NLCPF-back end of epitope. Weaker than front end. Also shows AGTR2 receptor signal.
http://www.swisstargetprediction.ch/result.php?job=361534046&organism=Homo_sapiens
A novel method of initiating an immune response is with mRNA. Moderna, Inc., CureVac, Inc. and BionTECH Gmbh are leaders in mRNA therapy. Rather than using whole virus. The focus is on mRNA that when translated to protein initiates an immune response thereby producing antibodies. Clinical trials are underway right now for Moderna mRNA-1273, spike protein in its prefusion state.
I have uploaded the rna fold for sars-cov-2 spike glycoprotein with help the the Eterna team. The fold is from a Chinese patient released by the Chinese government. I procured it from Entrez or the US National Library of Medicine.
I am not done with this puzzle so it is not yet published on Eterna. The Spike protein controls binding S1 and fusion S2 for the viral genome to enter the host cell. I think we need to find the most important domain within the spike protein then get the Eterna community to generate every possible variant to the specific domain without altering the fold or any amino acids. This will help us to find the alternative sequence which will improve the efficacy and effectiveness of any vaccine based on mRNA therapeutics.
This is my two cents.
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NITNL- mid epitope w repeat N amino-acid. Good HLA-A3 signal as primary hit. Only 10 active hits ALL known antiviral or therapeutic targets.
http://www.swisstargetprediction.ch/result.php?job=132134355&organism=Homo_sapiens
VRFPNITNL epitope w most Human Coverage. Has Three different HLA-antigen class hits & AGTR1 & AGTR2. Individual signals not particularly strong.
http://www.swisstargetprediction.ch/result.php?job=71478836&organism=Homo_sapiens
Hmm…NITNL peptide above is in two of the Major Epitopes with most coverage in humans. It is the end of one epitope [VRFPNITNL] and in the middle of another [FPNITNLCPF] and gives a great signal all by itself.
Ah. PNITNL is even stronger and in both epitopes. Good strond HLA-A3 signal.http://www.swisstargetprediction.ch/result.php?job=490705726&organism=Homo_sapiens
And of course the 7-peptide is conserved in both epitopes. HLA-A3 antigenic
[http://www.swisstargetprediction.ch/result.php?job=1325346938&organism=Homo_sapiens
I find QALNTLVKQL in two epitopes [DVVNQNAQALNTLVKQL] and
[QALNTLVKQLSSNFGAI] don’t know yet how it looks.
QALNTLVKQL in two epitopes with good signal. Lots of sneaky activity, all things you don’t want a virus messing with.
http://www.swisstargetprediction.ch/result.php?job=488327694&organism=Homo_sapiens
I find [QALNTL] in epitopes LQDVVNQNAQALNTL, AQALNTLVK, QALNTLVKQLSSNFGAI, DVVNQNAQALNTLVKQL. Let see what it does.
Also AQALNTL in three of the above.
QALNTL in 4 SARS-CoV2 epitopes. Looks good. 3 HLA-antigen
types.
http://www.swisstargetprediction.ch/result.php?job=311304736&organism=Homo_sapiens
AQALNTLVK in 3 SARS-CoV2 epitopes. Solid protease with HLA-antigen activity.
http://www.swisstargetprediction.ch/result.php?job=1750153178&organism=Homo_sapiens
Yes the E-protein is expressed in the cytoplasm and is available for antigen generation.
Link to their viral informatics site.
https://www.sib.swiss/about-sib/news/10643-sib-experts-and-resources-in-the-fight-against-coronaviru…
SARS coronavirus 2 (SARS-CoV-2) proteome via Swiss Institute of Bioinformatics.https://viralzone.expasy.org/8996
This might be useful…
Multivariate Analyses of Codon Usage of SARS-CoV-2 and other betacoronaviruses.
https://www.biorxiv.org/content/10.1101/2020.02.15.950568v3.full.pdf
Nucleoprotein - the protein Swiss army knife
Nucleoproteins are not just hiding inside of the virus capsule. They can have multiple functions and are an active player throughout the virus production.
According to this review paper, the nucleoprotein can:
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forms complexes with genomic RNA
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interacts with the viral membrane protein during virion assembly
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enhancing the efficiency of virus transcription
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enhancing the efficiency of virus assembly
And these are just some of the mentioned functions from the paper.
The Coronavirus Nucleocapsid Is a Multifunctional Protein
I found this preprint really interesting too. Excerpt from the abstract:
“An analysis of virus-specific CD8+ T-cell immunity in 30 survivors showed that 26 of those individuals had a CD8+ response to at least one EBOV protein. The dominant response (25/26 subjects) was specific to the EBOV nucleocapsid protein (NP). It has been suggested that epitopes on the EBOV NP could form an important part of an effective T-cell vaccine for Ebola Zaire. We show that a 9-amino-acid peptide NP44-52 (YQVNNLEEI) located in a conserved region of EBOV NP provides protection against morbidity and mortality after mouse adapted EBOV challenge.”
Can short RNA (5-10 nucleotides) be used to inhibit the binding of the nucleoprotein to viral RNA?
If short RNA could bind to the nucleoprotein, the nucleoprotein might be prevented from binding and winding the viral RNA into the nucleocapsid.
There would be problems with such an approach that would have to be overcome, such off target binding, degradation and getting RNA through the cell membrane. Also, short RNA may not readily bind to nucleoprotein monomers.
Has this approach been tried?
If not, what sort of modifications could be done to short RNA to get around the potential problems?
This is a great idea, and it has been proposed for SARS and again recently. It would be very interesting to set these up as lab puzzles in Eterna, and I hope you can work with others to set up player puzzles that can pilot the concept. Oligonucleotide binding can be simulated in Eterna, bu tsetting up the puzzle requires some special access at the moment. Please float in chat, and also post links here if you get things set up.
PTVYVY peptide C-terminus of E-protein. Good antigen hit.
http://www.swisstargetprediction.ch/result.php?job=859501568&organism=Homo_sapiens
LLV occurs in C-terminus & Transmembrane regions while the reverse VLL is also in Transmembrane region. LLV peptide hits DPP4 protease as top hit & is involved in viral propagation.
“…Hocke et al. (2013) undertake highly focused research on coronavirus disease. They bring out that MERS-CoV continues to cause lethal lower respiratory tract disease, raising urgent fundamental questions as to its cellular tropism and receptor usage in alveolar lung tissue, as well as to its pathogenic mechanism(s). As stated by these authors, then, in the absence of autopsy data from human victims, they succeed in modeling MERS-CoV propagation in human lung tissue and demonstrate an almost pantropic infection, as well as ubiquitous DPP4 receptor expression in bronchiole, alveoli, or vessels. Thus, Hocke et al. (2013) emphasize that antiviral approaches that block DPP4 usage are expected to reduce virus propagation in the distal parts of the respiratory tract.”
http://www.swisstargetprediction.ch/result.php?job=1699439445&organism=Homo_sapiens
