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Endonuclease fingerprint indicates a synthetic origin of SARS-CoV-2?

biorxiv.org

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Re: Endonuclease fingerprint indicates a synthetic origin of SARS-CoV-2?

#151

Post by Protostome »

jpeloquin wrote: post #91

"To avoid losing power with multiple comparisons, we focus our analysis on the BsaI/BsmBI sites in SARS-CoV-2 and compare the BsaI/BsmBI map in SARS-CoV-2 to all other restriction maps of all other CoVs used in our analysis." It's important to know whether or not the authors picked BsaI & BmBI blind, before looking at the genome. If they picked BsaI & BmBI with knowledge of the SARS-CoV-2 genome, that doesn't dodge t…

Bioinformatician here, BsaI and BsmBI are Type IIS restriction enzymes. Which means, they are unique in the fact that they cleave DNA at a defined distance outside of their recognition sequence.

BsaI has been used in high throughput assembly techniques such as Golden Gate assembly and Golden Braid assembly.

Golden Gate assembly is an extremely robust method for building modular genetic components. For example, one can create plasmids (circular pieces of DNA) with billions of variants of the spike proteins, each carrying a different combination of mutations. Then, those plasmids are transfected into corona viruses and incubated in a tissue culture. Now, one usually let natural selection do its thing and the most infective variants replicate in the tissue much faster and take over the population.

Having said all that, type 2s restriction sites usually are cut out during assembly so I'm not sure how having those is a good evidence for engineering. Actually, the opposite is true. Having none at all is one evidence which is very much suspicious

Re: Endonuclease fingerprint indicates a synthetic origin of SARS-CoV-2?

#152

Post by emsign »

xupybd wrote: post #100
m0llusk wrote: post #18

There are at least a couple of suspicious points in this study: First and foremost the central claim is that 5 potential restriction binding sites versus 2 means that SARS-CoV2 is non natural. That does not necessarily follow. Just as SARS-CoV2 is unusually infectious and damaging to humans it could just happen to have an additional 3 restriction binding sites. So there is nothing inconsistent with natural selection…

>Thirdly, this paper emphasizes the strong impact of the COVID pandemic and asserts that understanding the origins of the virus would necessarily aid in preventing future pandemics. This does not clearly follow. Especially if the virus had natural selection origins there is no clear and obvious way of systematically reducing risk. Simply living or traveling where host populations like bats live could be enough to gen…

People could just try and stop eating them first instead, that's my humble idea.

Re: Endonuclease fingerprint indicates a synthetic origin of SARS-CoV-2?

#153

Post by mikeyouse »

mzs wrote: post #141
mikeyouse wrote: post #130

Earlier quoted context omitted.

The authors of this paper are confused about the technology they're using... it's not a good sign about their conclusions.. https://twitter.com/matias_kaplan/status/1583235087067336704 https://twitter.com/NoahOlsman/status/1583275862442807299

or not: https://twitter.com/VBruttel/status/1583233001319956480

It feels telling that when I click that link, the associated tweets are the kookiest of conspiracy theories about Pfizer execs, vaccine mandates and people screeching about things they clearly don't understand. I suspect in a few days, with Bloom and others reviewing the preprint they're going to be forced to pull it down and "rework" it.

Re: Endonuclease fingerprint indicates a synthetic origin of SARS-CoV-2?

#154

Post by gary_0 »

rossdavidh wrote: post #129

The opening line: "To prevent future pandemics, it is important that we understand whether SARS-CoV-2 spilled over directly from animals to people, or indirectly in a laboratory accident." Is that true? I mean I understand why people would be curious, but does it really matter, in terms of what we need to do? We know that viruses _can_ spillover from animals to people, and we know that viruses in a laboratory setting…

Good point. Arguing about who or what to point the finger at for SARS-CoV-2 seems more like politics than epidemiology. The evidence of a laboratory source is unclear enough, and the chance of a natural source plausible enough, that I'm not sure how the cost/benefit is supposed to work out here.

Not to mention if your goal is just to point out the ethical lapses of the Chinese government, you don't really need any extra ammunition.

Re: Endonuclease fingerprint indicates a synthetic origin of SARS-CoV-2?

#155

Post by emsign »

rossdavidh wrote: post #129

The opening line: "To prevent future pandemics, it is important that we understand whether SARS-CoV-2 spilled over directly from animals to people, or indirectly in a laboratory accident." Is that true? I mean I understand why people would be curious, but does it really matter, in terms of what we need to do? We know that viruses _can_ spillover from animals to people, and we know that viruses in a laboratory setting…

I think the way in which we prevent lab made viruses to break free is fundamentally different from how prevention of a spill over would need to be done. Because it causes problems at the exact opposite ends of the chain of events. The first couldn't be more detached and isolated from nature, while the other happens if hygience and mixing of species is sloppily disregarded. This is a challenge if both sites are right next to each other of course.

Re: Endonuclease fingerprint indicates a synthetic origin of SARS-CoV-2?

#156

Post by emsign »

XorNot wrote: post #109

There's a line in this paper which has been cited a few times in this thread which really stands out to me: > 100,000 random in silico mutants were generated for both RaTG13 and BANAl-20-52...Only 1.2% of RaTG13 mutants resulted in a BsaI/BsmBI restriction map with a larger z-score than SARS-CoV-2. BANAL52 is the closer relative to SARS-CoV-2 by over 200 nucleotides, yet only 0.1% of mutants yielded z-scores as great…

But the actual question is not how likely it is of those naturally occuring mutations (which also happen to be exactly like the commercial ones used for cutting genomes) to occur at the exact positions you would expect them to be in engineered genomes.

The real question is how probable it is if such a naturally mutated virus actually develops into a pandemic. First it has to spawn from nature and then it also has to be lucky enough to cause a pandemic.

You have to multiply those two probabilities as well. And only then you have a model that can be compared to what happened with the SARS-CoV-2, is it still that likely to be a natural spill over?

Re: Endonuclease fingerprint indicates a synthetic origin of SARS-CoV-2?

#157

Post by tgv »

lamontcg wrote: post #124
Fomite wrote: post #104

Earlier quoted context omitted.

To my mind, there are a few reasons: 1) It makes the pandemic deterministic (bad lab security means an outbreak) instead of stochastic (wildlife spillover). That is, to be frank, even as an epidemiologist who is very skeptical of the lab leak hypothesis, a comforting thought. 2) It's a popular topic in the Substack/Medium set, because it moves the pandemic back into their wheelhouse of expertise, international relati…

Zoonotic spillover is likely increasing in China due to climate change, more human-animal contact and animal farming, it probably has a large "determinstic" background. Of course if you go down that rabbithole then you might wind up concluding that the vegans have been right all along, which certain groups might find an unpalatable result.

I don't think you have to attribute it to some interest at stake: if it is zoonotic, people see it as the cost of living. Of course, that has to be changed, but it's a boring conclusion, and unlikely to cause a change quickly, because we are slow as molasses. A lab leak is more exciting, should not happen, gives more to discuss, and can be outlawed easier. I think that explains that there's more interest.

I'm still on the fence, BTW.

Re: Endonuclease fingerprint indicates a synthetic origin of SARS-CoV-2?

#158

Post by rleigh »

VagueMag wrote: post #138
Fomite wrote: post #135

Earlier quoted context omitted.

There have been a huge number of knock on ramifications in the field to the idea that the lab leak hypothesis might be true already.

You're talking about the field of above-board academic research. Academics didn't create SARS-CoV-2 and cover up their own role in it.

It is not possible to be certain of this. You can't state that as an incontrovertible fact.

Is it beyond reasonable doubt that a virus created as part of a gain-of-function research programme escaped? We simply don't know definitively one way or the other, and it's rather unscientific to make blanket statements about these things one way or the other in the absence of evidence to validate the claim. (I'm an immunologist, by the way.)

Re: Endonuclease fingerprint indicates a synthetic origin of SARS-CoV-2?

#159

Post by emsign »

shadowgovt wrote: post #37
jalino23 wrote: post #13

do I understand this correctly? that the paper is saying that covid 19 is highly likely a synthetic virus?

It's claiming that there are sequences on the viral code that are unlikely to have occurred naturally, but are really convenient for slicing the genetic sequence in a lab context. Sort of like if you shaved the fur on a hyena and discovered a "THIS END UP" tattoo on its skin.

Or rather: you have many hyenas without fur, and on the skin you can see scars that suggest the skin has been cut at very specific places, places where you'd normally see operation scars. Now all the discussion has come down to is how likely it is that the positional patterns and the type of scar itself could occur in nature. For example whether Hyena bites and scratches make the same scars as human scalpel.

Re: Endonuclease fingerprint indicates a synthetic origin of SARS-CoV-2?

#160

Post by tgv »

astrange wrote: post #84
guelo wrote: post #66

I've seen several papers with the opposite conclusion. Why do we only see the lab leak hypothesis front paged on HN?

Cynical engineers are required to believe in it because it's 1. "the opposite of the current thing" 2. contains more rationality than the other leading hypothesis (i.e. more of what happened was planned, rather than an accident) 3. and lets them blame a person rather than a bat. An ironically fitting end for them would be that it is true, they get all similar research banned, and then the next virus is zoonotic and n…

None of the gain-of-function research has been any help at all in the CoVID pandemic, nor in the SARS outbreaks. I also fail to see how it could have helped. What particularly helpful insight or technique came from that particular lab in Wuhan?
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