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

In coronaviruses, Nsp12 is an RNA-dependent RNA Polymerase (RDRP). It carries out both primer-independent and primer-dependent synthesis of viral RNA with Mn 2+ as its metallic co-factor and viral Nsp7 and 8 as protein co-factors [151] . As aforementioned, a 3.1Ã… resolution structure of Human SARS Nsp12 in association with Nsp7 and Nsp8 proteins (PDB ID: 6NUR) has been reported using electron microscopy ( Figure 25D ). Nsp12 has a polymerase domain similar to "right hand", finger domain (398-581, 628-687 residues), palm domain (582-627, 688-815 residues) and a thumb domain (816-919) [144] . SARS-CoV-2 Nsp12 protein has a highly conserved C-terminal region (Supplementary Figure S2E) . It is found to share a 96.35% sequence identity with Human SARS Nsp12 and 95.60% with Bat CoV Nsp12. Mean PPID values for all three Nsp12s are estimated to be 0.43% (Table 3) . Figures 29A, 29B, and 29C show that although these proteins are mostly ordered, they have multiple flexible regions. As RDRP protein is observed to be mostly structured, significant MoRFs in disordered regions are not found ( Table 2, Supplementary Table 7 and 8).