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bioRxiv · 10.1101/2020.03.28.013789

Structural analysis of SARS-CoV-2 andprediction of the human interactome

Vandelli, A.·Monti, M.·Milanetti, E.·Delli Ponti, R.·Tartaglia, G. G.
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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.

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Vandelli, A., Monti, M., Milanetti, E., Delli Ponti, R., Tartaglia, G. G.. 2020-03-31. Structural analysis of SARS-CoV-2 andprediction of the human interactome. https://doi.org/10.1101/2020.03.28.013789

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