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The evolutionary making of SARS-CoV-2

View ORCID ProfileRuben Iruegas, Julian Dosch, View ORCID ProfileMateusz Sikora, View ORCID ProfileGerhard Hummer, View ORCID ProfileRoberto Covino, View ORCID ProfileIngo Ebersberger
doi: https://doi.org/10.1101/2021.01.29.428808
Ruben Iruegas
1Applied Bioinformatics Group, Inst of Cell Biology and Neuroscience, Goethe University Frankfurt, Frankfurt am Main, Germany
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  • ORCID record for Ruben Iruegas
Julian Dosch
1Applied Bioinformatics Group, Inst of Cell Biology and Neuroscience, Goethe University Frankfurt, Frankfurt am Main, Germany
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Mateusz Sikora
2Department of Theoretical Biophysics, Max Planck Institute of Biophysics, Frankfurt am Main, Germany
3Faculty of Physics, University of Vienna, Vienna, Austria
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Gerhard Hummer
2Department of Theoretical Biophysics, Max Planck Institute of Biophysics, Frankfurt am Main, Germany
4Institute of Biophysics, Goethe University Frankfurt, Frankfurt am Main, Germany
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Roberto Covino
5Frankfurt Institute for Advanced Studies (FIAS), Frankfurt am Main, Germany
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Ingo Ebersberger
1Applied Bioinformatics Group, Inst of Cell Biology and Neuroscience, Goethe University Frankfurt, Frankfurt am Main, Germany
6Senckenberg Biodiversity and Climate Research Centre (S-BIK-F), Frankfurt am Main, Germany
7LOEWE Centre for Translational Biodiversity Genomics (TBG), Frankfurt am Main, Germany
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  • For correspondence: ebersberger@bio.uni-frankfurt.de
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Abstract

A mechanistic understanding of how SARS-CoV-2 (sarbecovirus, betacoronavirus) infects human cells is emerging, but the evolutionary trajectory that gave rise to this pathogen is poorly understood. Here we scan SARS-CoV-2 protein sequences in-silico for innovations along the evolutionary lineage starting with the last common ancestor of coronaviruses. SARS-CoV-2 substantially differs from viruses outside sarbecovirus both in its set of encoded proteins and in their domain architectures, indicating divergent functional demands. Within sarbecoviruses, sub-domain level profiling using predicted linear epitopes reveals how the primary interface between host cell and virus, the spike, was gradually reshaped. The only epitope that is private to SARS-CoV-2 overlaps with the furin cleavage site, a “switch” that modulates spike’s conformational landscape in response to host-cell interaction. This cleavage site has fundamental relevance for both immune evasion and cell infection, and the apparently ongoing evolutionary fine-tuning of its use by SARS-CoV-2 should be monitored.

Competing Interest Statement

The authors have declared no competing interest.

Footnotes

  • The discussion related to the gain of the furin claevage site has been adjusted to better reflect the diverse role of this site during SARS-CoV-2 infection.

  • https://applbio.biologie.uni-frankfurt.de/download/SARS-CoV-2/

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY 4.0 International license.
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Posted February 05, 2021.
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The evolutionary making of SARS-CoV-2
Ruben Iruegas, Julian Dosch, Mateusz Sikora, Gerhard Hummer, Roberto Covino, Ingo Ebersberger
bioRxiv 2021.01.29.428808; doi: https://doi.org/10.1101/2021.01.29.428808
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The evolutionary making of SARS-CoV-2
Ruben Iruegas, Julian Dosch, Mateusz Sikora, Gerhard Hummer, Roberto Covino, Ingo Ebersberger
bioRxiv 2021.01.29.428808; doi: https://doi.org/10.1101/2021.01.29.428808

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