Taken from Latham & Wilson’s piece:
Conceding that SARS-CoV-2 was preadapted, some have argued that SARS-CoV-2 is a ‘generalist’ virus (Frutos et al., 2020). There seems to be very little evidence for this. SARS-CoV-2 does not infect most mammal species (Kock and Caceres-Escobar, 2022). It can be actively transmitted by far fewer species still, and, when those few do transmit the virus, adaptive mutations occur (Gu et al., 2021; Sawatzki et al., 2021; Tan et al., 2022). In short, SARS-CoV-2 has not proven preadapted to any mammalian host species tested so far (except humans) and so it bears none of the hallmarks of a generalist virus.
Mink
Linx, House Cats, Cougars, Lions, Tigers, Snow Leopards
Hyenas
Dogs
Mule Deer, White-tailed Deer
Hamsters
Ferrets
Giant Anteaters
HIppopotamuses
Manatees
Otters
Binturongs
Beavers
Primates, including us.
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Yeah it’s kinda irrelevant that it doesn’t infect “most” mammals. There’s quite a lot of those. But it still infects numerous, and among them are ones held as pets, domesticated for use, or wildlife typically encountered, hunted/traded etc.
It’s more of an open question how easily it jumps from individual to individual for each of these species.
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That’s now synonymous with ‘suspect’.
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I’m educated in virology and you don’t believe me, so that’s obviously not a criterion you are using. The only criterion you apply consistently is if someone says something you wish to be true.
Please stop pretending that you are behaving objectively.
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Which is exactly what SARS-CoV-2 did.
I don’t see any indication of that in the phylogeny.
That’s very rapid evolution. Note that you are conflating mutation with fixation of a mutation. They aren’t the same thing.
I think you just made that up. Which other zoonoses have you studied in detail?
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Not surprisingly, we do not have a full accounting. For instance, Covid has been pretty rampant in wild deer. Does that mean other ruminants are susceptible? Moose? Elk? Probably, but would we necessarily know?
So there are clear counter-examples to the Latham & Wilson argument that the basal SARS-CoV-2 was specifically adapted to humans. It is something of a straw man to argue against most mammal species being vulnerably to infection, because, as with all such viruses, it would be at best many mammal species.
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Yes, I believe so. The detail in contention here is whether the Wuhan market was the actual site of the original spillover(s); or whether the original spillover happened elsewhere and only later ended up in the Wuhan market where it caused a superspreader event.
However, how is this relevant to zoonosis? The authors of the “independent science article” say that if the latter scenario is true, then the fact that the outbreak was first detected at a market where a lot of live wild animals were sold isn’t - in and of itself - evidence for a zoonotic spillover. That may be true, but I don’t see how the latter scenario would preclude zoonosis; and again, as I pointed out before, the authors (who did the MOA analysis) that argue for the latter scenario where virus circulated long before it arrived in Wuhan also entertain zoonosis.
Firstly, that eight mutation (which happened in the spike protein) was present in samples collected 31 days after the first sample was collected in 24 December 2019 at Wuhan. This mutant likely happened earlier before it was collected in samples. How is this not fast enough? What exactly do you expect? That (every single one of) the first mutation(s) after a spillover must (all) be positive with respect to fitness? Why?
This logic relies on the assumption that either:
(1) mutations arise out of a need, i.e. when a virus enters a new host species, it requires mutations that will enable it to spread more efficiently, thus these mutations will happened immediately at the moment of first contact; or…
(2) Selection is the only mechanism that affects changes in allele frequencies (genetic drift and the founder effect aren’t a thing). So, we wouldn’t expect neutral or even (slightly) deleterious mutations to be involved in the earliest phase of an outbreak after a spillover; or…
(3) Both
These are faulty assumptions. Beneficial mutations don’t arise out of a need and genetic drift & founder effects are very relevant, especially during the early days of the pandemic when the population size was small and every time the virus spread to a new area or continent, you are dealing with a founder population. Selection is obviously important, but it’s not the only relevant factor. There is actually a whole paragraph dedicated to this subject in one of the papers you cited (Kumar et al. 2021) emphasis mine. I would recommend actually reading your own citations.
Episodic Evolution and Selection
The order of some mutations in the mutational history is not established with high BCLs, for example, the relative order of ε1, ε2, and ε3 mutations. This is because the three ε variants almost always occur together (7,624 genomes), and the intermediate combinations of ε variants were found in only 42 genomes. Similarly, the count of genomes harboring all three β variants (22,739 genomes) far exceeded those with two or fewer β variants (201 genomes). There is a strong temporal tendency of variants to be sampled together (e.g., ε1–ε3 and α1a–α1d), suggesting an episodic spread of variants (Wald–Wolfowitz run tests P ≪ 0.01; see Materials and Methods) that does not allow for determining the precise order of some mutations’ appearance. Episodic variant spread may be caused by founder effects, positive selection, or both (e.g., MacLean et al. 2021). It may also be an artifact of highly uneven regional and temporal genome sequencing that will produce a biased representative sample of the actual worldwide population (fig. 1b).
In this mutation history, the ratio of nonsynonymous to synonymous changes (N/S) is 1.9, which is almost ten times larger than their ratio of 0.18 for the inferred proCoV2 and observed Bat CoV proteins. The McDonald–Kreitman test (McDonald and Kreitman 1991) rejected the similarity of molecular evolutionary patterns observed within the SARS-CoV-2 population (29KG data set) and between human proCoV2 and the bat coronavirus. However, the selective interpretation of such a difference is complicated by the fact that polymorphisms in SARS-CoV-2 genomes are affected by molecular mechanisms (e.g., RNA editing) (Giorgio et al. 2020; Rice et al. 2021), not just selection, and slightly deleterious alleles can become common when there is a population expansion (Casals and Bertranpetit 2012). Furthermore, selection may have played a significant role during the divergence of human CoV-2 and bat CoV sequences (MacLean et al. 2021; Martin et al. 2021; Tegally et al. 2021). Nevertheless, N/S patterns derived from common variants show that molecular evolutionary patterns observed within SARS-CoV-2 genomes infecting humans differ from those spanning the divergence between the bat RaTG13 and SARS-CoV-2 genomes, even though positive selection in the early SARS-CoV-2 pandemic history may have been limited (Chiara et al. 2021; MacLean et al. 2021).
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It is relevant to zoonosis in the sense that if the Huanan market is not the epicenter of the epidemic, the proponents of the zoonosis theory loose their best trump card.
This was not observed for SARS- CoV, which, unlike SARS-CoV2, evolved very rapidly during the early stages of the epidemic. See figure 1 of the article below.
No. SARS-CoV-1 evolved more rapidly, but claiming that 2 did not is ludicrous, particularly given that it doesn’t have a complete or representative sample. Moreover, this preprint was posted in 2020; almost 3 years later, it hasn’t been published anywhere as far as I can see. Given the low bar for publishing COVID papers, that indicates that it’s pretty bad.
Remember, I’m a virologist and you wrote:
That wasn’t the criterion you really used, though, was it? 
Real scientists are trying to learn what happened, not win a debate. There are no “trump cards,” even figuratively.
I already mentioned that argument from the “independent science article” right in the following sentences and after that I also point out that this doesn’t preclude zoonosis either.
However, how is this relevant to zoonosis? The authors of the “independent science article” say that if the latter scenario is true, then the fact that the outbreak was first detected at a market where a lot of live wild animals were sold isn’t - in and of itself - evidence for a zoonotic spillover. That may be true, but I don’t see how the latter scenario would preclude zoonosis; and again, as I pointed out before, the authors (who did the MOA analysis) that argue for the latter scenario where virus circulated long before it arrived in Wuhan also entertain zoonosis.
Furthermore, I don’t know about you but this isn’t a game to me. This isn’t a card game where if one side looses its - quote - “best trump card” that means the other side automatically wins or at the very least deserves more credence. That’s not how this works. Each hypothesis must stand on its own merit. What is the evidence for that the virus was genetically engineered? We have it’s genome and genetic engineering would leave its marks, but despite argument to the contrary, none have survived scrutiny so far. A “weaker” version of the lab leak would say that while it’s just a natural virus that was collected by lab workers who were careless and it accidentally escaped (without any artificial alteration). In this case the genome wouldn’t provide any clues, but then (just like in the former genetic engineered version of the lab leak) you would have to propose an implausibly huge conspiracy that involves a whole bunch of people internationally working together to hide the evidence. Not just the Chinese government. The larger the scope of the conspiracy, the faster they are exposed. And yet, here we are, three years later.
When you said “well-adapted”, I thought you meant that the virus was able to infect humans and spread effectively (live-on-arrival is a prerequisite of any spillover that results in a pandemic). Now it seems that the argument is that SARS-CoV-2 was seemingly TOO well-adapted, almost like it had adapted to infecting humans for a while similar to SARS-CoV of 2003 in the later phases of its respective pandemic.
Alright, red flags. One of the authors is Alina Chan who wrote the book “Viral: The Search for the Origin of COVID-19” along with Matt Ridley (who also has a known history of climate change denial). Neither of these people are actually virologists though. Secondly, this is a preprint (not peer reviewed). Not just that. It was put up all the way back in May 2020… almost three years ago by now. Surely enough for it be reviewed and published, but it wasn’t. Is there a reason for this? Sure enough, the study is very flawed. One commenter is Robert F. Garry of Tulane University (an actual virologist) who wrote an extensive breakdown of this three months ago. I will mostly summarize what he said here:
In the figure above (A). They note that SARS-CoV of 2003 (SARS-1 for short) exhibited large genetic diversity among the 11 genomes of the early to mid phase of the epidemic (blue). In contrast, the later phase there was low genetic diversity, which is comparable to the early phase of SARS-CoV-2 (SARS-2) pandemic from Dec 2019 to March 2020. The Authors interpret this data as indicating that SARS-1 underwent rapid evolutionary adaption in the early phases, and with a lower substitution rate in the later phase after it was well-adapted to humans. In contrast, SARS-2 didn’t undergo rapid adaptation and maintained low genetic variation indicating it was adapted to humans on the same level as SARS-1 in its later phase.
This conclusion is flawed. The 11 genomes (blue dots) are NOT part of the same lineage that spilled over into humans in 2003. These first eleven cases of SARS-CoV in 2003 were distributed across a wide area (from Foshan to Dongguan in the Pearl River Delta area of southern China) and time (4 months). These early cases were not linked, i.e. originating via human-to-human transmission from the same human patient zero, and they also did not sustain human-to-human transmissions (unlike in the latter phase). Other studies have already shown that SARS-1 had experienced diversification in animals before the first human cases. Thus, the high genetic diversity among these 11 isolates isn’t an indication of rapid adaptation while it was transmitting among humans. Instead, these early cases reflect multiple independent spillovers from widespread and diverse populations of SARS-1, having diverged from each other and circulated among wild animals for a long time prior. This is similarly observed in other viruses (e.g. LASV) which has experiences thousands of spillovers every year but human-to-human transmission is limited. Subsequently, these cases exhibit high genetic diversity because these come from a wild reservoir with an established diverse gene pool.
In contrast, low diversity is the result of a few lineages that are able to sustain human-to-human transmission (producing a genetic bottle-neck). This is seen in the latter phase of SARS-1 outbreak. This involved a variant that experienced a 27-nt deletion in orf 8. A physician was exposed at his hospital in Guangzhou who later traveled to Hong Kong. There he stayed at one hotel, transmitting the virus to 16 other guests, which subsequently transmitted it further among humans in Hong Kong, Toronto, Singapore and Vietnam. Eventually it infected over 8000 people in 25 countries on five continents (killing at least 774). These cases exhibited minimal genetic variability because these were all transmitted from person to person coming from one individual. This is similarly seen in Ebola outbreaks, wherein a spillover can sustain large number of human-to-human transmissions, which exhibit lower genetic diversity.
This means that using the diversity among the 11 (blue dots) genomes to calculate the substitution rate of SARS-1 during the first 3 months in 2003 is erroneous. The diversification actually happened over during a longer time period within the animal reservoir, likely over a period of years (not 3 months) starting long before to the first detected case in humans. Thus, comparing this calculated rate with the rates seen in the later phase of SARS-1 and the pandemic of SARS-2 is completely flawed. When accounting for progenitor viruses among the wild reservoir shows that the substitution rate in the genomes within the SARS-1-like clade varies up to 6-fold, with median rates of 4.0x10^-4 and 1.91x0^-3. These are actually slightly lower (not faster) than the rates observed in the SARS-2-like clade.
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Ouch. That’s really bad, @Giltil.
That would be a very good explanation for why it never has been published. I dismissed it based on small sample size, but what you describe is far, far worse.
Interesting that they aren’t challenging the fact that half of the earliest infections were amongst workers at the Wuhan market or those adjacent to the market. They are also not disputing the fact that the virus was found in animal cages and associated with equipment used on animals. They are also not disputing the fact that SARS-CoV-1 was also associated with a wet market.
Speaking of a Bayesian approach:
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The Wuhan market was the center of the epidemic. They even found the virus in animal cages that held animals known to be susceptible to the virus. Half of the earliest cases were from workers at the market or those adjacent to the market.
The evidence isn’t lacking for a zoonotic origin. The evidence for zoonotic origin is everywhere.
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It does infect racoon dogs, and cages that held racoon dogs at the Wuhan market tested positive for the virus.
There is also tons of evidence for humans and minks spreading the virus between each other.
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This is typical of the abysmal logic used by Lab Leak believers.
The Wuhan Institute of Virology was not the epicenter of the epidemic. Not even the truest believers in the Lab Leak claim that.
So, by your “logic”, wouldn’t that mean the Lab Leak is no longer a viable hypothesis? That is to say, you think it’s a big problem for those who accept zoonosis if they lose a “trump card” that the Lab Leakers have never had to begin with. The logic of such a claim is not apparent.
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Okay, but what do you do with the fact that samples taken from vegetable stalls also tested positive for the virus?
Many proponents of the lab leak think that the very first human to be infected by SARS2 was working at the WIV.
How is that a problem? Please explain the thought process, such as it is, behind that question.