Posts by Mathieu

    A very good structural and genomic analysis of Cov-2 compated to CoV-1, others and some other joyfulness ahead.

    https://www.youtube.com/watch?v=8_bOhZd6ieM&t=1224s
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    Here are my notes, from what I understood.... this is highly technical so thanks for your understanding :
    20200402
    Quotes and notes from the video, everything within parenteses is from the autor:

    1. Coronaviruses will continue to jump from bats to intermediaries animal and humans (CoViD-19 is the third in less than two decades) at a higher rate.
    2. MERS the second in the list, has recurrent spillovers from human populations where CoV-1 does not, what about CoV-2?
    3. For SARS-CoV (CoV-1), the transmission has happen mainly hospital settings, not this time. Previously it was 24 to 36h of asymptomatic period, then symptoms arrive and the patient slowly starts to be contagious. Here we have mild-cases and the patient is unaware of being contagious (we know he is expelling the higher number of viruses at the beginning of the coughs).
    4. 125nm in diameter (contradiction w/ other sources ~450nm) but 30kb+ RNA genome. “ This is Huge!"
    5. The receptor binders (spike protein) of the coronavirus genome is the most variable part of the virus. And it makes it longer live inside (and outside the body as well). It is difficult for other cells to identify it.
    6. The spike protein is an identical mean of penetration into the cell membrane we can find for Ebola and HIV viral infections.
    7. Significant differences between cov-1 and cov-2. 5 amino-acids receptors are different over 6 critical that necessary for making the binding domain a little less effective. Have a good interaction with cellules enveloppe though.
    8. 19:30 Has supposedly acquired Polybasic cleavage site: increase transmissibility, “efficient cleavage”.
    9. When integrated, the virus is capable of translating 27 proteins. This is “quite remarkable”.
    10. 24:00 to 32:00 The virus is well optimized for replication. It has specific endings sequence that mark segments of specific portions, but the beginning sequence are identical between mRNAs sequence as well, which is new. And this allows “dislinear transcription” of the virus. This enable "extremely high recombination rate" of the virus when replicating, since portion or “template” of the virus are available to be reassembled by blocks. RNA viruses are not known to do this, this is a première.
    11. 36:46 Large increase in mutation activity x20 compared to SARS. Greatly sensitive to mutagen and increase it adaptation.
    12. Some vaccine strategy are discussed and show promising options.
    13. It uses a double membrane vassicles that might prevent antibodies mechanism to take place during transcription.
    14. It has a pathogenicity factor that restrict host gene expression. This means the host cell will not be able to integrate part of it own genetic code during transcription. This has an enormous impact on interferon survival time, delaying its messenging capabilities.
    15. Additional accessory proteins seems designed to impact interferon activity.
    16. CoVs are remarkable because they induce very low interferon release in those cells.
    17. The final effect is an important delay in release of interferon, that is improperly arriving after the virus damaged the lungs, triggering an inflammation post infection.This makes it even worse for the patient.

    Conclusion on what is new:

    • The RNA sequence of the virus is very long.
    • The virus has a greater transmission factor due its receptor binders architecture compared to CoV-1. It is much more infectious.
    • The virus is able to translate with 27 different proteins, that increase it mutation rate by a large factor
    • The whole code is organized in sub-parts that are processed in a non-linear fashion.
    • The ends and now the beginning (compared to CoV-1) of the sequences are all identical, so it makes it facilitates the reassembly.
    • This last feature also prevents interferons efficiently
    • When the inflammatory response arrives, it is too late and the viral load is already lower and the inflammation hurts more than makes good.

    Best