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

Andrea Vandelli; Michele Monti; Edoardo Milanetti; Riccardo Delli Ponti; Gian Gaetano Tartaglia

The interactome of each fragment was then analysed using cleverGO, a tool for Gene Ontology 206 (GO) enrichment analysis 38 . Proteins interacting with fragments 1, 2 and 29 were associated with 207 annotations related to viral processes ( Fig. 4C ; Supp. Table 1) . Considering the three thresholds 208 applied (Materials and Methods), we found 22 viral proteins for fragment 1, 2 proteins for 209 fragment 2 and 11 proteins for fragment 29 (Fig. 4D) . 210 211 Among the high-confidence interactors of fragment 1, we discovered RBPs involved in positive 212 regulation of viral processes and viral genome replication, such as double-stranded RNA-specific 213 editase 1 ADARB1 (Uniprot P78563 39 ) and 2-5A-dependent ribonuclease RNASEL (Q05823). We 214 also identified proteins related to the establishment of integrated proviral latency, including X-ray 215 repair cross-complementing protein 5 XRCC5 (P13010) and X-ray repair cross-complementing 216 protein 6 XRCC6 (P12956; Fig. 4B ,E). Nucleolin NCL (P19338), a protein known to be involved 217 in coronavirus processing, was predicted to bind tightly to the 5' (Supp. Table 1 ) 40 . 218 219 Importantly, we found proteins related to defence response to viruses, such as ATP-dependent RNA 220 helicase DDX1 (Q92499), that are involved in negative regulation of viral genome replication. MYC and MAX that have been previously connected to viral infection processes (Fig. 4E) 44, 45 . 235