Structural analysis of SARS-CoV-2 genome and predictions of the human interactome
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- dc.contributor.author Vandelli, Andrea
- dc.contributor.author Monti, Michele
- dc.contributor.author Milanetti, Edoardo
- dc.contributor.author Armaos, Alexandros, 1989-
- dc.contributor.author Rupert, Jakob
- dc.contributor.author Zacco, Elsa
- dc.contributor.author Bechara, Elias
- dc.contributor.author Delli Ponti, Riccardo, 1987-
- dc.contributor.author Tartaglia, Gian Gaetano
- dc.date.accessioned 2020-11-23T07:04:48Z
- dc.date.available 2020-11-23T07:04:48Z
- dc.date.issued 2020
- dc.description.abstract Specific elements of viral genomes regulate interactions within host cells. Here, we calculated the secondary structure content of >2000 coronaviruses and computed >100 000 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 22 500-23 000 is conserved both at the sequence and structural level. The regions upstream and downstream, however, vary significantly. This part of the viral sequence codes for the Spike S protein that interacts with the human receptor angiotensin-converting enzyme 2 (ACE2). Thus, variability of Spike S is 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, include double-stranded RNA specific editases and ATP-dependent RNA-helicases and have strong propensity to form stress granules and phase-separated assemblies. 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.
- dc.description.sponsorship European Research Council [RIBOMYLOME_309545, ASTRA_855923]; H2020 projects [IASIS_727658 and INFORE_825080]; Spanish Ministry of Economy and Competitiveness [BFU2017-86970-P]; collaboration with Peter St. George-Hyslop financed by the Wellcome Trust. Funding for open access charge: ERC [ASTRA 855923].
- dc.format.mimetype application/pdf
- dc.identifier.citation Vandelli A, Monti M, Milanetti E, Armaos A, Rupert J, Zacco E, Bechara E, Delli Ponti R, Tartaglia GG. Structural analysis of SARS-CoV-2 genome and predictions of the human interactome. Nucleic Acids Res. 2020; 48(20):11270-83. DOI: 10.1093/nar/gkaa864
- dc.identifier.doi http://dx.doi.org/10.1093/nar/gkaa864
- dc.identifier.issn 0305-1048
- dc.identifier.uri http://hdl.handle.net/10230/45849
- dc.language.iso eng
- dc.publisher Oxford University Press
- dc.relation.ispartof Nucleic Acids Res. 2020; 48(20):11270-83
- dc.relation.projectID info:eu-repo/grantAgreement/EC/FP7/309545
- dc.relation.projectID info:eu-repo/grantAgreement/EC/H2020/855923
- dc.relation.projectID info:eu-repo/grantAgreement/EC/H2020/727658
- dc.relation.projectID info:eu-repo/grantAgreement/EC/H2020/825070
- dc.relation.projectID info:eu-repo/grantAgreement/ES/2PE/BFU2017-86970-P
- dc.rights © The Author(s) 2020. Published by Oxford University Press on behalf of Nucleic Acids Research. This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com
- dc.rights.accessRights info:eu-repo/semantics/openAccess
- dc.rights.uri http://creativecommons.org/licenses/by-nc/4.0/
- dc.title Structural analysis of SARS-CoV-2 genome and predictions of the human interactome
- dc.type info:eu-repo/semantics/article
- dc.type.version info:eu-repo/semantics/publishedVersion