Thread by @VBruttel

@ydeigin So to sum this up:
1) SARS2 Omicron genome looks like it was "separated/frozen" between June 2020 and late summer 2021 -
This has never before been seen in nature, only in lab leaked pandemics
en.wikipedia.org/wiki/1977_Russ…

@ydeigin 2) SARS2 Omicron has 25:1 non-synonymous:synonymous mutations ratio.

Natural evolution would result in 25:50-100 ratios.
The only logical explanation here is targeted manipulation.

@ydeigin 3) No SARS2 Omicron predecessors have been detected between June 2020 and fall 2021, despite their supposedly already higher infectivity.
So in this time,
- a single isolated patient bred more mutations than >100Mio others?
- survived continous infection in complete isolation?

@ydeigin 4) Omicron is better adapted to humans and likely also to vaccinated/recovered humans.
If this was acquired in a large pool of humans, we would have seen predecessors of this variant before.
Evolution in animals should have resulted in a less-well adapted variant.

@ydeigin 5) The only plausible explanation how this huge number of mutations could have been acquired completely below the radar is:
- scientists enabled SARS2 samples to escape antibody responses by passaging them in presence of diluted convalescent serum on human/humanized cell lines.

@ydeigin 6) Exactly this extremely risky research, which could render all of world wide vaccination efforts useless, was done in South Africa.
nature.com/articles/s4158…
And not even at their BSL4 lab, no, in Durban, which only has a BSL3 lab😱.

@ydeigin 7) Durban, as you mentioned above @ydeigin, is exactly the city where omicron was first detected in one of the patients.
Where they "trained" SARS2 variants to become resistant to neutralizing antibodies by slowly and carefully increasing covalescent plasma concentrations...

@ydeigin 8) and not just any SARS2 varian, no the had sampled their viruses in JUNE 2020, when the closest omicron relative was last seen out there.
And not any variant, no, e.g. a B.1.1.117, B.1.1.1 and a B.1.1.56 virus.
Omicron is B.1.1.529, sounds somewhat similar, right?

@ydeigin 9) of course they used cell lines transfected for human ACE2, and froze their viral samples, which still is the only logical explanation for omicron completely splitting off from all other variants of in June 2020.

@ydeigin 10) IMO someone:
1. bred different antibody-escape-mutations w/ diluted convalescent plasma
2. maybe also wondered what happened if those were combined & made a recombinant AV.1. SARS2 variant with all these mutations for 3000$
4. inhaled some aerosols/dropped a flask
➡️ omicron

@ydeigin 11) The most sickening part is that all of this work could have been done with basically no risk by just putting the spike protein into a harmless pseudovirus.
Like done here:
nature.com/articles/s4158…
With strikingly similar results btw:

@ydeigin 12) These are just my thoughts Saturday morning 2.30am after an intense work week. Please correct me whereever I may be wrong.
This deserves a proper investigation that goes into the labs.
Fact is that virologists keep doing highly risky research at very questionable conditions.

@ydeigin 13) We must end this research, at least until we can develop safe international experimental, ethical and reporting guidelines and maybe move it to an isolated island.
Otherwise this research could just end us.

I'm out for now, live long and prosper🖖

@ydeigin 14) have to add a few points:
artificial viruses that acombine resistance-enhancing mutations from several strains are called polymutants:

Someone could have copied that strategy w/ real SARS2, or a pseudovirus spike could have leaked and recombined.

@ydeigin 15) high selective pressure + high viral loads can lead to pretty high non-silent:silent (dN:dS) mutation ratios.
In normal CoV-evolution, this is 0.1 to 0.2.
However, e.g. in immunocompromized patients (long term high viral loads) can increase to 2-3.
academic.oup.com/jid/article/22…

@ydeigin 16) The very same should be true, if not even more so, when passaging CoVs in presence of antibodies/convalescent sera.
This study has generated synthetic polymutant SARS2 spikes with mutations generated through exactly this process, and even many mutations are identical:

@ydeigin 17) Thus far, we have only seen 1-7 spike mutations in immunocompromised patients, way less than in synthetic polymutants or omicron (33).

@ydeigin 18) Also, in immunocompromised patients, nonsilent mutations seem to be less concentrated in the spike.
After all, such patients may not have sufficient antibodies to maintain selective pressure, as opposed to cell culture with finely tuned patient sera concentrations.

@ydeigin 19) I have also learned that even some of the lead scientists working on vaccine-resistant SARS2 spike proteins seem to still believe that lab leaks (en.wikipedia.org/wiki/List_of_l…) cannot happen.
Should we trust s.o. who hasn't heard of Chernobyl/Fukushima to run a nuclear power plant?

@ydeigin 20) IMO, lab leak is still the most plausible explanation for omicron.
Connects all the dots: location, isolations since ~06/2020, strong selective pressure on spike, not so safe lab...
But not 100% sure anymore it was engineered, maybe only passaging w/ patient sera?
Let's look!

@ydeigin correction: dN:dS in omicron spike alone could be even as high as 33:1, depending on the variant. Typical dN:dS is 1:5 (0.2) in stable sarbeco-viruses.
If this was natural, best explained by continuous passaging (high viral loads) with patient/vacc. sera (high sel. pressure).