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Yuri Deigin Profile picture
@ydeigin
Oct 2, 2021 • 11 tweets • 5 min read • Read on X
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Ok, just to show that I am not biased against zoonosis, here is a much more plausible NATURAL way the FCS could have arisen in SARS2 than what virologists could muster so far — via recombination with host mRNA. Namely, pangolin mRNA. In fact, I found a 14-nt match to PRRA insert
in the GIABR pangolin dataset. Yes, that’s the same dataset that contains the SARS2 RBM and was the source for the MP789 pangolin CoV. I was checking it for the PRRA insert and found 3 reads in lung08 run (SRX6893154) that match a 14-nt stretch that fully covers the PRRA insert:
The first read actually mapped to a COMPLEMENT (minus strand) of pangolin mRNA, which is perfect for coronaviral RdRp recombination, as the CoV template strand is a minus strand.
The second read I couldn't really map to anything conclusive:
The third read again mapped to a complement of pangolin methyltransferase mRNA:
Oh and by the way another pangolin enzyme matched the 14-nt fragment, DUSP4:
While we haven't yet observed CoV recombination with host mRNA, it has actually been observed for other viruses. In fact, it was observed to increase cleavability in influenza:

pubmed.ncbi.nlm.nih.gov/2544809/
Recombination with host mRNA was also observed in another +ssRNA virus:

pubmed.ncbi.nlm.nih.gov/30232612/
So could the novel furin cleavage site have arisen naturally? Of course. Recombination with host (pangolin?) mRNA is much more plausible in my book than some mythical recombination with HKU9 as per Gallagher or "clade X" as per Lytras.

Does this rule out a lab leak? Not for me.
Why not? Even if FCS in SARS2 arose naturally, it could still have emerged in Wuhan via a lab leak - the recombination in a pangolin could well have happened in a lab, or a lab staffer could have been infected with a pangolin CoV with an FCS during field work.
Plus the possibility that the SARS2 FCS has been purposefully engineered (as per the EcoHealth and WIV DARPA proposal) is still on the table.

But all hypothesis must be evaluated based only on data, not preconceived notions or groupthink (relevant for both zoo and LL groups).

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More from @ydeigin

Yuri Deigin Profile picture
Dec 28, 2024
Excellent analysis of SARS2 cryptic lineages from persistent human infections (those nightmare scenarios happen when the virus colonizes your gut and remains there for months or years). Some implications for Covid origins there that I’d like to address in the thread below.
First an aside on extrapolating insertions found in SARS2 circulating in humans to the likelihood of insertions occurring (and getting fixed) in a SARS2 progenitor circulating in an intermediate host — SARS2 has now been circulating for years in hundreds of millions of humans, while in the wild it could not have had even a sliver of such a reservoir of non-bat hosts (and we all agree the FCS insertion could not have arisen in bats because it is detrimental to their preferred enteric tropism).
Of course, “a long time” for passaging in a lab could be just a few months, especially if we’re talking about in vitro passaging. Moreover, many novel mutations would arise quickly when the virus is put into cells from a novel host and organ system (respiratory vs. enteric).
Read 7 tweets
Yuri Deigin Profile picture
Dec 18, 2024
🧵 Covid Origins: Lab leak critics claim the coincidence of a novel coronavirus emerging near the Wuhan Institute of Virology is dwarfed by the “counter-coincidence” of it first being noticed at a wildlife market. But the market was actually one of the most likely places for a lab-leaked virus to get noticed.

Here’s a clip from my podcast with @robertwrighter and a deep dive in the thread below:
Basically, if we imagine the map of Wuhan as a “probability landscape”, where each location has an inherent probability that a roaming lab-leaked virus would get noticed if it got there, the Huanan seafood market would dominate that landscape like Mount Everest.
Now, let’s walk through the thought experiment: How would a lab-leaked virus get noticed in Wuhan in late 2019?
Read 16 tweets
Yuri Deigin Profile picture
Nov 29, 2024
Some critics of the Covid lab leak hypothesis say the SARS2 furin cleavage site is unlikely to have been engineered because in previous cases of creating novel FCSes in coronaviruses virologists have never inserted an FCS but rather created them in place via point mutations. But!
A close collaborator of Zhengli Shi and the Wuhan Institute of Virology, Shibo Jiang, in 2013 published a paper creating a furin cleavage site in a non-CoV synthetic vector via a 12-nt insertion (note the CGG codon for the leading arginine): Image
In 2016-17, WIV has created a novel reverse genetics system ("backbone") for the WIV1 virus, and Shibo Jiang subsequently coauthored a paper with Lei-Ping Zeng, the author of that backbone. (Lanying Du, another key collaborator of both WIV and Shibo Jiang, was also on the paper. She was also the editor for the 2013 paper inserting the RIRR FCS):

pmc.ncbi.nlm.nih.gov/articles/PMC70…
Read 20 tweets
Yuri Deigin Profile picture
Jul 13, 2024
🚀 More amazing partial reprogramming news! This time from @davidasinclair — he mentioned some unpublished animal results for:

- *reversing* Alzheimer’s symptoms
- hearing loss
- ALS
- glaucoma (anticipating clinical trials in 2025!)
- rejuvenating skin, kidneys and liver
Great to hear that the FDA is ok with Tet-inducible (via rtTA3) partial reprogramming gene therapies, and that Life Bio is so close to the clinic. They presented encouraging results in monkeys in an eye stroke model (NIAON); I didn’t know they also tried a glaucoma monkey model.


Image
Image
Image
Image
PS: while Life Bio seems closest to human clinical trials among partial reprogramming companies, others aren’t far behind:

- Turn Bio with their skin therapy
- we at YouthBio with our Alzheimer’s therapy
Read 6 tweets
Yuri Deigin Profile picture
May 8, 2024
🧵 I wrote a new Medium article about how Ralph Baric's January 2024 testimony provides new insights into the origins of COVID-19. Check out the article here:

yurideigin.medium.com/why-ralph-bari…
2/
 Highlights:

- Ralph Baric confirmed that DEFUSE proposed inserting novel furin cleavage sites into live viruses, inspired by feline coronaviruses
- SARS-CoV-2’s furin cleavage sites is identical to the one found in several lethal feline coronavirus strains
- Ralph Baric strongly believes WIV had unpublished viruses and viral reverse genetics systems
- Most plausible Covid origin is the result of research on identifying new SARS-like viruses and developing broad vaccines against them
3/
 Quick Summary:

Ralph Baric’s January 2024 testimony provided crucial insights into the DEFUSE grant proposal, a collaborative project involving EcoHealth and the Wuhan Institute of Virology (WIV), and the research interests of WIV prior to the Covid outbreak. The pre-Covid landscape of coronavirology research saw intense US-China collaboration aimed at creating broad-spectrum vaccines for SARS- and MERS-like viruses. Key players like Baric, along with researchers Lanying Du, Yusen Zhou, Fang Li, and Shibo Jiang, focused on overcoming challenges such as antibody-dependent enhancement (ADE). By 2018–2019, as collaboration between Baric and his counterparts shifted, WIV became central in SARS-like virus research.

Drawing on Baric’s testimony, I argue that the emergence of SARS-CoV-2 in Wuhan wasn’t coincidental but a likely result of research at WIV. In particular, I outline how WIV researchers, after a post-2018 shift in focus, concentrated on identifying SARS-like viruses with spike proteins 10–25% different from SARS1, capable of evading SARS1-based antibodies, and potentially causing ADE. They were plausibly inspired by Baric’s ideas on furin cleavage sites and his work with Fang Li on SARS and MERS spike cleavage, leading them to engineer furin cleavage sites into novel SARS-like strains. Baric’s testimony suggests that feline coronaviruses inspired this suggestion, and the identical furin cleavage sites in lethal feline coronavirus strains and SARS-CoV-2 strongly indicate that the WIV could have inserted such a site into a SARS-CoV-2 precursor to extend their research from MERS to novel SARS-like coronaviruses. This suggests the emergence of SARS-CoV-2 was not a coincidence but a potential result of this focused research.
Read 39 tweets
Yuri Deigin Profile picture
May 2, 2024
I was curious to hear Peter Dazsak mention at the @COVIDSelect hearing that prior to the Covid outbreak, he actually met with Dr. (Yi-Gang) Tong who was working on a SARS-like CoV found in pangolin samples. In his Feb 2020 paper, Dr. Tong mentions that they isolated this virus long before the outbreak and routinely cultured it at BSL2. More info in the thread below.

PS: Daszak erroneously claiming in 2020
that WIV didn’t have live bats goes to show that he could well be unaware of what other research relevant to Covid origins WIV was engaged in.
While Dr. Tong's lab is in Beijing, he did collaborate with WIV and EcoHealth previously, e.g. in 2018 on a SADS-CoV paper titled "Fatal swine acute diarrhoea syndrome caused by an HKU2-related coronavirus of bat origin":

pubmed.ncbi.nlm.nih.gov/29618817/
But I am more intrigued about the collaboration between Yi-Gang Tong and Yusen Zhou, the author of the Feb 2020 Covid vaccine patent who died a few months later under mysterious circumstances. They both hail from the same "State Key Laboratory of Pathogen and Biosecurity" at the Beijing Institute of Microbiology and Epidemiology. Here is their joint 2016 paper:

ijbs.com/v12p1104.htm
Read 10 tweets

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