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The copyright holder for this preprint (which was not peer-reviewed) is the .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 9 (Nsp9). Nsp9 protein is a single-stranded RNA-binding protein [145] . It might protect RNA from nucleases by binding and stabilizing viral nucleic acids during replication or transcription [145] . Our results on nucleotide-binding tendency of Nsp9 shows the presence of several RNA binding and few DNA binding residues in Nsp9 of SARS-CoV-2, Human SARS, and Bat CoV (Supplementary Tables 9, 10, and 11) . Presumed to evolve from a protease, Nsp9 forms a dimer using its GXXXG motif [146, 147] . Figure 27D shows a 2.7 Å crystal structure of the homodimer of Human SARS Nsp9 (PDB ID: 1QZ8) that identified a unique and previously unreported for other proteins, oligosaccharide/oligonucleotide fold-like fold [145] . Here, each monomer contains a coneshaped β-barrel and a C-terminal α-helix arranged into a compact domain [145] . Nsp9 of SARS-CoV-2 is equally similar to Nsp9s from both Human SARS and Bat CoV, having a percentage identity of 97.35%. The difference in three amino acids at 34, 35 and 48 positions accounts for these similarity scores ( Figure 27E ). As calculated, the mean PPIDs of Nsp9s of SARS-CoV-2, Human SARS CoV, and Bat CoV are 7.08%, 7.96%, and 7.08% respectively. Figures 27A, 27B , and 27C depict the predicted intrinsic disorder propensity in the Nsp9 protein from SARS-CoV-2, Human SARS, and Bat CoV. According to our analysis, all three Nsp9s are rather structured but contain flexible regions. Nsp9 contains conserved residues (R10, K52, Y53, R55, R74, F75, K86, Y87, F90, K92, R99, and R111) of positively charged side chains suitable for binding with the negatively charged phosphate backbone of RNA and aromatic side-chain amino acids providing stacking interactions [145] . author/funder. All rights reserved. No reuse allowed without permission.