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Research Article Open access CC BY 4.0

Comparative Analyses of ACE2 Receptor Binding Corona Viruses that Cause Mild versus Severe Acute Respiratory Syndrome in Humans

Peramachi Palanivelu

Microbiology Research Journal International · pp. 64–85 · Published 23 Apr 2021

10.9734/mrji/2021/v31i230299

Abstract

Aim: To analyze the spike proteins and Replication-Transcription Complexes (RTCs) of the Mild and Severe Acute Respiratory Syndrome (SARS) and SARS-related coronaviruses (CoVs) to find out the similarities and differences between them, as both of groups bind to angiotensin-converting enzyme 2 (ACE2) receptor for human cell entry. Study Design: Bioinformatics, Biochemical, Site-Directed Mutagenesis (SDM), X-ray crystallographic, cryo-Electron microscopic (cryo-EM) and Mass Spectrometric (MS) data were analyzed. Methodology: The protein sequence data for spike proteins and the proteins of the RTCs, viz. the RNA- dependent RNA polymerases (RdRps), primases and the nonstructural protein 7 (NSP7) were obtained from PUBMED and SWISS-PROT databases. The advanced version of Clustal Omega was used for protein sequence analysis. Along with the conserved motifs identified by the bioinformatics analysis, the data already available by biochemical and SDM experiments and X-ray crystallographic and cryo-EM  studies on these  proteins were used to confirm the possible amino acids involved in ACE2 receptor binding and active sites of the RTCs. For identification of probable N-linked and O-linked glycosylation sites, NetNGlyc 1.0 and NetOGlyc 4.0 tools of Technical University of Denmark were used. ExPASy tool was used for pI analysis. Results: The spike protein of human CoV (HCoV)-NL63 is ~90 amino acids longer than the spike proteins of SARS and SARS-related CoVs. The additions are mostly found in the N-terminal regions and few insertions are also found in the crucial receptor binding domain (RBD). The SARS and SARS-related CoVs and HCoV-NL63 showed several conserved residues, motifs and large peptide regions. The most important aspect between the recent pandemic causing SARS-CoV-2 and HCoV-NL63 is a unique but different tetrapeptide insertions very close to the S1/S2 cleavage region, i.e., -PRRA-  and  -IPVR-, respectively. The next cleavage point S2’ and the transmembrane domains are conserved between the two groups. The RdRps are highly conserved between the two groups. The catalytic regions, catalytic amino acids and the NTP selection tripeptide regions are completely conserved between SARS-CoVs and HCoV-NL63.  However, one of the metal binding sites, viz. the universal –GDD- reported in all RdRps is aligning with– KDG- in the RdRp of HCoV-NL63. The other metal binding site, viz. –SDD- is completely conserved in both the groups. The NiRAN domains of the RdRps differed from the possible catalytic amino acid and NTP selection tripeptide regions. The primases (NSP8) and the NSP7 subunits of the RTC are highly conserved in both the groups. The NSP8 and NSP7 subunits exhibit closer similarities between the MERS-CoV and HCoV-NL63. Unlike other SARS and SARS-related CoVs, the HCoV-NL63 possesses only a single accessory protein. Interestingly, a large number of amino acids are replaced with Ns in the spike proteins (which is also reflected in the number of N-linked glycosylation sites in it) as well as in the RTC. Conclusions: Detailed analysis revealed several unique features in the HCoV-NL63 pathogen. As all the pandemic strains like SARS-CoV-1, SARS-CoV-2 and the milder HCoV-NL63 strain, use the same ACE2 receptor for entry into human cells, the frequent infection of humans by HCoV-NL63, especially in children, suggests that there is an ample opportunity for highly pathogenic variants to evolve in the future.

Coronaviruses SARS-CoVs HCoV-NL63 angiotensin-converting enzyme 2 spike proteins transcription-replication complex

References (41)

  1. 1 Two new Later Stone Age sites from the Final Pleistocene in the Falémé Valley, eastern Senegal [DOI]
  2. 2 A new coronavirus associated with human respiratory disease in China [DOI]
  3. 3 Genomic characterization of the 2019 novel human-pathogenic coronavirus isolated from a patient with atypical pneumonia after visiting Wuhan [DOI]
  4. 4 The Genome Sequence of the SARS-Associated Coronavirus [DOI]
  5. 5 Identification of a new human coronavirus [DOI]
  6. 6 Structure of the RNA-dependent RNA polymerase from COVID-19 virus [DOI]
  7. 7 Site-specific glycan analysis of the SARS-CoV-2 spike [DOI]
  8. 8 Hydrolysis of Biological Peptides by Human Angiotensin-converting Enzyme-related Carboxypeptidase [DOI]
  9. 9 Human coronavirus NL63 employs the severe acute respiratory syndrome coronavirus receptor for cellular entry [DOI]
  10. 10 ACE2 X-Ray Structures Reveal a Large Hinge-bending Motion Important for Inhibitor Binding and Catalysis [DOI]
  11. 11 Circulating SARS-CoV-2 spike N439K variants maintain fitness while evading antibody-mediated immunity [DOI]
  12. 12 One severe acute respiratory syndrome coronavirus protein complex integrates processive RNA polymerase and exonuclease activities [DOI]
  13. 13 Human Coronaviruses: A Review of Virus–Host Interactions [DOI]
  14. 14 Glycan shield and epitope masking of a coronavirus spike protein observed by cryo-electron microscopy [DOI]
  15. 15 The SARS-CoV-2 Spike Glycoprotein Biosynthesis, Structure, Function, and Antigenicity: Implications for the Design of Spike-Based Vaccine Immunogens [DOI]
  16. 16 Association between a Novel Human Coronavirus and Kawasaki Disease [DOI]
  17. 17 Crystal structure of NL63 respiratory coronavirus receptor-binding domain complexed with its human receptor [DOI]
  18. 18 Human Coronavirus NL63 Infection and Other Coronavirus Infections in Children Hospitalized with Acute Respiratory Disease in Hong Kong, China [DOI]
  19. 19 Croup Is Associated with the Novel Coronavirus NL63 [DOI]
  20. 20 A second, non‐canonical RNA‐dependent RNA polymerase in SARS Coronavirus [DOI]
  21. 21 Antagonism of the Interferon-Induced OAS-RNase L Pathway by Murine Coronavirus ns2 Protein Is Required for Virus Replication and Liver Pathology [DOI]
  22. 22 The SARS-coronavirus nsp7+nsp8 complex is a unique multimeric RNA polymerase capable of both de novo initiation and primer extension [DOI]
  23. 23 Discovery of an essential nucleotidylating activity associated with a newly delineated conserved domain in the RNA polymerase-containing protein of all nidoviruses [DOI]
  24. 24 Coronaviruses [DOI]
  25. 25 Understanding Human Coronavirus HCoV-NL63~!2009-11-13~!2010-04-09~!2010-05-25~! [DOI]
  26. 26 Glycosylation Quality Control by the Golgi Structure [DOI]
  27. 27 Two Mutations Were Critical for Bat-to-Human Transmission of Middle East Respiratory Syndrome Coronavirus [DOI]
  28. 28 Hemagglutinin-esterase, a novel structural protein of torovirus [DOI]
  29. 29 Identification of residues in the receptor-binding domain (RBD) of the spike protein of human coronavirus NL63 that are critical for the RBD–ACE2 receptor interaction [DOI]
  30. 30 Genome structure and transcriptional regulation of human coronavirus NL63 [DOI]
  31. 31 Subcellular localization and membrane association of SARS-CoV 3a protein [DOI]
  32. 32 Human Coronavirus-NL63 infections in Korean children, 2004–2006 [DOI]
  33. 33 Mutants of T7 RNA polymerase that are able to synthesize both RNA and DNA [DOI]
  34. 34 Advances and Trends in Biotechnology and Genetics Vol. 1 [DOI]
  35. 35 Association Between a Novel Human Coronavirus and Kawasaki Disease [DOI]
  36. 36 Characterization and Complete Genome Sequence of Human Coronavirus NL63 Isolated in China [DOI]
  37. 37 RNA Dependent RNA Polymerases of Severe Acute Respiratory Syndrome-Related Coronaviruses- An Insight into their Active Sites and Mechanism of Action [DOI]
  38. 38 Analyses of the Spike Proteins of Severe Acute Respiratory Syndrome-Related Coronaviruses [DOI]
  39. 39 Complete Genome Sequence of Human Coronavirus NL63 CN0601/14, First Isolated in South Korea [DOI]
  40. 40 Inhibition of HCoV-NL63 infection at early stages of the replication cycle [DOI]
  41. 41 Structure of replicating SARS-CoV-2 polymerase [DOI]

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