20 ms·

There is an interesting peer reviewed paper published last month with analysis of existing facts about the origin of covid-19. A part from their conclusion: Mo

There is an interesting peer reviewed paper published last month with analysis of existing facts about the origin of covid-19. A part from their conclusion: More than a year after the initial documented cases in Wuhan, the source of SARS-CoV-2 has yet to be identified, and the search for a direct or intermediate host in nature has been so far unsuccessful. The low binding affinity of SARS-CoV-2 to bat ACE2 studied to date does not support Chiroptera as a direct zoonotic agent. Furthermore, the reliance on pangolin coronavirus receptor binding domain (RBD) similarity to SARS-CoV-2 as evidence for natural zoonotic spillover is flawed, as pangolins are unlikely to play a role in SARS-CoV-2′s origin and recombination is not supported by recent analysis. At the same time, genomic analyses pointed out that SARS-CoV-2 exhibits multiple peculiar characteristics not found in other Sarbecoviruses. A novel multibasic furin cleavage site (FCS) confers numerous pathogenetically advantageous capabilities, the existence of which is difficult to explain though natural evolution... source: https://link.springer.com/article/10.1007/s10311-021-01211-0 https://link.springer.com/article/10.1007/s10311-021-01211-0

torgian 5y ago
I don’t pretend to understand everything here, but it sounds like the paper is saying it is very unlikely to have originated from animals?
ximeng 5y ago
https://www.sciencedirect.com/science/article/pii/S1873506120304165 https://www.sciencedirect.com/science/article/pii/S187350612... Here is a paper that states that the furin cleavage site appears naturally in a number of viruses. I looked into these lab origin theories for the furin cleavage site last year. The problem with it being a laboratory insertion was that although performing an insertion is relatively easy once you know what to insert, generally it’s beyond current science to independently create mutations for a specific purpose. It’s a bit beyond me as a non-biologist but my feeling based on the literature was that the lab origin was unlikely. However it is pushed in certain circles partly for ideological reasons, based on evidence that is plausible at first glance but with a lot more digging not entirely convincing evidence. However, there didn’t really seem to be much neutral expert analysis of the evidence.
- trevelyan 5y ago
  > generally it’s beyond current science to independently create mutations for a specific purpose. No it isn't. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4810786/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4810786/
  - ximeng 5y ago
    Quite a long article, but skimming it it looks like that experiment involves applying naturally occurring mutations to an existing virus?
    - pclmulqdq 5y ago
      Yes. Gain of function research involves putting evolutionary pressure on an organism to give it certain traits that can be found in the wild, but the resulting virus is anything but natural. I think a lot of people dismiss the lab leak hypothesis based on the idea that a lab-created virus must have an engineered genome rather than an evolved one.
- Pepe1vo 5y ago
  From the OP, it appears that scientists knew exactly where to insert a furin cleavage site: >“Since 1992 the virology community has known that the one sure way to make a virus deadlier is to give it a furin cleavage site at the S1/S2 junction in the laboratory,” writes Steven Quay, a biotech entrepreneur interested in the origins of SARS2.
  - ximeng 5y ago
    The problem is knowing how to put in the furin cleavage site, and generally if it's done in the lab it's done by copying a particular sequence from an existing virus as scientists can't predict how to do it themselves (without copying) with current state of knowledge.
  - matzab 5y ago
    That's such a mischaracterisation, I don't even know where to start. That Quay-guy obviously searched for "furin" on pubmed, found some papers (that don't even say that - and most definitely not for any coronaviruses) and thought it fit his thesis. If only viruses and infections were that simple!
analyte123 5y ago
This is covered in detail in the article. To me the smoking gun in this article is the linked video of Daszak saying "we have now found... over 100 new SARS-related coronaviruses, very close to SARS...some of them get into human cells in the lab, some of them can cause SARS disease in humanized mice models...these are a clear and present danger". I've been aware of this for many months after reading this tweet [1] which says essentially the same thing. [1] https://twitter.com/PeterDaszak/status/1197631383470034951?s=20 https://twitter.com/PeterDaszak/status/1197631383470034951?s...
lamontcg 5y ago
> "Furin cleavage sites naturally occur in coronaviruses" > https://www.sciencedirect.com/science/article/pii/S1873506120304165 https://www.sciencedirect.com/science/article/pii/S187350612... They exist in the human HCoV-HKU1, HCoV-OC43, MERS-CoV and appear to have evolved independently at least 6 times in betacoronaviruses. Furthermore while this article claims that the furin cleavage site has not found in any sarbecoviruses, that is now outdated information: > "Evidence for SARS-CoV-2 related coronaviruses circulating in bats and pangolins in Southeast Asia" > https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7873279/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7873279/ Both RacCS203 (91.5% similar to SARS-CoV-2) and RmYN02 (93.3% similar to SARS-CoV-2) have furin cleavage sites. So we're up to 7-to-9 times now that evolution has evolved a furin cleavage site in betacoronaviruses, including 3 sarbecoviruses that may or may not be directly related. The whole "furin cleavage site is an indication of human engineering" argument is just falsified at this point.
- tripletao 5y ago
  What's your estimate of the relative prevalence of an FCS among the likely space of lab-created SARS-like coronaviruses vs. among natural, SARS-like coronaviruses? My understanding is that adding an FCS is a very common method of lab gain of function, but rare among such viruses in nature. I don't think the FCS is determinative, and I agree Wade's article overstates its significance. In a Bayesian analysis, it still seems to me like it points weakly (at least 3x prevalence?) towards lab origin, though.
  - lamontcg 5y ago
    It evolved at least 5+ times completely independently in nature in coronaviruses (and in other viruses). The significance is zero. Nature itself knows how to figure it out. > but rare among such viruses in nature. This assertion is false. It is common among betacoronaviruses in nature, not rare. That was the point of those two articles. We have even found two sarbecoviruses now (directly related to SARS-CoV-1 and SARS-CoV-2) in bats in Thailand which have an FCS. It points literally 0% towards lab origin.
    - 5y ago

torgian 5y ago

I don’t pretend to understand everything here, but it sounds like the paper is saying it is very unlikely to have originated from animals?

ximeng 5y ago

https://www.sciencedirect.com/science/article/pii/S1873506120304165 https://www.sciencedirect.com/science/article/pii/S187350612... Here is a paper that states that the furin cleavage site appears naturally in a number of viruses. I looked into these lab origin theories for the furin cleavage site last year. The problem with it being a laboratory insertion was that although performing an insertion is relatively easy once you know what to insert, generally it’s beyond current science to independently create mutations for a specific purpose. It’s a bit beyond me as a non-biologist but my feeling based on the literature was that the lab origin was unlikely. However it is pushed in certain circles partly for ideological reasons, based on evidence that is plausible at first glance but with a lot more digging not entirely convincing evidence. However, there didn’t really seem to be much neutral expert analysis of the evidence.

trevelyan 5y ago
> generally it’s beyond current science to independently create mutations for a specific purpose. No it isn't. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4810786/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4810786/
- ximeng 5y ago
  Quite a long article, but skimming it it looks like that experiment involves applying naturally occurring mutations to an existing virus?
  - pclmulqdq 5y ago
    Yes. Gain of function research involves putting evolutionary pressure on an organism to give it certain traits that can be found in the wild, but the resulting virus is anything but natural. I think a lot of people dismiss the lab leak hypothesis based on the idea that a lab-created virus must have an engineered genome rather than an evolved one.
Pepe1vo 5y ago
From the OP, it appears that scientists knew exactly where to insert a furin cleavage site: >“Since 1992 the virology community has known that the one sure way to make a virus deadlier is to give it a furin cleavage site at the S1/S2 junction in the laboratory,” writes Steven Quay, a biotech entrepreneur interested in the origins of SARS2.
- ximeng 5y ago
  The problem is knowing how to put in the furin cleavage site, and generally if it's done in the lab it's done by copying a particular sequence from an existing virus as scientists can't predict how to do it themselves (without copying) with current state of knowledge.
- matzab 5y ago
  That's such a mischaracterisation, I don't even know where to start. That Quay-guy obviously searched for "furin" on pubmed, found some papers (that don't even say that - and most definitely not for any coronaviruses) and thought it fit his thesis. If only viruses and infections were that simple!

analyte123 5y ago

This is covered in detail in the article. To me the smoking gun in this article is the linked video of Daszak saying "we have now found... over 100 new SARS-related coronaviruses, very close to SARS...some of them get into human cells in the lab, some of them can cause SARS disease in humanized mice models...these are a clear and present danger". I've been aware of this for many months after reading this tweet [1] which says essentially the same thing. [1] https://twitter.com/PeterDaszak/status/1197631383470034951?s=20 https://twitter.com/PeterDaszak/status/1197631383470034951?s...

lamontcg 5y ago

> "Furin cleavage sites naturally occur in coronaviruses" > https://www.sciencedirect.com/science/article/pii/S1873506120304165 https://www.sciencedirect.com/science/article/pii/S187350612... They exist in the human HCoV-HKU1, HCoV-OC43, MERS-CoV and appear to have evolved independently at least 6 times in betacoronaviruses. Furthermore while this article claims that the furin cleavage site has not found in any sarbecoviruses, that is now outdated information: > "Evidence for SARS-CoV-2 related coronaviruses circulating in bats and pangolins in Southeast Asia" > https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7873279/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7873279/ Both RacCS203 (91.5% similar to SARS-CoV-2) and RmYN02 (93.3% similar to SARS-CoV-2) have furin cleavage sites. So we're up to 7-to-9 times now that evolution has evolved a furin cleavage site in betacoronaviruses, including 3 sarbecoviruses that may or may not be directly related. The whole "furin cleavage site is an indication of human engineering" argument is just falsified at this point.

tripletao 5y ago
What's your estimate of the relative prevalence of an FCS among the likely space of lab-created SARS-like coronaviruses vs. among natural, SARS-like coronaviruses? My understanding is that adding an FCS is a very common method of lab gain of function, but rare among such viruses in nature. I don't think the FCS is determinative, and I agree Wade's article overstates its significance. In a Bayesian analysis, it still seems to me like it points weakly (at least 3x prevalence?) towards lab origin, though.
- lamontcg 5y ago
  It evolved at least 5+ times completely independently in nature in coronaviruses (and in other viruses). The significance is zero. Nature itself knows how to figure it out. > but rare among such viruses in nature. This assertion is false. It is common among betacoronaviruses in nature, not rare. That was the point of those two articles. We have even found two sarbecoviruses now (directly related to SARS-CoV-1 and SARS-CoV-2) in bats in Thailand which have an FCS. It points literally 0% towards lab origin.
  - 5y ago