N-protein
To prevent the replication of SARS-CoV-2 RNA, the N-protein of the virus may also be the potential target. N-proteins comprise three domains, including an N-terminal RNA-binding domain (NTD), a Ser/Arg rich central linker region and a C-terminal dimerization domain (CTD). The N-proteins plays a major role in packing the viral RNA into viral ribonucleoproteins (McBride, van Zyl & Fielding, 2014). It also helps in viral RNA transcription and replication (Cong et al., 2020). The NTD functions for RNA-binding and the CTD domain plays a role in oligomerization, while the central linker is necessary for primary phosphorylation (Kang et al., 2020). However, targeting N-protein for vaccine should be careful, since the increased titer of IgG antibody against N-protein has been associated with poor prognosis, increasing ICU admission and longer hospital stay (Batra et al., 2021). But the higher N-protein antibody titer may indicate the higher viral load and more severe disease, which cause the poor outcomes, not the N-protein antibody itself leads to the poor prognosis. Further studies could be performed to clarify the underlying association.
Recently, the sequences that interact with B and T cells in the NTD domain have been found by single immuno-informatics and structure-based drug discovery techniques (Kwarteng, Asiedu, Sylverken, Larbi, Sakyi & Asiedu, 2021), suggesting that N-protein might be associated with overactive immune responses and the development of the NTD inhibitors may hold some promises. The role of N-protein inhibition in the treatment of anti-SARS-CoV-2 should be further evaluated.