From the structural protein of coronavirus the spiked glycoprotein play very essential role in the entry of the corona virus in to the host cells. The name of coronavirus also related by its S-protein have a crown appearance which is derived their name; corona in Latin means crowns. The spiked protein has the receptor-binding domain (RBD). Thus, the virus use S-protein to bind its receptor with host cells by its S1 subunit followed by fused the viral and hast cell membrane through its S2 subunits.30,31S-proteins coronavirus are the large heavily N-glycosylated proteins which mediate the interaction of the virus with the host cell surface receptors.30,32 Angiotensin-converting enzyme 2 (ACE2) is an entry receptor on human for SARS-CoV-2 and SARS-CoV-113,18,33-35 Angiotensin-converting enzyme 2 (ACE2) is an enzyme found in the outer surface cells such as nasal mucosa, nasopharynx, lung, stomach, small intestine, colon, skin, lymph nodes, thymus, bone marrow, spleen, liver, kidney, and brain. ACE2 regulates the renin-angiotensin system, which has an important role on regulation of blood pressure and heart functions.30,35-37
The genomic sequence result of (COVID-19) SARS-CoV-2 has shown 79.6% identical with SARS-CoV-1 and 96% with bat coronavirus respectively.38 Furthermore, in vitro based recent experimental study using the ACE recombinant protein and ACE2 expressing cell lines indicated that the SARS-CoV-2 and SARS-CoV-1 showed the similar binding affinity to the host ACE2 receptor.18
S-protein has very essential role to produce a potentially effective antibody and vaccine. Recently the receptor-biding domain (RBM) in the S-protein apparently amino acid residue (Gln493) provide favorable interactions with human ACE2, which enabled the virus for human cell infections. This might be related the infectivity potential of the COVID-19.39 The amino acid sequence result analysis of SARS-CoV and SARS-CoV-2 SAR showed that similarity 75% in S-protein, 73.7% in receptor-biding domain (RBM) and 50% receptor binding motif (RBM).18
Since the COVID-19 (SARS-CoV-2) and SARS-CoV-1 showed sequence similarity, identify the common cross-reactive epitopes (CREs) is the key point. The shared CREs are similar epitope regions on the antigen surface among viruses that can be bound or neutralized by the same antibodies. Interestingly, very similar epitope was identified in between COVID-19 and SARS-CoV-1 at the biding site of S-protein with human ACE2 receptor.39 Recently, robust anti-ACE-2 Blocking antibody showed limited binding and neutralization activity against SARS-CoV-1. However, anti-ACE2 nonbanking SARS CoV-1 antibody showed positive cross-neutralizing activities to SARS-CoV-2. Indeed the reason is unknown yet. 18 This might be due to the RBD conserved immunogenic part that antibody able to recognize in SARS-CoV-1 and the SARS-CoV-2. This provides a scientific evidence to develop a potent antibody or vaccine based on RBD against COVID-19.
Figure 2. ABO blood group. a phenotypic distribution of ABO blood group by race and Ethnicity,29 bRelationship between the ABO Blood Group and the COVID-19 Susceptibility.12
Histo‐blood group antigens which are responsible for ABO blood group are highly expressed on epithelial cells and many other normal cells.40 In the same fashion, epithelial cells of respiratory and digestive tracts are the main site for replication of SARS-CoV-2 and SARS-CoV-1.6,37 Thus, SARS-CoV can produce the ABH carbohydrate epitope in the epithelia cells. S-protein of virions produced by either A or B individuals could be decorated with A or B carbohydrate epitopes, respectively. Naturally, with unknown reason we huma acquired natural anti-histo-blood group antibodies. These natural antibodies from blood group O, B, and A individuals could bind to the S-protein and block its interaction with ACE2. Surprisingly, O blood group individual showed very low risk of infection by COVID-19 and SARS-CoV-1 as compared with non O blood group.12,28,41The major reason is that the O blood group individuals have anti-A and anti-B antibodies in plasma. Interestingly, the plasma contained high anti-A antibody titer able to inhibit the S-protein interacting with ACE2 receptors.13 This indicated that ABO polymorphism has significant effect of the SARS-CoV outbreak further more study is needed to produce broadly neutralizing antibody and vaccine.
Green fluorescent tagged the C-terminal of S-protein was expressed in Chinese hamster ovary cells cotransfected with an α1,2-fucosyltransferase and an A-transferase (antigen A) in order to coexpress the S-glycoprotein ectodomain. The vitro result showed that anti-A monoclonal antibody and anti-A natural antibody from O blood group inhibited ACE2 and S-protein of SARS-CoV-1 interaction.13,42 Furthermore, convalescent plasma therapy taken from O blood group result in better recovery including for pregnant woman.22 In erectly, SARS-CoV-2 S- protein peptide are identified in human leukocyte antigen (HLA) complexes. The protein glycosylation has role in the adaptive immune response; this could leads for development of potential antibody and vaccine.43 Therefore, furthermore studies based on these evidence are suggested.
The potential of natural antibody in human varies from person to person. The natural antibodies possibly decrease over years in developed countries due to good environmental and person hygiene. Peoples who lived in less developed countries may elicit good natural antibodies. Plasma taken from O blood group with high anti-A antibody dramatically inhibits the interaction of S-protein with ACE2. However, Plasma from O blood group with low anti-A antibody did not inhibit S-protein and ACE2 in cell adhesion assay.13 ABO blood group based intervention of the COVID-19 may slowdown the fast spread the outbreak. Moreover, antigen-A based further study could lead to get potent antibody and vaccine.
Figure 3. SARS-CoV-2 entry to host cell and inhibition by antibody mechanism. The SARS-CoV-2 attaches by its spiked protein sub unit 1 (S1) to the host Angiotensin-converting enzyme 2 (ACE2) receptors. The host natural antibody and lab made and neutralizing monoclonal antibody can inhibited the interaction of the S-protein and host ACE2.The membrane fusion is carried out by its S2-proten. The RNA virus replicate inside the host genome and finally RNA virus released.