They are also already present in wild coronoviruses and the initial cluster don't support a lab leak theory, even if they were sloppily working on gain of function via that mechanism.
"Harrison and Sachs’s (1) claim that alignment of sarbecovirus Spike amino acid sequences illustrates“the unusual nature of the [SARS-CoV-2] FCS” is misleading. FCSs are common in coronaviruses, and present in representatives of four out of five betacoronavirus subgenuses (8). The highly variable nature of the S1/S2 junction is easily ascertained by inspecting a precise alignment of sarbecovirus Spikes (Fig. 1C)."
"As more bat CoVs are sampled, it is possible that another SARSr-CoV will be discovered with an S1/S2 FCS insertion. FCSs have evolved naturally in other non-sarbecovirus families of betacoronaviruses (Wu and Zhao 2020). Therefore, an S1/S2 FCS emerging in a sarbecovirus is consistent with natural evolution. Even so, the knowledge that scientists had a workflow for identifying novel cleavage sites in diverse SARSr-CoVs and experimentally characterizing these cleavage sites in SARSr-CoVs—likely in a manner that makes the resulting recombinant SARSr-CoV practically indistinguishable from a rare SARSr-CoV with a naturally emerging FCS—makes it challenging to rule out an artificial origin of the SARS-CoV-2 S1/S2 FCS"
It's saying they can arise naturally and it's hard to distinguish origin. Your claim is debatable on its own, and sar-covid-19 GoF resource origin is extremely debatable, even unlikely. At any rate, this article doesn't appear to add anything new to the discussion beyond mixing some anonymous sources with existing public information in a sensationalized way.
edit: let me add, I don't want you downvoted. It may be that this it came from gain of function research at WIV and that the Huanan market cluster was a result of this research. But as of right now, there are other better explanations. I await the Directorate of National Intelligence declassified information this article claims is coming. I do not see how this would have changed the global response to the pandemic.
edit 2: I can't reply to you, stainablesteel. HN thinks I'm posting too much. I am done after this, maybe they are right. I would reply to you with this, though:
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The furin cleavage site did not have to come from gain of function research. My "wall of text" explains that pretty clearly, even for a layman. That claim is what I said was debatable.
Whether or not it came from GoF research remains to be seen. This article didn't expose any new information, with the possible exception of the names of the WIV researchers.
I have a question for you: what do you think would change the lab origin theory were proven? What should have everyone have done differently during the pandemic? What should we do differently now? I genuinely want to understand your opinion.
there is literally a grant written by an american scientist who sent money for that exact research to that exact lab. a literal paper trail as a grant, and a paper trail in funds.
Sure its evolutionarily possible to insert 12nt. Inserts are not common though. Whats key is that the insert -in a 30kbp sequence was at exactly a position that would give it functional properties to allow the virus much higher tropism for human tissues. Furin cleavage site appear to selected against in bats.
There is no known source from where it came from, coronaviruses often recombine, but there is no other known sarbecovirus from where the fcs could have come from.
Bob Garry tries to explain away his documented "I cant think of a plausible natural scenario for how this 12nt insert occurred" in an interview here.
What is often totally ignored by virologists and evolutionary biologists with potential funding to loose if a kab origin is proven is that the WIV was partner in a proposal to insert exactly the sort of furin cleavage site we see in SARS-CoV-2
Then like magic (a unicorn as Bob Garry says) a SARS-related CoV appears, appears down the road from the lab, that is highly infectious to humans, with the first ever furin cleavage site in a sarbecovirus, which even Zhengli Shi says was a recent inroduction to humans: "almost identical sequences of this virus in different patients imply a probably recent introduction in humans"
Lab escape through a lab acquired infection with a SARS related virus is by far the most likely scenario and should be the default hypothesis to disprove.
Natural origin scenario requires a series of events to occur, each very unlikely.
https://www.pnas.org/doi/10.1073/pnas.2211107119
"Harrison and Sachs’s (1) claim that alignment of sarbecovirus Spike amino acid sequences illustrates“the unusual nature of the [SARS-CoV-2] FCS” is misleading. FCSs are common in coronaviruses, and present in representatives of four out of five betacoronavirus subgenuses (8). The highly variable nature of the S1/S2 junction is easily ascertained by inspecting a precise alignment of sarbecovirus Spikes (Fig. 1C)."
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8689951/
"As more bat CoVs are sampled, it is possible that another SARSr-CoV will be discovered with an S1/S2 FCS insertion. FCSs have evolved naturally in other non-sarbecovirus families of betacoronaviruses (Wu and Zhao 2020). Therefore, an S1/S2 FCS emerging in a sarbecovirus is consistent with natural evolution. Even so, the knowledge that scientists had a workflow for identifying novel cleavage sites in diverse SARSr-CoVs and experimentally characterizing these cleavage sites in SARSr-CoVs—likely in a manner that makes the resulting recombinant SARSr-CoV practically indistinguishable from a rare SARSr-CoV with a naturally emerging FCS—makes it challenging to rule out an artificial origin of the SARS-CoV-2 S1/S2 FCS"
It's saying they can arise naturally and it's hard to distinguish origin. Your claim is debatable on its own, and sar-covid-19 GoF resource origin is extremely debatable, even unlikely. At any rate, this article doesn't appear to add anything new to the discussion beyond mixing some anonymous sources with existing public information in a sensationalized way.
edit: let me add, I don't want you downvoted. It may be that this it came from gain of function research at WIV and that the Huanan market cluster was a result of this research. But as of right now, there are other better explanations. I await the Directorate of National Intelligence declassified information this article claims is coming. I do not see how this would have changed the global response to the pandemic.
edit 2: I can't reply to you, stainablesteel. HN thinks I'm posting too much. I am done after this, maybe they are right. I would reply to you with this, though:
---
The furin cleavage site did not have to come from gain of function research. My "wall of text" explains that pretty clearly, even for a layman. That claim is what I said was debatable.
Whether or not it came from GoF research remains to be seen. This article didn't expose any new information, with the possible exception of the names of the WIV researchers.
I have a question for you: what do you think would change the lab origin theory were proven? What should have everyone have done differently during the pandemic? What should we do differently now? I genuinely want to understand your opinion.