. and Albaiu, D. 2020. “Research and development on therapeutic agents and vaccines for COVID-19 and related human Coronavirus diseases”. ACS Central Science, 6(3), 315–331.
  • Mahajan, M., Chatterjee, D., Bhuvaneswari, K., Pillay, S. and Bhattacharjya, S. 2018. “NMR structure and localization of a large fragment of the SARS-CoV fusion protein: Implications in viral cell fusion”. Biochimica et Biophysica Acta-Biomembranes, 1860(2), 407–415.
  • McBride, R. and Fielding, B. C. 2012. “The role of severe acute respiratory syndrome (SARS)-coronavirus accessory proteins in virus pathogenesis”. Viruses, 4(11), 2902–2923.
  • McWilliam, H., Li, W., Uludag, M., Squizzato, S., Park, Y. M., Buso, N., Cowley, A. P. and Lopez, R. 2013. “Analysis tool web services from the EMBL-EBI”. Nucleic Acids Research, 41(1), 597–600.
  • Muto, A. and Osawa, S. 1987. “The guanine and cytosine content of genomic DNA and bacterial evolution”. Proceedings of the National Academy of Sciences of the USA, 84(1), 166–169.
  • Overington, J. P., Al-Lazikani, B. and Hopkins, A. L. 2006. “How many drug targets are there?”. Nature Reviews Drug Discovery, 5(12), 993–996.
  • Panagiotou, E. and Plaxco, K. 2020. “A topological study of protein folding kinetics”. Topology and Geometry Biopolymers, 746, 223–234.
  • Pardi, N., Hogan, M. J., Porter, F. W. and Weissman, D. 2018. “mRNA vaccines-a new era in vaccinology”. Natere Reviews Drug Discovery, 17(4), 261–279.
  • Regla-Nava, J. A., Nieto-Torres, J. L., Jimenez-Guardeño, J. M., Fernandez-Delgado, R., Fett, C., Castaño-Rodríguez, C., Perlman, S., Enjuanes, L. and DeDiego, M. L. 2015. “Severe acute respiratory syndrome Coronaviruses with mutations in the E protein are attenuated and promising vaccine candidates”. Journal of Virology, 89(7), 3870–3887.
  • Rice, P., Longden, L. and Bleasby, A. 2000. “EMBOSS: The European Molecular Biology Open Software Suite”. Trends in Genetics, 16(6), 276–277.
  • Sémon, M., Mouchiroud, D. and Duret, L. 2005. “Relationship between gene expression and GC-content in mammals: Statistical significance and biological relevance”. Human Molecular Genetics, 14(3), 421–427.
  • Shen, S., Wen, Z. L. and Liu, D. X. 2003. “Emergence of a coronavirus infectious bronchitis virus mutant with a truncated 3b gene: Functional characterization of the 3b protein in pathogenesis and replication”. Virology, 311(1), 16–27.
  • Shereen, M. A., Khan, S., Kazmi, A., Bashir, N. and Siddique, R. 2020. “COVID-19 infection: Origin, transmission, and characteristics of human coronaviruses”. Journal of Advanced Research, 24, 91–98.
  • Tilocca, B., Soggiu, A., Sanguinetti, M., Musella, V., Britti, D., Bonizzi, L., Urbani, A. and Roncada, P. 2020. “Comparative computational analysis of SARS-CoV-2 nucleocapsid protein epitopes in taxonomically related coronaviruses”. Microbes and Infection, 22(4), 188-194.
  • Ul-Qamar, M. T., Alqahtani, S. M., Alamri, M. A., Chen, L. L. 2020. “Structural basis of SARS-CoV-2 3CLpro and anti-COVID-19 drug discovery from medicinal plants”. Journal of Pharmaceutical Analysis, 1-7.
  • Walls, A. C., Park, Y. J., Tortorici, M. A., Wall, A., McGuire, A. T. and Veesler, D. 2020. “Structure, function, and antigenicity of the SARS-CoV-2 spike glycoprotein”. Cell, 181(2), 281-292. Weiss, S. R. and Leibowitz, J. L. 2011. “Coronavirus pathogenesis”. Advances in Virus Research, 81, 85–164.
  • Wilkins, M. R., Gasteiger, E., Bairoch, A., Sanchez, J. C., Williams, K. L., Appel, R. D. and Hochstrasser, D. F. 1999. “Protein identification and analysis tools in the ExPASy server”. 2-D Proteome Analysis Protocols, 112, 531–552.
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  • Zhu, N., Zhang, D., Wang, W., Li, X., Yang, B., Song, J., Zhao, X., Huang, B., Shi, W., Lu, R., Niu, P., Zhan, F., Ma, X., Wang, D., Xu, W., Wu, G., Gao, G. F. and Tan, W. 2020. “A novel coronavirus from patients with pneumonia in China 2019”. New England Journal of Medicine, 382, 727–733.
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Comparative Genomic and Proteomic Analysis of SARS CoV-2 - with Potential Mutation Probabilities and Drug Targeting

Year 2020, Volume: 13 Issue: 3, 1187 - 1197, 31.12.2020
https://doi.org/10.18185/erzifbed.758406

Abstract

COVID-19 caused by the highly pathogenic SARS-CoV-2 has caused the death of over 470 thousand people worldwide. High mutation potentials of RNA viruses require the determination of the most accurate structure to be targeted for treatment. In this study, comparative genomic and proteomic analyses of SARS-CoV-2 were performed using SARS-CoV and MERS-CoV, and the mutation potential of the residues was analyzed using bioinformatics tools. SARS-CoV-2 was found to be 80.08% and 58.79% similar to SARS-CoV and MERS-CoV, respectively, at the nucleotide level. G+C content were 38%, 40.8% and 41.2% for SARS-CoV-2, SARS-CoV and MERS-CoV, respectively. 5ʹUTR G+C content was 44.6%, 43.5% and 44.7% for SARS-CoV-2, MERS-CoV and SARS-CoV, respectively. At the amino acid level, SARS-CoV-2 and SARS-CoV showed 83.3% similarity, whereas SARS-CoV-2 and MERS-CoV showed 42.5% similarity. The E, M, N and S proteins of SARS-CoV-2 and SARS-CoV were found to be 94%, 90.1%, 90.6% and 76.1% identical, respectively. For SARS-CoV-2, 14 residues with a high risk of mutation and their repeat numbers in the genome were identified. Data from this study reveal that non-functional conserved proteins such as ORF6 and ORF7b with low risk of mutation may be appropriate targets for the treatment because of their functional properties.

References

  • Abubucker, S., Martin, J., Taylor, C. M. and Mitreva, M. 2011. “HelmCoP: An online resource for Helminth functional genomics and drug and vaccine targets prioritization”. PLoS One, 6(7), 1-12.
  • Al-Osail, A. M. and Al-Wazzah, M. J. 2017. “The history and epidemiology of Middle East respiratory syndrome corona virüs”. Multidisciplinary Respiratory Medicine, 12(20), 1-6.
  • Badani, H., Garry, R. F. and Wimley, W. C. 2014. “Peptide entry inhibitors of enveloped viruses: The importance of interfacial hydrophobicity”. Biochimica et Biophysica Acta (BBA) – Biomembranes, 1838(9), 2180–2197.
  • Baltimore, D. 1971. “Expression of animal virus genomes”. Bacteriological Reviews, 35(3), 235–241.
  • Banerjee, A., Santra, D. and Maiti, S. 2020. “Energetics based epitope screening in SARS CoV-2 (COVID 19) spike glycoprotein by Immuno-informatic analysis aiming to a suitable vaccine development”. bioRxiv, 021725, 1-28.
  • Carroll, H., Beckstead, W., O’Connor, T., Ebbert, M., Clement, M., Snell, Q. and Mcclellan, D. 2007. “DNA reference alignment benchmarks based on tertiary structure of encoded proteins”. Bioinformatics, 23(19), 2648–2649.
  • Chan, J. F. W., Yuan, S., Kok, K. H., To, K. K. W., Chu, H., Yang, J., Xing, F., Liu, J., Yip, C. C. Y., Poon, R. W. S., Tsoi, H. W., Lo, S. K. F., Chan, K.H., Poon, V. K. M., Chan, W. M., Ip, J. D., Cai, J. P., Cheng, V. C. C., Chen, H., Hui, C. K. M. and Yuen, K. Y. 2020. “A familial cluster of pneumonia associated with the 2019 novel coronavirus indicating person-to-person transmission: a study of a family cluster”. Lancet, 395(10223), 514–523.
  • Chatterjee, S. 2020. “Understanding the nature of variations in structural sequences coding for Coronavirus spike, envelope, membrane and nucleocapsid proteins of SARS CoV-2”. SSRN Electron Journal, 1-12.
  • Drosten, C., Günther, S., Preiser, W., Van der Werf, S., Brodt, H. R., Becker, S., Rabenau, H., Panning, M., Kolesnikova, L., Fouchier, R. A. M., Berger, A., Burguière, A. M., Cinatl, J., Eickmann, M., Escriou, N., Grywna, K., Kramme, S., Manuguerra, J. C., Müller, S., Rickerts, V., Stürmer, M., Vieth, S., Klenk, H. D., Osterhaus, A. D. M. E., Schmitz, H. and Doerr, H. W. 2003. “Identification of a novel coronavirus in patients with severe acute respiratory syndrome”. New England Journal of Medicine, 348(20), 1967–1976.
  • Huang, C., Wang, Y., Li, X., Ren, L., Zhao, J., Hu, Y., Zhang, L., Fan, G., Xu, J., Gu, X., Cheng, Z., Yu, T., Xia, J., Wei, Y., Wu, W., Xie, X., Yin, W., Li, H., Liu, M., Xiao, Y., Gao, H., Guo, L., Xie, J., Wang, G., Jiang, R., Gao, Z., Jin, Q., Wang, J. and Cao, B. 2020a. “Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China”. Lancet, 395(10223), 497–506.
  • Huang, J. M., Jan, S. S., Wei, X., Wan, Y. and Ouyang, S. 2020b. “Evidence of the Recombinant Origin and Ongoing Mutations in Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2)”. bioRxiv, 993816, 1-16.
  • Ibrahim, I. M., Abdelmalek, D. H., Elshahat, M. E. and Elfiky, A. A. 2020. “COVID-19 spike-host cell receptor GRP78 binding site prediction”. Journal of Infection, 80, 554–562.
  • Jones, D. T., Taylor, W. R. and Thornton, J. M. 1992. “The rapid generation of mutation data matrices from protein sequences”. Bioinformatics, 8(3), 275–282.
  • Katoh, K. 2002. “MAFFT: a novel method for rapid multiple sequence alignment based on fast fourier transform”. Nucleic Acids Research, 30(14), 3059–3066.
  • Katoh, K., Rozewicki, J., Yamada, K. D. 2018. “MAFFT online service: Multiple sequence alignment, interactive sequence choice and visualization”. Briefings in Bioinformatics, 20(4), 1160–1166.
  • Kudla, G., Lipinski, L., Caffin, F., Helwak, A. and Zylicz, M. 2006. “High guanine and cytosine content increases mRNA levels in mammalian cells”. PLoS Biology, 4(6), 933–942.
  • Kumar, S. and Gadagkar, S. R. 2001. “Disparity index: A simple statistic to measure and test the homogeneity of substitution patterns between molecular sequences”. Genetics, 158, 1321–1327.
  • Kumar, S., Stecher, G., Li, M., Knyaz, C. and Tamura, K. 2018. “MEGA X: Molecular evolutionary genetics analysis across computing platforms”. Molecular Biology and Evolution, 35(6), 1547–1549.
  • Lam, T. T. Y., Shum, M. H. H., Zhu, H. C., Tong, Y. G., Ni, X. B., Liao, Y. S., Wei, W., Cheung, W. Y. M., Li, W. J., Li, L. F., Leung, G. M., Holmes, E. C., Hu, Y. L. and Guan, Y. 2020. “Identification of 2019-nCoV related coronaviruses in Malayan pangolins in southern China”. bioRxiv, 945485, 1-22.
  • Li, C., Yang, Y. and Ren, L. 2020. “Genetic evolution analysis of 2019 novel coronavirus and coronavirus from other species”. Infection Genetics and Evolution, 82(104285), 1-3.
  • Lin, R. W., Chen, G. W., Sung, H. H., Lin, R. J., Yen, L. C., Tseng, Y. L., Chang, Y. K., Lien, S. P., Shih, S. R. and Liao, C. L. 2019. “Naturally occurring mutations in PB1 affect influenza A virus replication fidelity, virulence, and adaptability”. Journal of Biomedical Science, 26(55), 1-14.
  • Liu, C., Zhou, Q., Li, Y., Garner, L. V., Watkins, S. P., Carter, L. J., Smoot, J., Gregg, A. C., Daniels, A. D., Jervey, S. and Albaiu, D. 2020. “Research and development on therapeutic agents and vaccines for COVID-19 and related human Coronavirus diseases”. ACS Central Science, 6(3), 315–331.
  • Mahajan, M., Chatterjee, D., Bhuvaneswari, K., Pillay, S. and Bhattacharjya, S. 2018. “NMR structure and localization of a large fragment of the SARS-CoV fusion protein: Implications in viral cell fusion”. Biochimica et Biophysica Acta-Biomembranes, 1860(2), 407–415.
  • McBride, R. and Fielding, B. C. 2012. “The role of severe acute respiratory syndrome (SARS)-coronavirus accessory proteins in virus pathogenesis”. Viruses, 4(11), 2902–2923.
  • McWilliam, H., Li, W., Uludag, M., Squizzato, S., Park, Y. M., Buso, N., Cowley, A. P. and Lopez, R. 2013. “Analysis tool web services from the EMBL-EBI”. Nucleic Acids Research, 41(1), 597–600.
  • Muto, A. and Osawa, S. 1987. “The guanine and cytosine content of genomic DNA and bacterial evolution”. Proceedings of the National Academy of Sciences of the USA, 84(1), 166–169.
  • Overington, J. P., Al-Lazikani, B. and Hopkins, A. L. 2006. “How many drug targets are there?”. Nature Reviews Drug Discovery, 5(12), 993–996.
  • Panagiotou, E. and Plaxco, K. 2020. “A topological study of protein folding kinetics”. Topology and Geometry Biopolymers, 746, 223–234.
  • Pardi, N., Hogan, M. J., Porter, F. W. and Weissman, D. 2018. “mRNA vaccines-a new era in vaccinology”. Natere Reviews Drug Discovery, 17(4), 261–279.
  • Regla-Nava, J. A., Nieto-Torres, J. L., Jimenez-Guardeño, J. M., Fernandez-Delgado, R., Fett, C., Castaño-Rodríguez, C., Perlman, S., Enjuanes, L. and DeDiego, M. L. 2015. “Severe acute respiratory syndrome Coronaviruses with mutations in the E protein are attenuated and promising vaccine candidates”. Journal of Virology, 89(7), 3870–3887.
  • Rice, P., Longden, L. and Bleasby, A. 2000. “EMBOSS: The European Molecular Biology Open Software Suite”. Trends in Genetics, 16(6), 276–277.
  • Sémon, M., Mouchiroud, D. and Duret, L. 2005. “Relationship between gene expression and GC-content in mammals: Statistical significance and biological relevance”. Human Molecular Genetics, 14(3), 421–427.
  • Shen, S., Wen, Z. L. and Liu, D. X. 2003. “Emergence of a coronavirus infectious bronchitis virus mutant with a truncated 3b gene: Functional characterization of the 3b protein in pathogenesis and replication”. Virology, 311(1), 16–27.
  • Shereen, M. A., Khan, S., Kazmi, A., Bashir, N. and Siddique, R. 2020. “COVID-19 infection: Origin, transmission, and characteristics of human coronaviruses”. Journal of Advanced Research, 24, 91–98.
  • Tilocca, B., Soggiu, A., Sanguinetti, M., Musella, V., Britti, D., Bonizzi, L., Urbani, A. and Roncada, P. 2020. “Comparative computational analysis of SARS-CoV-2 nucleocapsid protein epitopes in taxonomically related coronaviruses”. Microbes and Infection, 22(4), 188-194.
  • Ul-Qamar, M. T., Alqahtani, S. M., Alamri, M. A., Chen, L. L. 2020. “Structural basis of SARS-CoV-2 3CLpro and anti-COVID-19 drug discovery from medicinal plants”. Journal of Pharmaceutical Analysis, 1-7.
  • Walls, A. C., Park, Y. J., Tortorici, M. A., Wall, A., McGuire, A. T. and Veesler, D. 2020. “Structure, function, and antigenicity of the SARS-CoV-2 spike glycoprotein”. Cell, 181(2), 281-292. Weiss, S. R. and Leibowitz, J. L. 2011. “Coronavirus pathogenesis”. Advances in Virus Research, 81, 85–164.
  • Wilkins, M. R., Gasteiger, E., Bairoch, A., Sanchez, J. C., Williams, K. L., Appel, R. D. and Hochstrasser, D. F. 1999. “Protein identification and analysis tools in the ExPASy server”. 2-D Proteome Analysis Protocols, 112, 531–552.
  • Worldometer. “Coronavirus Cases”, https://www.worldometers.info/coronavirus/?, 25.06.2020
  • Zaki, A. M., Van Boheemen, S., Bestebroer, T. M., Osterhaus, A. D. M. E. and Fouchier, R. A. M. 2012. “Isolation of a novel coronavirus from a man with pneumonia in Saudi Arabia”. New England Journal of Medicine, 367(19), 1814–1820.
  • Zhu, N., Zhang, D., Wang, W., Li, X., Yang, B., Song, J., Zhao, X., Huang, B., Shi, W., Lu, R., Niu, P., Zhan, F., Ma, X., Wang, D., Xu, W., Wu, G., Gao, G. F. and Tan, W. 2020. “A novel coronavirus from patients with pneumonia in China 2019”. New England Journal of Medicine, 382, 727–733.
  • Zuckerkandl, E. and Pauling, L. 1965. “Evolutionary divergence and convergence in proteins”. Evolving Genes and Proteins, Academic Press, pp. 97–166.
There are 42 citations in total.

Details

Primary Language English
Subjects Engineering
Journal Section Makaleler
Authors

Ekrem Akbulut 0000-0002-7526-9835

Publication Date December 31, 2020
Published in Issue Year 2020 Volume: 13 Issue: 3

Cite

APA Akbulut, E. (2020). Comparative Genomic and Proteomic Analysis of SARS CoV-2 - with Potential Mutation Probabilities and Drug Targeting. Erzincan University Journal of Science and Technology, 13(3), 1187-1197. https://doi.org/10.18185/erzifbed.758406