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Structural analysis of SARS-CoV-2 genome and predictions of the human interactome

Andrea Vandelli, Michele Monti, Edoardo Milanetti, Alexandros Armaos, Jakob Rupert, Elsa Zacco, Elias Bechara, Riccardo Delli Ponti, View ORCID ProfileGian Gaetano Tartaglia
doi: https://doi.org/10.1101/2020.03.28.013789
Andrea Vandelli
1Centre for Genomic Regulation (CRG), The Barcelona Institute for Science and Technology, Dr. Aiguader 88, 08003 Barcelona, Spain and Universitat Pompeu Fabra (UPF), 08003 Barcelona, Spain
2Systems Biology of Infection Lab, Department of Biochemistry and Molecular Biology, Biosciences Faculty, Universitat Autònoma de Barcelona, 08193 Cerdanyola del Vallès, Spain
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Michele Monti
1Centre for Genomic Regulation (CRG), The Barcelona Institute for Science and Technology, Dr. Aiguader 88, 08003 Barcelona, Spain and Universitat Pompeu Fabra (UPF), 08003 Barcelona, Spain
3Center for Human Technologies, Istituto Italiano di Tecnologia, Via Enrico Melen 83, 16152, Genoa, Italy
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Edoardo Milanetti
4Department of Physics, Sapienza University, Piazzale Aldo Moro 5, 00185, Rome, Italy
5Center for Life Nanoscience, Istituto Italiano di Tecnologia, Viale Regina Elena 291, 00161, Rome, Italy
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Alexandros Armaos
1Centre for Genomic Regulation (CRG), The Barcelona Institute for Science and Technology, Dr. Aiguader 88, 08003 Barcelona, Spain and Universitat Pompeu Fabra (UPF), 08003 Barcelona, Spain
3Center for Human Technologies, Istituto Italiano di Tecnologia, Via Enrico Melen 83, 16152, Genoa, Italy
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Jakob Rupert
3Center for Human Technologies, Istituto Italiano di Tecnologia, Via Enrico Melen 83, 16152, Genoa, Italy
6Department of Biology ‘Charles Darwin’, Sapienza University of Rome, P.le A. Moro 5, Rome 00185, Italy
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Elsa Zacco
3Center for Human Technologies, Istituto Italiano di Tecnologia, Via Enrico Melen 83, 16152, Genoa, Italy
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Elias Bechara
1Centre for Genomic Regulation (CRG), The Barcelona Institute for Science and Technology, Dr. Aiguader 88, 08003 Barcelona, Spain and Universitat Pompeu Fabra (UPF), 08003 Barcelona, Spain
3Center for Human Technologies, Istituto Italiano di Tecnologia, Via Enrico Melen 83, 16152, Genoa, Italy
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Riccardo Delli Ponti
7School of Biological Sciences, Nanyang Technological University, 60 Nanyang Drive, Singapore, 637551, Singapore
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  • For correspondence: riccardo.ponti@ntu.edu.sg giangaetano.tartaglia@uniroma1.it gian.tartaglia@iit.it
Gian Gaetano Tartaglia
1Centre for Genomic Regulation (CRG), The Barcelona Institute for Science and Technology, Dr. Aiguader 88, 08003 Barcelona, Spain and Universitat Pompeu Fabra (UPF), 08003 Barcelona, Spain
3Center for Human Technologies, Istituto Italiano di Tecnologia, Via Enrico Melen 83, 16152, Genoa, Italy
6Department of Biology ‘Charles Darwin’, Sapienza University of Rome, P.le A. Moro 5, Rome 00185, Italy
8Institucio Catalana de Recerca i Estudis Avançats (ICREA), 23 Passeig Lluis Companys, 08010 Barcelona, Spain
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  • ORCID record for Gian Gaetano Tartaglia
  • For correspondence: riccardo.ponti@ntu.edu.sg giangaetano.tartaglia@uniroma1.it gian.tartaglia@iit.it
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ABSTRACT

Specific elements of viral genomes regulate interactions within host cells. Here, we calculated the secondary structure content of >2000 coronaviruses and computed >100000 human protein interactions with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The genomic regions display different degrees of conservation. SARS-CoV-2 domain encompassing nucleotides 22500 – 23000 is conserved both at the sequence and structural level. The regions upstream and downstream, however, vary significantly. This part codes for the Spike S protein that interacts with the human receptor angiotensin-converting enzyme 2 (ACE2). Thus, variability of Spike S may be connected to different levels of viral entry in human cells within the population.

Our predictions indicate that the 5’ end of SARS-CoV-2 is highly structured and interacts with several human proteins. The binding proteins are involved in viral RNA processing such as double-stranded RNA specific editases and ATP-dependent RNA-helicases and have strong propensity to form stress granules and phase-separated complexes. We propose that these proteins, also implicated in viral infections such as HIV, are selectively recruited by SARS-CoV-2 genome to alter transcriptional and post-transcriptional regulation of host cells and to promote viral replication.

Competing Interest Statement

The authors have declared no competing interest.

Footnotes

  • Added a complete list of predictions for the experimental interactors (https://www.biorxiv.org/content/10.1101/2020.07.15.204404v1)

Copyright 
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 July 24, 2020.
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Structural analysis of SARS-CoV-2 genome and predictions of the human interactome
Andrea Vandelli, Michele Monti, Edoardo Milanetti, Alexandros Armaos, Jakob Rupert, Elsa Zacco, Elias Bechara, Riccardo Delli Ponti, Gian Gaetano Tartaglia
bioRxiv 2020.03.28.013789; doi: https://doi.org/10.1101/2020.03.28.013789
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Structural analysis of SARS-CoV-2 genome and predictions of the human interactome
Andrea Vandelli, Michele Monti, Edoardo Milanetti, Alexandros Armaos, Jakob Rupert, Elsa Zacco, Elias Bechara, Riccardo Delli Ponti, Gian Gaetano Tartaglia
bioRxiv 2020.03.28.013789; doi: https://doi.org/10.1101/2020.03.28.013789

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