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Effect of SARS-CoV-2 proteins on vascular permeability

Rossana Rauti, Meishar Shahoha, Yael Leichtmann-Bardoogo, Rami Nasser, Rina Tamir, Victoria Miller, Tal Babich, Kfir Shaked, Avner Ehrlich, Konstantinos Ioannidis, Yaakov Nahmias, Roded Sharan, Uri Ashery, View ORCID ProfileBen M. Maoz
doi: https://doi.org/10.1101/2021.02.27.433186
Rossana Rauti
1Department of Biomedical Engineering, Tel Aviv University, Israel
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Meishar Shahoha
2School of Neurobiology, Biochemistry and Biophysics, The George S. Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv, Israel
3Sagol School of Neuroscience, Tel Aviv University, Tel Aviv, Israel
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Yael Leichtmann-Bardoogo
1Department of Biomedical Engineering, Tel Aviv University, Israel
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Rami Nasser
4Blavatnik School of Computer Science, Tel Aviv University, Tel Aviv, Israel
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Rina Tamir
1Department of Biomedical Engineering, Tel Aviv University, Israel
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Victoria Miller
1Department of Biomedical Engineering, Tel Aviv University, Israel
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Tal Babich
1Department of Biomedical Engineering, Tel Aviv University, Israel
2School of Neurobiology, Biochemistry and Biophysics, The George S. Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv, Israel
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Kfir Shaked
1Department of Biomedical Engineering, Tel Aviv University, Israel
2School of Neurobiology, Biochemistry and Biophysics, The George S. Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv, Israel
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Avner Ehrlich
5Grass Center for Bioengineering, The Hebrew University of Jerusalem, Jerusalem, Israel
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Konstantinos Ioannidis
5Grass Center for Bioengineering, The Hebrew University of Jerusalem, Jerusalem, Israel
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Yaakov Nahmias
5Grass Center for Bioengineering, The Hebrew University of Jerusalem, Jerusalem, Israel
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Roded Sharan
4Blavatnik School of Computer Science, Tel Aviv University, Tel Aviv, Israel
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Uri Ashery
2School of Neurobiology, Biochemistry and Biophysics, The George S. Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv, Israel
3Sagol School of Neuroscience, Tel Aviv University, Tel Aviv, Israel
6The Center for Nanoscience and Nanotechnology, Tel Aviv University, Israel
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  • For correspondence: uriashery@gmail.com bmaoz@tauex.tau.ac.il
Ben M. Maoz
1Department of Biomedical Engineering, Tel Aviv University, Israel
3Sagol School of Neuroscience, Tel Aviv University, Tel Aviv, Israel
6The Center for Nanoscience and Nanotechnology, Tel Aviv University, Israel
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  • ORCID record for Ben M. Maoz
  • For correspondence: uriashery@gmail.com bmaoz@tauex.tau.ac.il
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Abstract

SARS-CoV-2 infection leads to severe disease associated with cytokine storm, vascular dysfunction, coagulation, and progressive lung damage. It affects several vital organs, seemingly through a pathological effect on endothelial cells. The SARS-CoV-2 genome encodes 29 proteins, whose contribution to the disease manifestations, and especially endothelial complications, is unknown. We cloned and expressed 26 of these proteins in human cells and characterized the endothelial response to overexpression of each, individually. Whereas most proteins induced significant changes in endothelial permeability, nsp2, nsp5_c145a (catalytic dead mutant of nsp5) and nsp7 also reduced CD31, and increased von Willebrand factor expression and IL-6, suggesting endothelial dysfunction. Using propagation-based analysis of a protein–protein interaction (PPI) network, we predicted the endothelial proteins affected by the viral proteins that potentially mediate these effects. We further applied our PPI model to identify the role of each SARS-CoV-2 protein in other tissues affected by COVID-19. Overall, this work identifies the SARS-CoV-2 proteins that might be most detrimental in terms of endothelial dysfunction, thereby shedding light on vascular aspects of COVID-19.

Competing Interest Statement

The authors have declared no competing interest.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
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Posted March 01, 2021.
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Effect of SARS-CoV-2 proteins on vascular permeability
Rossana Rauti, Meishar Shahoha, Yael Leichtmann-Bardoogo, Rami Nasser, Rina Tamir, Victoria Miller, Tal Babich, Kfir Shaked, Avner Ehrlich, Konstantinos Ioannidis, Yaakov Nahmias, Roded Sharan, Uri Ashery, Ben M. Maoz
bioRxiv 2021.02.27.433186; doi: https://doi.org/10.1101/2021.02.27.433186
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Effect of SARS-CoV-2 proteins on vascular permeability
Rossana Rauti, Meishar Shahoha, Yael Leichtmann-Bardoogo, Rami Nasser, Rina Tamir, Victoria Miller, Tal Babich, Kfir Shaked, Avner Ehrlich, Konstantinos Ioannidis, Yaakov Nahmias, Roded Sharan, Uri Ashery, Ben M. Maoz
bioRxiv 2021.02.27.433186; doi: https://doi.org/10.1101/2021.02.27.433186

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