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Biological Sciences - Article
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The coronavirus named as SARS-CoV-2 is the cause of the COVID-19 pandemic and spreading rapidly1. It is a pneumonia outbreak2 with T cell exhaustion, cytokine storm and coagulation3,4. Short motifs on proteins play important roles on protein-protein interactions5,6. We hypothetized role of molecular mimicry of small-xxx-small motifs for the spike protein of SARS-CoV-2. Here we show that a unique and evolutionary conserved motif is found only on the spike protein of SARS-CoV-2 and stimulator of interferon genes (STING) proteins. Surprisingly we could not find this motif on any other protein of any living form. We found a similar, but not identical motif mimicry for the spike and regulator of G protein signaling 12 (RGS12), C1QT4 and also for proteins of Archaea and beta-lactamase enzymes of bacteria including Mycobacterium tuberculosis. STING proteins have roles on coagulation, T cell exhaustion, cytokine release1-3 and RGS12 on inflammation7. In contrast to cGAS-STING pathway8, the motif mimicry indicated a direct interaction between spike and STING proteins suggesting the importance of STING, RGS12 and C1QT4 on the pathogenesis of COVID-19. To our surprise, the molecular mimicry showed that beta-lactamase inhibitors may be effective against SARS-CoV-2. The motif is unique, as found on Archaea and Cnidaria it is evolutionary old but a new target and mechanism for the COVID-19.
Keywords
T cell exhaustion, Cytokine Storm, Coagulation, Protein Motifs, Interferon Genes, Pathogenesis, Molecular Mimicry
Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
There is NO Competing Interest.
This is a list of supplementary files associated with this preprint. Click to download.
- extendeddatafig01.pdf
Extended Data Fig. 1 Dendrogram showing the phylogenetic relationships of the STING and the spike proteins of all coronaviruses based on alignment of amino acid sequences generated by Clustal Omega and hierarchical cluster analysis using R.
- extendeddatafig02.pdf
Extended Data Fig. 2 A motif similarity between the spike protein of SARS-Cov-2 and the TRPM ion channels (TRPM1,TRPM2, TRPM3 and TRPM4) which is very different from the unique motif.
- extendeddatafig03.pdf
Extended Data Fig. 3 Motif similarity (A) for the protein of Mycoplasma pneumonia and the STING proteins, (B) for the proteins of Mycobacterium tuberculosis and the STING proteins and (C) for the proteins of STING proteins and the Klebsialla and Yersinia species.
- extendeddatafig04.pdf
Extended Data Fig. 4 Motif similarity (A) for the C1QT4, beta-lactamase enzymes, STING and the spike protein of SARS-CoV-2, (B) for the beta-lactamase enzymes and C1QT4, spike proteins of SARS-CoV, SARS-CoV-2, ribosomal protein of Methanosprillum hungatei and membrane protein of Methanococcus maripaludis of Archaea and (D) for the spike proteins of SARS-CoV, SARS-CoV- 2 and beta-lactamase enzymes. There is a new motif similarity different from the unique motif located adjacent to the unique motif. The new motif was shaded and the unique motif adjacent to it was shown by a red square.
- supplementforfigures.pdf
An ancient motif unique for human STING, RGS12 and SARS-CoV-2 spike
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A new preprint design is coming!
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This is a preprint, a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
Biological Sciences - Article
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
History
CURRENT STATUS: Posted
Version 2
Posted 11 Jan, 2021
No community comments so far
No comments provided
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
License:
This work is licensed under a CC BY 4.0 License. Read Full License
The coronavirus named as SARS-CoV-2 is the cause of the COVID-19 pandemic and spreading rapidly1. It is a pneumonia outbreak2 with T cell exhaustion, cytokine storm and coagulation3,4. Short motifs on proteins play important roles on protein-protein interactions5,6. We hypothetized role of molecular mimicry of small-xxx-small motifs for the spike protein of SARS-CoV-2. Here we show that a unique and evolutionary conserved motif is found only on the spike protein of SARS-CoV-2 and stimulator of interferon genes (STING) proteins. Surprisingly we could not find this motif on any other protein of any living form. We found a similar, but not identical motif mimicry for the spike and regulator of G protein signaling 12 (RGS12), C1QT4 and also for proteins of Archaea and beta-lactamase enzymes of bacteria including Mycobacterium tuberculosis. STING proteins have roles on coagulation, T cell exhaustion, cytokine release1-3 and RGS12 on inflammation7. In contrast to cGAS-STING pathway8, the motif mimicry indicated a direct interaction between spike and STING proteins suggesting the importance of STING, RGS12 and C1QT4 on the pathogenesis of COVID-19. To our surprise, the molecular mimicry showed that beta-lactamase inhibitors may be effective against SARS-CoV-2. The motif is unique, as found on Archaea and Cnidaria it is evolutionary old but a new target and mechanism for the COVID-19.
Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
There is NO Competing Interest.
This is a list of supplementary files associated with this preprint. Click to download.
- extendeddatafig01.pdf
Extended Data Fig. 1 Dendrogram showing the phylogenetic relationships of the STING and the spike proteins of all coronaviruses based on alignment of amino acid sequences generated by Clustal Omega and hierarchical cluster analysis using R.
- extendeddatafig02.pdf
Extended Data Fig. 2 A motif similarity between the spike protein of SARS-Cov-2 and the TRPM ion channels (TRPM1,TRPM2, TRPM3 and TRPM4) which is very different from the unique motif.
- extendeddatafig03.pdf
Extended Data Fig. 3 Motif similarity (A) for the protein of Mycoplasma pneumonia and the STING proteins, (B) for the proteins of Mycobacterium tuberculosis and the STING proteins and (C) for the proteins of STING proteins and the Klebsialla and Yersinia species.
- extendeddatafig04.pdf
Extended Data Fig. 4 Motif similarity (A) for the C1QT4, beta-lactamase enzymes, STING and the spike protein of SARS-CoV-2, (B) for the beta-lactamase enzymes and C1QT4, spike proteins of SARS-CoV, SARS-CoV-2, ribosomal protein of Methanosprillum hungatei and membrane protein of Methanococcus maripaludis of Archaea and (D) for the spike proteins of SARS-CoV, SARS-CoV- 2 and beta-lactamase enzymes. There is a new motif similarity different from the unique motif located adjacent to the unique motif. The new motif was shaded and the unique motif adjacent to it was shown by a red square.
- supplementforfigures.pdf
An ancient motif unique for human STING, RGS12 and SARS-CoV-2 spike
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