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The copyright holder for this preprint (which was not peer-reviewed) is the .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 type inhibitor. Another crystal structure resolved to 1.96 Å revealed a chymotrypsin-like fold and a conserved substrate-binding site connected to a novel α-helical fold [140] . Recently, the X-ray crystal structure (resolution 2.16 Å) was solved for the SARS-CoV-2 Nsp5 in complex with an inhibitor N3 (PDB ID: 6LU7) (Figure 23E ). Nsp5 protein is found to be highly conserved in all three studied CoV viruses. SARS-CoV-2 Nsp5 shares a 96.08% sequence identity with Human SARS Nsp5 and 95.42% with Nsp5 of Bat CoV (Supplementary Figure S2D) . Therefore, it not surprising that our analysis demonstrated the identical mean PPID values of 1.96% for Nsp5s from SARS-CoV-2, Human SARS, and Bat CoV ( Table 3) . The predicted per-residue intrinsic disorder propensity of SARS-CoV-2, Human SARS, and Bat CoV Nsp5s are presented in Figures 23A, 23B , and 23C, respectively. As the graphs depict, Nsp5s have several flexible regions and N-terminally IDPR of six residues. Due to the low flexibility of this protein, a single MoRF predicted by MoRFchibi_web is present in the N-terminal region (residues 3-8) in Nsp5s of all three viruses (Table 2, Supplementary Tables 7 and 8) . Further, the identified nucleotide-binding residues in Nsp5 of all three viruses are tabulated in Supplementary Tables 9, 10, and 11 .