I am a molecular biologist but not a virologist. This article is stupid. The furin cleavage site, with almost identical sequences is present in several ancestral coronaviruses to Sars cov II. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7836551/
Serious virologists went over the furin cleavage site in close detail already and none of them seemed very convinced it was anything but natural in 2020.
Also, stick any 13 bp dna sequence into BLAST and you will find some strange matches if you include the right databases. That this particular 13 base pairs matches some bit of the human genome (inverted, mind you) is not really that surprising.
Omg you fell for that article. Look at those dendrograms carefully. They bias to load up the dendrograms with "degenerate sequences" with very close/obscure accession numbers, and basically hide the diversity of viral sequences between the furin-bearing coronaviruses and SARS-CoV-2 (fig 5, which completely omits betacoronaviruses, a clade that contains SARS-CoV-2).
Furin cleavage sites are rare in coronaviruses, and even rarer in the closest ones to SARS-CoV-2. It's the case that there was a research proposal to put a furin cleavage site into bat coronaviruses to fuck around and find out precisely because they are rare in most classes but conspicuous (and possibly related to pathogenicity) in others (https://www.documentcloud.org/documents/21066966-defuse-prop...).
(Ps i am also a former molecular biologist that worked in gain of function for non pathogenic bioengineering and I used to look at dendrograms to steal ideas from nature to improve enzyme function -- and I was successful: https://jbioleng.biomedcentral.com/articles/10.1186/1754-161...)
Edit: clarified that betacoronaviruses contains SARS-CoV-2, because some armchair analysts don't stop to understand figures
At minimum, an explanation of how the linked research (which shows that the cleavage sites are indeed common, as the parent comment explained) is somehow wrong. It doesn’t make any sense to insist they aren’t common in response to a paper showing specific examples of them occurring in nearby SARS-CoV-2 ancestors.
You badly broke the site guidelines repeatedly in this thread, and you also discredited your own case by giving open-minded readers a strong reason to discount what you're saying. None of that does anybody any good, so please stop doing it.
Obviously we moderate and eventually ban accounts that post like this—we have to, or this place will destroy itself even faster than it already is. But regardless of whether that moves you or not, you should take in the point that by being an asshole in the comments, you're creating the very situation that is presumably frustrating you in the first place, by discrediting the view that you believe to be the truth.
It would be far more in your interest to make your substantive points neutrally, thoughtfully, and respectfully. Then you wouldn't be undermining your own argument so badly. See https://hn.algolia.com/?dateRange=all&page=0&prefix=true&sor... for past explanations.
The point was that the furin cleavage site does appear in other Coronaviruses, and therefore it’s not a random appearance in this one.
The specific details of the paper you’re nit-picking aren’t relevant. The sequence either appears elsewhere or it doesn’t, but it clearly appears elsewhere in Coronaviruses.
Therefore, comparing the appearance of the sequence in another Coronavirus to random chance is a flawed comparison.
The next question, to my mind, is "How common is that cleavage site in other viruses, especially other viruses endemic to the origin location of SARS-Cov-2?" With a follow-up of "How possible would it be for multi-virus splicing to generate that sequence from two otherwise-unrelated, possibly damaged sequences ending up head-to-tail in the DNA of a host cell?"
We know of other novel viruses that have resulted from sequences of multiple viruses being spliced together in a living host naturally. I don't know how we'd disambiguate that possibility from human synthesis.
I'm sorry, that is simply not the case, neither at the protein level nor at the DNA level. Furin cleavage sites have diversity.
The canonical minimal furin cleavage site sequence is RX(R/K)R, which had a highly variable amino acid and a choice between the two basic amino acids in another position. This variability is sampled across the coronavirus furin cleavage site sequences.
> Did you look at figure five and wonder why the fuck betacoronaviruses were not in the dendrogram?
So the lack of a single family of coronaviruses in a single figure inverts the entire claim? Come on.
> Peer review is not perfect.
I’m inclined to trust it far more than a random internet commenter who can’t really explain their argument but instead spends more time swearing and writing childish insults like this:
> Use that thing under your cranial bone, and exercise discernment.
You're free to call me an armchair analyst and trivialize my 10 years of experience in the biological sciences, sometimes working 100 days straight, 100 hour weeks (paid at 26k USD in an expensive us city, no less), more importantly brutally failing about half of those years to learn enough to come out with a successful bioengineering project that used the exact skills necessary to perform a critical analysis of the paper.
I'm also free to claim that you're just projecting.
>single family of coronaviruses in a single figure inverts the entire claim
Yes, considering that SARS-CoV-2 is part of the betacoronaviruse clade. Did you miss that?
I hear you. Personal observations using negative psychological language are likely to come across as attacks no matter what you do, and they're also not particularly substantive, as well as nearly always off topic. Best to avoid.
> I am a molecular biologist but not a virologist. This article is stupid. The furin cleavage site, with almost identical sequences is present in several ancestral coronaviruses to Sars cov II. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7836551/
It seems the presence of the furin cleavage site in any other Coronavirus would be enough to invalidate this paper’s comparison to pure random chance.
Why would the authors misuse statistics comparing this to random chance when there are published examples of the furin cleavage site appearing elsewhere? It doesn’t make any sense.
Yes, possible DNA sequences do not occur with equal frequencies. The whole point of selection pressure is that it selects for specific sequences. The same sequence occurring in a host species and a parasite is also not surprising. Rare events could result in horizontal transfer of genetics between host and parasite. Such things have been documented before.
Whoa, that says a lot about what kind of scientist you are ...
I have a published paper under the "Frontiers in" brand and can assure you that the people behind it (staff and editors) are among the most professional in what they do. "Frontiers in" does not publish fringe science, they are quite rigorous in their process.
Also the paper is written by quite reputable people and backed by several institutions. If their claims were "stupid" (as you arrogantly put it) they would have spotted it before you, trust me.
Anyone taking a discipline seriously would never link to Wikipedia, with the exception of when Wikipedia, itself, is topical. It is usually a sign of laziness and weak positions on the part of the person linking to the article.
The fact is that the state of research, peer review, and publication in academia is in complete shambles, in my professional opinion. The amount of system gaming in research has lead me to question most publications and claims I see anymore, unfortunately. I know the system, many of pressures / incentives, and I know a lot of the games played to optimize around these. It's impossible to be any bit lazy and give into any semblance of authoritative findings anymore unless you too just want to play the publication ranking game to stay afloat or get ahead in your career.
We need a massive overhaul of research culture in the US, IMHO.
When it comes to heavily manipulated "sources" like Wikipedia, I "throw the baby out with the bathwater" (yet another lazy attempt at reasoning is to use phrases like that as justification for, well, anything) is because you cannot see what is not presented in the article, usually in the form of others who will contradict the claims of whatever criticism the page is presenting with equal or stronger sources. Wikipedia guards such open discussion with a lot of dirty tactics which include collusion between article guardians and admins who will have your account locked and IP address blocked from editing in less than one hour of a "violation", and they do not notify you through email of their activities so you have to go discovering what they are doing through their Kafkaesque procedures of adjudication which are decided without any defense from the accused and evidence that doesn't truly qualify as evidence based on any reasonable standard for evidence.
A relatively newer policy implemented through their MediaWiki project is a "feature" whereby an edit can be permanently hidden from view, so future editors cannot go back and see what edits were removed or reverted. This goes completely against the original concept of a wiki and bolsters my claims that Wikipedia should never be used as a source because in the most contentious articles they will hide removed edits containing information they don't like.
The result of this is editors who have contradicting opinions from the Wikipedia-approved opinion will stop editing simply because it isn't worth the effort as Wikipedia always wins (because it is Wikipedia's website).
Wikipedia is a dumpster fire full of bias, pettiness, and structured manipulation. Linking there or using those pages demonstrates laziness and a near complete lack of higher reasoning.
Well, it is not lazy to use the phrase, "throw the baby out with the bathwater." That is a well defined, well understood phrase of the English language that means, "Discard something valuable along with something not wanted." [1]
If you throw the baby out with the bath water, you lose the good parts of something as well as the bad parts, because you reject it as a whole instead of just removing what is bad. [2]
The meaning is that you were throwing out the clear links in the wiki article due to them being presented at wikipedia.org. Footnote 37 and onwards.
The phrase, as with many others, is used to hand-wavy dismiss arguments. For example, you completely ignored basically >90% of my comment, which is what people with really poor positions do to attempt to maintain some position of superiority in their minds.
The points you made don't apply here, because they were already answered - in an answer you completely ignored and were tone-deaf about in order to type again about the dangers of wikipedia. What you have glossed over is that I was talking not about a wikipedia article but the links in the footnote section of that wikipedia article.
I specifically stated and made the case that Wikipedia will only allow what Wikipedia wants published to their site. To conclude some measure of criticism exists without competing claims against the criticism is a naive position. This applies to what you are linking to.
Your points do not acknowledgement this central thesis. Wikipedia is garbage, using it as a base of aggregated links is ignorant or naive.
To put it more bluntly: I don't care about the opinions you express regarding this topic, as you are demonstrating very arrogant behavior, particularly in linking to a dictionary dot com article on a common English phrase, as if I've demonstrated some lack of understanding in English require some assistance there. Then completely ignoring my points. You are terrible at discussion.
Seriously? Is this the quality of discussion HN is regularly becoming? You want me to make an assumption? Is that how you operate in conversation - assumptions to fill in the gaps when something isn't clear?
You realize that their saying "natural" or "unnatural" completely changes what they're saying to the polar opposite, right?
So now clarity is pedantic?
Seriously?
If HN had subreddits there'd be one similar to /r/WatchRedditDie
There are arguments from improbability in the article that rely on implicit assumptions that are obviously wrong once made explicit, akin to a creationist arguing for the improbability of the human genome's complexity as though it arose like a shuffled deck of cards.
> Serious virologists went over the furin cleavage site in close detail already and none of them seemed very convinced it was anything but natural in 2020.
Serious virologists went over the furin cleavage site in close detail already and none of them seemed very convinced it was anything but natural in 2020.
Also, stick any 13 bp dna sequence into BLAST and you will find some strange matches if you include the right databases. That this particular 13 base pairs matches some bit of the human genome (inverted, mind you) is not really that surprising.