Some want to dispute the natural origin of COVID-19

The last two blog posts we have dedicated to going over a controversial, non-peer reviewed online report outlining reasons why the SARS-CoV-2 virus could not have been of natural origin. The authors (we will refer to them as such for the remainder of the post, with any other publication authors specified by name) promised to follow up that initial report with further proof of why a number of published coronavirus genomes from different animals are fake. This is important because these publications are a significant piece of evidence pointing to the natural origin of SARS-CoV-2.

The authors who proclaimed that all these viruses are fabricated, and have been published to obfuscate the synthetic origin of the SARS-CoV-2 coronavirus, have released a second report at the start of October 2020 with aim to “prove” these coronaviruses are fake!

We were looking forward to this report which came out the day before our second blog post which was dedicated to the analysis of their first report. We were really curious what kind of evidence they would propose to build their case to claim an academic fraud of such massive proportion. These are very libelous statements which, without substantial proof, according to one of the online reviews of the same report, would be “defamatory, grossly negligent, and ethically dubious.”

Let us continue with this dramatic saga.

We took a strong stance against the authors’ prior claims for not having enough concrete evidence. The authors start their second report with a questionable statement right in the abstract of their work: “we disproved the possibility of SARS-CoV-2 arising naturally through evolution”. Definitely not!

What was provided was speculation and no analysis to support many of its hypothetical claims. No statistical significance was assigned to any of the claims in terms of probability score to show how likely or unlikely anything they disputed could occur in nature.

Then, the authors were under the impression that they “instead proved that SARS-CoV-2 must have been a product of laboratory modification”. Also definitely not! These are extremely far fetched claims! As the authors even say themselves, this is only an “assertion”. Assertion is not a proof of anything.

The authors put it simply: “the natural origin theory remains supported by several novel coronaviruses published after the start of the outbreak”, all of which have very high genome sequence similarity to SARS-CoV-2 virus that caused the COVID-19 pandemic. These viruses are the RaTG13 bat coronavirus (highest similarity), a series of pangolin coronaviruses (highest similarity between the spike protein, the component of the virus used to enter human cells), and the RmYN02 bat coronavirus (the only bat coronavirus that has a furin-cleavage like site, a feature of SARS-CoV-2 virus that makes it so extremely unusual compared to closest known virus relatives), all published by Chinese scientists (which makes sense, it is their arena of expertise; it is their country that is under the constant threat of human exposure to these viruses).

Bat coronavirus is fake?

First let us examine the proof against the RaTG13 bat coronavirus, which has 96% similarity with SARS-CoV-2. The virus itself has never been isolated or recovered from any sample and the sample itself is no longer available for any further validation. The published genome sequence of RaTG13 (which oddly was published out of nowhere in the same issue as one of the first genome code publications of SARS-CoV-2) is the stand-alone proof its existence. The authors claim it would be easy to submit fake raw data into genome database and get away with it.

The biggest red flag is that when looking at RaTG13 raw data, previously spotted by researchers in India, only 0.7% of them are of bacterial origin, which should actually constitute the bulk (70-90%) of DNA sequences isolated from a bat fecal sample. 30% of the data did not match anything, and the rest instead matched with number of different bats and other animals such as Mexican bats, squirrels, flying foxes, red foxes, etc, whereas it should be primarily the same bat that the sample came from. It indeed looked as if someone just tossed bunch of raw files from variety of sources. Further, their date stamp reveals that sequencing was done in 2017 and 2018, something that was also not revealed in the 2020 publication of RaTG13 (by Dr. Zhengli Shi of the Wuhan Institute of Virology). Too bad Dr. Shi did not publish it then because that would have alleviated so much of the current suspicion of what looks like concealing information.

The virus itself comprised only 0.003% of the total sample, casting doubt it would be enough to produce a full genome sequence.

This was the primary and most condemning evidence the authors used to conclude that the RaTG13 “shows signs of fabrication.” Not even close. Not to mention that this analysis was in a preprint scientific publication, meaning that this information has not yet been peer reviewed by other experts, and well, could be total garbage. Not that peer review of science prevents total garbage from being published, but it sure diminishes the odds. Thus, it is an important step in the validation process of scientific integrity behind proposed claims. Now though, we are under a mountain of online published preprints that can be used as evidence and an unsuspecting person may not know the difference between a preprint and a real scientific publication in accredited scientific journal.

On the other hand, the authors and others are using the preprints forum to explore if the coronavirus science can be trusted (the work of Dr. Shi, especially). Sure her works passed peer review enough to get published, but then different "peers" reviewed her work (at the least finding sizable ethical holes and at the worst outright fraud), by commenting with preprints from all different angles and... what?

Thus another way to look at it is that preprints seem to be like the social media of peer reviewing. And in this situation they could be pointing out and uncovering damning evidence, quicker and more efficiently than "peer review" did or can do. The potential irony is that preprints are a becoming a better map to the scientific truth through their courage and fearlessness where as the old guard with their publish or perish in peer reviewed journals are failing to keep up.

To the point, more interesting we thought (in terms of a build up of condemnation) was the analysis of another preprint indicating that RaTG13 submitted sequence revealed multiple anomalies, none of which would be expected:

• Anomalous enrichment of telomere-like repeat sequence – indicating the original sample could not have contained enough material to produce complete RaTG13 genome sequence
• Anomalous enrichment of sequences that are either non-attributable to any specific organism or are low-quality matches to nearly all domains of life - but especially suggesting that Mexican dried bat poop was mixed in to the sample as filler!
• Depletion of bacterial-like sequence reads
• Observation of anomalous and unexpected data in the sequence
• Inability of the data to prove published claims related to RaTG13

This report’s conclusion was that not enough of a virus RNA template would have been present to publish the full genome sequence, and the raw sequence suggests a fraudulent mix of DNA as opposed to true RNA isolated from fecal sample. However, and quite unfortunately, this is not a peer reviewed, published scientific analysis, either. They are just reports made without further scrutiny.

However, these are very serious claims proposing that academic fraud was made and therefore they deserve closer observation to either substantiate these claims or discard them. This is not some obscure academic curiosity; we are talking about substantiating the origins of a global pandemic that is currently decimating the world!

This is especially in light of the history of RaTG13 already being shrouded in a bizarre mystery.

Interestingly, the authors then go into the story we just published in our last blog post, about miners in China afflicted with a mysterious pneumonia in 2012, and how subsequently, the same team who in 2020 published the genome of RaTG13, also published a fragment of sequence labelled RaBtCoV/4991 isolated in 2013 (and published in 2016) from the same cave where those same miners were working. We also explained that in detail in the last blog post. Importantly, apparently the RaBtCoV/4991 sequence source is the same as that for the RaTG13, although this required some serious detective work to confirm. This is indeed extremely important because it is a direct link between the bat coronavirus (that is most closely related to SARS-CoV-2) and a mysterious disease that would appear to be very similar in symptoms to current COVID-19 (where three of six miners who worked collecting bat feces died) which has been isolated from the same cave!

It is no doubt bizarre that this is not getting more attention and scrutiny to figure out if there is a link between these miners and the closest bat virus relative to SARS-CoV-2. As we outlined in our previous blog post, it has been proposed that perhaps these miners were the first victims of COVID-19 (obviously speculative ).

We will say we do agree with authors’ statement: “it is unethical for [the 2020 RaTG13 publication] authors to change the name of a previously published virus without any notice or description. It is also unethical for authors to not cite their own publication where they had characterized and reported the same virus.” Indeed, this type of behaviour should not be dismissed lightly.

How mutations describe evolution… or laboratory design?

The authors claim that the sequence comparison between RaTG13 and SARS-CoV-2 indicates an abnormal pattern of evolution between these two viruses. To get into this we first need to define a couple of types of mutations that can happen in the genes: synonymous mutations and non-synonymous mutations.

Synonymous mutations are those that lead to gene code difference but do not actually alter the code of the resulting protein that is being build based on the genetic code. Remember the dogma, a genetic code is used as a template to produce proteins, which are your cellular robots doing most of the work in your cells. The genetic code is used to determine how amino acids, the building blocks of proteins, are linked together to create a protein. Three specific nucleotides (the building blocks of genetic material) define a specific amino acid to be used, and that is referred to as a codon. But multiple options of codons are available for same amino acids. This allows a certain level of mutations to occur in genetic material without actually affecting how the final protein products are built. In other words, you can think of these as silent mutations.

Non-synonymous mutations are conversely genetic mutations that consequently also change the amino acid sequence of the resulting protein. Sometimes a single amino acid change can have a dramatic effect and alter the behaviour of the protein product. You can think of these as non-silent mutations with some resulting in really loud impact (excuse the punniness).

You can look at the ratio of one type mutation versus the other, and the more non-synonymous mutations are present (those that change the protein) in relation to synonymous mutations (those that do not affect the protein), this can be inferred as evolutionary pressure towards adaptation. The environmental pressure to expend mutations in a population will help that population adapt to that environment. This is referred to as positive selection.

The exact opposite of that is a pressure to not observe new mutations in a protein and preserve the protein sequence and function as intact as possible as that is what will serve the population best for survival/adaptation chances. This would result in lower ratio of non-synonymous mutations (those that change the protein) in relation to synonymous mutations (those that do not). This is referred to as purifying selection.

The authors looked at these ratios between RaTG13 and SARS-CoV-2 genomes, and here is what the uncovered. Typically, the synonymous mutations outnumbered non-synonymous mutations about 5ꟷ6:1 for nearly every virus gene. This is similar to a ratio observed in other coronaviruses of similar genome sequence similarity. But focusing specifically on the spike protein (the SARS-CoV-2 virus protein that is used to gain entry into human cells), when they looked at one of its sections, referred to as the S2 domain of coronavirus spike protein (see our past post for great visual details), that ratio was 44:1. What this means is that for this specific section of the gene, for whatever reason, there would have to be a very strong purifying selection to preserve the sequence between RaTG13 and SARS-CoV-2 genomes. In contrast, in another gene, which is one of the most conserved genes between coronaviruses, that ratio was only 10:1. Thus this part of the RaTG13 genome shows unusual evolutionary conservation. Then the authors cited a publication that analyzed nearly 3000 SARS-CoV-2 virus genomes isolated around the world to show that the S2 domain of spike gene definitely shows tolerance towards mutagenesis. Thus, this type of conservation between RaTG13 and SARS-CoV-2 genomes is just weird according to them.

Their conclusion is that at least one of these genomes then has to be artificial to show this type of pattern of mutagenesis. They of course think that both of the viruses are not natural. What the authors suggest is that fake non-synonymous mutations had to be introduced in the receptor binding domain of RaTG13 spike protein (the region of the spike protein responsible for interacting with receptors on human cells, to gain entry, present in the S1 domain of the protein) so as not to arouse suspicion as to the too high similarity of this ultra important region between the RaTG13 and SARS-CoV-2 genomes. Then the presumed fabricators were smart enough to aim for maintaining the 5ꟷ6:1 ratio between synonymous and non-synonymous mutations across the entire spike gene, and as a consequence compensated by not introducing any non-synonymous mutations in the S2 domain. The outcome is the high 44:1 synonymous to non-synonymous mutations ratio in the S2 domain of the spike gene.

We would not jump to this conclusion just based on this anomaly alone. Nature can play weird tricks. But hey, we are recounting what they are saying, and overall, we would be curious to see how truly unlikely this would be. The authors do not provide logical evidence, only a collection of assertion to tell a story. This is not science, this is a script.

But the authors are very keen to jump to the conclusion that this “collectively prove that RaTG13 does not exist in nature and its sequence has been fabricated.” Very keen!

Then the authors continue with their conjectures on what the fabricators must have done, and start to stipulate that the RaBtCoV/4991 was conveniently used to be able to claim that RaTG13 was discovered all the way in 2013. The fabricators did not want to draw attention to RaBtCoV/4991, but if anyone was asking too many questions about RaTG13, it could be pointed to its 2013 discovery.

Agatha Christie would be jealous of this plot!

2012 pandemic origins theory

Next was the fun part, where the authors discredited the theory proposed by Drs. Jonathan Latham and Allison Wilson that SARS-CoV-2 evolved from RaTG13 or related virus in the lungs of the miners mentioned above (see our last blog post for details). The authors disclaim this theory on few accounts:

• No evidence of coronavirus in samples from miners was identified
• The antibodies that would be expected to be triggered by the viral infection were not present in their blood
• The pandemic did not erupt in 2012
• The RaTG13 virus is fake and the next closest relative has at best 90% similarity which would render rapid mutagenesis in the lungs impossible
• Still unknown how SARS-CoV-2 could have obtained the spike protein furin-cleavage site(see our previous post for detailed explanation)
• The authors own evidence that SARS-CoV-2 was fabricated

Interestingly, the only really good argument is the one about antibodies, as other arguments are the authors’ own assertions (apart from the obvious no coronavirus isolation). The authors also point to a PhD dissertation that also discussed these miners, and that document apparently actually claims that the antibodies were present in some of the miners’ samples. Thus, even that one is on shaky ground. What we thought was going to be a real battle ground is the unique proposition by Drs. Latham and Wilson that lungs can act as a host organ mimicking a viral passage process that is done in laboratory settings (virus passaging is forcing a virus to evolve by continuously exposing it to an environment it is not adapted to). That was not even touched. Sad face.

Pangolin viruses are fake?

This also gets interesting. We previously wrote that coronaviruses were recently isolated from pangolins. The reason why this is significant is because the receptor binding domain of the spike protein in these pangolin viruses is the most closely related to SARS-CoV-2 virus. The authors point out that these pangolin coronavirus samples were first reported in October 2019 from animals smuggled into China. Subsequent data analysis indicated that every published pangolin coronavirus genome actually stems from that single data set of October 2019 (with one of them appearing to attempt to hide this)! This is indeed quite creepy because this similarity between the pangolin coronavirus spike protein receptor binding domain to that of SARS-CoV-2 has resulted in suggesting that pangolins could have been an intermediate host of SARS-CoV-2 prior to it being transmitted into humans. That article put into question whether these pangolin viruses then can even be used as a statement of these animals being potential carriers on the account that if only smuggled pangolins were found to possess these coronaviruses, the viruses could have actually come from other species held in captivity alongside pangolins. A different intermediate species.

To support this, a recent extensive analysis of wild pangolins did not find any coronaviruses in these animals.

Poor pangolins just cannot catch a break.

And the authors of course jump to a conclusion that pangolin viruses were fabricated! To further support that, the authors list number of publications that indicated that the spike protein receptor binding domain has higher affinity for human ACE2 receptor (the receptor through which SARS-CoV-2 gains entry into our cells) than the pangolin receptor. This argument of theirs used in previous report was already put into question by another virology expert. They also use their favourite analysis, the ratio between the synonymous mutations (those that do not affect the protein) and non-synonymous mutations (those that change the protein) to once again show very unusually high ration of 24:1, indicative of very highly purifying evolutionary selection for conserving the receptor binding domain. This part of the spike protein in fact is expected to experience the opposite, very high positive selection, so that the virus can mutate and adapt to infect new host. In comparison the ratio just between some bat viruses for same area was 4:1 or 0.8:1, indicating how much this region can mutate to help viruses do their dirty tricks. They also pointed once again to similar unusual purifying selection ratio of the S2 domain of the spike protein.

We are not convinced that this means the virus has to be fake though. None of this has to be seen as so unusual if pangolins were simply accidentally infected while in captivity. In terms of the sequence conservation appearing as an unnatural course of evolution, that premise hinges on the fact that no other unusual events take place, such as recombination (where two separate organisms exchange fragments of their genomes).

What is weird is that a group of scientists published pangolin genomes without this deeper analysis, in the least to avoid drawing such condemning suspicions afterwards.

Poor conniving scientists just cannot catch a break.

But the authors do not stop there! They actually think that it was the October 2019 publication that was already fake (submitted for publication in September 2019)! This would mean, according to them, that the forgery of evidence of SARS-CoV-2 coronavirus origins have started even before the COVID-19 pandemic started! For now we will leave it at that and come back to their meaning behind this terrifying suggestion.

Another bat coronavirus is fake?

In June 2020, another novel bat coronavirus, RmYN02, was reported, appearing to be the second closest coronavirus to SARS-CoV-2. More significantly, it had a degenerate furin-cleavage site which is the most unusual feature of SARS-CoV-2, and the one that greatly enhances the virus infectivity (ability to gain entry into our cells, see our past blog posts for details).

What is the biggest issue the authors find with this publication? Apparently, the raw sequence data of the spike gene has still never been reported to the public database! Therefore, this could be as fake as anyone would want as there is nothing to verify the claim of the reported sequence!

Thus the pattern of publicly available sequence data persists between the RaTG13 coronavirus (where portion of its sequence was submitted to the public database months after genome publication and the quality of the sequences is supposedly problematic), the pangolin sequences (same data set was used for all published genomes with some data still not submitted to the public database as well, preventing thorough investigation of the genome raw data) and finally the RmYN02 (again, data still missing from public database).

The authors of course propose that the RmYN02 is also fake and go back to the synonymous to non-synonymous mutations ratio, this time between the RmYN02 and RaTG13 coronaviruses. It will not surprise you that once again they found anomalous ratio of 57:1, respectively, in the S2 domain of the spike protein, “severely inconsistent with what is observed naturally.”

But the authors final conclusion is really interesting: the person(s) actually responsible for faking the bat RaTG13 coronavirus is/are the same involved in faking the pangolin viruses and the bat RmYN02 virus, leaving same tell-tale signs of fabrication.

Did not see that coming!

It will be interesting if these claims will be scrutinized in published scientific literature. But they certainly should be. We need to know the veracity of such claims. But let’s come back to that in a moment. The final conclusion by the authors is the most disturbing one.

Why fake viruses in the first place?

As we mentioned, the authors believe the obfuscation of evidence was already started last year. In their words: “Evidently, the cover-up had been planned and initiated before the COVID-19 outbreak. Therefore, the unleashing of the virus must be a planned execution rather than an accident.”

As a consequence of their convictions, the authors see SARS-CoV-2 as an “Unrestricted Bioweapon” and the COVID-19 as an “Unrestricted Biowarfare”.

These are very disturbing claims, proposing that China has deliberately attacked the world with a bioweapon. We don’t get it. What is not explained are the motives of such a biowarfare that is clearly borderless and would affect all the citizens of the world, including China. The greatest impact of the virus is not an immediate cause of death, but instead it is the economic impact, and potentially the unknown long-term damage to our bodies, both of which could curtail the entire global lifespan .

Perhaps one could argue that China prepared itself by either having a vaccine available already, or by producing herd immunity with a different related virus, or they have some medication at hand that works extremely effectively. Using the authors’ own deductive techniques, the extremely low numbers of infection and deaths would corroborate that (since April to October, less than 100 people have been reported to die of COVID-19 in China! These are truly unbelievable numbers in such populous country).

But China is not going to get out of this pandemic unscathed economically! The entire world is being affected economically and no matter what, these effects will also be impacting China. It would be hard to reconcile the logic behind this kind of biological attack on the entire world without expectation of self-inflicted damage. To us this looks like a desire to smear Chinese Communist Party to the greatest degree by the authors. Such gross claims should be substantiated by a high level evidence, and not just some assertions. It also detracts from any quality of evidence they might have presented against natural origin claims of SARS-CoV-2 as it poses the question what is the purpose behind their campaign: to get to the bottom of scientific truth, or to smear the image of China?

We agree though that all of the presented data by the authors and others about the quality of the discussed viruses indeed looks awfully suspicious - like a classic case of planting distracting information where only a few would or could ever be able to detect issues with the data - by which time the intended story is already deeply planted in the public narrative. To overcome the outcome of such a fake news approach would require constant repetition of the fallacy of the “evidence” to the same or greater extent as it was repeated in the first place when assumed to be true.

We do not know if this information is fake (this is beyond the scope of our expertise, we are passive science observers only stating opinions about the presented theories), but such a concerted effort to distort science and commit academic fraud would indeed be absolutely shocking.

Shocking enough that only an extremely desperate situation would persuade a group of people to act in such disingenuous scientific manner.

Like perhaps covering up the true origins of the pandemic?

We are more of the opinion that these discrepancies described are not born out of malice, but if anything, natural human incompetence, a dose of which is present in every single one of us, and will creep into every facet of a human construct. Perhaps the incompetence is there in the first place without the publisher of information even being aware of potential mistakes, or deliberate missteps are taken to cover up embarrassment associated with mistakes made due to past incompetence.

We are only humans. Sometimes humans will do dumb things by accident, sometimes on purpose thinking we are doing something right to benefit ourselves.

The good news (and the reason why we love science) is that science eventually uncovers the real evidence. You can plant fake information in the scientific world and indeed it can derail scientific endeavours by steering research in a wrong direction, sometimes for many years, but ultimately science is based on empirical evidence and slowly but relentlessly, it leads to accumulation of evidence.

Thus, no matter what the case might be, whether the story presented by the authors is true or not, the truth will come out if it continues to be researched and analyzed.

But the fact that such serious claims of fraud are being directed against a scientific community means that the scientific community itself should investigate these in great and comprehensive detail to either corroborate or discredit these claims.

Right now, we find this extremely lacking, with a bulk of the proposed evidence relegated to published online reports without proper scientific peer review and publication in actual scientific journals. Luckily, the authors have triggered some response from the scientific community, not positive one at that, and the authors claim they will respond to the critics. We look forward to this!

Let science prevail (not fail)!

This article has been produced by Merogenomics Inc. and edited by Jason Chouinard, B.Sc. Reproduction and reuse of any portion of this content requires Merogenomics Inc. permission and source acknowledgment. It is your responsibility to obtain additional permissions from the third party owners that might be cited by Merogenomics Inc. Merogenomics Inc. disclaims any responsibility for any use you make of content owned by third parties without their permission.

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