7 ms·
You spend an awful lot of time attacking me and not very much time attacking my arguments. That's not very scientific of you. I said I had no way to know you we
by jeduehr 6y ago
You spend an awful lot of time attacking me and not very much time attacking my arguments. That's not very scientific of you. I said I had no way to know you were actually a virologist, which I didn't. It isn't really important to the discussion though, as I said. Can we talk about this like adults? Thanks.
I'm only gonna address the science in your post from here on out. I want to make it clear I never insulted you or attacked your character, I only said I had no way to know you were a virologist and only could go off of your word.
I get your hypothesis now that you have fully stated it.
And here are some questions that need answers.
Where did they get the virus? It's not anything like any coronavirus we know of before SARS-CoV-2 emerged in humans, it's 1200 away from RATG-13.
What experimental question were they trying to answer? We already know that the furin cleavage site is necessary for some aspects of pathogenicity, but not the ones canonically thought important (cell entry for SARS-1 for example, since furin doesn't actually cleave SARS-1 or MERS). Why would they test a random unrelated coronavirus' site? Why not try the SARS-CoV-1 site? Or the MERS site? Why was it a furin site in the first place? And why did they do it on the weirdly promiscuous SARS-2 ACE2 and not in a virus like RATG-13?
Re: cleavage site, I go into extreme detail about how possible it is for cleavage sites to evolve in nature here and here:
-https://www.reddit.com/r/science/comments/gk6y95/covid19_did_not_come_from_the_wuhan_institute_of/fqpbys1/ https://www.reddit.com/r/science/comments/gk6y95/covid19_did...
-https://news.ycombinator.com/item?id=26757881 https://news.ycombinator.com/item?id=26757881
It's really not that unusual for a cleavage site to evolve in nature, and especially not when we consider that furin cleavage sites are mutagenicity islands. It absolutely could have evolved from recombination with a distantly related coronavirus that has an extremely similar site.
Also, the cleavage site isn't even that long. Short stretches of nucleotides like that, upwards of 15-30 nucleotides, can absolutely evolve over the course of 50-70 years. Happens literally all the time. In influenza it happens on much shorter time scales. I provide evidence to that effect in the above posts.
Yes I actually address the idea of using recombinatorial cloning to make SARS-CoV-2 at several points in my post.
Nothing about the furin cleavage site makes it more likely to be unnatural than it is natural?
And so far, I don't see any compelling reason to believe that anyone would take a completely undiscovered and undescribed virus out of nature, not describe it or publish on it at all, and then start inserting random furin sites into it from random other coronaviruses.
Why would they be doing that? Is it technically /possible/? Yes, but I see no reason why it is more likely than a natural emergence.
- COGlory 6y ago>You spend an awful lot of time attacking me and not very much time attacking my arguments. That's not very scientific of you. I said I had no way to know you were actually a virologist, which I didn't. It isn't really important to the discussion though, as I said. Can we talk about this like adults? Thanks. Unfortunately that is impossible for two reasons: 1) Because you have inextricably tied your argument to who you are with lines like: >All of that aside, the consensus among people who actually use or study dangerous viruses in biosafety labs (both those for and against gain of function research, btw) is that the virus likely came from a wild zoonotic crossover event. 2) Because you refused to present your argument here in a way that stands against my hypothesis, and instead relied on simply introduction of yourself and your credentials. >Where did they get the virus? It's not anything like any coronavirus we know of before SARS-CoV-2 emerged in humans, it's 1200 away from RATG-13. 1200 mutations away from RATG-13 is how significant exactly? I will propose that it is not particularly significant. One virus I work with, I have 14 variants ranging from 300 to 500 base-pair differences. That is from passing in a laboratory only. I have one variant that has a 14000 BP deletion! (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7217056/#mmi14435-sup-0001 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7217056/#mmi144... TABLE S2) However, it is noteworthy for that reason. That said, these are dsDNA viruses with comparatively much slower mutation rates. 1200-base differences are almost nothing. >Why would they test a random unrelated coronavirus' site? That's a good question, and not one that I can answer suitably with this hypothesis. Perhaps because they were looking for a cleavable one? >And why did they do it on the weirdly promiscuous SARS-2 ACE2 and not in a virus like RATG-13? To me this is obvious. SARS-2 ACE2 is extremely promiscuous. That's a very good reason to study it - it has broad potential for cross-species jumps. If you are trying to narrow down what it is that causes the jump, you want to study on the virus that is most capable of making that jump. >Re: cleavage site, I go into extreme detail about how possible it is for cleavage sites to evolve in nature here and here: Again, I don't think that applies my hypothesis. Of course it had to evolve in nature. Otherwise there would be no furin site. The ability of a furin site to evolve in nature has almost no bearing on whether or not one could be inserted into coronavirus by humans, unless I'm totally misunderstanding what you're suggesting here. >Also, the cleavage site isn't even that long. Sure, and again, this furin site likely did evolve in nature (at least in amino acid form). Whether or not it evolved in coronavirus is the topic here. >Nothing about the furin cleavage site makes it more likely to be unnatural than it is natural? The two non-canonical arginines don't make it less likely? >And so far, I don't see any compelling reason to believe that anyone would take a completely undiscovered and undescribed virus out of nature, not describe it or publish on it at all, and then start inserting random furin sites into it from random other coronaviruses. I have some of viruses I work with I haven't published on yet, because I am either waiting to complete work, or they aren't significant enough compared to their peers for me to publish on them. >Why would they be doing that? Is it technically /possible/? Yes, but I see no reason why it is more likely than a natural emergence. OK so that's the crux of my argument. There's some interesting anomalies that point to it being a possibility. There's no way to rule it out. At the end of the day, it comes down to one opinion vs another, which is why statements like: >The virus itself, to the eye of any virologist, is clearly not engineered. ...are so infuriating to me.