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.