Spike glycoprotein (S) is a structural protein that protrudes from the lipid envelop to form a typical bulbous, crown-like halo surrounding the viral particle. The S protein of SARS-CoV-2 functions to recognize the receptor, attach to and fuse with the host cell membrane during viral infection. Proteolysis by TMPRSS2 and cathepsin B/L exerts a vital role in priming SARS-CoV-2 S for entry. The S protein consists of two subunits: S1 (bulbous head region) and S2 (stalk region). The receptor-binding domain (RBD) within the S1 subunit is responsible for the recognition and binding to the host receptor ACE2. The S2 subunit is composed of fusion peptide (FP), heptapeptide repeat sequence 1 (HR1), HR2, transmembrane (TM) domain, and cytoplasmic domain fusion (CT), and is involved in the virus-cell fusion and viral entry. As the main antigen component of the SARS-CoV-2, S protein-targeted neutralizing antibodies (nAbs) can induce protective immunity against viral infection.
Nucleocapsid (N) phosphoprotein, a structural protein of SARS-CoV-2, binds to the viral RNA, a process known as RNA encapsidation, forming the nucleocapsid. The N protein of SARS-CoV-2 comprises an N-terminal domain (NTD) that captures the viral RNA genome and a C-terminal domain (CTD) that anchors the ribonucleoprotein complex to the membrane by interacting with the viral membrane (M) protein during viral assembly. As a multifunctional molecule, the N protein not only participates in the process of RNA synthesis and folding but also affects host cellular responses to viral infection, including cell cycle and translation. It also contributes to viral transcription efficiency and pathogenesis.