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If this is the "peak lab leak" argument, which seems still more rejected than accepted by scientist, what is the general rebuttal? "Yes it's unlikely but less u

If this is the "peak lab leak" argument, which seems still more rejected than accepted by scientist, what is the general rebuttal? "Yes it's unlikely but less unlikely than a leak"? Or something more technical?

sudosysgen 5y ago
The rebuttal is that the above argument is a mischaracterization of the evidence. The fact we haven't seen an ancestor virus is absolutely expected and normal, and has happened for every other virus. Furin cleavage sites are present in a dozen other coronaviruses. The closest relative known is fairly likely not to be an ancestor, so there is no real expectation you wouldn't see an arginine. It's totally normal for there to be a misalignment, that's exactly what you would expect for random evolution, to find anything that works. So basically, there is almost no argument above, and zoonoses have happened hundreds of times and are thus expected.
- COGlory 5y ago
  My understanding is that the interesting bit is not about the misalignment, but rather the fact that the furin site is an insertion, not a mutation. Additionally, a non-canonical codon that encodes a restriction site. The idea as I understand is something like this: 1) I want to study what makes coronaviruses go from infecting bats to infecting humans 2) I add a furin site because my hypothesis is that a furin in the spike protein is important (because other coronaviruses like MERS have it) 3) I then try to passage the virus through many generations to see if it preserves the furin site I added (i.e. selects for it) because if it mutates at less than baseline, I know it's important (this also explains the "mosaic" aspect of the other mutations in the virus) 4) To be able to track that, when I add the furin site, I make sure to insert a restriction site that isn't found elsewhere in the genome, so I can do a quick RNA extraction, and restriction digest to see if it's preserved. Please note. That is my understanding of this one aspect of the lab leak hypothesis. It's not necessarily what I believe to be true. Additionally, it is not the only piece of evidence cited as part of the lab leak hypothesis, either.
- rich_sasha 5y ago
  Thanks, this is really interesting. What about the SARS-CoV-2 virus being a chimera of 2 other viruses? Is that wrong, or not unusual, or irrelevant? Sorry if I’m barking up a wrong tree...

sudosysgen 5y ago

The rebuttal is that the above argument is a mischaracterization of the evidence. The fact we haven't seen an ancestor virus is absolutely expected and normal, and has happened for every other virus. Furin cleavage sites are present in a dozen other coronaviruses. The closest relative known is fairly likely not to be an ancestor, so there is no real expectation you wouldn't see an arginine. It's totally normal for there to be a misalignment, that's exactly what you would expect for random evolution, to find anything that works. So basically, there is almost no argument above, and zoonoses have happened hundreds of times and are thus expected.

COGlory 5y ago
My understanding is that the interesting bit is not about the misalignment, but rather the fact that the furin site is an insertion, not a mutation. Additionally, a non-canonical codon that encodes a restriction site. The idea as I understand is something like this: 1) I want to study what makes coronaviruses go from infecting bats to infecting humans 2) I add a furin site because my hypothesis is that a furin in the spike protein is important (because other coronaviruses like MERS have it) 3) I then try to passage the virus through many generations to see if it preserves the furin site I added (i.e. selects for it) because if it mutates at less than baseline, I know it's important (this also explains the "mosaic" aspect of the other mutations in the virus) 4) To be able to track that, when I add the furin site, I make sure to insert a restriction site that isn't found elsewhere in the genome, so I can do a quick RNA extraction, and restriction digest to see if it's preserved. Please note. That is my understanding of this one aspect of the lab leak hypothesis. It's not necessarily what I believe to be true. Additionally, it is not the only piece of evidence cited as part of the lab leak hypothesis, either.
rich_sasha 5y ago
Thanks, this is really interesting. What about the SARS-CoV-2 virus being a chimera of 2 other viruses? Is that wrong, or not unusual, or irrelevant? Sorry if I’m barking up a wrong tree...