1. Gain of function research primarily uses samples collected from nature, and seeks to stimulate their evolution in as natural a way as possible to learn how viruses evolve in nature. If such viruses were to escape the lab, they would appear "natural"
2. It's not xenophobic for people from the US to suggest the possibility of a lab leak, because the US was itself funding gain of function research on novel coronaviruses in the Wuhan BSL4 lab
3. Lab leaks happen more often than most people realize[1]
[1]https://www.vox.com/future-perfect/2019/3/20/18260669/deadly...
There is, from my understanding, reasonable evidence to conclude the virus was not engineered from the perspective of "we took genes from one virus and moved them to this virus," but there's no evidence disproving the idea that it was the result of gain of function research.
My personal feeling is that these statements are true:
* The virus is unlikely to have been engineered (in the way I described above) and leaked.
* There is circumstantial evidence the virus was the result of gain of function research and it leaked.
* There is circumstantial evidence the virus was a natural research sample and it leaked.
* There is circumstantial evidence the virus was introduced by an animal/person who traveled to the wet market.
Some of these are more likely than others, and an individual's own calibration for what is likely or unlikely will probably come into play more than evidence in the short term and possibly long term as well. I can say the vast majority of us are not qualified to answer the question either way though.
1) Chimeric viruses (copy and paste) are what scientists make in the lab. They take a piece of one virus and paste it into the genome of another, en masse. This is very different from what SARS-2 is, which is more accurately described as a "mosaic" (lots of little changes all over the genome). This is much much more difficult (if not very close to impossible in the case of SARS-2) to make in the lab, at least not and have it be done and "cooked" by the time the pandemic started. See the part of my post here: https://www.reddit.com/r/science/comments/gk6y95/covid19_did...
2) He makes it sound like the techniques Shi Zhengli uses in the lab could create SARS-CoV-2. This is not true. For the reasons I describe above in point 1, and others, this is not really a likely possibility. Modern virology just does not have the tools to do this. Only mother nature with its many millions of hosts and diversity of hosts (in different mammals) could do this in the span of time molecular clock analysis says it took to take similar viruses like RaTG-13 and mutate them into SARS-CoV-2. I go into extreme detail about this in this part of my original post: https://www.reddit.com/r/science/comments/gk6y95/covid19_did...
3) He also says things like "Considering the heights of user friendliness and automation that genetic engineering tools have attained, creating a synthetic CoV2 via the above methodology would be in reach of even a grad student." Yeah, in 2020. Not in 2000 when they would have needed to start doing this. We did not have these tools back then. We did not understand enough about viruses, and this is /before/ we even discovered SARS-CoV-1!
The molecular clock + the synonymous/nonsynonymous criteria + the mosaic nature of the virus together put constraints on how this virus could have evolved. The first says it takes about 50-70 years to evolve a virus like this, evolving as fast as it does in nature. The second says it evolved in a fashion that wasn't putting more selective pressure on it than nature usually does. The third says it happened in a semi-random way, the way natural mutations occur. All of these together (plus other stuff) mean that it's unlikely that anyone /grew/ the virus in a lab intentionally.
I go into extreme detail about the synonymous nonsynonymous stuff in 3.1.1 of my post.
4) Also, it doesn't actually look like a virus that was grown in a petri dish or one that was grown in a single species of animals. It has O-linked glycans on it that cell culture wouldn't add. See here: https://www.reddit.com/r/science/comments/gk6y95/covid19_did...
Also, if it were grown in a single species of animal, then the SARS-2 spike protein would bind most tightly to that receptor. That's not actually what it is. As best we can tell, the S from SARS-2 binds just ~okay~ to a lot of different ACE2 receptors, and it just happens to work to bind human ACE2 kinda well. It's not at all how anyone would have actually designed it if they wanted to make a virus that kills humans. If they were designing it that way, they were some really shitty super villains, let me tell you that. I go into some extreme detail about this in this part of my post: https://www.reddit.com/r/science/comments/gk6y95/covid19_did...
5) Yuri gets really hot and bothered about the furin cleavage site. But what he seems to misunderstand is that these cleavage sites have evolved in nature too. It's likely either A) a recombinatorial event between SARS-2 and similar viruses in nature or B) it mutated over a short period of time in a way similar to other "mutagenicity islands." We have actually seen this before in nature. See here: https://www.reddit.com/r/science/comments/gk6y95/covid19_did...
He even says it has been shown to be disabled in a relatively short period of time in lab animals, so why wouldn't it be able to show up in nature in 50-70 years in millions of wild animals? It's really not that unlikely when you consider that certain areas of viral genomes mutate a lot faster than others in the wild.
6) He even points out that the only viruses in nature that share the cleavage site share only 40% of the rest of their genomes with SARS-2. But that just shows it's likely that SARS-2 and one of these other viruses happened to infect the same animal at the same time, and their genomes had a cross-over event. This happens ALL. THE. TIME. in viruses in nature. It's basically how flu pandemics occur. See:
-https://www.nature.com/articles/nrg2053 -https://www.euro.who.int/en/health-topics/communicable-disea... -https://academic.oup.com/mbe/article-pdf/26/1/177/13640305/m...
Why is it not likely this sort of thing was involved in this coronavirus pandemic?
Honestly I can't keep going because I need to be studying for the most important exam of my career (USMLE Step 1) but I can tell you just from the first couple pages of this extremely long thing that Yuri is not a virologist and has never taken a formal viral genetics class. He is making fundamental mistakes in how viruses evolve and change over time. He clearly knows a lot about biochemistry and regular genetics, but viruses are a whole different ballgame.