**3.6 Nucleocapsid (N)**

SARS-CoV-2's N (Nucleocapsid) protein is a putative RNA-binding protein responsible for gathering the viral RNA genome for encapsulation in the viral membrane into compact ribonucleoprotein (RNP) complexes [45]. N is the structural unit present in the nucleocapsid of the SARS-CoV-2 genome, 46 kDa protein and comprises of 419 amino acids (aa) containing three distinctly diverse domains: The N-terminal domain (NTD)/RNA-binding domain (46–174 aa), the serine/argininerich (SR-rich; 184–197 aa) linker region (LKR; 175–254 aa) and the C-terminal domain (CTD; 255–364 aa) (**Figure 8**) [46]. Both domains (NTD & CTD) are flanked by an inherently disordered region IDR, which is the central linker region (LKR) with a Ser/Arg (SR)-rich area containing alleged phosphorylation sites [47, 48]. An asymmetric unit crystal configuration of the N-terminal RNA nuclear protein binding field showed the sandwiched fold shared by the CoV N-NTD with the same right hand (loop) - (β-sheet core) - (loop), with the order β1-η1 β2- β3- β4- β5- β6- β7. The core β-sheet consists of five β-strands with just 3₁₀ helix ahead of strand β2 and a β-strand between the strands β2 and β 5. The β-hairpin is functionally important in mutational analysis of amino acid residues at the RNA binding N-terminal domain of SARS-CoV2 [49]. The structures of the N-CTD RNA binding domain highlight the reserved architecture of 3₁₀ helix acidic coil containing a β-sheet core of 5 antiparallel β-sheets, and an expanded β3–4 hairpin with the order η1-α1-α2-η2-α3-α4-β1-β2-α5-η3. Generally, the RNA binding domain of the N protein is essentially simple and sometimes defined as a right hand-like shape with a protruding fundamental finger, basic palm and acidic wrist [50].

#### **Figure 8.**

*Schematic representation of SARS-CoV-2 Nucleocapsid (N) protein domains. Three intrinsically disordered regions, i.e., N-arm, linker region (LKR) and C-tail, and the N-terminal domain (NTD) and C-terminal domain (CTD) are illustrated. The charged Ser/Arg (SR)-rich motif (colored light yellow) is shown. Cartoon view of the N protein NTD domain (PDB ID: 6M3M), a monomer, colored by the number variants at different positions, and CTD (PDB ID: 7C22), a heterodimer with one monomer colored gray and the other colored blue indicating various regions within the structure as observed in SARS-CoV-2 genomes.*

*Repurposed Therapeutic Strategies towards COVID-19 Potential Targets Based on Genomics… DOI: http://dx.doi.org/10.5772/intechopen.96728*
