4 ms·

> Really (4) has the most evidence at this point No, there is literally zero evidence of this. The BANAL viruses are a couple of mutations away from a workabl

> Really (4) has the most evidence at this point No, there is literally zero evidence of this. The BANAL viruses are a couple of mutations away from a workable furin cleavage site, nature can engineer them just as easily as we do, and has done so multiple different times that we know of across beta-coronaviruses.

tripletao 4y ago
> The BANAL viruses are a couple of mutations away from a workable furin cleavage site, That's true, but you can argue it in either direction. It proves the mutations to create that FCS are possible and indeed likely; but it also proves they're selected against in their usual hosts, or else we'd have observed the complete FCS. So you need the mutation to happen concurrently with the species jump (or in a yet-undiscovered intermediate host), which gets less likely.
- lamontcg 4y ago
  > it also proves they're selected against in their usual hosts No it doesn't. They can be neutral. And BtCoV-HKU5 is a MERS-like bat coronavirus with a functional FCS and BtHpCoV-ZJ13 is even closer to sarbecoviruses than MERS and is another bat coronavirus with an FCS. It is more likely that the absence of an FCS in BANAL-like viruses is due to us not having found them yet, our surveillance coverage is immeasurably poor. And a species jump involving coinfection with proto-SARS-CoV-2 and some other coronavirus and a recombination event is actually a likely way to start a pandemic. The 2009 H1N1 pandemic was started by a triple reassortment with three viruses in a pig. Pandemics are very uncommon infection events so the conditions that create them are necessarily highly unlikely.
  - tripletao 4y ago
    > No it doesn't. They can be neutral. That's a fair point. Properly I guess we should try to quantify the number of samples expected before we observe an FCS if it's neutral, but that math seems nontrivial. It's at least definitely not beneficial, though. I do agree that the FCS could have evolved naturally, though I guess we'll continue to disagree on the relative probabilities of natural vs. lab-inserted. That sick pig was probably infected with each virus for days or longer, so that coinfection seems less unlikely to me than a simultaneous species jump and mutation to create the FCS (since those are both roughly instantaneous by comparison). I'm not sure what I'd consider the most likely zoonotic path now; the close identity between the BANAL and SARS-CoV-2 spikes seems like it removes the need for an intermediate host with human-like ACE2, though it's pretty mysterious.
    - lamontcg 4y ago
      > a simultaneous species jump and mutation to create the FCS (since those are both roughly instantaneous by comparison). I don't know why you think this is necessary. The FCS shouldn't preclude the infection continuing in the original species, like I said it probably doesn't infectivity in bats and is neutral. And if the intermediate animal was infected with a common coronavirus for the species, all it takes is coinfection from a bat with the precursor to SARS-CoV-2 and a recombination event to create the FCS. Animals and humans across china are almost certainly getting infected with novel sarbecoviruses from bats every day. Most of them don't go anywhere. This one got "lucky" and stole some genetic material which made it better in the new host organism and now it is off to the races. Which is unlikely, but, again, pandemics are unlikely.
      - tripletao 4y ago
        Assuming the FCS is neutral in bats (which I don't think we could prove or disprove without more sampling, but which I agree is possible), I agree that the mutation wouldn't have to happen concurrently with the species jump. Even if the FCS is negative in bats, it's also possible that the FCS evolved naturally in a different animal host. I agree there's no evidence to exclude those scenarios; I just don't see any specific evidence to favor them either.
ckw 4y ago
The notion that sars-cov-2 arose naturally is risible. From https://s3.documentcloud.org/documents/21066966/defuse-proposal.pdf https://s3.documentcloud.org/documents/21066966/defuse-propo... > “We will conduct in vitro pseudovirus binding assays, using established techniques2, and live virus binding assays (at WIV to prevent delays and unnecessary dissemination of viral cultures) for isolated strains.” (D1, p.12) > “We will validate results from chimeric viruses by re-characterizing full-length genome versions, testing whether backbone genome sequence alters full length SARSr-CoV spillover potential. QS for full-genome characterization will be selected to reflect strain differences in antigenicity, receptor usage, growth in human cells and pathogenesis.”(D1, p.13) > “We will test growth in primary HAE cultures and in vivo in hACE2 transgenic mice. We anticipate recovering ~3-5 full length genome viruses/year.”(D1, p.13) > “We will analyze all SARSr-CoV S gene sequences for appropriately conserved proteolytic cleavage sites in S2 and for the presence of potential Furin cleavage sites74,75. SARSr-CoV S with mismatches in proteolytic cleavage sites can be activated by exogenous Trypsin or Cathepsin L. Where clear mismatches occur, we will introduce appropriate human-specific cleavage sites and evaluate growth potential in Vero cells and HAE cultures.” > “We will also review deep sequence data for low abundant high risk SARSr-CoV that encode functional proteolytic cleavage sites, and if so, introduce these changes into the appropriate high abundant, low risk parental strain.” (D1, p.13)
- lamontcg 4y ago
  SARS-CoV-2 isn't based on a SARS-CoV-1 backbone or spike or any known backbone or spike that would have been used in a lab. The closest known viral backbone is a few decades of random mutations away from SARS-CoV-2 and there's no evidence that WIV even tried to work with RaTG13 and did anything beyond sequencing it. And you have the usual Schroedingers-Information problem that plagues conspiracy theories. You have to assume that on the one had all that information you just cited would be available to you, while a fairly massive project involving forming a chimera from an unknown spike protein and unknown backbone would have been going on in perfect secrecy in 2019 before there was any reason to keep that information secret. In 2019 if they had sequences of those viruses they would have just published them, they certainly would have published them before going through the effort to create chimeras from them. They would have used those sequences to get justification to get grants to do studies. The idea that all of that happened in perfect secrecy, before there was a need for perfect secrecy is the idea that is fucking laughable. And nature creates "chimeras" and does "gain of function experiments" all the time on a massive scale using many billions of animals in the "lab". That is what recombination and serial passage does -- particularly as viruses burn through bioreactors in animal farms in close proximity to humans. And when it comes to the FCS, the PRRAR sequence is unlike any other known FCS. If humans engineered it they would have picked another one that they already knew worked. That sequence absolutely screams that it was zoonotic in origin. It was novel and never previously seen before. Nobody would have added that in a lab.
6nf 4y ago
> literally zero evidence of this. What about the Moderna patented sequence?
johndfsgdgdfg 4y ago
Thank you for posting this. Racists are claiming that COVID came from China. But WHO-China investigation has found that COVID couldn't have come from China. Even virologists have been expressing their support for Chinese scientists. [1] https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)30418-9/fulltext https://www.thelancet.com/journals/lancet/article/PIIS0140-6...

tripletao 4y ago

> The BANAL viruses are a couple of mutations away from a workable furin cleavage site, That's true, but you can argue it in either direction. It proves the mutations to create that FCS are possible and indeed likely; but it also proves they're selected against in their usual hosts, or else we'd have observed the complete FCS. So you need the mutation to happen concurrently with the species jump (or in a yet-undiscovered intermediate host), which gets less likely.

lamontcg 4y ago
> it also proves they're selected against in their usual hosts No it doesn't. They can be neutral. And BtCoV-HKU5 is a MERS-like bat coronavirus with a functional FCS and BtHpCoV-ZJ13 is even closer to sarbecoviruses than MERS and is another bat coronavirus with an FCS. It is more likely that the absence of an FCS in BANAL-like viruses is due to us not having found them yet, our surveillance coverage is immeasurably poor. And a species jump involving coinfection with proto-SARS-CoV-2 and some other coronavirus and a recombination event is actually a likely way to start a pandemic. The 2009 H1N1 pandemic was started by a triple reassortment with three viruses in a pig. Pandemics are very uncommon infection events so the conditions that create them are necessarily highly unlikely.
- tripletao 4y ago
  > No it doesn't. They can be neutral. That's a fair point. Properly I guess we should try to quantify the number of samples expected before we observe an FCS if it's neutral, but that math seems nontrivial. It's at least definitely not beneficial, though. I do agree that the FCS could have evolved naturally, though I guess we'll continue to disagree on the relative probabilities of natural vs. lab-inserted. That sick pig was probably infected with each virus for days or longer, so that coinfection seems less unlikely to me than a simultaneous species jump and mutation to create the FCS (since those are both roughly instantaneous by comparison). I'm not sure what I'd consider the most likely zoonotic path now; the close identity between the BANAL and SARS-CoV-2 spikes seems like it removes the need for an intermediate host with human-like ACE2, though it's pretty mysterious.
  - lamontcg 4y ago
    > a simultaneous species jump and mutation to create the FCS (since those are both roughly instantaneous by comparison). I don't know why you think this is necessary. The FCS shouldn't preclude the infection continuing in the original species, like I said it probably doesn't infectivity in bats and is neutral. And if the intermediate animal was infected with a common coronavirus for the species, all it takes is coinfection from a bat with the precursor to SARS-CoV-2 and a recombination event to create the FCS. Animals and humans across china are almost certainly getting infected with novel sarbecoviruses from bats every day. Most of them don't go anywhere. This one got "lucky" and stole some genetic material which made it better in the new host organism and now it is off to the races. Which is unlikely, but, again, pandemics are unlikely.
    - tripletao 4y ago
      Assuming the FCS is neutral in bats (which I don't think we could prove or disprove without more sampling, but which I agree is possible), I agree that the mutation wouldn't have to happen concurrently with the species jump. Even if the FCS is negative in bats, it's also possible that the FCS evolved naturally in a different animal host. I agree there's no evidence to exclude those scenarios; I just don't see any specific evidence to favor them either.

ckw 4y ago

The notion that sars-cov-2 arose naturally is risible. From https://s3.documentcloud.org/documents/21066966/defuse-proposal.pdf https://s3.documentcloud.org/documents/21066966/defuse-propo... > “We will conduct in vitro pseudovirus binding assays, using established techniques2, and live virus binding assays (at WIV to prevent delays and unnecessary dissemination of viral cultures) for isolated strains.” (D1, p.12) > “We will validate results from chimeric viruses by re-characterizing full-length genome versions, testing whether backbone genome sequence alters full length SARSr-CoV spillover potential. QS for full-genome characterization will be selected to reflect strain differences in antigenicity, receptor usage, growth in human cells and pathogenesis.”(D1, p.13) > “We will test growth in primary HAE cultures and in vivo in hACE2 transgenic mice. We anticipate recovering ~3-5 full length genome viruses/year.”(D1, p.13) > “We will analyze all SARSr-CoV S gene sequences for appropriately conserved proteolytic cleavage sites in S2 and for the presence of potential Furin cleavage sites74,75. SARSr-CoV S with mismatches in proteolytic cleavage sites can be activated by exogenous Trypsin or Cathepsin L. Where clear mismatches occur, we will introduce appropriate human-specific cleavage sites and evaluate growth potential in Vero cells and HAE cultures.” > “We will also review deep sequence data for low abundant high risk SARSr-CoV that encode functional proteolytic cleavage sites, and if so, introduce these changes into the appropriate high abundant, low risk parental strain.” (D1, p.13)

lamontcg 4y ago
SARS-CoV-2 isn't based on a SARS-CoV-1 backbone or spike or any known backbone or spike that would have been used in a lab. The closest known viral backbone is a few decades of random mutations away from SARS-CoV-2 and there's no evidence that WIV even tried to work with RaTG13 and did anything beyond sequencing it. And you have the usual Schroedingers-Information problem that plagues conspiracy theories. You have to assume that on the one had all that information you just cited would be available to you, while a fairly massive project involving forming a chimera from an unknown spike protein and unknown backbone would have been going on in perfect secrecy in 2019 before there was any reason to keep that information secret. In 2019 if they had sequences of those viruses they would have just published them, they certainly would have published them before going through the effort to create chimeras from them. They would have used those sequences to get justification to get grants to do studies. The idea that all of that happened in perfect secrecy, before there was a need for perfect secrecy is the idea that is fucking laughable. And nature creates "chimeras" and does "gain of function experiments" all the time on a massive scale using many billions of animals in the "lab". That is what recombination and serial passage does -- particularly as viruses burn through bioreactors in animal farms in close proximity to humans. And when it comes to the FCS, the PRRAR sequence is unlike any other known FCS. If humans engineered it they would have picked another one that they already knew worked. That sequence absolutely screams that it was zoonotic in origin. It was novel and never previously seen before. Nobody would have added that in a lab.

6nf 4y ago

> literally zero evidence of this. What about the Moderna patented sequence?

johndfsgdgdfg 4y ago

Thank you for posting this. Racists are claiming that COVID came from China. But WHO-China investigation has found that COVID couldn't have come from China. Even virologists have been expressing their support for Chinese scientists. [1] https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)30418-9/fulltext https://www.thelancet.com/journals/lancet/article/PIIS0140-6...