Higher rate of mutation in the S1 domain of the spike protein

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  • Mon, Sep 27, 2021 - 05:30pm

    #1
    derek1ee

    derek1ee

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    Higher rate of mutation in the S1 domain of the spike protein

This was posted two weeks ago but I don’t think I’ve seen it mentioned here.

The PP community should be pretty familiar with Trevor Bedford from Fred Hutch who have been tracking the virus and its mutation since the early days.

The TL;DR I got from the tweets are: there are high rate of mutation in the S1 domain of the virus’ spike protein.

He contributed it to “Most of this rapid pace of evolution is likely due to adaptation to a new host, but in general, this suggests to me that the S1 domain of spike in SARS-CoV-2 is a readily evolvable domain.”

This, in my opinion, matches very well to what Geert Vanden Boossche, et. al have been saying: a non-sterilizing vaccine, and the mass vaccination of it, will increase the evolution pressure and selecting vaccine resistant variants.

  • Mon, Sep 27, 2021 - 11:09pm

    #2
    XZBD2

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    Higher rate of mutation in the S1 domain of the spike protein

Thanks for the link.  It is an interesting paper, but I think while it is true that there are more mutations in the spike, there are also a lot of mutations in the more prevalent N protein, so I suspect it is more complicated as the paper suggest.

Here is my thinking:

1) In order for the vaccines to be selective they have to provide some sort of barrier to reproduction and/or transmission of the virus that the mutations would enable to be bypassed.  As far as I can tell the mRNA/DNA vaccines provide little on no barrier thus little or no selective pressure in fact may even produce super spreaders (those spreading it without knowing they are sick, thus taking no precautions)  thus actually facilitating transmission.

2) I  believe the Chinese & Russian vaccines, as they are based on inactivated virus, would provide different selective pressures.

3) The largest portion of spreaders to this point are still likely to be those unvaccinated as they make up a larger percentage of those infected. Unvaccinated produce a much larger array of antibody targeting  and children seem to produce fewer antibodies to N and S proteins and have elevated response to E and ORF6.    See Antibody landscapes of SARS-Cov-2:

https://europepmc.org/article/PMC/PMC8376662

To be clear I am not disagreeing that the vaccines might be providing sufficient selective pressure such that the last mutation that modeling shows is all that is needed to allow for vaccine escape in the most prevalent strains will indeed occur.  It is just that I suspect there are a lot of other selective pressures that need to be considered, though Im quite certain I know much less than Geert Vanden Boossche about this.

  • Tue, Sep 28, 2021 - 12:19am

    #3
    derek1ee

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    Higher rate of mutation in the S1 domain of the spike protein





“But if we look at particularly in the S1 domain of spike, … [omit], up until September 2020, there’s like 3-ish mutation that have occurred, maybe 4-ish in this S1 domain, but when we start to see these variant of concern viruses, they all generally have multiple mutations in S1 that are kind of showing 6, 7, 8, 9, 10 mutations in S1 domain. And you can see this fairly rapid increase in the degree of divergence in S1 relative to the rest of the genome.

So this is kind of the slightly anecdotal pattern here where it looks like S1 domain of spike is mutating rapidly and that’s kind of all that we can say here.”

The video then continuous to discuss this topic and compares it with S2/M/N/etc. which is also worth watching.

  • Tue, Sep 28, 2021 - 12:27am   (Reply to #2)

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    derek1ee

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    Higher rate of mutation in the S1 domain of the spike protein

Interesting, thanks for sharing the paper.

1) In order for the vaccines to be selective they have to provide some sort of barrier to reproduction and/or transmission of the virus that the mutations would enable to be bypassed.  As far as I can tell the mRNA/DNA vaccines provide little on no barrier thus little or no selective pressure in fact may even produce super spreaders (those spreading it without knowing they are sick, thus taking no precautions)  thus actually facilitating transmission.

I’m not sure I agree with the argument of mRNA/DNA vaccines (which is coded for S1 protein) provide little or no barrier selective pressure. The fact that it will produce S1 protein means it will favor virus with more mutation in S1 because it may evade the antibody generated from the vaccine.

I do agree that vaccinated people, not know they are sick, can actually spread the virus (and virus with mutations in S1).

2) I  believe the Chinese & Russian vaccines, as they are based on inactivated virus, would provide different selective pressures.

No argument here, agreed.

3) The largest portion of spreaders to this point are still likely to be those unvaccinated as they make up a larger percentage of those infected. Unvaccinated produce a much larger array of antibody targeting  and children seem to produce fewer antibodies to N and S proteins and have elevated response to E and ORF6.    See Antibody landscapes of SARS-Cov-2:

Agreed that unvaccinated people are still accounted for a significant % of spreading the virus, but I think that could change as the vaccination rate ramps up. I don’t know enough/haven’t finished reading the paper to comment on the second half of the statement.

I don’t know if the data is available, but I think it could be interesting to look at the rate of mutation in S1 across different country/state with different vaccination rate and see if there’s a correlation.

 

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