Virus not from Animals(?)

SelfSim

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'Virus did NOT come from animals in Wuhan market', landmark study claims as Beijing thwarts global efforts to establish the source of Covid-19
The Mail on Sunday can reveal that analysis of the coronavirus by specialist biologists suggests that all available data shows it was taken into the market by someone already carrying the disease.

They also say they were ‘surprised’ to find the virus was ‘already pre-adapted to human transmission’, contrasting it to another coronavirus that evolved rapidly as it spread around the planet in a previous epidemic.
The paper here more or less confirms the news report:
According to the Chinese CDC’s website, accessed on April 27, 2020, SARS-CoV-2 was detected in environmental samples at the Huanan seafood market, and the Chinese CDC suggested that the virus originated from animals sold there (51). However, phylogenetic tracking suggests that SARS-CoV-2 had been imported into the market by humans.
They conclude:
It is therefore unlikely for the January market isolates, which all share 99.9-100% genome and S identity with a December human SARS-CoV-2, to have originated from an intermediate animal host, particularly if the most recent common ancestor jumped into humans as early as October, 2019 (54,55). The SARS-CoV-2 genomes in the market samples were most likely from humans infected with SARS-CoV-2 who were vendors or visitors at the market. If intermediate animal hosts were present at the market, no evidence remains in the genetic samples available.
.. and then:
It would be curious if no precursors or branches of SARS-CoV-2 evolution are discovered in humans or animals.
 

SelfSim

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I don't think they explicitly say it .. but it sort of looks like maybe SARS-1 may have been mutating, undetected, amongst humans, since the last documented case in 2004 .. but how did SARS-Cov-2 get to be a better match with known bat coronaviruses than it is with SARS-Cov-1?
 
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FrumiousBandersnatch

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From what I heard, there were very few testable animal remains from the market, as it was blitzed as soon as it became suspect.

But if a trader had bought infected animals from a hunter/trapper/poacher who had been handling the creatures prior to them being brought to market, it's likely that both would be infected, and the trader might well have been infected by his source. All speculation.

What is clear is that a number of labs have said that the genetics of the virus are more characteristic of natural mutations than experimental mutations.
 
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Tanj

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I don't think they explicitly say it .. but it sort of looks like maybe SARS-1 may have been mutating, undetected, amongst humans, since the last documented case in 2004

Nope.

but how did SARS-Cov-2 get to be a better match with known bat coronaviruses than it is with SARS-Cov-1?

Because your first statement is incorrect. It's a new virus, and it came from some animals, probably bats. Possibly didn't originate from the wet market, but that's just not that interesting or earth shattering. Zoonoses occur, there's been dozens of these outbreaks over the years.
 
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SelfSim

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From what I heard, there were very few testable animal remains from the market, as it was blitzed as soon as it became suspect.
Makes sense .. the report says:
Details about the sampling are sparse: 515 out of 585 samples are environmental samples, and the other 70 were collected from wild animal vendors; it is unclear whether the latter samples are from animals, humans, and/or the environment. Only 4 of the samples, which were all environmental samples from the market, have passable coverage of SARS-CoV-2 genomes for analysis.

FrumiousBandersnatch said:
But if a trader had bought infected animals from a hunter/trapper/poacher who had been handling the creatures prior to them being brought to market, it's likely that both would be infected, and the trader might well have been infected by his source. All speculation.
Sure .. and if so, it looks like that infection could have happened around the November/December timeframe (1st patient was December) which would likely make early October the date they think when the most recent common ancestor transferred the virus to humans (ie: maybe the trapper?)

FrumiousBandersnatch said:
What is clear is that a number of labs have said that the genetics of the virus are more characteristic of natural mutations than experimental mutations.
That seems to be pretty well agreed but as they say:
Even the possibility that a non-genetically-engineered precursor could have adapted to humans while being studied in a laboratory should be considered, regardless of how likely or unlikely.
The Director of the Wuhan lab (aka: the 'bat-woman'), said she checked the first human isolates she was given and found they didn't match the animal sequences she had in her lab (whereupon she said she breathed a sigh of relief). Presumably she still has that comparison data(?) Pity she didn't think of testing her staff too, at that same time? They could also interrogate the staff as to whether or not they visted the markets around those timeframes also, I suppose.
 
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SelfSim

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Nope. .. Because your first statement is incorrect.
Ok .. acknowledged.

Tanj said:
.. It's a new virus, and it came from some animals, probably bats. Possibly didn't originate from the wet market, but that's just not that interesting or earth shattering. Zoonoses occur, there's been dozens of these outbreaks over the years.
Sure.
So, the report also says:
The CoV that is most closely related to SARS-CoV-2 is RaTG13, a bat CoV that was identified at the Wuhan Institute of Virology and originally isolated from the Yunnan Province of China (45). RaTG13 shares 96.2% genome identity with the Wuhan-Hu-1 SARS-CoV-2 isolate.
Then it says:
.. it is plausible for SARS-CoV-2 S to have evolved its broad species tropism naturally in bats or a wide range of intermediate species. The SARS-CoV-2 S is predicted to bind to ACE2 from potentially more than 100 diverse species (4648), and was demonstrated to bind more strongly than the SARS-CoV S to ACE2 from both bat and human (33). The S of RaTG13 is also capable of binding to human ACE2 although the virus does not infect humans (49).
So if I understand this correctly(?) the 'spikes' and their ACE-2 binding capabilities have been with these bats for a while, but the genome (capsid/RNA) itself, looks like the part which has mutated to the new strain?
 
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Tanj

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So, the report also says:
The CoV that is most closely related to SARS-CoV-2 is RaTG13

Right, that's the closest we have. Doesn't mean they are specially related, it just means that RaTG13 is the virus we happened to pull out of the virus universe earlier that is most similar. If we didn't have RaTG13 then some other virus that we isolated from somewhere some when would be "the most similar"

RaTG13 isn't the father of cov2, it's cov2's second cousin, 3 times removed.

So if I understand this correctly(?) the 'spikes' and their ACE-2 binding capabilities have been with these bats for a while, but the genome (capsid/RNA) itself, looks like the part which has mutated to the new strain?

Umm... I'm not sure what you mean, but I think it's related to your previous comment? There's no direct line from RaTG13 to cov2...or at least there absolutely no way to determine that.

At the end of the day, it's of passing academic interest and that's it. Knowing the "true" source of the virus doesn't affect anything.
 
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SelfSim

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...
So if I understand this correctly(?) the 'spikes' and their ACE-2 binding capabilities have been with these bats for a while, but the genome (capsid/RNA) itself, looks like the part which has mutated to the new strain?
Ok so it looks like it has to do with the presence/absence of the correct protein sequence for cleavage. More info here.
That site then explains:
The furin cleavage site might have been acquired by recombination with another virus possessing that site. This event could have happened thousands of years ago, or weeks ago. Upon introduction into a human – likely in an outdoor meat market – the virus began its epidemic spread.
...
Acquisition of the furin cleavage site might be viewed as a ‘gain of function’ that enabled a bat CoV to jump into humans and begin its current epidemic spread.
 
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Tanj

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Ok so it looks like it has to do with the presence/absence of the correct protein sequence for cleavage. More info here.
That site then explains:

That's one bit. The affinity and aividity of binding is another, there's a bunch of other perfect storm stuff this virus has, and you'd be hard pressed to point at any one of them and shout eureka...which what you seem to want to do? Sorry, biology is messy.
 
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SelfSim

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That's one bit. The affinity and aividity of binding is another, there's a bunch of other perfect storm stuff this virus has, and you'd be hard pressed to point at any one of them and shout eureka...which what you seem to want to do? Sorry, biology is messy.
Yes .. I was just reading the comments at the bottom of that page .. and yep .. I can see the complexity in this. There are clearly multiple levels these things can operate at, in order to cause ('successful') infection.
Someone there even cites a reference which ventures into postdicting that the human infection capable virus may have come into existence around the 1950s .. (then, of course, someone else 'corrects' them and recalculates that it was the 1980s! Lol.)
 
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SelfSim

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Here's another recent study which more or less rules out that SARS-Cov-2 evolved directly from Pangolins:
Pangolins May Not Have Been The Intermediary Host of SARS-CoV-2 After All
The current hypothesis goes something like this: SARS-CoV-2 passed through a mystery animal host in its suspected evolutionary journey from bats to humans. Critically endangered pangolins have been a favoured candidate for this intermediary host, but now a genomic analysis led by geneticist Ping Liu from Guangdong Academy of Science in China has provided evidence this may not be the case.
However, it does make the case that recombination events (affecting that cleavage site) amongst coronaviruses in multiple animals in nature, is likely.
From the study paper
Are pangolins the intermediate host of the 2019 novel coronavirus (SARS-CoV-2)?:
Recombination analysis showed that S gene of pangolin-CoV-2020 might be constructed by fragment from Bat-CoV-ZC45 or Bat-CoV-ZXC21 and fragment from Bat-CoV-RaTG13. Interestingly, the cleavage site between S1 and S2 in SARS-CoV-2 had multiple insertions (i.e. PRRA), compared with those of Bat-CoV-RaTG13 and pangolin-CoV-2020, which may result from an additional recombination event. A new study reported a novel bat-derived coronavirus (RmYN02) identified from a metagenomics analysis of samples from 227 bats collected from the Yunnan province in China between May and October of 2019. Although RmYN02 showed a relatively low nucleotide sequence identity (93.3%) to SARS-CoV-2, it had a similar manner of the insertion of multiple amino acids at the junction site of the S1 and S2 subunits of the S protein as SARS-CoV-2, providing strong evidence that such insertion events can occur in nature [11]. Thus, these data suggest that SARS-CoV-2 originated from multiple naturally occurring recombination events among viruses present in bats and other wildlife species.
.. beats me how Bear Grylls is still alive and kicking!?
 
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SelfSim

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Does any of this have any bearing on how fast we can develop a vaccine?
I think pursuing a deeper understanding how a specific novel virus evolved and how those steps affects the way it spreads disease, (compared with other known similar virus types), directly impacts the technologies used in the production of a vaccine.
Two of the key causes of failure of a vaccine are inadequacies of the technologies used in the vaccine itself, directly resulting in incomplete efficacy and; impacts of assumptions made about the condition of a target recipient's genetic/health status. Many/most vaccines fail during the preclinical phase (ie: 'The probability of success for an infectious disease vaccine candidate to pass preclinical barriers and reach Phase I of human testing is 41-57%').
So knowing such information before one sets out designing a vaccine can significantly impact the speed (and effectiveness) of its ultimate rollout, (IMO).
 
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