I was wondering about the conserved sequences of COVID-19 which can be used in immunoprotection or diagnosis of the virus. It is unclear to me that in spite of the N-protein, that is a highly immunogenic sequence, and it is normally very conserved in COVID-19 and SARS, the projects are focusing on S protein.
Your question has been partly answered in this article
Therapeutic strategies in an outbreak scenario to treat the novel coronavirus originating in Wuhan, China
Article Therapeutic strategies in an outbreak scenario to treat the ...
Hi Fateme,
Coronavirus (CoV) infection is a complex process that requires the synergistic effects of receptor binding (S protein binding to host ACE2) and proteolysis of the S protein to promote virus-cell fusion. Of course, some non-structural proteins such as 3-chymotrypsin-like protease, papain-like protease, helicase, and RNA-dependent RNA polymerase are potential drug targets. Creative Biostructure has established a COVID-19 targeted discovery platform for structure/function study and novel drug discovery. https://www.creative-biostructure.com/Discovery-Program-for-COVID-19-Targets-669.htm
Proteins near or at the surface of the coronavirus include the spike protein (S, 150 kD), the hemagglutinin-esterase protein (HE, 65 kD), membrane/matrix glycoprotein (M, 25 kDa), and the small envelope glycoprotein (E, 9–12 kD). A protein that is closer to the RNA is the nucleo-capsid protein (N, 60 kD). They are all likely to play roles in protecting the virions. Since the M glycoproteins are the most abundant structural proteins in the coronavirus, they are likely to play a greater role in protecting the virion from damage.
The M-protein is a triple-spanning trans-membrane protein and has a short amino-terminal ecto-domain. Other than its protective function, M-protein also plays a role in the capsid self-assembly and serves as a major determinant of the virion morphogenesis via selecting the S protein for incorporation into virions during viral assembly. Another protein of interest to this paper is the N-protein. The N-protein is an RNA binding protein. While many of its functions remain unknown, it is likely that the N-protein is involved in packaging and protecting the viral RNA and also plays a role in viral replication participating in transcription. Do you now see why the S protein is targeted? See the attached for details:Article Understanding Viral Transmission Behavior via Protein Intrin...
Fateme Araste Probably due to the major surface proteins, spike proteins, are outside the virus membrane, and easy to be 'catch' by antibody, once immunization is done on a person. Or, when an antibody is directed used to treat a patient. Besides, spike protein like a key for the virus to get into our cell by working on membrane fusion of the virus particle and our cells, so it is reasonable to produce antibody to neutralize these proteins [For the whole view of the picture, click on it]
Due to the major surface proteins, spike proteins, are outside the virus membrane, and easy to be 'catch' by antibody, once immunization is done on a person. Or, when an antibody is directed used to treat a patient. Besides, spike protein like a key for the virus to get into our cell by working on membrane fusion of the virus particle and our cells, so it is reasonable to produce antibody to neutralize these proteins
Article Understanding Viral Transmission Behavior via Protein Intrin...
N protein is highly immunogenic and conserved. But we would like to generate antibodies that can block the virus infection (neutralizing antibodies). Not all antibodies do that. Because S protein is the protein that engages ACE2 receptor and plays an important role in virus cell entry. Antibodies against S protein are more likely neutralizing. That is why researches are focusing on S protein.
As far as I know the S protein has three "legs" which are called S1 and are folded inside the S2 protein so the antigens can't easily bind to the S1 part which is protruding (only 1 leg and the other 2 are closed) when the virus is docked on an ACE2 receptor of a cell, there is also a furin cleavage sequence between the S1 and S2 parts of the S protein and the virus uses that in order to finalize the steps of RNA entry into the host cell, this is one of the differences of SARS-2 and SARS-1 , SARS-1 doesn't have a furin cleavage site but was cleaved by trypsin. There are other ways for viral entry such as lipid rafts and others.
Please go through the link.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7151553/
COVID-19 Coronavirus spike protein analysis for synthetic ...
www.ncbi.nlm.nih.gov › pmc › articles › PMC7151553
Apr 11, 2020 - COVID-19
The answer is simple. S-protein lies on the surface and accessible to antibodies. N-protein lies inside the virus and is released inside the host cells. For an antibody to N-protein, the virus membrane need to be perforated for antibody to bind. If perforated, the virus is already non-viable and there is no need to use the antibody! The abundance of S-protein also ensures highly efficacy binding to the virion. Low abundance proteins may not be suitable as they require a higher dose/concentration of antiboduy to generate a "signal".
Well actually the S protein may not be a good target READ : Preprint Profound CD8 T cell responses towards the SARS-CoV-2 ORF1ab ...
Fateme Araste Its the "Achilles Heel" of Corona virus. Scientists are thinking that they can easily arrow it down.