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

Vandelli, Andrea; Monti, Michele; Milanetti, Edoardo; Armaos, Alexandros, 1989-; Rupert, Jakob; Zacco, Elsa; Bechara, Elias; Delli Ponti, Riccardo, 1987-; Tartaglia, Gian Gaetano

doi:http://dx.doi.org/10.1093/nar/gkaa864

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

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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

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.