What is the best coronavirus vaccine or therapeutic to Eternalize?

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Here is a good list of the vaccines (and treatments) getting the most buzz among researchers: https://www.statnews.com/2020/03/19/an-updated-guide-to-the-coronavirus-drugs-and-vaccines-in-development/
(Inovio has a poor track record, never has gotten a drug approved.)

Do you maybe want to consider the mRNA vaccines recently developed for SARS-1 or Ebola? Might be more info available.

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I cannot say for sure that these E-protein segments are presented on the outside, though my understanding is that parts of the E-protein may be. So spatially where is the C-terminus of the E-protein in the virion? I don’t know.

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Re-reading the paper on the E-protein makes me think that it is often expressed outwardly to the cytoplasm but sometimes inwardly depending on conditions.

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Found the Disks Large DGL4 signal in peptide SSEGV. This is a major player in the invasion of the virus to the cell.
http://www.swisstargetprediction.ch/result.php?job=438018502&organism=Homo_sapiens

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Wonderful. 

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Fantastic. I bet the other 2 big companies in this space (as well as others) have defined their formulations  but have not disclosed them yet. @DigitalEmbrace, if you can find more information on what formulations have been reported by these companies or other groups, particularly if the lipids are commercially available, the links and written out information would be extremely helpful to collect in this thread.  We would order those reagents immediately for Eterna experiments. Thanks!

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SEGVP peptide C-terminus E-protein SARS-CoV2.
This one also expresses as an antigen target.
http://www.swisstargetprediction.ch/result.php?job=1615539764&organism=Homo_sapiens

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SSEGVP peptide even better DLG4 & antigen signals.
http://www.swisstargetprediction.ch/result.php?job=2135788011&organism=Homo_sapiens

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Anybody able to find the sequence for Moderna’s mRNA-1273 vaccine or which part of the virus it challenges? I’m not having any luck.

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A human monoclonal antibody blocking SARS-CoV-2 infection
https://www.biorxiv.org/content/10.1101/2020.03.11.987958v1.full.pdf
![](https://d2r1vs3d9006ap.cloudfront.net/s3_images/1829183/RackMultipart20200322-97193-1d7n6dd-S1b_Receptor_Binding_Domain RBD of_SARS-CoV2_Spike_Protein_inline.png?1584903782 “Image httpsd2r1vs3d9006apcloudfrontnets3_images1829183RackMultipart20200322-97193-1d7n6dd-S1b_Receptor_Binding_Domain__RBD__of_SARS-CoV2_Spike_Protein_inlinepng1584903782”)

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Hi all,

I have been reading about the SARS-CoV-2, vaccines, and how the Eterna community can help address the recent pandemic. I wanted to share my thoughts on choosing an mRNA molecule that can serve as a starting point for the Eterna community to design a vaccine against the virus. I strongly believe Eterna-based designs will not only have an impact on the current outbreak, but the lessons learned from this effort will change our approach to many other infectious disease vaccines in the future. 

Before I reveal my antigen target, here is a brief summary of what I’ve learned from my research. I include links/sources that hopefully will allow for those looking to develop a quick understanding of this topic to get caught up. I want to give much credit to Ivan (Vanya) Zheludev, a graduate student in the Das Lab at Stanford for initial research and pointing me to key papers.

  1. Moderna has a vaccine (named mRNA-1273) that is currently going into clinical trials. Of note, no mRNA vaccine has gained FDA approval, although many candidates are in the clinical trial pipeline. mRNA vaccines are faster to production than traditional protein-based vaccines, so their accelerated development timeline highlights one of the advantage of mRNA-based vaccines. As their antigen, they have chosen a prefusion stabilized form of the S (spike) protein like the one described here.
  2. Antigens against viruses are often chunks of proteins from the virus that allow B cells and T cells to recognize and develop an immune response. A more specific portion of the antigen is an epitope, which is the part of the antigen that is bound by the antibody. Epitopes by definition are smaller than antigens, which will come into play later. For reference, epitopes are around 7-11 amino acids long, and the binding groove of MHC (major histocompatibility complex, responsible for binding antigens) accommodates ~9 amino acids.
  3. An obvious choice for an antigen is the entire membrane (M), nucleocapsid (N), spike (S), or envelope (E) proteins, along with various other proteins from the viruses’s genomes (called Open Reading Frames, or ORFs). However, this can be tough because these proteins can be large (the spike protein is 1273 amino acids–so the mRNA encoding it is over 3600 nucleotides long), the immune responses may not be robust, or hard to express.
  4. Thus, designing a vaccine that encodes for an epitope can be advantageous. Advancements in computational biology have enabled predictions of epitopes from viral genomes (like the example here, and explained here), and because epitopes individually are smaller than an antigen, you get more “shots on goal” when it comes to eliciting an immune response by stringing together multiple epitopes. Such an example of multiple epitope vaccines (MEVs) have shown promise for mRNA-based  cancer vaccines. A recent paper applied computational techniques to predict MEV designs for SARS-CoV-2.
  5. In the case of SARS-CoV-2, the virus which causes COVID-19 (coronavirus disease-2019), we can borrow from previous literature that have identified epitopes from SARS-Coronavirus which is a previously known/studied version of the virus. The hypothesis is that if the epitopes (or more accurately, protein sequences of those epitopes) are also encoded in the genome of SARS-CoV-2, those epitopes can be applied to fight SARS-CoV-2. A peer-reviewed article showcasing that approach can be found here. The epitopes identified in Table 2, Table 3, and Table 4 may be good starting targets.
    For the first Eterna challenge, I suggest the following amino acid sequences (epitopes) linked together by glycine-serine linkers:

  • FIAGLIAIV, GLIAIVMVTI, IITTDNTFV, ALNTLVKQL, LITGRLQSL, LLLQYGSFC, LQYGSFCT, NLNESLIDL, RLDKVEAEV, RLNEVAKNL, RLQSLQTYV, VLNDILSRL, VVFLHVTYV, ILLNKHID, FPRGQGVPI, LLLLDRLNQ, GMSRIGMEV, ILLNKHIDA, ALNTPKDHI, LALLLLDRL, LLLDRLNQL, LLLLDRLNQL, LQLPQGTTL, AQFAPSASA, TTLPKGFYA, VLQLPQGTTL
    and if space allows, these additional epitopes linked to the one above:

  • GYQPYRVVVL, PYRVVVLSF, LSPRWYFYY

  • DSFKEELDKY, LIDLQELGKY, PYRVVVLSF, GTTLPKGFY, VTPSGTWLTY
    A parallel target is:

  • GSFCTQLNR, GVVFLHVTY, AQALNTLVK, MTSCCSCLK, ASANLAATK, SLIDLQELGK, SVLNDILSR, TQNVLYENQK, CMTSCCSCLK, VQIDRLITGR, KTFPPTEPK, KTFPPTEPKK, LSPRWYFYY, ASAFFGMSR, ATEGALNTPK, QLPQGTTLPK, QQQGQTVTK, QQQQGQTVTK, SASAFFGMSR, SQASSRSSSR, TPSGTWLTY
    Excited to discuss further and launch these puzzles!

-dsk

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@eternacac, from what I can tell, I think the sequence can be gleaned from the links below. Particular Item number 1 in my post.

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FIAGLIAIV peptide by SwissTargetPrediction - good antigen signal
(makes me feel good about my submissions :slight_smile:
http://www.swisstargetprediction.ch/result.php?job=1154855391&organism=Homo_sapiens

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Thnx

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Yes–and that one was shown to elicit a positive T-cell response! I think your approach of checking with SwissTargetPrediction is a really good one. If you see “HLA” pop up under the “Target” column, that is probably a really good hit!

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Near the bottom of this paper on COVID-19 drugs and vaccines https://pubs.acs.org/doi/10.1021/acscentsci.0c00272
I found the patent relevant to the Moderna vaccine listed as W02017070626: https://patents.google.com/patent/WO2017070626A2/en?oq=WO2017070626
And a general formula: Formula IA):

Figure imgf000136_0001

or a salt or isomer thereof, wherein 1 is selected from 1, 2, 3, 4, and 5; m is selected from 5, 6, 7, 8, and 9; Mi is a bond or M’ ; R4 is unsubstituted Ci_3 alkyl, or -(CH2)nQ, in which Q is OH, -NHC(S)N®2, -NHC(0)N®2, -N®C(0)R, -N®S(0)2R, -N®R8, -NHC(=NR9)N®2, -NHC(=CHR9)N®2, -OC(0)N®2, -N®C(0)OR, heteroaryl or heterocycloalkyl; M and M’ are independently selected

from -C(0)0-, -OC(O)-, -C(0)N(R’)-, -P(0)(OR’)0-, -S-S-, an aryl group, and a heteroaryl group; and R2 and R3 are independently selected from the group consisting of H, CM4 alkyl, and C2-i4 alkenyl.

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Fantastic! Thanks. I hadn’t gotten to the patent yet…too hurried.

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The other patent mentioned in the article is the Curevac MERS intervention that may be informing their SARS-CoV-2 vaccine development: https://patents.google.com/patent/WO2018115527A2/en

Formula (I) (stem-loop sequence without stem bordering elements):
JNo-2G 3-53INo-4(U/T) o-4l [NS-SCNQ-Z],

steml loop stem2 formula (II) (stem-loop sequence with stem bordering elements):
^i-e^No^G ^J o^U D o^ Na-sC o-z^Ni-s ,
—^-— Y Y Y Y

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FPNITNLCPF epitope as SwissTargetPrediction  sees it.
http://www.swisstargetprediction.ch/result.php?job=404840912&organism=Homo_sapiens

Image httpsd2r1vs3d9006apcloudfrontnets3_images1829221RackMultipart20200323-51669-1gn5dxt-FPNITNLCPF_epitope_SARS-CoV2_inlinepng1584925181490×1556 303 KB

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FPNIT- front end of above epitope. Better signal. And has distinct AGTR2 receptor signal missing in the full epitope, fwiw.
http://www.swisstargetprediction.ch/result.php?job=333366002&organism=Homo_sapiens