Part 2 of 3
The significance of the Master’s thesisThese findings of the thesis are significant in several ways.
First, in the light of the current coronavirus pandemic
it is evident the miners’ symptoms very closely resemble those of COVID-19 (Huang et al, 2020; Tay et al., 2020; M. Zhou et al., 2020).
Anyone presenting with them today would immediately be assumed to have COVID-19. Likewise, many of the treatments given to the miners have become standard for COVID-19 (Tay et al., 2020).
Second, the remote meeting with Zhong Nanshan is significant. It implies that the illnesses of the six miners were of high concern and, second, that a SARS-like coronavirus was considered a likely cause.Third, the abstract, the conclusions, and the general inferences to be made from the Master’s thesis contradict Zheng-li Shi’s assertion that the miners died from a fungal infection. Fungal infection as a potential primary cause was raised but largely discarded.
Fourth, if a SARS-like coronavirus was the source of their illness the implication is that it could directly infect human cells. This would be unusual for a bat coronavirus (Ge et al., 2013). People do sometimes get ill from bat faeces but the standard explanation is histoplasmosis, a fungal infection and not a virus (McKinsey and McKinsey, 2011; Pan et al., 2013).
Fifth, the sampling by the Shi lab found that bat coronaviruses were unusually abundant in the mine (Ge at al., 2016). Among their findings were two betacoronaviruses, one of which was RaTG13 (then known as BtCoV/4991). In the coronavirus world betacoronaviruses are special in that both SARS and MERS, the most deadly of all coronaviruses, are both betacoronaviruses. Thus they are considered to have special pandemic potential, as the concluding sentence of the Shi lab publication which found RaTG13 implied: “special attention should particularly be paid to these lineages of coronaviruses” (Ge at al., 2016). In fact, the Shi and other labs have for years been predicting that bat betacoronaviruses like RaTG13 would go pandemic; so to find RaTG13 where the miners fell ill was a scenario in perfect alignment with their expectations.The Mojiang miners passaging proposalHow does the Master’s thesis inform the search for a plausible origin of the pandemic?
In our previous article we briefly discussed how the pandemic might have been caused either by a virus collection accident, or through viral passaging, or through genetic engineering and a subsequent lab escape. The genetic engineering possibility deserves attention and is extensively assessed in an important preprint (Segreto and Deigin, 2020).
The origin of SARS-CoV-2 is still controversial. Comparative genomic analyses have shown that SARSCoV-2 is likely to be chimeric, most of its sequence being very close to the CoV detected from a bat, whereas its receptor binding domain is almost identical to that of CoV obtained from pangolins. The furin cleavage site in the spike protein of SARS-CoV-2 was previously not identified in other SARS-like CoVs and might have conferred the ability to cross species and tissue barriers. Chimeric viruses can be the product of natural recombination or genetic manipulation. The latter could have aimed to identify pangolins as possible intermediate hosts for bat-CoV potentially pathogenic for humans. Theories that consider a possible artificial origin for SARS-CoV-2 are censored as they seem to support conspiracy theories. Researchers have the responsibility to carry out a thorough analysis, beyond any personal research interests, of all possible causes for SARS-CoV-2 emergence for preventing this from happening in the future.
Several months have passed since the outbreak of SARS-CoV-2 in Wuhan, China, and its origin is still controversial. The theory that the Wuhan’s Huanan Seafood Wholesale Market was the first source for animal–human virus transmission has lost credibility. During the first phase of the epidemic in Wuhan, several hospitalized patients with confirmed SARS-CoV-2 infections had no link with the market.1 Unfortunately, the market was quickly closed and sanitized before enough animal samples could have been collected; the few market samples that did get collected exhibit only human-adapted SARS-CoV-2 and no traces of zoonotic predecessor strains.2-- Is Considering a Genetic-Manipulation Origin for SARS-CoV-2 a Conspiracy Theory That Must Be Censored?, by Rossana Segreto, University of Innsbruck, and Yuri Deigrin, Youthereum Genetics Inc.
We do not definitively rule out these possibilities. Indeed
it now seems that the Shi lab at the WIV did not forget about RaTG13 but were sequencing its genome in 2017 and 2018. However, we believe that the Master’s thesis indicates a much simpler explanation.We suggest, first, that inside the miners RaTG13 (or a very similar virus) evolved into SARS-CoV-2, an unusually pathogenic coronavirus highly adapted to humans. Second, that the Shi lab used medical samples taken from the miners and sent to them by Kunming University Hospital for their research. It was this human-adapted virus, now known as SARS-CoV-2, that escaped from the WIV in 2019.We refer to this COVID-19 origin hypothesis as the Mojiang Miners Passage (MMP) hypothesis.
Passaging is a standard virological technique for adapting viruses to new species, tissues, or cell types. It is normally done by deliberately infecting a new host species or a new host cell type with a high dose of virus. This initial viral infection would ordinarily die out because the host’s immune system vanquishes the ill-adapted virus. But, in passaging, before it does die out a sample is extracted and transferred to a new identical tissue, where viral infection restarts. Done iteratively, this technique (called “serial passaging” or just “passaging”) intensively selects for viruses adapted to the new host or cell type (Herfst et al., 2012).
At first glance RaTG13 is unlikely to have evolved into SARS-CoV-2 since RaTG13 is approximately 1,200 nucleotides (3.8%) different from SARS-CoV-2. Although RaTG13 is the most closely related virus to SARS-CoV-2, this sequence difference still represents a considerable gap. In a media statement evolutionary virologist Edward Holmes has suggested this gap represents 20-50 years of evolution and others have suggested similar figures.
We agree that ordinary rates of evolution would not allow RaTG13 to evolve into SARS-CoV-2 but we also believe that conditions inside the lungs of the miners were far from ordinary. Five major factors specific to the hospitalised miners favoured a very high rate of evolution inside them.
i) When viruses infect new species they typically undergo a period of very rapid evolution because the selection pressure on the invading pathogen is high. The phenomenon of rapid evolution in new hosts is well attested among corona- and other viruses (Makino et al., 1986; Baric et al., 1997; Dudas and Rambaut 2016; Forni et al., 2017).
ii) Judging by their clinical symptoms such as the CT scans,
all the miner’s infections were primarily of the lungs. This localisation likely occurred initially because the miners were exerting themselves and therefore inhaling the disturbed bat guano deeply. As miners, they may already have had damaged lung tissues (patient 3 had suspected pneumoconiosis) and/or particulate matter was present that irritated the tissues and may have facilitated initial viral entry.
In contrast,
standard coronavirus infections are confined to the throat and upper respiratory tract. They do not normally reach the lungs (Perlman and Netland, 2009).
Lungs are far larger tissues by weight (kilos vs grammes) than the upper respiratory tract. There was therefore likely a much larger quantity of virus inside the miners than would be the case in an ordinary coronavirus infection.Comparing a typical coronavirus respiratory tract infection with the extent of infected lungs in the miners from a purely mathematical point of view indicates the potential scale of this quantitative difference.
The human aerodigestive tract is approximately 20cm in length and 5cm in circumference, i.e. approximately 100 cm2 in surface area. The surface area of a human lung ranges from 260,000-680,000 cm2(Hasleton, 1972). The amount of potentially infected tissue in an average lung is therefore approximately 4500-fold greater than that available to a normal coronavirus infection. The amount of virus present in the infected miners, sufficient to hospitalise all of them and kill half of them, was thus proportionately very large.Evolutionary change is in large part a function of the population size.
The lungs of the miners, we suggest, supported a very high viral load leading to proportionately rapid viral evolution.
Furthermore, according to the Master’s thesis, the immune systems of the miners were compromised and remained so even for those discharged. This weakness on the part of the miners may also have encouraged evolution of the virus.
iii) The length of infection experienced by the miners (especially patients 2, 3 and 4) far exceeded that of an ordinary coronavirus infection. From first becoming too sick to work in the mine, patient 2 survived 57 days until he died. Patient 3 survived 120 days after stopping work. Patient 4 survived 117 days and then was discharged as cured. Each had been exposed in the mine for 14 days prior to the onset of severe symptoms; thus each presumably had nascent infections for some time before calling in sick (See Table 2 of the thesis).
In contrast, in ordinary coronavirus infections the viral infection is cleared within about ten to fourteen days after being acquired (Tay et al., 2020). Thus, unlike most sufferers from coronavirus infection, the hospitalised miners had very long-term bouts of disease characterised by a continuous high load of virus. In the cases of patients 3 and 4 their illnesses lasted over 4 months.
iv) Coronaviruses are well known to recombine at very high rates: 10% of all progeny in a cell can be recombinants (Makino et al., 1986; Banner and Lai, 1991; Dudas and Rambaut, 2016). In normal virus evolution the mutation rate and the selection pressure are the main foci of attention. But in the case of a coronavirus adapting to a new host where many mutations distributed all over the genome are required to fully adapt to the new host, the recombination rate is likely to be highly influential in determining the overall speed of adaptation by the virus population (Baric et al., 1997).
Inside the miners a large tissue was simultaneously infected by a population of poorly-adapted viruses, with each therefore under pressure to adapt. Even if the starting population of virus lacked any diversity, many individual viruses would have acquired mutations independently but only recombination would have allowed these mutations to unite in the same genome. To recombine, viruses must be present in the same cell. In such a situation the particularities of lung tissues become potentially important because the existence of airways (bronchial tubes, etc.) allows partially-adapted viruses from independent viral populations to travel to distal parts of the lung (or even the other lung) and encounter other such partially-adapted viruses and populations. This movement around the lungs would likely have resulted in what amounted to a passaging effect without the need for a researcher to infect new tissues. Indeed, in the Master’s thesis the observation is several times made that areas of the lungs of a specific patient would appear to heal even while other parts of the lungs would become infected.
v) There were also a number of unusual things about the bat coronaviruses in the mine. They were abnormally abundant but also there were many different kinds, often causing co-infections of the bats (Ge et al., 2016). Viral co-infections are often more infectious or more pathogenic (Latham and Wilson, 2007).As the WIV researchers remarked about the bats in the mine:
“we observed a high rate of co-infection with two coronavirus species and interspecies infection with the same coronavirus species within or across bat families. These phenomena may be owing to the diversity and high density of bat populations in the same cave, facilitating coronavirus intra- and interspecies transmissions, which may result in recombination and acceleration of coronavirus evolution.” (Ge et al., 2016).
The diversity of coronaviruses in the mine suggests that the miners were similarly exposed and that their illness may potentially have begun as co-infections.
Combining these observations, we propose that the miners’ lungs offered an unprecedented opportunity for accelerated evolution of a highly bat-adapted coronavirus into a highly human-adapted coronavirus and that decades of ordinary coronavirus evolution could easily have been condensed into months. However, we acknowledge that these conditions were unique. They and their scale have no exact scientific precedent we can refer to and they would be hard to replicate in a lab; thus it is important to emphasize that our proposal is fully consistent with the underlying principles of viral evolution as understood today.
In support of the MMP theory we also know something about the samples taken from the miners. According to the Master’s thesis, samples were taken from patients for “scientific research” and blood samples (at least) were sent to the WIV.
“In the later stage we worked with Dr. Zhong Nan Shan and did some sampling. The patient* tested positive for serum IgM by the WuHan Institute of Virology. It suggested the existence of virus infection” (p62 in the section “Comprehensive Analysis”.)
(*The original does not specify the number of patients tested.)
The Master’s thesis also states its regret that no samples for research were taken from patients 1 and 2, implying that samples were taken from all the others.
We further know that, on June 27th, 2012, the doctors performed an unexplained thymectomy on patient 4. The thymus is an immune organ that can potentially be removed without greatly harming the patient and it could have contained large quantities of virus. Beyond this the Master’s thesis is unfortunately unclear on the specifics of what sampling was done, for what purpose, and where each particular sample went.Given the interests of the Shi lab in zoonotic origins of human disease, once such a sample was sent to them, it would have been obvious and straightforward for them to investigate how a virus from bats had managed to infect these miners. Any viruses recoverable from the miners would likely have been viewed by them as a unique natural experiment in human passaging offering unprecedented and otherwise-impossible-to-obtain insights into how bat coronaviruses can adapt to humans.
The logical course of such research would be to sequence viral RNA extracted directly from unfrozen tissue or blood samples and/or to generate live infectious clones for which it would be useful (if not imperative) to amplify the virus by placing it in human cell culture. Either technique could have led to accidental infection of a lab researcher.Our supposition as to why there was a time lag between sample collection (in 2012/2013) and the COVID-19 outbreak is that the researchers were awaiting BSL-4 lab construction and certification, which was underway in 2013 but delayed until 2018.
We propose that, when frozen samples derived from the miners were eventually opened in the Wuhan lab they were already highly adapted to humans to an extent possibly not anticipated by the researchers. One small mistake or mechanical breakdown could have led directly to the first human infection in late 2019.
Thus, one of the miners, most likely patient 3, or patient 4 (whose thymus was removed), was effectively patient zero of the COVID-19 epidemic. In this scenario, COVID-19 is not an engineered virus; but, equally, if it had not been taken to Wuhan and no further molecular research had been performed or planned for it then the virus would have died out from natural causes, rather than escaped to initiate the COVID-19 pandemic.Evidence in favour of the MMP proposalOur proposal is consistent with all the principal undisputed facts concerning SARS-CoV-2 and its origin. The MMP proposal has the additional benefit of reconciling many observations concerning SARS-CoV-2 that have proven difficult to reconcile with any natural zoonotic hypothesis.
For instance, using different approaches, numerous researchers have concluded that the SARS-CoV-2 spike protein has a very high affinity for the human ACE2 receptor (Walls et al., 2020; Piplani et al., 2020; Shang and Ye et al., 2020; Wrapp et al., 2020). Such exceptional affinities, ten to twenty times as great as that of the original SARS virus, do not arise at random, making it very hard to explain in any other way than for the virus to have been strongly selected in the presence of a human ACE2 receptor (Piplani et al., 2020).
In addition to this, a recent report found that the spike of RaTG13 binds the human ACE2 receptor (Shang and Ye et al., 2020). We proposed above that the virus in the mine directly infected humans lung cells. The main determinant of cell infection and species specificity of coronaviruses is initial receptor binding (Perlman and Netland, 2009). Thus RaTG13, unlike most bat coronaviruses, probably can enter and infect human cells, providing biological plausibility to the idea that the miners became infected with a coronavirus resembling RaTG13.
Moreover, the receptor binding domain (RBD) of SARS-CoV-2, which is the region of the spike that physically contacts the human ACE2 receptor, has recently been crystallised to reveal its spatial structure (Shang and Ye et al., 2020). These authors found close structural similarities between the spikes of SARS-CoV-2 and RaTG13 in how they bound the human ACE2 receptor:“Second, as with SARS-CoV-2, bat RaTG13 RBM [a region of the RBD] contains a similar four-residue motif in the ACE2 binding ridge, supporting the notion that SARS-CoV-2 may have evolved from RaTG13 or a RaTG13-related bat coronavirus (Extended Data Table 3 and Extended Data Fig. 7). Third, the L486F, Y493Q and D501N residue changes from RaTG13 to SARS CoV-2 enhance ACE2 recognition and may have facilitated the bat-to-human transmission of SARS-CoV-2 (Extended Data Table 3 and Extended Data Fig. 7). A lysine-to-asparagine mutation at the 479 position in the SARS-CoV-2 RBD (corresponding to the 493 position in the SARS-CoV-2 RBD) enabled SARS-CoV to infect humans. Fourth, Leu455 contributes favourably to ACE2 recognition, and it is conserved between RaTG13 and SARS CoV-2; its presence in the SARS CoV-2 RBM may be important for the bat-to-human transmission of SARS-CoV-2″ (Shang and Ye et al., 2020). (italics added)
The significance of this molecular similarity is very great. Coronaviruses have evolved a diverse set of molecular solutions to solve the problem of binding ACE2 (Perlman and Netland, 2009; Forni et al., 2017). The fact that RaTG13 and SARS CoV-2 share the same solution makes RaTG13 a highly likely direct ancestor of Sars-CoV-2.
A further widely noted feature of SARS-CoV-2 is its furin site (Coutard et al., 2020). This site is absent from RaTG13 and other closely related coronaviruses. The most closely related virus with such a site is the highly lethal MERS (which broke out in 2012). Possession of a furin site enables SARS-CoV-2 (like MERS) to infect lungs and many other body tissues (such as the gastrointestinal tract and neurons), explaining much of its lethality (Hoffman et al., 2020; Lamers et al., 2020). However, no convincing explanation for how SARS-CoV-2 acquired this site has yet been offered. Our suggestion is that it arose due to the high selection pressure which existed in the miner’s lungs and which in general worked to ensure that the virus became highly adapted to the lungs. This explanation, which encompasses how SARS-CoV-2 came to target lung tissues in general, is an important aspect of our proposal.
The implication is therefore that the furin site was not acquired by recombination with another coronavirus and simply represents convergent evolution (as suggested by Andersen et al., 2020).
An intriguing alternative possibility is that SARS-CoV-2 acquired its furin site directly from the miner’s lungs. Humans possess an epithelial sodium channel protein called ENaC-a whose furin cleavage site is identical over eight amino acids to SARS-CoV-2 (Anand et al., 2020). ENaC-a protein is present in the same airway epithelial and lung tissues infected by SARS-CoV-2. It is known from plants that positive-stranded RNA viruses recombine readily with host mRNAs (Greene and Allison, 1994; Greene and Allison, 1996; Lommel and Xiong, 1991; Borja et al., 2007). The same evidence base is not available for positive-stranded animal RNA viruses, (though see Gorbalenya, 1992) but if plant viruses are a guide then acquisition of its furin site via recombination with the mRNA which encodes ENaC-a by SARS-CoV-2 is a strong possibility.
A further feature of SARS-CoV-2 has been the very limited adaptive evolution of its genome since the pandemic began (Zhan et al., 2020; van Dorp et al., 2020; Starr et al., 2020). It is a well-established principle that viruses that jump species undergo accelerated evolutionary change in their new host (e.g. Baric et al., 1997). Thus,
SARS and MERS (both coronaviruses) underwent rapid and readily detectable adaptation to their new human hosts (Forni et al., 2017; Dudas and Rambaut, 2016). Such an adaptation period has not been observed for SARS-CoV-2 even though it has now infected many more individuals than SARS or MERS did. This has even led to suggestions that the SARS-CoV-2 virus had a period of cryptic circulation in humans infections that predated the pandemic (
Chaw et al., 2020). The sole mutation consistently observed to accumulate across multiple studies is a D614G substitution in the spike protein (e.g. Korber et al., 2020). The numerically largest analysis of SARS-CoV-2 genomes, however, found no evidence at all for adaptive evolution, even for D614G (van Dorp et al., 2020).
The general observation is therefore that Sars-CoV-2 has remained functionally unchanged or virtually so (except for inconsequential genetic changes) since the pandemic began. This is a very important observation. It implies that SARS-CoV-2 is highly adapted across its whole set of component proteins and not just at the spike (Zhan et al., 2020). That is to say, its evolutionary leap to humans was completed before the 2019 pandemic began.
It is hard to imagine an explanation for this high adaptiveness other than some kind of passaging in a human body (Zhan et al., 2020). Not even passaging in human cells could have achieved such an outcome.Two examples illustrate this point. In a follow up to Shang and Ye et al., (2020), a similar group of Minnesota researchers identified a distinct strategy by which the spike (S) protein (which contains the receptor bind domain; RBD) of SARS-CoV-2 evades the human immune system (Shang and Wan et al., 2020). This strategy involves more effective hiding of its RBD, but it implies again that the spike and the RBD evolved in tandem and in the presence of the human immune system (i.e. in a human body and not in tissue culture).
The Andersen authors, in their critique of a possible engineered origin for SARS-CoV-2, also stress the need for passaging in whole humans:“Finally, the generation of the predicted O-linked glycans is also unlikely to have occurred during cell-culture passage, as such features suggest the involvement of an immune system” (Andersen et al., 2020).
The final point that we would like to make is that the principal zoonotic origin thesis is the one proposed by Andersen et al. Apart from being poorly supported this thesis is very complex. It requires two species jumps, at least two recombination events between quite distantly related coronaviruses and the physical transfer of a pangolin (having a coronavirus infection) from outside China (Andersen et al., 2020). Even then it provides no logical explanation of the adaptedness of SARS-CoV-2 across its whole genome or why the virus emerged in Wuhan.
By contrast, our MMP proposal requires only the one species jump, which is documented in the Master’s thesis. Although we do not rule out a possible role for mixed infections in the lungs of the miners, nor the possibility of recombination between closely related variants in those lungs, nor the potential acquisition of the furin site from a host mRNA,
only mutation was needed to derive SARS-CoV-2 from RaTG13. Hence our attention earlier to the figure from P. Zhou et al., 2020 showing that RaTG13 is the most closely related virus to SARS-CoV-2 over its entire length. This extended similarity is perfectly consistent with a mutational origin of SARS-CoV-2 from RaTG13.In short, the MMP theory is a plausible and parsimonious explanation of all the key features of the COVID-19 pandemic and its origin. It accounts for the propensity of SARS-CoV-2 infections to target the lungs; the apparent preadapted nature of the virus; and its transmission from bats in Yunnan to humans in Wuhan.Further questionsThe hypothesis that SARS-CoV-2 evolved in the Mojiang miner’s lungs potentially resolves many scientific questions about the origin of the pandemic. But it raises others having to do with why this information has not come to light hitherto. The most obvious of these concern the actions of the Shi lab at the WIV.
Why did the Shi lab not acknowledge the miners’ deaths in any paper describing samples taken from the mine (Ge et al., 2016 and P. Zhou et al., 2020)? Why in the title of the Ge at al. 2016 paper did the Shi lab call it an “abandoned” mine? When they published the sequence of RaTG13 in Feb. 2020, why did the Shi lab provide a new name (RaTG13) for BtCoV/4991 when they had by then cited BtCoV/4991 twice in publications and once in a genome sequence database and when their sequences were from the same sample and 100% identical (P. Zhou et al., 2020)? If it was just a name change, why no acknowledgement of this in their 2020 paper describing RaTG13 (Bengston, 2020)? These strange and unscientific actions have obscured the origins of the closest viral relatives of SARS-CoV-2, viruses that are suspected to have caused a COVID-like illness in 2012 and which may be key to understanding not just the origin of the COVID-19 pandemic but the future behaviour of SARS-CoV-2.These are not the only questionable actions associated with the provenance of samples from the mine.
There were five scientific publications that very early in the pandemic reported whole genome sequences for SARS-CoV-2 (Chan et al., 2020; Chen et al., 2020; Wu et al., 2020; P. Zhou et al., 2020; Zhu et al., 2020). Despite three of them having experienced viral evolutionary biologists as authors (George Gao, Zheng-li Shi and Edward Holmes) only one of these (Chen et al., 2020) succeeded in identifying the most closely related viral sequence by far: BtCoV/4991 a viral sequence in the possession of the Shi lab at the WIV that differed from SARS-CoV-2 by just 5 nucleotides.As we noted in our earlier article, the most important of the questions surrounding the origins of SARS-CoV-2 could potentially be resolved by a simple examination of the complete lab notebooks and biosafety records of relevant researchers at the WIV. Now that a credible and testable lab escape hypothesis exists this task becomes potentially much easier. This moment thus represents an opportune one to renew that call for an independent and transparent investigation of the WIV.
In requesting an investigation we are aware that no scientific institution anywhere has made a comparable request. We believe that this failure undermines public trust in a “scientific response” to the pandemic. Instead, the scientific establishment has labeled the lab escape theory a “rumor“, an “unverified theory” and a “conspiracy” when its proper name is a hypothesis. By taking this stance the scientific establishment has given the unambiguous message that scientists who take the possibility of a lab origin seriously are jeopardising their careers. Thus, while countless scientific publications on the pandemic assert in their introductions that a zoonotic origin for SARS-CoV-2 is a matter of fact or near-certainty (and Andersen et al has 860 citations as of July 14th), there is still not one published scientific paper asserting that a lab escape is even a credible hypothesis that deserves investigation.
Anyone who doubts this pressure should read the interview with Birger Sørensen in Norway’s Minerva magazine in which Sørensen discusses the “reluctance” of journals to publish his assessment that the existence of a virus that is “exceptionally well adjusted to infect humans” is “suspicious” and “cannot have evolved naturally”. The source of this reluctance, says Sørensen, is not rationality or scientific evidence. It results from conflicts of interest. This mirrors our experience. To find genuinely critical analysis of COVID-19 origin theories one has to go to Twitter, blog posts, and preprint servers. The malaise runs deep when even scientists start to complain that they don’t trust science.Therefore we hypothesise the reconstructed historical aetiology of the Spike as follows:
In 2008, Dr Zheng-Li Si and WIV colleagues successfully demonstrated technical capabilities to interchange RBD’s between bat SARS-like and human SARS viruses. Building upon this, the 2010 work (Hou et al, 2010) perfected the ability to express receptors on human cells. On these foundations, the central Gain of Function work that underpins the functionalities of SARS-CoV-2 took place, carrying the WIV spike and plasmid materials to bond successfully to a UNC Chapel Hill human epithelial cell-line. This work (Menachery et al) produced a highly infectious chimeric virus optimised to the human upper respiratory tract. In convergent support of this hypothesis, both Lu (Lu et al, 2020) and Jia (Jia et al, 2020) have now, in January and April 2020, shown that SARS-CoV-2 has a bat SARS-like backbone but is carrying an RBD from a human SARS and Zhan et al have, like us, noted unusual adaption to humans from the first isolate. In the 2015 Chapel Hill work it was only ACE2 receptors that were discussed. However, in 2018 Zhou P. et al demonstrated capabilities to clone other receptors like APN and DPP4 and to test and compare these against the (intestine) tissue specific SADS-CoV identified. Then, in the 2019-20 Covid-19 pandemic, profuse symptoms indicating compromise of the bitter/sweet receptors are reported.
Taken all together, this implies that by employing insights gained after 2015, as just deduced, a further optimization of the 2015 chimeric virus for additional binding to receptors/co-receptors such as bitter/sweet specific upper airway epithelia receptors occurred. That would help to explain the otherwise puzzling high infectivity and pathology associated with SARS-CoV-2 and hence also help to explain the social epidemiology of its spread.-- The Evidence which Suggests that This Is No Naturally Evolved Virus: A Reconstructed Historical Aetiology of the SARS-CoV-2 Spike, by Birger Sørensen, Angus Dalgleish & Andres Susrud
We nevertheless hope that journalists will investigate some of the conflicts of interest that are keeping scientists and institutions from properly investigating the lab escape hypothesis.
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