Structural analysis of SARS-CoV-2 and prediction of the human interactome.

We calculated the structural properties of >2500 coronaviruses and computed >100000 human protein interactions with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Using the CROSS method, we found that the SARS-CoV-2 region encompassing nucleotides 23000 and 24000 is highly conserved at the structural level, while the region 1000 nucleotides up-stream varies significantly. The two sequences code for a domain of the spike S protein that binds to the host receptor angiotensin-converting enzyme 2 (ACE2) that mediates human infection and in the homologue from Middle East respiratory syndrome coronavirus (MERS-CoV) interacts with sialic acids. We predicted structured regions at the 5 prime and 3 prime ends where our calculations also indicate strong propensity to bind proteins. Using the catRAPID method, we computed 3500 protein interactions with the 5 prime end and identified Cyclin T1 CCNT1, ATP-dependent RNA helicase DDX1, Zinc Finger Protein ZNF175 and other 20 high-confidence candidate partners. We propose these proteins, also implicated in HIV replication, to be further investigated for a better understanding of host-virus interaction mechanisms.