Dark Proteome of Newly Emerged SARS-CoV-2 in Comparison with Human and Bat Coronaviruses

Rajanish Giri; Taniya Bhardwaj; Meenakshi Shegane; Bhuvaneshwari R. Gehi; Prateek Kumar; Kundlik Gadhave

The copyright holder for this preprint (which was not peer-reviewed) is the . https://doi.org/10.1101/2020.03.13.990598 doi: bioRxiv preprint Non-structural protein 14. Nsp14 is a multifunctional viral protein that acts as an Exoribonuclease (ExoN) and methyltransferase (N7-MTase) in SARS coronaviruses. It's 3' to 5' exonuclease activity lies in the conserved DEDD residues related to exonuclease superfamily [154] . Its guanine-N7 methyltransferase activity depends upon the S-adenosyl-Lmethionine (AdoMet) as a cofactor [149] . As aforementioned, Nsp14 requires Nsp10 for activating its ExoN and N7-MTase activity inside the host cells. Figure 28D depicts the 3.2 Ã… crystal structure of human SARS nsp10/nsp14 complex (PDB ID: 5C8T), where amino acids 1-287 form the ExoN domain and 288-527 residues form the N7-MTase domain of nsp14. A loop (residues 288-301) is essential for its N7-MTase activity [150] . SARS-CoV-2 Nsp14 protein shares a 95.07% identity with Human SARS Nsp14 and 94.69% with Bat CoV Nsp14 (Supplementary Figure S2G) . Mean PPID values for Nsp14s from SARS-CoV-2 and Human SARS is calculated to be 0.38%, while the Nsp14 from Bat CoV has a mean PPID 0.57%. Predicted per-residue intrinsic disorder propensity of Nsp14s from SARS-CoV-2, Human SARS, and Bat CoV is represented in Figures 31A, 31B , and 31C, respectively. As can be observed from these plots and corresponding PPID values, all Nsp14s are found to be highly structured. Likewise, Table 2 shows Nsp14 contains two protein binding regions (residues 8-13 and 441-445) predicted by the MoRFPred server in all three viruses. As shown in Supplementary Tables 9, 10, and 11, the ORF14 represents multiple nucleotide-binding residues.