Acta Scientific Medical Sciences (ISSN: 2582-0931)

Research Article Volume 4 Issue 5

Clinical, Diagnostic and Therapeutic Implications of Coronavirus ORFab Polyprotein Associated Nsp16 Protein-A Bioinformatics Approach

Asit Kumar Chakraborty

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

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

Received: April 06, 2020; Published: May 04, 2020

×

Abstract

  COVID-19 infections are rapidly spreading worldwide with more than 100000 death and thus understanding the molecular mechanism of tropism of human cells is an urgent need for drug design. We have described here a bioinformatics approach to predict the functional aspects of non-structural nsp16 protein of Corona virus. The COVID-19 7096 AA large polyprotein was degraded into sixteen proteins and last nsp16 protein was found an RlmE type rRNA Methyltransferase. Nsp16 has no similarity to bacterial RlmABCD but has 25 percent similarity to the bacterial RlmE MTase protein which methylates the U2551 2-hydroxy group of Ribose. The nsp16 proteins of different corona viruses like Covid-19, bat-coronavirus, SARS and MERS have strong homology. Mrm2 and Dim1 like yeast and mammalian rRNA methyltransferases have 26-33 percent homologies but not with 2’-O-capping MTase as reported previously. Rrp8 MTases also has no similarity to nsp16. We postulated that mitochondrial rRNA methylation of bronchial cells were mediated by the nsp16 protein causing inhibition of protein synthesis due to poor assembly of aminoacyl-tRNA or mRNA and peptidyl transferase at the PTC. This is one of the new molecular mechanism of corona virus cellular tropism and different than ACE-2 mediated blockage of cellular signalling to inhibit aldesterone biosynthesis with abnormal Na+ ions in cells. We also designed primers based on nsp16 cDNA sequence (nt 20659-21552, accession no MT121215) specific for Covid-19 diagnosis by RT-PCR. Antisense and ribozyme against Nsp16 may be another molecular approach to stop Coronavirus translation using nano-carrier drug delivery. Whereas phyto-chemicals from Indian medicinal plants may be studied to stop functions of Nsp16 RlmE Methyltransferase as another therapeutic approach against Coronavirus pathogenesis.

Keywords:Covid-19; rlmE MTase; New Drug Target; Corona Diagnosis; Corona Pandemic

×

References

  1. Woo PC., et al. “Coronavirus diversity, phylogeny and interspecies jumping”. Experimental Biology and Medicine 10 (2009): 1117-1127.
  2. Woo PC., et al. “Comparative analysis of complete genome sequences of three avian coronaviruses reveals a novel group 3c coronavirus”. Journal of Virology 2 (2009): 908-917.
  3. Dominguez SR., et al. “Isolation, propagation, genome analysis and epidemiology of HKU1 betacoronaviruses”. Journal of General Virology 4 (2014): 836-848.
  4. Lau SK., et al. “Discovery of a novel coronavirus, China Rattus coronavirus HKU24,from Norway rats supports the murine origin of Betacoronavirus 1 and has implications for the ancestor of Betacoronavirus lineage A”. Journal of Virology 6 (2015): 3076-3092.
  5. 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.
  6. Liu DX., et al. “Accessory proteins of SARS-CoV and other coronaviruses”. Antiviral Research 109 (2014): 97-109.
  7. Zhao Y., et al. “Single-cell RNA expression profiling of ACE2, the putative receptor of Wuhan 2019-nCov”. Bio Rxiv (2020).
  8. Bauerle MR., et al. “Mechanistic diversity of radical S‐Adenosyl methionine SAM-dependent methylation”. Journal of Biological Chemistry 290 (2015): 3995-4002.
  9. Jiang Y., et al. “Unveiling the structural features that determine the dual methyltransferase activities of Streptococcus pneumonia RlmCD”. PLOS Pathogens 11 (2018): e1007379.
  10. 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.
  11. Michel G., et al. “The structure of the RlmB 23S rRNA methyltransferase reveals a new methyltransferase fold with a unique knot”. Structure 10 (2002): 1303-1315.
  12. Madsen CT., et al. “Identifying the methyltransferases for m5U747 and m5U1939 in 23S rRNA using MALDI mass spectrometry”. Nucleic Acids Research 31 (2003): 4738- 4746.
  13. Punekar AS., et al. “Structural and functional insights into the molecular mechanism of rRNA m6A methyltransferase RlmJ”. Nucleic Acids Research 20 (2013): 9537-9548.
  14. Toh SM., et al. “The methyltransferase YfgB/RlmN is responsible for modification of adenosine 2503 in 23S rRNA”. RNA 14 (2008): 98-106.
  15. Smietanski M., et al. “Structural analysis of human 2'-O ribose methyltransferases involved in mRNA cap structure formation”. Nature Communications 5 (2014): 3004.
  16. Ching YP., et al. “Identification and characterization of FTSJ2, a novel human nucleolar protein homologous to bacterial ribosomal RNA methyltransferase”. Genomics2 (2002): 2-6.
  17. Lee KW and Bogenhagen DF. “Assignment of 2'-O-methyltransferases to modification sites on the mammalian mitochondrial large subunit 16 S ribosomal RNA (rRNA)”. Journal of Biological Chemistry 36 (2014): 24936-24942.
  18. Egloff MP., et al. “An RNA cap (nucleoside-2′-O-)-methyltransferase in the flavivirus RNA polymerase NS5: crystal structure and functional characterization”. The EMBO Journal 21 (2002): 2757-2768.
  19. 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.
  20. Belanger F., et al. “Characterization of hMTr1, a human Cap1 2'-O-ribose methyltransferase”. Journal of Biological Chemistry 43 (2010): 33037-33044.
  21. Mungall AJ., et al. “The DNA sequence and analysis of human chromosome 6”. Nature6960 (2003): 805-811.
  22. Von Grotthuss M., et al. “mRNA cap-1 methyltransferase in the SARS genome”. Cell 113 (2003): 701-702.
  23. Chakraborty AK., et al. “Universal Primer Design for the Detection of Diverged CTX-M Extended Spectrum β-Lactamases (ESBL) That Give Penicillin and Cephalosporin Resistance During Superbug Infections”. In book “Biotechnological Applications in Human Health” Editors: Sadhukhan and Premi, Springer-Nature Singapore Pte Ltd, Chapter (2020): 6.
  24. Decroly E., et al. “Coronavirus non-structural protein 16 is a cap-O-binding enzyme possessing Nucleoside-2’-O)-methyltransferase activity”. Journal of Virology 16 (2008): 8071-8084.
  25. Ferron F., et al. “The viral RNA capping machinery as a target for antiviral drugs”. Antiviral Research 96 (2012): 21-31.
  26. 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.
  27. Zust R., et al. “Ribose 2′-O-methylation provides a molecular signature for the distinction of self and non-self mRNA dependent on the RNA sensor Mda5”. Nature Immunology 12 (2011): 137-143.
  28. Premkumar A., et al. “Cation-selective ion channels formed by p7 of hepatitis C virus are blocked by hexamethylene amiloride”. FEBS Letters 1-3 (2004): 99-103.
  29. Pham T., et al. “The rotavirus NSP4 viroporin domain is a calcium-conducting ion channel”. Scientific Reports 7 (2017): 43487.
  30. Schoeman D and Fielding BC. “Coronavirus envelope protein: current knowledge”. Virology Journal 1 (2019): 69.
  31. Ulasli M., et al. “The effects of Nigella sativa (Ns), Anthemis hyalina (Ah) and Citrus sinensis (Cs) extracts on the replication of coronavirus and the expression of TRP genes family”. Molecular Biology Reports 3 (2014):1703-1711.
  32. Kilianski A and Baker SC. “Cell-based antiviral screening against coronaviruses: Developing virus-specific and broad-spectrum inhibitors”. Antiviral Research 101 (2014): 105-112.
  33. De Wilde AH., et al. “Host Factors in Coronavirus Replication”. Current Topics in Microbiology and Immunology 419 (2018): 1-42.
  34. De Wilde AH., et al. “Alisporivir inhibits MERS- and SARS-coronavirus replication in cell culture, but not SARS coronavirus infection in a mouse model”. Virus Research 228 (2017): 7-13.
  35. Prentice E., et al. “Coronavirus replication complex formation utilizes components of cellular autophagy”. Journal of Biological Chemistry 11 (2004): 10136-10141.
  36. Chakraborty AK. “Heterogeneous phyto-antibiotics and other future therapeutics against multi-drug resistant bacteria”. Advances in Biochemical 2 (2019): 34-50.
  37. Newman DJ and Cragg GM. “Natural products as sources of new drugs over the 30 years from 1981 to 2010”. Journal of Natural Products 3 (2012): 311-335.
  38. 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 Advanced Drug Delivery 1 (2018): 1-9.
  39. Chakraborty AK. “Nucleic-Acids Based Nanocarriers”. In: “Nanocarriers for Drug Delivery”. editions. Mahapatra., et al. chapter-5 (2018): 155-172.
  40. Tan Y-J., et al. “Overexpression of 7a, a protein specifically encoded by the severe acute respiratory syndrome coronavirus, induces apoptosis via a caspase-dependent pathway”. Journal of Virology 24 (2004): 14043-14047.
  41. Falzarano D., et al. “ Treatment with interferon-alpha2b and ribavirin improves outcome in MERS-CoV-infected rhesus macaques”. Nature Medicine 19 (2013): 1313-1317.
  42. Cao J., et al. “A screen of the NIH Clinical Collection small molecule library identifies potential anti-coronavirus drugs”. Antiviral Research 114 (2015): 1-10.
  43. Mao X., et al. “Yeast mRNA cap methyltransferase is a 50-kilodalton protein encoded by an essential gene”. Molecular and Cellular Biology 15 (1995): 4167-4174.
  44. Rother M., et al. “Mode RNA: a tool for comparative modeling of RNA 3D structure”. Nucleic Acids Research 39 (2011): 4007-4022.
  45. Surya W., et al. “MERS coronavirus envelope protein has a single transmembrane domain that forms pentameric ion channels”. Virus Research 201 (2015): 61-66.
×

Citation

Citation: Asit Kumar Chakraborty. “Clinical, Diagnostic and Therapeutic Implications of Coronavirus ORFab Polyprotein Associated Nsp16 Protein-A Bioinformatics Approach". Acta Scientific Medical Sciences 4.5 (2020): 97-103.




Metrics

Acceptance rate30%
Acceptance to publication20-30 days
Impact Factor1.403

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 April 30th, 2024.
  • 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