SARS-CoV-2 Spike P681H Antikörper (Alpha, Mu-Variante)

The genomic features of SARS-CoV-2

The SARS-CoV-2 is a spherical virion containing a positive-strand RNA virus with a genome length of approximately 29,700  nucleotides  .  The 5ˊ end spans more than two-thirds of the genome and includes a long ORF1ab  polyprotein  that encodes 16 nonstructural proteins.  The 3ˊ end encodes four major structural proteins, namely the spike (S) protein,  nucleocapsid  (N) protein, membrane (M) protein and coat protein (E).   In addition, the virus contains six accessory proteins encoded by the genes ORF3a, ORF6, ORF7a, ORF7b, ORF8 and ORF9b.  ORF3a is a Transmembrane protein that forms ion channels in the host membrane and encodes ORF7a, a type I transmembrane protein(10). ORF8 is a protein with an N-terminal  signal sequence  for  endoplasmic reticulum transport  and ORF9b represses the IFN-I response(9).

Structure, function and antigenicity of the SARS-CoV-2 spike glycoprotein

S protein  , a  glycoprotein  , is a  homotrimer that   plays a crucial role in the first step of infection.   The  monomer  of S protein contains 1273 amino acids and has a molecular weight of approximately 140 kDa.  The primary function of S protein is to bind to the ACE2 (angiotensin-converting enzyme 2) receptor, which after binding enters the host cell.  ACE2  is a type I integral membrane protein that functions as a carboxypeptidase and  angiotensin Cleaves II to blood pressure regulating angiotensin.

• The virus binds to ACE2 on the host cell (lung, heart, etc.) for viral entry and subsequent pathogenesis, resulting in severe respiratory infection. Therefore, the S protein-ACE2 interaction is an easy target for vaccines.  First, it is exposed on the surface and can be directly recognized by the host’s immune system. 
• Second, it mediates the interaction with the host cell’s binding to the ACE2 receptor, which is essential for the subsequent entry of the virus into the target cells, causing subsequent  pathogenicity  . ^fifteen   Finally, the homologous proteins have already been used for vaccine development against SARS-CoV and MERS-CoV and have been shown to be effective.
• The S protein consists of two functional subunits, including an N-terminal S1 subunit (Val16–Gln690). It consists of S1A, S1B, S1C and S1D domains. The latter is responsible for binding to the host cell  receptor  .
• A C-terminal membrane-proximal S2 subunit contains the essential elements and is responsible for the fusion of the viral and cellular membranes. This subunit consists of four parts, including an internal  membrane fusion  peptide (FP), two 7-peptide repeats, a membrane-proximal external region, and a  transmembrane domain  (TM). 
• The S1A domain, called the N-terminal domain (NTD), recognizes carbohydrates such as  sialic acid  , which is required for the virus to attach to the host cell surface.  The S1B domain (Arg319–Phe541), termed the receptor binding domain (RBD) of the SARS-CoV-2 spike protein, interacts with the human ACE2 receptor. The S1 subunit can be further defined into two domains referred to as the N-terminal domain (NTD) and the C-terminal domain (CTD). The River Basin District is in the CTD. The structural parts within the S2 subunit include three long α-helices, several α-helical segments, extensive twisted β-sheets, a membrane-spanning α-helix, and an intracellular cysteine-rich segment.  Located between the S1 and S2 subunits in SARS-CoV-2, the PRRA  sequence motif  features a furin cleavage site. In the S2 subunit there is a second proteolytic cleavage site S20, upstream of the fusion peptide. These two interfaces are involved in viral entry into host cells