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.
Structural analysis of SARS-CoV-2 genome and predictions of the human interactome / Vandelli, Andrea; Monti, Michele; Milanetti, Edoardo; Armaos, Alexandros; Rupert, Jakob; Zacco, Elsa; Bechara, Elias; Delli Ponti, Riccardo; Tartaglia, Gian Gaetano. - In: NUCLEIC ACIDS RESEARCH. - ISSN 0305-1048. - (2020). [10.1093/nar/gkaa864]
Titolo: | Structural analysis of SARS-CoV-2 genome and predictions of the human interactome | |
Autori: | ||
Data di pubblicazione: | 2020 | |
Rivista: | ||
Citazione: | Structural analysis of SARS-CoV-2 genome and predictions of the human interactome / Vandelli, Andrea; Monti, Michele; Milanetti, Edoardo; Armaos, Alexandros; Rupert, Jakob; Zacco, Elsa; Bechara, Elias; Delli Ponti, Riccardo; Tartaglia, Gian Gaetano. - In: NUCLEIC ACIDS RESEARCH. - ISSN 0305-1048. - (2020). [10.1093/nar/gkaa864] | |
Handle: | http://hdl.handle.net/11573/1450092 | |
Appartiene alla tipologia: | 01a Articolo in rivista |
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