5 ms·

> Wade devoted a full section to the “furin cleavage site,” a distinctive segment of SARS-CoV-2’s genetic code that makes the virus more infectious by allowing

> Wade devoted a full section to the “furin cleavage site,” a distinctive segment of SARS-CoV-2’s genetic code that makes the virus more infectious by allowing it to efficiently enter human cells. > Within the scientific community, one thing leapt off the page. Wade quoted one of the world’s most famous microbiologists, Dr. David Baltimore, saying that he believed the furin cleavage site “was the smoking gun for the origin of the virus.” Baltimore, a Nobel Laureate and pioneer in molecular biology, was about as far from Steve Bannon and the conspiracy theorists as it was possible to get. His judgment, that the furin cleavage site raised the prospect of gene manipulation, had to be taken seriously. Furin cleavage sites have evolved and are present in multiple coronaviruses: - HCoV-OC43 (infects humans) - HCoV-HKU1 (infects humans) - MHV-A59 - ChRCoV-HKU24 - BtCoV-ENT - BtNeCoV-PML-PHE1 - BtCoV-HKU4 - BtCoV-HKU5 - MERS-CoV - BtHpCoV-Zhejiang2013 - SARS-CoV-2 Phylogenetic analysis suggests that it has evolved independently at least 6 times that we know of. https://www.sciencedirect.com/science/article/pii/S187350612 https://www.sciencedirect.com/science/article/pii/S187350612... After that article was published a team in Thailand found furin cleavage sites in sarbecoviruses closely related to SARS-CoV-2 called RacCS203 (91.5% similarity to SARS-CoV-2) and RmYN02 (93.3% similarity to SARS-CoV-2) https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7873279/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7873279/ Furin cleavage sites are common, nature understands how to utilize that trick very well, and continuously has re-discovered it.

Throwawayaerlei 5y ago
<s>The</s> A gravamen of the SARS-CoV-2 furin cleavage site claim is that it's not aligned like others in the coronaviruses you cite.
- henearkr 5y ago
  I'd love more information if you have. Because per se it does not prove the claim of bioengineering.
  - Throwawayaerlei 5y ago
    It's not in Nicolas Wade's article, which I now see has been unfairly maligned along with David Baltimore who's been selectively quoted to leave out the technical detail of what made the latter say the SARS-CoV-2 is a smoking gun, see the 4) A Question of Codons: https://nicholaswade.medium.com/origin-of-covid-following-the-clues-6f03564c038 https://nicholaswade.medium.com/origin-of-covid-following-th... If correct, that's getting strongly into bioengineering evidence. You are of course more likely correct about the alignment issue, I can't find my source now, and the above is probably much stronger evidence. For the alignment you'd have to be a virologist, probably one specializing in coronaviruses, to be able to really judge this. Of course a whole bunch of biologists have shifted their focus to coronaviruses in the last year and a half.
    - lamontcg 5y ago
      So you don't have any idea what you're talking about and don't have any ability to weigh if what you're looking at is human bioengineering or natural bionengineering, but you're going to strongly assert that its evidence of human tampering.
      - deugo 5y ago
        Yes.
    - deleted 5y ago
      [deleted]
    - henearkr 5y ago
      The author is contradicting himself: said that virus engineering is done by splicing of existing other coronavirii, and then also said that the two codons CGG is very unusual for coronavirii. Splicing is also naturally done everywhere and all the time, just by natural genetic events, so if there was splicing to create the two CGG codons, it can be natural. So still nothing to point out to bioengineering in my opinion.
      - 5y ago
canadianfella 5y ago
What does 93.3% similar mean? We’re 90% similar to cats and mice by some measures of DNA.
Jarwain 5y ago
There are so many "shocking" articles, but here's something I don't get: The closest genetic match is only 3.8% similar. When it only has 29,903 base pairs, that's 1,136 mutations. I'm no bioscientist but my friends who are tell me that's a lot of changes, and that experiments might change a few base pairs or proteins at a time. A lab leak theory doesn't explain how gain of function study resulted in so many mutations, unless they were blasting these viruses with radiation, and what would be the point of that? Radiation mutations would cause too many changes to do useful science. Everyone keeps looking at bats but the closest bat coronavorus is 20 years of evolution away. SARS and MERS came from palm covets and dromedary camels respectively, so what's the deal? Every time I read about this I keep thinking "huh that's sketchy but circumstantial" and I've yet to find an answer to how the lab would've gotten to this point, undiscovered, with no published papers or research or notes or preprints anywhere
- Throwawayaerlei 5y ago
  but my friends who are tell me that's a lot of changes, and that experiments might change a few base pairs or proteins at a time. A lab leak theory doesn't explain how gain of function study resulted in so many mutations, unless they were blasting these viruses with radiation Or explicitly creating chimeric coronaviruses, which has been the state of the are for some time. Here's https://pubmed.ncbi.nlm.nih.gov/26552008/ https://pubmed.ncbi.nlm.nih.gov/26552008/ one of the sources of smoke on this, a 2015 paper co-authored by the Bat Woman (2nd to last author), the key sentence from the abstract: Using the SARS-CoV reverse genetics system, we generated and characterized a chimeric virus expressing the spike of bat coronavirus SHC014 in a mouse-adapted SARS-CoV backbone. Have you read the fine article? It cites more than a few papers.
  - Jarwain 5y ago
    I've read a few articles, skimmed a few papers and sent them to friends. The counterargument is that there still aren't enough similarities. The mutations on covid 19 are Really Different compared to the known and studied viruses. If it was a lab leak of an engineered chimera, you'd be able to see that A proteins came from virus X and B proteins came from virus Y and Z, but that hasn't been shown to be the case. From what I understand there are a bunch of smaller mutations across a lot of proteins resulting in something that doesn't really line up with known and studied genomes. This paper actually goes through and compares the DNA of covid 19 against several other studied viruses: https://www.nature.com/articles/s41579-020-00459-7 https://www.nature.com/articles/s41579-020-00459-7
deugo 5y ago
Put me in the screenshot when you report your progress. lamontcg has definitely convinced me, and did a great job disrupting the conversation re-using a playbook template. We all gave him upvotes to increase the visibility of his well-crafted post. Soon, most Americans went home to have beer and watch Superbowl. Job well done.
teorema 5y ago
In one of these recent articles (the Wade piece?) they explain it's not the presence of a furin cleavage site, it's this particular furin cleavage site pattern including its flanking regions. There's discussion about the existence of furin cleavage sites in other coronaviruses, but also explanation for why it's unusual in SARS-CoV-2.
eutropia 5y ago
The “smoking gun” was the “human” (arginine as CGG) way the AA seq was coded for at the furin cleavage site: Only 5 percent of SARS2’s arginine codons are CGG, and the double codon CGG-CGG has not been found in any other beta-coronavirus.
- lamontcg 5y ago
  > has not been found in any other beta-coronavirus. That does not mean it doesn't exist, just that we haven't found it. We didn't know of any other sarbecoviruses that had furin cleavage sites, then we found them in bats in Thailand, then the goalposts moved to how this paricular furin cleavage site is weird. Once a decade passes and we find animals with beta-coronviruses which have the same kinds of furin cleavage sites, I'm sure the goalposts will move again.
  - eutropia 5y ago
    Granting that, or even granting that the virus wasn't modified in the WIV (merely collected and then accidentally released) at all: we need to find the animal population that it supposedly jumped into people from -- and 18 months later we haven't.
tim333 5y ago
Wade's section is about: >There are several curious features about this insert but the oddest is that of the two side-by-side CGG codons. Only 5 percent of SARS2’s arginine codons are CGG, and the double codon CGG-CGG has not been found in any other beta-coronavirus. https://thebulletin.org/2021/05/the-origin-of-covid-did-people-or-nature-open-pandoras-box-at-wuhan/ https://thebulletin.org/2021/05/the-origin-of-covid-did-peop...

Throwawayaerlei 5y ago

<s>The</s> A gravamen of the SARS-CoV-2 furin cleavage site claim is that it's not aligned like others in the coronaviruses you cite.

henearkr 5y ago
I'd love more information if you have. Because per se it does not prove the claim of bioengineering.
- Throwawayaerlei 5y ago
  It's not in Nicolas Wade's article, which I now see has been unfairly maligned along with David Baltimore who's been selectively quoted to leave out the technical detail of what made the latter say the SARS-CoV-2 is a smoking gun, see the 4) A Question of Codons: https://nicholaswade.medium.com/origin-of-covid-following-the-clues-6f03564c038 https://nicholaswade.medium.com/origin-of-covid-following-th... If correct, that's getting strongly into bioengineering evidence. You are of course more likely correct about the alignment issue, I can't find my source now, and the above is probably much stronger evidence. For the alignment you'd have to be a virologist, probably one specializing in coronaviruses, to be able to really judge this. Of course a whole bunch of biologists have shifted their focus to coronaviruses in the last year and a half.
  - lamontcg 5y ago
    So you don't have any idea what you're talking about and don't have any ability to weigh if what you're looking at is human bioengineering or natural bionengineering, but you're going to strongly assert that its evidence of human tampering.
    - deugo 5y ago
      Yes.
  - deleted 5y ago
    [deleted]
  - henearkr 5y ago
    The author is contradicting himself: said that virus engineering is done by splicing of existing other coronavirii, and then also said that the two codons CGG is very unusual for coronavirii. Splicing is also naturally done everywhere and all the time, just by natural genetic events, so if there was splicing to create the two CGG codons, it can be natural. So still nothing to point out to bioengineering in my opinion.
    - 5y ago

canadianfella 5y ago

What does 93.3% similar mean? We’re 90% similar to cats and mice by some measures of DNA.

Jarwain 5y ago

There are so many "shocking" articles, but here's something I don't get: The closest genetic match is only 3.8% similar. When it only has 29,903 base pairs, that's 1,136 mutations. I'm no bioscientist but my friends who are tell me that's a lot of changes, and that experiments might change a few base pairs or proteins at a time. A lab leak theory doesn't explain how gain of function study resulted in so many mutations, unless they were blasting these viruses with radiation, and what would be the point of that? Radiation mutations would cause too many changes to do useful science. Everyone keeps looking at bats but the closest bat coronavorus is 20 years of evolution away. SARS and MERS came from palm covets and dromedary camels respectively, so what's the deal? Every time I read about this I keep thinking "huh that's sketchy but circumstantial" and I've yet to find an answer to how the lab would've gotten to this point, undiscovered, with no published papers or research or notes or preprints anywhere

Throwawayaerlei 5y ago
but my friends who are tell me that's a lot of changes, and that experiments might change a few base pairs or proteins at a time. A lab leak theory doesn't explain how gain of function study resulted in so many mutations, unless they were blasting these viruses with radiation Or explicitly creating chimeric coronaviruses, which has been the state of the are for some time. Here's https://pubmed.ncbi.nlm.nih.gov/26552008/ https://pubmed.ncbi.nlm.nih.gov/26552008/ one of the sources of smoke on this, a 2015 paper co-authored by the Bat Woman (2nd to last author), the key sentence from the abstract: Using the SARS-CoV reverse genetics system, we generated and characterized a chimeric virus expressing the spike of bat coronavirus SHC014 in a mouse-adapted SARS-CoV backbone. Have you read the fine article? It cites more than a few papers.
- Jarwain 5y ago
  I've read a few articles, skimmed a few papers and sent them to friends. The counterargument is that there still aren't enough similarities. The mutations on covid 19 are Really Different compared to the known and studied viruses. If it was a lab leak of an engineered chimera, you'd be able to see that A proteins came from virus X and B proteins came from virus Y and Z, but that hasn't been shown to be the case. From what I understand there are a bunch of smaller mutations across a lot of proteins resulting in something that doesn't really line up with known and studied genomes. This paper actually goes through and compares the DNA of covid 19 against several other studied viruses: https://www.nature.com/articles/s41579-020-00459-7 https://www.nature.com/articles/s41579-020-00459-7

deugo 5y ago

Put me in the screenshot when you report your progress. lamontcg has definitely convinced me, and did a great job disrupting the conversation re-using a playbook template. We all gave him upvotes to increase the visibility of his well-crafted post. Soon, most Americans went home to have beer and watch Superbowl. Job well done.

teorema 5y ago

In one of these recent articles (the Wade piece?) they explain it's not the presence of a furin cleavage site, it's this particular furin cleavage site pattern including its flanking regions. There's discussion about the existence of furin cleavage sites in other coronaviruses, but also explanation for why it's unusual in SARS-CoV-2.

eutropia 5y ago

The “smoking gun” was the “human” (arginine as CGG) way the AA seq was coded for at the furin cleavage site: Only 5 percent of SARS2’s arginine codons are CGG, and the double codon CGG-CGG has not been found in any other beta-coronavirus.

lamontcg 5y ago
> has not been found in any other beta-coronavirus. That does not mean it doesn't exist, just that we haven't found it. We didn't know of any other sarbecoviruses that had furin cleavage sites, then we found them in bats in Thailand, then the goalposts moved to how this paricular furin cleavage site is weird. Once a decade passes and we find animals with beta-coronviruses which have the same kinds of furin cleavage sites, I'm sure the goalposts will move again.
- eutropia 5y ago
  Granting that, or even granting that the virus wasn't modified in the WIV (merely collected and then accidentally released) at all: we need to find the animal population that it supposedly jumped into people from -- and 18 months later we haven't.

tim333 5y ago

Wade's section is about: >There are several curious features about this insert but the oddest is that of the two side-by-side CGG codons. Only 5 percent of SARS2’s arginine codons are CGG, and the double codon CGG-CGG has not been found in any other beta-coronavirus. https://thebulletin.org/2021/05/the-origin-of-covid-did-people-or-nature-open-pandoras-box-at-wuhan/ https://thebulletin.org/2021/05/the-origin-of-covid-did-peop...