>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/#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.
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/#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.
You're comparing apples and oranges. 14 mutational sites across a virus with 17k ssDNA genome is not comparable to RATG-13 vs SARS-2, which have not just 1200 mutations different, they're spread out over HUNDREDS of SNPs.
That's the important comparator. And why it will take so long to mutate one into the other by natural mutation rates.
>The two non-canonical arginines don't make it less likely?
Not particularly. CGG exists in MERS 15 times. NL63, 29 times. It even exists twice in a row in Human coronavirus 229E. Throughout all of the known alphacoronaviruses (94 described) CGG exists 1575 times. In betacoronaviruses, it exists more times than my processor can count without hanging, and I believe it tops out at 9,999 events.
Why is it so unlikely that synonymous mutational drift over the course of 70 years of infections in millions of viral generations could create these arginine codons that are not the most optimized but still work in the mammals this virus infects? CGG works. It makes an arginine when this virus infects its host.
Why couldn't it be a recombination event between SARS-2 and one of the known coronaviruses with an extremely similar cleavage site? We know already coronaviruses have recombined with viruses totally outside of their family on occasion: https://www.virology.ws/2016/10/27/genome-recombination-acro...
>You're comparing apples and oranges. 14 mutational sites across a virus with 17k ssDNA genome is not comparable to RATG-13 vs SARS-2, which have not just 1200 mutations different, they're spread out over HUNDREDS of SNPs.
If memory serves, that was a single generation. An rdrp produces one error per thousand bases, which comes out to 30 mutations per generation, so we're talking 40 generations away? That hardly seems significant.
>Not particularly. CGG exists in MERS 15 times. NL63, 29 times. It even exists twice in a row in Human coronavirus 229E. Throughout all of the known alphacoronaviruses (94 described) CGG exists 1575 times. In betacoronaviruses, it exists more times than my processor can count without hanging, and I believe it tops out at 9,999 events.
How many of those are in frame for an amino acid? How many of those are two in frame for arginine in a protein, next to each other?
>Why is it so unlikely that synonymous mutational drift over the course of 70 years of infections in millions of viral generations could create these arginine codons that are not the most optimized but still work in the mammals this virus infects? CGG works. It makes an arginine when this virus infects its host.
There are many reasons why it's unlikely. The first is pure statistics. But the statistics are almost certainly influenced by millions of years of biology.
>Why couldn't it be a recombination event between SARS-2 and one of the known coronaviruses with an extremely similar cleavage site?
It's absolutely possible and I would never dispute this. The possibility of it isn't a refutation of the possibility of other hypotheses, and I don't think it's in the scientific spirit to discount other viable hypotheses.
> If memory serves, that was a single generation. An rdrp produces one error per thousand bases, which comes out to 30 mutations per generation, so we're talking 40 generations away? That hardly seems significant.
SARS-CoV-2 is mutating at the rate of about 2 changes/month (68,69,70,71), out there in society, circulating in millions of humans. 2/month in the overall population of millions of tiny viruses, among 30,000 letters in each genome.
So, at the fixation rate (~2 fixed mutations/month), with all the many billions of SARS-2 viruses making copies inside all those people, how long would it take to change RaTG-13 into SARS-CoV-2?
Answer: about 50 years. 30 years before the world even knew about SARS or MERS or any other pandemic-potential coronavirus. Before we knew these viruses even existed. Before we knew they liked to live in bats (72,73,74,75). And, for the record, they didn’t even build a BSL4 (the kind of lab you really need to handle this kind of virus in animals) in Wuhan until 2016 (76).
And that estimate (50 years) is with all the many mutations that are happening in all the many infected humans during a pandemic situation.
We know that with a smaller group of lab animals (or even human subjects), the virus is much slower at “finding” mutations that “stick around” (77,78). You have to picture it kind of like a big room full of millions of slot machines. Each machine is a virus, pulling the lever each time it makes a copy of itself. And you only win a payoff when you’ve found a change in the virus that A) makes it look different, and B) doesn’t screw it up, so it can still survive and do its job (infect people). A lot of these mutations screw the virus up, so they wouldn’t be a payoff. They wouldn’t be a “fixed” mutation.
>>>>>>>>>>>>
We can't just focus on random mutation, we have to think about fixation. Because virus populations don't just evolve in one concerted direction. They evolve /outwards/ in a cloud. It's not simply A to B, it's A to B then back to A then over to C then to D, then back to B, then over to A again, then finally settled on C. A random walk.
That's why the population level data is so important.
> How many of those are in frame for an amino acid? How many of those are two in frame for arginine in a protein, next to each other?
Who said recombination events only happen in frame? Or that viruses only drift in frame?
> There are many reasons why it's unlikely. The first is pure statistics. But the statistics are almost certainly influenced by millions of years of biology.
I would respond to this if it contained any evidence other than 'statistics say it is so.'
> I don't think it's in the scientific spirit to discount other viable hypotheses.
Who said I'm discounting anything? I said it's just not very likely. Extraordinary claims require extraordinary evidence.
>We can't just focus on random mutation, we have to think about fixation. Because virus populations don't just evolve in one concerted direction. They evolve /outwards/ in a cloud. It's not simply A to B, it's A to B then back to A then over to C then to D, then back to B, then over to A again, then finally settled on C. A random walk.
Fixation relies on selection, which is entirely different in a laboratory environment than in a population with immune systems.
>Who said recombination events only happen in frame? Or that viruses only drift in frame? No one, but the fact is that two in-frame CGGs next to each other are substantially less likely "to be fixed" than two CGGs out of frame, or in a non-coding region. Almost every gene evolves more slowly than non-coding space, beyond very few specific non-coding regions. CGGCGG is very different than ACGGCGG and we both know that. You get an entirely different peptide out of each one. And selection almost exclusively happens at the protein level.
This is the part that's confusing me. I haven't made any claims other than that it's possible? And I have provided plenty of evidence that it's possible. I'm not sure what claims you think I'm making.
Hi, I want to apologize. I was the one who did not see that you from the very beginning said you did not put much stock into the lab theory, and I basically ignored that. I didn't see it. I also did not read closely enough some other things as well. I was attacking some strawmen, some of which I have seen in the real world and others I have not.
I'm sorry, that colored a lot of my responses to you because I made unfair assumptions about what you were saying. I sent you a longer form email to your protonmail about it.
>Fixation relies on selection, which is entirely different in a laboratory environment than in a population with immune systems.
This is actually extremely controversial. There's a great deal of evidence that random walks are more important than selection in fixation events. Does selection play a role? Yes! Definitely! But the evidence is mounting and almost at consensus that random chance is actually what dictates most fixation events. It just can't be /deleterious/ but it does not have to be /helpful/ to fix. The evidence shows that most mutations, on median, are neutral or slightly deleterious. But the ones that are beneficial are so beneficial that the average is neutral-to-net-positive. A lot more of it is actually stochastic than you think! A lot of the transmission between hosts, for example, is stochastic and not selective.
See these reviews/studies from Bloom, Audino, etc:
This is why it's less easy to maintain a virus at the proper S/NS ratio in the lab. It becomes too stochastic. too little selection. So your mad scientist would have to have extremely few viral genera.
You say every gene evolves more slowly than non-coding, which is true. but synonymous mutations happen at the same rate as one would expect it to occur in both.
Are you trying to say it isn't ever going to happen? From what I'm reading, there's actually no reason to believe the CGG in that site is fixed in any way. It's not always CGG. In fact, it rarely is in CoV-2 isolates. Maybe that was a fluke of the sequencer or the isolate?
Wow, now I'm starting to think Yuri just didn't do his homework.
but that's just in the isolates they're analyzing.
"All human coronaviruses analyzed in this study did not use two synonymous codons (CGC, CGG) for arginine as well as CCG for proline and UGA for stop codon at all"
I couldn't find CGG in the cleavage site sequence anywhere in the early pandemic. Not in any of the earliest papers.
I could only find it in clinical sequences from later on in the pandemic, suggesting it may have been a random mutant that fixed /after/ the emergence into humans. Which pokes a big ol hole in the idea that it represents a smoking gun of genetic manipulation:
I shouldn't have taken it as a given that CGGCGG was actually there in the beginning. Looks like it wasn't It certainly isn't in the refseq.
And the thing I'm asking here is: Are you really saying you think the lab leak is /as probable/ as the zoonotic crossover? Given that the A) the CGGCGG wasn't even there when the crossover happened, B) the probabilistic arguments I've made above, and C) the fact that you can't provide any actual evidence of a mechanism? I gave you lots of mechanisms and examples of how it would happen in nature. Why is one not more likely than the other?
And here is probably the most salient argument of all.
It comes down to occam's razor.
Sure, is it /possible/ that some scientist in a lab decided to use an entirely unknown and undescribed natural virus as the subject of their experiments? And use a completely out of nowhere cleavage site from a distant coronavirus that nobody talks about or really studies to do it? And then that virus escaped?
Sure.
But in order for that to be true, we need to make some new assumptions. We need to assume such a person exists, that they had that exact idea, and that it worked and they didn't tell anyone about it, or they all agreed to cover it up, and then some of them got sick (and again, covered it up) and it got out into the public, and voila, pandemic.
Or, it could have been a completely natural event that we know already happens all the time, in the contexts we know it to occur, using mechanisms that have already been described.
On a pure numbers game, on a scale of pure virus-host interactions, which do you think happens more often? People out in the provinces use bat guano as eye drops, eat bat in soups, use bat guano as fertilizer, harvest it without gloves, tour caves without any protection, etc. All of these are well-described. They are all known to occur on the scale of many thousands if not tens of thousands of events per day throughout rural China. Each one of these is a roll of the dice.
OR, how many times do we think a human contaminates themselves in a virology lab in china, working on coronaviruses? or with bats? Sure it probably happens some, but I have a hard time believing it happens more than 100 times per day in China. There just aren't that many bat colonies or virology labs.
So Occam's razor would tell us that the most likely of these two scenarios is the natural one. Is that conclusive proof? no, and I never said it was. I don't think at this point conclusive proof is possible. We're just making estimations. I've always just been making estimations.
A lab release is much less likely than a natural one, even if both are /technically/ possible.
A lot of things are /technically/ possible. On the scale of things, I think the lab leak is likely /enough/ that China should open up itself to international investigators, to show with all available evidence it probably didn't happen. But I don't think it's likely enough that we should all be condemning china, or fueling racist anti-chinese sentiment, or all the other consequences of these news stories. The consequences are right in front of you, anti-asian hate crimes are on the rise in the US, and 30+% of the US thinks the lab release is the most likely scenario.
I'm not saying we stop talking about the lab release, just that we need to put it in the proper context of probability. It is /possible/ but it really is not very /probable/.
Okay, let me know when you wanna talk about it like adults! I'll be around when you do.
Until then, I'm not really interested in being ad hominem attacked and so I'm gonna step back and study for my med school exams instead. It's important to have conversational ground rules and one of those for me is decency and no ad hominems.
As a last thought: You seem to kind of disregard the consensus that exists among virologists (even as pointed out in the very article we're discussing under, the OP). All those statements I made are consistent with the consensus.
And on a small scale, I had that post reviewed by 8ish working PhD virologists before I posted it as part of the editorial process. I say 8ish because some of them have PhDs in non-virology stuff but now work exclusively on virology. It's not a true peer review since I know them and it wasn't blinded. But I want to be clear it's not like I just wrote it out of nowhere.
Many of those same virologists helped me field comments on the original post! It was a great time we all got together on zoom to do it.
Anyway, let me know when you wanna discuss the science and not ad hominems.
>And on a small scale, I had that post reviewed by 8-10 working PhD virologists before I posted it as part of the editorial process. Not a true peer review since I know them and it wasn't blinded. But I want to be clear it's not like I just wrote it out of nowhere.
Again with the appeal to authority. Argue the merits of the argument. Not who is making it (which is almost all you've done). Except in this case, the merits of the argument were pretty weak and superficial, and only applied to people who weren't expert enough to realize that no one is suggesting CRISPR-Cas9 was used to make 1200 edits to a virus lmao. There's no talking your way out of that one. Anyone who knows anything about molecular biology or virology knows clearly that that was a total strawman rebuttal. I won't suggest motive, just that it was not ever a good faith argument.
>Okay, let me know when you wanna talk about it like adults!
If you point out where I'm not in that reply, I'll happily edit it to be less offensive.
*Still waiting for you to refute my hypothesis with an actual argument, by the way.*
as long as we're discussing the molecular science, I won't have to bring any credentials up. But you just /had/ to get those two little accusations in there, didn't you?
Let me go back to my original hypothesis, and then try to restate your arguments, and you can tell me where I'm restating them incorrectly.
My original hypothesis:
1) Major point of differentiation for this virus is that compared to it's closest known relatives, it has acquired a furin site (eukaryotic protein cleavage site) that enhances its virulence.
You said:
>And in there, I describe exactly how wrong your point 1 is.
I honestly can't find anything that refutes what I said. Please, just paste the line that points out how this is, to quote you, wrong. As in, disproves that compared to its closest known relatives (RATG-13) it has acquired a furin site, which increases its virulence"
I can find absolutely nothing* in either your Reddit posts, or your posts here on HN, that refute this. I can find plenty of things explaining how natural evolution could cause it, but nothing saying that it hasn't acquired a furin site that enhances its virulence that its closest known relative doesn't have.
2) That furin site RNA contains a non-canonical amino acid codon
To be fair, you didn't dispute this.
3) That non-canonical codon contains a restriction site that could easily be used to track, whether, say, your added furin site is surviving multiple cell passages, by performing a restriction digest and running the fragments on a cell.
You said:
>how misguided your point 3 is.
OK, let's examine my point #3. It is non-canonical, as in only 5% of the arginines in SARS-CoV 2 contain it. I guess we can get into what exactly non-canonical means, and you do make some points there, but at the end of the day, 5% is 5%, and 5%*5% is 0.25%, so it seems to me that the usage of the term "non-canonical" to describe a site that has a 0.25% chance of occurring is fitting.
OK, so let's talk about the restriction site. You don't dispute the presence of it anywhere, at least not that I can find. Please, if you have something to dispute the presence of it, just paste it in reply to this because I legitimately can't find it. You also don't dispute the usefulness of using a restriction site to track genetic engineering, presumably because it's done all the time.
So with all this in mind, it seems to me like your disagreement with me is not with any of the 3 major points I made, or even the two of those three points you called out in your initial reply. So I'm thoroughly confused by what you're trying to debate. Are you debating the interpretation of those facts? Because that interpretation appears to be almost entirely of your own imagination. Nowhere did I offer (at least not that I can see) an interpretation of those facts beyond speculating that they are a possibility. In fact, my entire first post was just to reframe the argument as I understood it, and comment that it's very difficult to rule out because of the nature of the evidence. For the record, I find the likelihood that it was a lab leak extremely slim, but I'm not going to discount it, especially not concretely.
On the other hand, the post you linked to was very much dancing around any of the concrete arguments about the topic, making absurd insinuations like that people are claiming the 1200 mutations came from engineered Cas9 usage, which I've personally never seen claimed (by the way I'm still waiting for you to address this). All while ignoring crucial facts like that the furin site was an insertion, not a polymorphism.
I'm thoroughly confused by whatever point you're trying to make here. To me, it seems like you've been arguing against words you imagined me saying.
And if you actually have been playing "devil's advocate" this whole time and don't believe the interpretation of facts that you've put forth, then that is very much "arguing in bad faith." You were not up front with your beliefs or positions, you just wanted "to ask questions."
If you did not believe in good faith the statements you made, or have substance behind the questions you asked as though you believed them to be true (CGG for example), that is very much insincere.
I am not going to be dragged into an endless debate with someone who wants to play devil's advocate. There are people with actual misunderstandings and misconceptions about science that are out there that need our help to understand the world around them.
Why waste time like this if we agree on the basic points? This is not a socratic discussion, you are not Socrates, and I am not Plato. This is not a PhD defense. It is not an academic conference.
I'm here to talk about this with people who have legitimate concerns that they actually believe about the subject matter at hand.
And please, I'm sorry if I mischaracterized your position or your actions thus far, but that's what it looks like. If you had said at some point "just playing devil's advocate here!" or "I don't 100% believe this but what about this thing I saw?" then if I had seen that, I would have engaged in a completely different way, and likely disengaged much earlier.
Thanks for the interesting ideas, but I have to go study for exams, and procrastinate in ways that are better for both of our mental health.
Have a great day, and I hope this hasn't taken up as much of your mental energy as it has mine. Because it took up a lot of mine.
All of this aside, the actual point I have been making the whole time is this:
Do you think these two possibilities are equally likely?
Do you think one is more likely than the other?
Which?
You say that you find the lab possibility not very likely, so do you find the zoonotic scenario any more likely? If so, then you and I are in agreement, of a kind. You never said that above, and you definitely argued in a way that implied something else. Especially given the CGG codons.
Probabilistic thinking is the nature of the discussion in the absence of conclusive evidence. Probabilistic thinking. Heuristics. That's what I've been discussing this entire time, that's what I was talking about in my original post, and it's what your reply comments were, therefore, replying to.
I never make any claims saying either is the only possible scenario or an impossible one.
I also was not "dancing around the concrete arguments on the topic." I was directly answering arguments that had been put forth to me by random people on the internet. That's it. That's the point of the post. To answer those arguments.
I get that you've never seen it claimed that engineering made all 1200 mutations, but plenty of people claim it. You can look on my original reddit post and see people in the comments claiming it's possible because "China is so far ahead of us, they could have generated the primers 20 years ago to do something like that."
That's why it's not a strawman, I was directly answering arguments that had been made to me by people on the internet. Just because you think they are ludicrous arguments does not mean that someone has not made them. The internet is larger and more diverse in its idiocy than you have conceived of in your dreams, Horatio. etc. etc.
>2) That furin site RNA contains a non-canonical amino acid codon. To be fair, you didn't dispute this.
Hi, I have disputed the claim you've made since that the virus contains two such codons in a row. That is patently not the case in the earliest examples of the virus known. And wow, I just checked, and those three sequences from the earliest part of the pandemic I linked, they don't contain the cgg in the furin site. Literally look yourself. The earliest sequences out of China, Korea, and Iran do not have the cgg where you're talking about. It isn't there. Not that I saw, lol. Show me where it is if you find it. I just used BLOSUM similarity alignment and looked where the cleavage is supposed to be. And I don't see CGG there.
I actually address the restriction site directly in the original discussion. I don't recall you mentioning it before now. if you did, my apologies I missed it. See my comments on that copy/pasted here:
"For sticky end ligation, for example, you can examine the relative length of homologous regions around restriction enzyme cutting motifs. And sort of detect it like a photoshopped gel almost. But in sequence form. Real mutations shouldn't occur predominately around restriction enzyme motifs. But engineered mutations would. You'd have to use evolutionary comparison of similar viral species to see if there are any mutations that appear too improbable to have happened by polymerase error alone.
Is it still possible to slip one by such a method? yes, of course. Especially small insertions or deletions would be easy to hide...
[But] it literally wouldn't make sense to do it. We have established backbones that would make more sense and be easier to use. The only reason would be to "hide your work." And that's like years and years worth of genetic manipulation, several post-docs worth of work, easy. All to "hide your work." When you could just use SARS-CoV-1 and be A) more deadly, B) more "natural", and C) easier to use."
It's just really funny if we do agree about both of these being possible, but one being more likely than the other. If we both agree that the zoonotic is probably more likely, what are we arguing about? I don't disagree that it is /technically/ possible, but I also find it more likely to have occurred in nature. Restriction sites can also occur in nature, btw. This is a case of the "lottery" fallacy. There are so many goddamn restriction sites throughout any viral genome, why is this surprising?
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/#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.