Acta Scientific Medical Sciences (ISSN: 2582-0931)

Research Article Volume 4 Issue 10

Corona Virus ORF1ab-Derived Nsp7 and Nsp8 Small Non-Structural Proteins Including Previously Published Nsp9/10/13/16 Share Homologies to the Ribosomal Proteins as Well as rRNA Methyltransferases and Inhibit Host Protein Synthesis

Asit Kumar Chakraborty*

Associate Professor of Biochemistry, Department of Biotechnology and Biochemistry, Oriental Institute of Science and Technology, West Bengal and Vidyasagar University, Midnapore, India

*Corresponding Author: Asit Kumar Chakraborty, Associate Professor of Biochemistry, Department of Biotechnology and Biochemistry, Oriental Institute of Science and Technology, West Bengal and Vidyasagar University, Midnapore, India.

Received: June 25, 2020; Published: September 17, 2020

×

Abstract

Corona virus ORF1ab polyprotein-derived Nsp7 and Nsp8 are small proteins of 83aa and 198aa whose functions remain elusive as replication factors of Nsp12 RNA-dependent RNA polymerase. Using multi-alignment approaches we found such RNA binding proteins might have rRNA methyltransferase activities resembling Escherichia coli RlmB and RlmH like enzymes. Phylogenetic analysis suggested Nsp7 was cryptic MTase enzyme as compared to other methyltransferases but Nsp8 could be a vital methylating enzyme with similarity to S30 transposase. Moreover, Nsp8 has weak similarity to S2 ribosomal protein and L16 ribosomal proteins and Nsp7 to S8 ribosomal protein. We surprised to describe that Nsp7/8, Nsp9/10, Nsp13-16 and Nsp2 all have similarities to different ribosomal proteins (< 25%) which were also small RNA-binding proteins. We postulated both orf1a (4405aa) and ORF1ab (7096aa) large proteins act as rRNAs sequesters affecting ribosome turnover. Thus, methylation is a preference mechanism of Corona virus pathogenesis whereas COXI and COXII host mitochondrial enzymes synthesis may be affected causing low ATP synthesis followed by platelets aggregation and blood clotting in the lungs, heart and brain. Other words, we demonstrated new Corona virus targets that were never explored. Never-the-less the patients who were dying have weak immune-system and maximum load of virus occurred leading to coma and death but in maximum young patients the Corona virus was cleared by immune-system before the viruses could spread into other organs and the patients were recovered within 3 - 4 weeks.

Keywords: Nsp7 and Nsp8; Nsp Methyltransferase; Corona Virus Polyprotein; Clustal-Omega Software; Ribosomal Proteins Homologies

×

References

  1. Woo PC., et al. “Coronavirus diversity, phylogeny and interspecies jumping”. Experimental Biology and Medicine 10 (2009): 1117-1127.
  2. Liu DX., et al. “Accessory proteins of SARS-CoV and other coronaviruses”. Antiviral Research 109 (2014): 97-109.
  3. Dogan O., et al. “A comparative phylogenomics and demographic evolutionary history of SARS-CoV-2 (2020).
  4. Kiemer L., et al. “Coronavirus 3CL-pro proteinase cleavage sites: possible relevance to SARS virus pathology”. BMC Bioinformatics 5 (2004): 72.
  5. Mounir S., et al. “Characterization of the nonstructural and spike proteins of the human respiratory coronavirus OC43: comparison with bovine enteric coronavirus”. Advances in Experimental Medicine and Biology 342 (1993): 61-67.
  6. Huang J., et al. “Pharmacological Therapeutics Targeting RNA-Dependent RNA Polymerase, Proteinase and Spike Protein: From Mechanistic Studies to Clinical Trials for COVID-19”. Journal of Clinical Medicine Research 4 (2020): E1131.
  7. Lu G., et al. “Bat-to-human: Spike features determining ‘host jump’of coronaviruses SARS-CoV, MERS-CoV, and beyond”. Trends in Microbiology 8 (2015): 468-478.
  8. Marra MA., et al. “The Genome sequence of the SARS-associated coronavirus”. Science 300 (2003): 1399-1404.
  9. Dominguez SR., et al. “Isolation, propagation, genome analysis and epidemiology of HKU1 betacoronaviruses”. Journal of General Virology 4 (2014): 836-848.
  10. Lu G., et al. “Bat-to-human: Spike features determining ‘host jump’ of coronaviruses SARS-CoV, MERS-CoV, and beyond”. Trends in Microbiology 8 (2015): 468-478.
  11. Peng Z., et al. “A pneumonia outbreak associated with a new coronavirus of probable bat origin”. Nature1 (2020): 270-273.
  12. Salemi M., et al. “Severe acute respiratory syndrome coronavirus sequence characteristics and evolutionary rate estimate from maximum likelihood analysis”. Journal of Virology 78 (2004): 1602-1603.
  13. Arentz M., et al. “Characteristics and outcomes of 21 critically ill patients with COVID-19 in Washington State”. The Journal of the American Medical Association 16 (2020): 1612-1614.
  14. Krempl C., et al. “Analysis of cellular receptors for human coronavirus OC43”. Advances in Experimental Medicine and Biology 380 (1995): 371-374.
  15. Dominguez SR., et al. “Isolation, propagation, genome analysis and epidemiology of HKU1 betacoronaviruses”. Journal of General Virology 4 (2014): 836-848.
  16. Chakraborty AK. “Clinical, Diagnostic and Therapeutic Implications of Coronavirus ORFab Polyprotein Associated Nsp16 Protein-A Bioinformatics Approach”. Acta Scientific Medical Sciences5 (2020): 97-103.
  17. Chakraborty AK. “Coronavirus ORF1ab Polyprotein Associated Nsp16 Protein is a RlmE Methyltransferase and May Methylate 21S Mitochondrial rRNA of Host Cells Inhibiting Protein Synthesis (2020).
  18. Chakraborty Y AK. “Multi-Alignment Comparison of Coronavirus Non-Structural Proteins Nsp13-16 with Ribosomal proteins and other DNA/RNA modifying Enzymes Suggested Their Roles in the Regulation of Host Protein Synthesis”. India Rxiv (2020).
  19. Chakraborty AK. “Multi-Alignment Comparison of Coronavirus Non-Structural Proteins Nsp13-16 with Ribosomal proteins and other DNA/RNA modifying Enzymes Suggested Their Roles in the Regulation of Host Protein Synthesis”. International Journal of Clinical Medical Informatics1 (2020): 7-19.
  20. Chakraborty AK. “Coronavirus Nsp2 Protein Homologies to the Bacterial DNA Topoisomerase I and IV Suggest Nsp2 Protein Is a Unique RNA Topoisomerase with Novel Target for Drug and Vaccine Development”. OSF Preprints (2020).
  21. Chakraborty AK. “Coronavirus Nsp2 Protein Homologies to the Bacterial DNA Topoisomerase I and IV Suggest Nsp2 Protein Is a Unique RNA Topoisomerase with Novel Target for Drug and Vaccine Development”. Virology and Micology 9 (2020): 185.
  22. Chakraborty AK. “Ribosomal Proteins Homologies and Methylation of Mitoribosome by Corona Virus Nsp9, Nsp10 and Previously Described Nsp13-16 Proteins Suggested Their Roles in the Inhibition of Host Protein Synthesis: Discovery of New Therapeutic Targets against Corona Virus Infections (2020).
  23. Chakraborty AK. “Corona Virus ORF1ab-derived Nsp9 and Nsp10 non-structural proteins have homologies to S8/S10 ribosomal proteins as well as RlmG/ErmD rRNA methyltransferase and may inhibit mitoribosome assembly and protein synthesis”. Virology and Mycology 9 (2020): 186.
  24. Werner M., et al. “2′-O-ribose methylation of cap2 in human: function and evolution in a horizontally mobile family”. Nucleic Acids Research 39 (2011): 4756-4768.
  25. Von Grotthuss M., et al. “mRNA cap-1 methyltransferase in the SARS genome”. Cell 113 (2003): 701-702.
  26. Pletnev P., et al. “Comprehensive Functional Analysis of Escherichia coli Ribosomal RNA Methyltransferases”. Frontiers in Genetics 11 (2020): 97.
  27. Punekar AS., et al. “Structural and functional insights into the molecular mechanism of rRNA m6A methyltransferase”. Nucleic Acids Research 20 (2013): 9537-9548.
  28. Toh SM., et al. “The methyltransferase YfgB/RlmN is responsible for modification of adenosine 2503 in 23S rRNA”. RNA 14 (2008): 98-106.
  29. Bollati M., et al. “Recognition of RNA cap in the Wesselsbron virus NS5 methyltransferase domain: implications for RNA-capping mechanisms in Flavivirus”. Journal of Molecular Biology 385 (2009): 140-152.
  30. Jiang Y., et al. “Unveiling the structural features that determine the dual methyltransferase activities of Streptococcus pneumonia Rlm CD”. PLOS Pathogens 11 (2018): e1007379.
  31. D'Aquino AE., et al. “Mutational characterization and mapping of the 70S ribosome active site”. Nucleic Acids Research (2020): 001.
  32. Albert B., et al. “A ribosome assembly stress response regulates transcription to maintain proteome homeostasis”. eLife 8 (2019): e45002.
  33. De laCruz J., et al. “Functions of Ribosomal Proteins in Assembly of Eukaryotic Ribosomes In Vivo”. Annual Review of Biochemistry 84 (2015): 93-129.
  34. Chakraborty AK., et al. “Multidrug- Resistant Bacteria with activated and diversified MDR Genes in Kolkata Water: Ganga Action Plan and Heterogeneous Phyto-Antibiotics tackling superbug spread in India”. American Journal of Drug Delivery and Therapeutics 1 (2018): 1-9.
  35. Chakraborty AK., et al. “Transforming function of proto-ras genes depends on heterologous promoters and is enhanced by specific point mutations”. Proceedings of the National Academy of Sciences of the United States of America 88 (1991): 2217-2221.
  36. Lovgren JM and Wikstrom PM. “The rlmB gene is essential for formation of Gm2251 in 23S rRNA but not for ribosome maturation in Escherichia coli”. Journal of Bacteriology 183 (2001): 6957-6960.
  37. Ero R., et al. “Specificity and kinetics of 23S rRNA modification enzymes RlmH and RluD”. RNA11 (2010): 2075-2084.
  38. Coutard B., et al. “The spike glycoprotein of the new coronavirus 2019-nCoV contains a furin-like cleavage site absent in CoV of the same clade”. Antiviral Research 176 (2020): 104742.
  39. Grunewald ME., et al. “The coronavirus nucleocapsid protein is ADP-ribosylated”. Virology 517 (2018): 62-68.
  40. Kilianski A and Baker SC. “Cell-based antiviral screening against coronaviruses: Developing virus-specific and broad-spectrum inhibitors”. Antiviral Research 101 (2014): 105-112.
×

Citation

Citation: Asit Kumar Chakraborty. “Corona Virus ORF1ab-Derived Nsp7 and Nsp8 Small Non-Structural Proteins Including Previously Published Nsp9/10/13/16 Share Homologies to the Ribosomal Proteins as Well as rRNA Methyltransferases and Inhibit Host Protein Synthesis".Acta Scientific Medical Sciences 4.10 (2020): 22-28.




Metrics

Acceptance rate30%
Acceptance to publication20-30 days
Impact Factor0.851

Indexed In





News and Events


  • Certification for Review
    Acta Scientific certifies the Editors/reviewers for their review done towards the assigned articles of the respective journals.
  • Submission Timeline for Upcoming Issue
    The last date for submission of articles for regular Issues is September 30, 2021.
  • Publication Certificate
    Authors will be issued a "Publication Certificate" as a mark of appreciation for publishing their work.
  • Best Article of the Issue
    The Editors will elect one Best Article after each issue release. The authors of this article will be provided with a certificate of “Best Article of the Issue”.
  • Welcoming Article Submission
    Acta Scientific delightfully welcomes active researchers for submission of articles towards the upcoming issue of respective journals.
  • Contact US