A new paper claims SARS-CoV-2 bears signs of genetic engineering

Discussion of the preprint 2 days ago: <a href="https:&#x2F;&#x2F;news.ycombinator.com&#x2F;item?id=33279281" rel="nofollow">https:&#x2F;&#x2F;news.ycombinator.com&#x2F;item?id=33279281</a>

<a href="https:&#x2F;&#x2F;archive.ph&#x2F;UE7x2" rel="nofollow">https:&#x2F;&#x2F;archive.ph&#x2F;UE7x2</a>

As someone who was a genetic engineer for a long while, watching HN talk about dodgy papers like this is painful.<p>This paper posits a completely crazy cloning strategy that makes no sense (ie doing something far more convoluted than typical bsaI&#x2F;bsmbi seamless cloning workflows that breaks the whole point of &quot;seamless&quot; workflows), and then tries to use that to make a case for a genomic signature that we could look for. They then look at a handpicked set of viral genomes, but leave a bunch out and duplicate others (I think WIV04 and WHu are the same), and largely seem to be observing without realizing it that yes, recombination occurs among these viral lineages.<p>This isn&#x27;t even getting into the fact that a restriction-ligation based cloning strategy would leave <i>glaringly</i> obvious fingerprints behind in the form of the hundreds of nucleotide differences that are present outside the cutsites across the lineages... it would be blindingly obvious if someone just cut-and-pasted sars-cov-2 from other studied genomes.

This discussion at virological.org is where virologists themselves are discussing issues around analysis of viruses in general. It is referring to ancestry and the likely host organism(s)<p><a href="https:&#x2F;&#x2F;virological.org&#x2F;t&#x2F;the-comparative-recency-of-the-proximal-ancestors-of-sars-cov-1-and-sars-cov-2&#x2F;906" rel="nofollow">https:&#x2F;&#x2F;virological.org&#x2F;t&#x2F;the-comparative-recency-of-the-pro...</a><p><i>Horseshoe bats are the likely reservoir of sarbecoviruses (1), including SARS-CoV-1 and SARS-CoV-2 (2–4). Since the emergence of SARS-CoV-1 in 2002 and SARS-CoV-2 in 2019, there has been an increase in the sampling of sarbecoviruses in bats, which can reveal how recently SARS-CoV-1-like and SARS-CoV-2-like viruses sampled in bats shared a common ancestor with, respectively, SARS-CoV-1 and SARS-CoV-2 (jointly referred to as SARS-CoVs)</i><p>It may lie to one side of a debate about &quot;engineering&quot; but I take heart from the virologists doing the ongoing detective work to unpack what we can know about this disease and its vectors.<p>(I posted this to HN directly before. It got very little traction which I doubt means very much)

The origin of SARS-CoV-2 is kind of irrelevant, since both proposed origins could cause future pandemics and so we need to prepare for <i>both</i> kinds. Bump up all animal virus research to BSL4 <i>and</i> mitigate&#x2F;reduce interaction between humans and wild animal populations.

I can believe that - after the Snowden revelation on BigTech&#x27;s close ties with the US Intelligence service, the increasing public awareness to invasive data collection and governments creating privacy focused legislation to minimise said data collection and enforcing data localisation laws that would make it illegal to store and process personal data in foreign countries, an artificially created pandemic that necessitated people to quarantine themselves and force all services through the internet &#x2F; BigTech could indeed be a partial last ditch effort to force countries to create better internet infrastructure and collect commercial, personal and government data on every global citizen, from every country. China and US are possible suspects, with US being the most likely one.

At least the title did not say<p>&quot;A new <i>controversial</i> paper claims SARS-Cov-2 bears signs of genetic engineering&quot;<p>Thats a good sign.

I have made some analyses on coronavirus sequences. To be honest I simply don’t understand those experts who are adamant about a likely natural origin of Covid-19. Let’s talk about the controversial furin cleavage site in the gene of the spike protein. Apart from this sequence motif, there is not a single(!) insertion or deletion along the entire spike protein between Covid-19 and RaTG13 (more than 3900 nucleotides). All the differences are substitutions, i.e. point mutations. In other words, every single nucleotide has its equivalent in the parallel sequence. (as opposed to this, more than five hundred different InDels were discovered in different variants after less than four years of evolution in humans) Covid-19 and RaTG13 have 96% of homology, which could be translated to about 50 years of divergent evolution. (that’s a popular argument of why RaTG13 couldn’t have evolved into Covid-19 during the several years after its discovery. (that’s not entirely true because the rate of the evolution is not constant, it can be accelerated for shorter periods, but let’s accept it for now) That means that RaTG13 and Covid-19 must have had a common ancestor at about 50 years ago. That either had or had not the furin site. If it had then RaTG13 lost it some time during the following years, if it hadn’t then Covid-19 acquired it. The first scenario is very unlikely because the furin cleavage has known to provide strong evolutionary advantage so in the presence of the bulk un-mutated viruses in the same cells, the new mutant must have been selected out and disappeared fast, right after its emergence. So Covid-19 acquired it. The question is only, how? If it were not an insertion then I could accept that it occurred step-by-step by consecutive single mutations such as evolution is known to work. First a very weak site being formed and then it becames stronger and stronger by each additional point mutation, driven by the selection force. But not in the case of an insertion, it must have happened in one single step. In the nature, Covid-19 could have acquired it only from another bat coronavirus by recombination (or more exactly by template switching). However there is no known member of the family of betacoronaviruses (where Covid-19, SARS and MERS belong) which contains furin site. Nor bat viruses and neither in other species. There is furin cleavage site in the spike protein of several alphacoronaviruses but their sequences are too different from Covid-19 to be able to recombine with it. Also, the furin site sequence in those bat viruses is very different from the one in Covid-19, even on protein level, let alone on RNA level. You can find similar sequences only in feline and canine coronaviruses. The site in Covid-19 looks to have optimized codon usage for human (or mouse) cells and highly suboptimal for protein translation in bats. (especially for those often mentioned Arginine codons) All these considerations taken together with the proven fact that Eco Alliance and Dr. Baric at University of North Carolina at least considered inserting a furin site into a bat coronavirus (see the links) strongly argues for the laboratory origin of Covid-19. <a href="https:&#x2F;&#x2F;theintercept.com&#x2F;2021&#x2F;09&#x2F;23&#x2F;coronavirus-research-grant-darpa&#x2F;" rel="nofollow">https:&#x2F;&#x2F;theintercept.com&#x2F;2021&#x2F;09&#x2F;23&#x2F;coronavirus-research-gra...</a> <a href="https:&#x2F;&#x2F;theintercept.com&#x2F;2021&#x2F;10&#x2F;06&#x2F;intercepted-covid-origins-lab-leak&#x2F;" rel="nofollow">https:&#x2F;&#x2F;theintercept.com&#x2F;2021&#x2F;10&#x2F;06&#x2F;intercepted-covid-origin...</a><p>I cannot render a percentage number to this probability but in my mind it’s close to certainty.

The Economist is reporting on 1 new paper ... of the 100k or so written so far. Almost clickbait :(