The Evolution of the SARS-COV-2 virus

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  • #26
atyy
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Claim: A classified US intelligence report - saying three researchers at the Wuhan laboratory were treated in hospital in November 2019, just before the virus began infecting humans in the city - began circulating in US media this week.

https://www.msn.com/en-us/news/worl...s-being-taken-seriously/ar-AAKrVdq?li=BBnb7Kz

Apparently, the 'lab-leak theory' has gained some traction, but the investigation is about the origin.
In the interview (summary: https://science.sciencemag.org/content/369/6503/487.full full: https://www.sciencemag.org/sites/default/files/Shi Zhengli Q&A.pdf), Shi Zhengli says all staff had sera tested negative. If that meant an antibody test, that would exclude the possibility that the staff referred to in the report about a classified US intelligence report were a source of COVID-19.
 
  • #27
Astronuc
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Claim: A classified US intelligence report - saying three researchers at the Wuhan laboratory were treated [edit: for what?] in hospital in November 2019, . . . .
Shi Zhengli says all staff had sera tested negative.
I added [edit: for what?] to indicate that there was no mention for what they were treated. A undetermined respiratory or flu-like, or pneumonia-like, illness?
 
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I read the article by Andersen et al - https://www.nature.com/articles/s41591-020-0820-9. It is very scholarly but somewhat misleading.

He starts the article by stating – “Our analyses clearly show that SARS-CoV-2 is not a laboratory construct or a purposefully manipulated virus.”

I certainly did not find the article to be QED.

What the article did demonstrate well is that although diverse, appearing in difference organisms, there are similar organic structures to parts of the SARS – CoV – 2 ex ante.

The case then becomes similar structures appear in Nature therefore somehow they must have fused via random mutation and natural selection.

To my knowledge there is no study that takes an existing structure and then illustrated how via random mutation and natural selection you get the SARS – CoV – 2 genome.

With respect to the Sars Cov -2 ACE2 receptor I find it to be very important. There is a significant difference between this receptor and that found in Sars Cov – 1 - https://www.frontiersin.org/articles/10.3389/fmolb.2020.591873/full

Andersen notes – “SARS-CoV-2 appears to be optimized for binding to the human receptor ACE2” (via random mutation and natural selection.)

Has anyone be able to demonstrate that starting with an existing source it is impossible to manifest the SARS – C oV – 2 in a lab?

The most honest answer to the source of the SARS – CoV -2 virus is it unknown. It may have originated in the wild or it is possible that it was influenced in a lab. At this time we are very far from having a definitive answer.
 
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I read the article by Andersen et al - https://www.nature.com/articles/s41591-020-0820-9. It is very scholarly but somewhat misleading.

He starts the article by stating – “Our analyses clearly show that SARS-CoV-2 is not a laboratory construct or a purposefully manipulated virus.”

I certainly did not find the article to be QED.

What the article did demonstrate well is that although diverse, appearing in difference organisms, there are similar organic structures to parts of the SARS – CoV – 2 ex ante.

The case then becomes similar structures appear in Nature therefore somehow they must have fused via random mutation and natural selection.

To my knowledge there is no study that takes an existing structure and then illustrated how via random mutation and natural selection you get the SARS – CoV – 2 genome.

With respect to the Sars Cov -2 ACE2 receptor I find it to be very important. There is a significant difference between this receptor and that found in Sars Cov – 1 - https://www.frontiersin.org/articles/10.3389/fmolb.2020.591873/full

Andersen notes – “SARS-CoV-2 appears to be optimized for binding to the human receptor ACE2” (via random mutation and natural selection.)

Has anyone be able to demonstrate that starting with an existing source it is impossible to manifest the SARS – C oV – 2 in a lab?

The most honest answer to the source of the SARS – CoV -2 virus is it unknown. It may have originated in the wild or it is possible that it was influenced in a lab. At this time we are very far from having a definitive answer.
It's important to understand that the article is a letter to the editor, not a peer reviewed scientific research article.
 
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The Andersen et al - letter to the editor - has been quoted several times in threads on this site. It summarizes well the opinion held by many.

You can not just say the source you quoted was not peer reviewed therefore everything is wrong.

What fault do you find with the Andersen "letter"?

I think it is important to note that the letter is over a year old and no advancement at all has been made with respect to the Nature- random mutation and natural selection- origin of the virus. None!
 
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The Andersen et al - letter to the editor - has been quoted several times in threads on this site. It summarizes well the opinion held by many.

You can not just say the source you quoted was not peer reviewed therefore everything is wrong.

What fault do you find with the Andersen "letter"?

I think it is important to note that the letter is over a year old and no advancement at all has been made with respect to the Nature- random mutation and natural selection- origin of the virus. None!
I didn't say anything about it except that it is not a peer reviewed scientific article. It would be better to read the criticisms from virologists than for me to try and scrutinize it.

But just as a note: The natural zoonotic hypothesis has been that it came about after a jump between bats and an intermediate species and then to humans. Originally it was thought to have occurred at the wet market because live animals of different species are near to each other.

If this could happen so easily and quickly naturally by placing animals near to each other, how could it be impossible to reproduce in a lab, where animals are placed near to each other and also infected with viruses?

Nobody is arguing we shouldn't investigate the wet market.

The truth is that you can't rule out a lab origin. There are many possible mechanisms, including ones that are indistinguishable from natural origins outside the lab.

It would be wrong to hype the lab origin hypothesis, but also wrong to hype the non-lab origin hypothesis in my opinion. If we don't thoroughly and transparently pursue lab leak possibilities, then I don't think people should be allowed to pursue lab research with dangerous viruses.
 
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With respect to the Sars Cov -2 ACE2 receptor I find it to be very important. There is a significant difference between this receptor and that found in Sars Cov – 1 - https://www.frontiersin.org/articles/10.3389/fmolb.2020.591873/full

The above article originally piqued my interest.

Now - https://www.dailymail.co.uk/news/ar...-lab-tried-cover-tracks-new-study-claims.html

Do not just disregard because of source Daily Mail. There are some very interesting diagrams about 1/2 the way through the article of the structure of the Cov - 2 virus and where it may have been altered.

Dalgleish is a London oncology professor known for breakthrough work on a vaccine for HIV. Sørensen is a virologist and chair of the pharmaceutical company Immunor, which developed a coronavirus vaccine candidate called Biovacc-19. Dalgleish also has a financial stake in that company.

It was during their COVID-19 vaccine research that the pair came across "unique fingerprints" indicating the virus didn’t come from nature, they said. The telltale clue: a rare finding in the COVID-carrying virus of a row of four amino acids, which give off a positive charge and bond to negative human cells.

"The laws of physics mean that you cannot have four positively charged amino acids in a row," Dalgleish told the Daily Mail. "The only way you can get this is if you artificially manufacture it."
 
  • #33
atyy
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The truth is that you can't rule out a lab origin. There are many possible mechanisms, including ones that are indistinguishable from natural origins outside the lab.

It would be wrong to hype the lab origin hypothesis, but also wrong to hype the non-lab origin hypothesis in my opinion. If we don't thoroughly and transparently pursue lab leak possibilities, then I don't think people should be allowed to pursue lab research with dangerous viruses.
It is true that one cannot rule out a lab origin. However, there is evidence against the lab origin as provided by the Andersen article and the Shi Zhengli interview. Recently there have been prominent arguments for the lab origin. Among these are an article by Nicholas Wade that attrbutes comments to David Baltimore, but as explained by Kristian Andersen, the comments are nonsense. There have been reports about staff of the Wuhan Institute having been hospitalized before the outbreak, and so may have been its source, but Shi Zhengli (of the Wuhan Institute) has said that sera testing has been done of all staff; it is a little unclear what and who was tested, but if it was an antibody test, it would mean that none of the staff tested had been infected by SARS-CoV-2, and so could not have been a source. Then there is speculation by Nick Paton Walsh on CNN that experiments on RaTG13 (a bat virus whose sequence is currently the closest to SARS-CoV-2) were the source of the leak, but that route would also be ruled by information provided by the Shi Zhengli that while they do have "isolated live" coronaviruses, RaTG13 was not among them (we know about the RaTG13 sequence from samples collected by and sequenced by the Wuhan Institute). So at this stage, unless Shi Zhengli was lying, even many exotic and improbable ways the virus may have leaked from the lab origin are excluded. Nonetheless, it is noteworthy that Shi Zhengli had commented that she would welcome a visit to investigate the lab.
 
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  • #34
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It's important to understand that the article is a letter to the editor, not a peer reviewed scientific research article.
The Andersen et al. publication may have been peer reviewed, but even if it was not, it at least passed screening by the editorial team at the journal, Nature Medicine. Here's the journal's policy on correspondences:
"Correspondence​
The Correspondence section provides a forum for discussion or to present a point of view on issues that are of interest to the readership of Nature Medicine. Correspondences should not contain new research data, nor should serve as a venue for technical comments on peer-reviewed research papers, which would be considered Matters Arising. A Correspondence is generally 800-1000 words; it is limited to one display item and up to 10 references. Article titles are omitted from the reference list.​
Correspondences are initially screened for general interest, and may be returned to the authors if the topic, angle or content is deemed not to be of high interest to the journal’s readership or when the topic has already been covered in other pieces. Nature Medicine receives a very high volume of correspondence and the editorial team reserves the right to return submissions to authors without further feedback. After screening, correspondences are edited for concision and clarity, and additional changes may be requested from the authors. Correspondences may be peer-reviewed at editorial discretion."​
https://www.nature.com/nm/about/content

He starts the article by stating – “Our analyses clearly show that SARS-CoV-2 is not a laboratory construct or a purposefully manipulated virus.”

I certainly did not find the article to be QED.

What the article did demonstrate well is that although diverse, appearing in difference organisms, there are similar organic structures to parts of the SARS – CoV – 2 ex ante.

The case then becomes similar structures appear in Nature therefore somehow they must have fused via random mutation and natural selection.

To my knowledge there is no study that takes an existing structure and then illustrated how via random mutation and natural selection you get the SARS – CoV – 2 genome.

With respect to the Sars Cov -2 ACE2 receptor I find it to be very important. There is a significant difference between this receptor and that found in Sars Cov – 1 - https://www.frontiersin.org/articles/10.3389/fmolb.2020.591873/full

Andersen notes – “SARS-CoV-2 appears to be optimized for binding to the human receptor ACE2” (via random mutation and natural selection.)
The Andersen et al. article presents evidence that 1) the receptor was not purposefully engineered in the lab, and that 2) the virus does not show signs of selection inside of a laboratory (if the virus was being cultured for study). Essentially, the virus evolved in the wild.

These possibilities do not necessarily exclude all possibilities related to an accidental lab release (e.g. researchers encountered the virus in the wild while collecting virus samples and infected others or got infected while miss-handling samples). However, whether a wild virus transmitted from the wild to the general populous or whether a wild virus got to the general populous via the lab is difficult to distinguish solely from looking at the genetics of the virus and would be nearly impossible to distinguish.

Has anyone be able to demonstrate that starting with an existing source it is impossible to manifest the SARS – C oV – 2 in a lab?

The most honest answer to the source of the SARS – CoV -2 virus is it unknown. It may have originated in the wild or it is possible that it was influenced in a lab. At this time we are very far from having a definitive answer.

But just as a note: The natural zoonotic hypothesis has been that it came about after a jump between bats and an intermediate species and then to humans. Originally it was thought to have occurred at the wet market because live animals of different species are near to each other.

If this could happen so easily and quickly naturally by placing animals near to each other, how could it be impossible to reproduce in a lab, where animals are placed near to each other and also infected with viruses?

Nobody is arguing we shouldn't investigate the wet market.

The truth is that you can't rule out a lab origin. There are many possible mechanisms, including ones that are indistinguishable from natural origins outside the lab.

It would be wrong to hype the lab origin hypothesis, but also wrong to hype the non-lab origin hypothesis in my opinion. If we don't thoroughly and transparently pursue lab leak possibilities, then I don't think people should be allowed to pursue lab research with dangerous viruses.

Research that tries to turn wild coronaviruses into viruses capable of causing pandemic disease is exactly the kind of dangerous research that people are claiming caused the pandemic. That sort of research is very dangerous and maybe should not even be pursued.

However, we have plenty of examples of the SARS-CoV-2 gaining naturally mutations that increase its transmissibility and decrease its succeptibility to antibodies as it spreads among humans (e.g. the variants from the UK, South Africa, Brazil, New York, California, India, etc.), and we have also observed new variants as it jumps species (e.g. to minks in Europe), showing that mutation of the virus and transmission across species is something that occurs pretty frequently with these types of viruses.

Also, while the wet market may have just been a superspreader event that transmitted the virus from an infected individual to others and not the source of the original animal to human transmission. It is likely that the jump from bats to intermediate species happened much earlier. Because people at the wet market handle wild animals, it is possible that one became infected while collecting, transporting or handling the wild animals and then spread the virus at the market (a large social gathering which would be conducive to spreading the disease to many people).

With respect to the Sars Cov -2 ACE2 receptor I find it to be very important. There is a significant difference between this receptor and that found in Sars Cov – 1 - https://www.frontiersin.org/articles/10.3389/fmolb.2020.591873/full

The above article originally piqued my interest.

Now - https://www.dailymail.co.uk/news/ar...-lab-tried-cover-tracks-new-study-claims.html

Do not just disregard because of source Daily Mail. There are some very interesting diagrams about 1/2 the way through the article of the structure of the Cov - 2 virus and where it may have been altered.

Dalgleish is a London oncology professor known for breakthrough work on a vaccine for HIV. Sørensen is a virologist and chair of the pharmaceutical company Immunor, which developed a coronavirus vaccine candidate called Biovacc-19. Dalgleish also has a financial stake in that company.

It was during their COVID-19 vaccine research that the pair came across "unique fingerprints" indicating the virus didn’t come from nature, they said. The telltale clue: a rare finding in the COVID-carrying virus of a row of four amino acids, which give off a positive charge and bond to negative human cells.

"The laws of physics mean that you cannot have four positively charged amino acids in a row," Dalgleish told the Daily Mail. "The only way you can get this is if you artificially manufacture it."

I have a PhD in biophysics, and you can absolutely have four positively charged amino acids in a row, and this can occur naturally. As noted by Kristian Andersen, similar sequences are found in many other coronavirus found in nature (e.g. feline coronaviruses).
 
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  • #35
atyy
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These possibilities do not necessarily exclude all possibilities related to an accidental lab release (e.g. researchers encountered the virus in the wild while collecting virus samples and infected others or got infected while miss-handling samples). However, whether a wild virus transmitted from the wild to the general populous or whether a wild virus got to the general populous via the lab is difficult to distinguish solely from looking at the genetics of the virus and would be nearly impossible to distinguish.
With the usual caveat that it is hard to prove a negative, there is some evidence against the possibility of accidental release during collection and handling of samples. In the addendum to the paper reporting RaTG13, https://www.nature.com/articles/s41586-020-2951-z, it seems that Shi Zhengli and colleagues briefly describes several samplings of bat caves, and to date the closest sequence is RaTG13, still quite far from SARS-CoV-2

Interestingly, the reason they sampled those particular caves was that there had been in 2012 a few people who visited the caves as preparation for copper mining, and they had pneumonia whose cause was not identified. The Wuhan researchers suspected the patients had been infected by an unknown virus, and therefore took samples from the cave to study that possibility. They have since retested the serum of those patients, and confirmed that they were not infected by SARS-CoV-2.
 
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1. Spike Proteins of SARS-CoV and SARS-CoV-2 Utilize Different Mechanisms to Bind With Human ACE2 - https://www.frontiersin.org/articles/10.3389/fmolb.2020.591873/full This article examines the differences between SARS-CoV and SARS-CoV-2

Conclusion​


S protein plays a crucial role in SARS-CoV-2 infection by binding to human ACE2. To understand the mechanisms of how S protein binds to ACE2, we compared SARS-CoV with SARS-CoV-2 in biophysical features such as electrostatic binding forces, electric field lines, salt bridges, and hydrogen bonds. We found that even though SARS-CoV and SARS-CoV-2 share very similar structures, there are significant differences in the process when their S proteins bind to ACE2. The common feature is that the calculations of electrostatic surfaces and electric field lines at the binding interfaces demonstrated that ACE2 has a negatively charged binding surface while S protein RBDs are overall positively charged, which provides dominantly attractive forces between ACE2 and S proteins. The differences of electrostatic features between SARS-CoV and SARS-CoV-2 are analyzed in various perspectives as well in this work. Comprehensive analyses were also performed after 100 ns MD simulations, which indicates that SARS-CoV-2 has more high-occupancy (>90%) hydrogen bonds at the interface area between its S protein RBD and ACE2 than SARS-CoV. The electric field line related residues are distributed quite differently, which results in a more robust binding strategy of SARS-CoV-2. Also, the SARS-CoV-2 has higher electric field line density than that of SARS-CoV, which indicates stronger interaction between SARS-CoV-2 and ACE2, compared to that of SARS-CoV. Those facts make the interactions of SARS-CoV-2 more robust than SARS-CoV, which may explain why COVID-19 spreads faster than SARS in 2003."

2. In the Andersen article he states - "Andersen notes – “SARS-CoV-2 appears to be "optimized" for binding to the human receptor ACE2” (via random mutation and natural selection.)

3. The references article by Dalgleish and Sorensen give an example of how the changes in SARS-CoV-2 might have came about.

The statement made in the article about the sequence of positively charged amino acids may be wrong. However, I still found the diagrams provided to be very stimulating. I will be very interested to see how their article is received in the scientific community. They both seem to have a firm grasp on this area of inquiry.

4. "However, we have plenty of examples of the SARS-CoV-2 gaining naturally mutations that increase its transmissibility and decrease its succeptibility to antibodies as it spreads among humans" I do not believe theses mutations are of the same magnitude as mutations needed to mutate viruses found in bats to the Cov-2 in humans.
 
  • #37
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1. Spike Proteins of SARS-CoV and SARS-CoV-2 Utilize Different Mechanisms to Bind With Human ACE2 - https://www.frontiersin.org/articles/10.3389/fmolb.2020.591873/full This article examines the differences between SARS-CoV and SARS-CoV-2
Yes, the SARS-CoV-2 spike protein can bind to ACE2 much more strongly than the SARS-CoV spike protein. This is very apparent in the difference in transmissible between the viruses. However, this says nothing about whether the SARS-CoV-2 spike protein could acquire those mutations naturally.

2. In the Andersen article he states - "Andersen notes – “SARS-CoV-2 appears to be "optimized" for binding to the human receptor ACE2” (via random mutation and natural selection.)
Of course, the virus is not completely optimized for binding to the human ACE2 receptor as various variants have evolved that bind the ACE2 receptor better (e.g. via the N501Y mutation in the B.1.1.7 variant from the UK).

3. The references article by Dalgleish and Sorensen give an example of how the changes in SARS-CoV-2 might have came about.

The statement made in the article about the sequence of positively charged amino acids may be wrong. However, I still found the diagrams provided to be very stimulating. I will be very interested to see how their article is received in the scientific community. They both seem to have a firm grasp on this area of inquiry.
It's worth noting that the full article has not yet been published in a peer reviewed journal. It is highly unusual for parts of a scientific paper to be released ahead of publication in any news outlet, especially when there are a variety of pre-print servers on which the entire paper could be published.

On the issue of how SARS-CoV-2 could acquire mutations to bind human ACE2 more strongly, it's worth noting that many of these mutations occur already in nature. For example, here's a figure comparing the receptor binding domain (RBD) of the SARS-CoV-2 spike protein to the RBD of other related coronaviruses (the RBD is the part of the spike protein responsible for binding to ACE2):
1622347889415.png

https://www.nature.com/articles/s41586-020-2169-0

There are very few mutations in the SARS-CoV-2 RBD that are not found in other coronavirus species found in nature.
 
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4. "However, we have plenty of examples of the SARS-CoV-2 gaining naturally mutations that increase its transmissibility and decrease its succeptibility to antibodies as it spreads among humans" I do not believe theses mutations are of the same magnitude as mutations needed to mutate viruses found in bats to the Cov-2 in humans.
Researchers compared the spike proteins of the RaTG13 bat coronavirus (the known coronavirus most closely related to SARS-CoV-2) and SARS-CoV-2 and concluded that changes at only three amino acids in the RBD of the spike protein largely account for the differences between RaTG13 and SARS-CoV-2 in binding affinity for human ACE2 receptor (https://www.nature.com/articles/s41467-021-21767-3). We have definitely seen variants of SARS-CoV-2 with three or more mutations in the spike RBD (e.g. in the B.1.1.7 variant from the UK, three amino acids are mutated in the RBD and in the B.1.351 variant from South Africa, three amino acids are mutated in the RBD).
 
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Shi Zhengli and colleagues briefly describes several samplings of bat caves, and to date the closest sequence is RaTG13, still quite far from SARS-CoV-2
Apparently one of the caves is the Mojiang cave.

https://www.nature.com/articles/s41586-020-2951-z
https://en.wikipedia.org/wiki/Mòjiāng_virus

https://www.sciencemag.org/news/2014/03/new-killer-virus-china

a cluster of eight SARS-related viruses mentioned briefly in an obscure section of one WIV paper had actually also come from the Mojiang mine. In other words, they hadn't found one relative of SARS-CoV-2 in that mineshaft; they'd found nine.
Newsweek - https://www.msn.com/en-us/news/tech...ab-story-and-embarrassed-the-media/ar-AAKDPPR

Right now, it's just circumstantial evidence.

AP, December 2020 - China clamps down in hidden hunt for coronavirus origins
https://apnews.com/article/united-n...y-on-ap-bats-24fbadc58cee3a40bca2ddf7a14d2955
 
  • #40
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Newsweek - https://www.msn.com/en-us/news/tech...ab-story-and-embarrassed-the-media/ar-AAKDPPR

Right now, it's just circumstantial evidence.
I think that's a very irresponsibly written article (but thank you for letting us know what influential media are publishing). Almost everything in there that is hinted at at being suspicious circumstantial evidence can in fact be known from what the WIV itself has published (or co-published) or information that it has released. The WIV has published (or co-published) quite a few papers on SARS-like viruses and in fact warned in some of those papers about their pandemic possibility, so it's not a secret that it has samples. It's also clear from the Scientific American article referenced by the Newsweek article that the WIV collected samples from the Mojiang caves to investigate the possibility of viral infection, and they found many coronaviruses in those samples. Furthermore, the Newsweek article ignores that the WIV has reported that it has actively investigated the lab leak theory and has evidence against it (even quite exotic possibilities). It doesn't rule out the lab leak theory, but the possibilities that remain are either very exotic, or Shi Zhengli (of the WIV) is lying or misleading us about the tests they did to investigate the lab leak theory.

One thing to note that the author of the Newsweek article may have misunderstood is that while many of the SARS-like viruses have been at least partially sequenced in that sense, that does not mean they have been "isolated live" which is the type of study relevant to version of the lab leak theory involving manipulation in the lab. So it is not clear to me that some of the comments, such as those attributed to Peter Daszak, have not been taken out of context.

Let me again present here the evidence against the lab leak theory (copied from another thread). While this does not exclude the lab leak theory, it does mean the theory has a very low probability of being right, until new evidence comes to light.

The reasons against lab creation are given in https://www.nature.com/articles/s41591-020-0820-9. Additionally, the Wuhan Institute (WIV) reports that although it has "isolated live" viruses, these have only about 80% similarity to SARS-CoV-2. The virus with the closest sequence is RaTG13 (about 96%), also in the samples of the WIV. The 96% similarity is too far for RaTg13 to be the direct ancestor of SARS-CoV-2 (estimated about 30 or more years apart), but one may consider the exotic possibility that WIV did experiments on RaTG13 and hastened the evolution. However, that is unlikely because the WIV reports that it did not have RaTG13 "isolated live".

Another possibility that can be considered is that SARS-CoV-2 was among their samples, and although not isolated live, did infect one of their staff. For example, they collected many viral samples, including RaTG13, from a cave, because in 2012 some workers who were preparing the cave for copper mining got sick with pneumonia potentially due to an unknown virus. So while the WIV staff collected the samples or handled them, they may have gotten infected in a similar way as conjectured for the workers. However, this possibility is also unlikely based on WIV reports that they had tested their staff for antibodies against SARS-CoV-2, and there was no evidence of any previous infection. Incidentally, after the discovery of SARS-CoV-2, they went back to serum samples from the mining workers who were conjectured to have been infected with an unknown virus to check if that conjectured virus could have been SARS-CoV-2, and it was not.

The above information about the WIV was drawn from an interview with Shi Zhengli, as well as an addendum to her group's paper on RaTG13.
https://science.sciencemag.org/content/369/6503/487.summary
https://www.sciencemag.org/sites/default/files/Shi Zhengli Q&A.pdf
https://www.nature.com/articles/s41586-020-2951-z

The same information is in the WHO report on SARS-CoV-2 origins, with a little extra detail.
https://www.who.int/publications/i/...bal-study-of-origins-of-sars-cov-2-china-part
"The three laboratories in Wuhan working with either CoVs diagnostics and/or CoVs isolation and vaccine development all had high quality biosafety level (BSL3 or 4) facilities that were well-managed, with a staff health monitoring programme with no reporting of COVID-19 compatible respiratory illness during the weeks/months prior to December 2019, and no serological evidence of infection in workers through SARS-CoV-2-specific serology-screening."

The WHO report says the lab release theory is unlikely, but it does not rule out revisiting the lab release theory if more evidence comes to light.
"What would be needed to increase knowledge? Regular administrative and internal review of high-level biosafety laboratories worldwide. Follow-up of new evidence supplied around possible laboratory leaks."
 
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"The laws of physics mean that you cannot have four positively charged amino acids in a row," Dalgleish told the Daily Mail. "The only way you can get this is if you artificially manufacture it."

I have a PhD in biophysics, and you can absolutely have four positively charged amino acids in a row, and this can occur naturally. As noted by Kristian Andersen, similar sequences are found in many other coronavirus found in nature (e.g. feline coronaviruses).

You know I find this funny, correct me if I am wrong, if the laws of physics don't allow four positively charged amino acids in a row, it should not only be impossible to have happened in nature but also in a lab right ? Our labs are also subjected to the same laws of physics.
 
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I think that's a very irresponsibly written article (but thank you for letting us know what influential media are publishing). Almost everything in there that is hinted at at being suspicious circumstantial evidence can in fact be known from what the WIV itself has published (or co-published) or information that it has released. The WIV has published (or co-published) quite a few papers on SARS-like viruses and in fact warned in some of those papers about their pandemic possibility, so it's not a secret that it has samples. It's also clear from the Scientific American article referenced by the Newsweek article that the WIV collected samples from the Mojiang caves to investigate the possibility of viral infection, and they found many coronaviruses in those samples. Furthermore, the Newsweek article ignores that the WIV has reported that it has actively investigated the lab leak theory and has evidence against it (even quite exotic possibilities). It doesn't rule out the lab leak theory, but the possibilities that remain are either very exotic, or Shi Zhengli (of the WIV) is lying or misleading us about the tests they did to investigate the lab leak theory.

One thing to note that the author of the Newsweek article may have misunderstood is that while many of the SARS-like viruses have been at least partially sequenced in that sense, that does not mean they have been "isolated live" which is the type of study relevant to version of the lab leak theory involving manipulation in the lab. So it is not clear to me that some of the comments, such as those attributed to Peter Daszak, have not been taken out of context.

Let me again present here the evidence against the lab leak theory (copied from another thread). While this does not exclude the lab leak theory, it does mean the theory has a very low probability of being right, until new evidence comes to light.

The reasons against lab creation are given in https://www.nature.com/articles/s41591-020-0820-9. Additionally, the Wuhan Institute (WIV) reports that although it has "isolated live" viruses, these have only about 80% similarity to SARS-CoV-2. The virus with the closest sequence is RaTG13 (about 96%), also in the samples of the WIV. The 96% similarity is too far for RaTg13 to be the direct ancestor of SARS-CoV-2 (estimated about 30 or more years apart), but one may consider the exotic possibility that WIV did experiments on RaTG13 and hastened the evolution. However, that is unlikely because the WIV reports that it did not have RaTG13 "isolated live".

Another possibility that can be considered is that SARS-CoV-2 was among their samples, and although not isolated live, did infect one of their staff. For example, they collected many viral samples, including RaTG13, from a cave, because in 2012 some workers who were preparing the cave for copper mining got sick with pneumonia potentially due to an unknown virus. So while the WIV staff collected the samples or handled them, they may have gotten infected in a similar way as conjectured for the workers. However, this possibility is also unlikely based on WIV reports that they had tested their staff for antibodies against SARS-CoV-2, and there was no evidence of any previous infection. Incidentally, after the discovery of SARS-CoV-2, they went back to serum samples from the mining workers who were conjectured to have been infected with an unknown virus to check if that conjectured virus could have been SARS-CoV-2, and it was not.

The above information about the WIV was drawn from an interview with Shi Zhengli, as well as an addendum to her group's paper on RaTG13.
https://science.sciencemag.org/content/369/6503/487.summary
https://www.sciencemag.org/sites/default/files/Shi Zhengli Q&A.pdf
https://www.nature.com/articles/s41586-020-2951-z

The same information is in the WHO report on SARS-CoV-2 origins, with a little extra detail.
https://www.who.int/publications/i/...bal-study-of-origins-of-sars-cov-2-china-part
"The three laboratories in Wuhan working with either CoVs diagnostics and/or CoVs isolation and vaccine development all had high quality biosafety level (BSL3 or 4) facilities that were well-managed, with a staff health monitoring programme with no reporting of COVID-19 compatible respiratory illness during the weeks/months prior to December 2019, and no serological evidence of infection in workers through SARS-CoV-2-specific serology-screening."

The WHO report says the lab release theory is unlikely, but it does not rule out revisiting the lab release theory if more evidence comes to light.
"What would be needed to increase knowledge? Regular administrative and internal review of high-level biosafety laboratories worldwide. Follow-up of new evidence supplied around possible laboratory leaks."
I thought the Newsweek article, that was intended for the general public, was informative.

I found the information on Peter Daszak to be something that everyone should be aware of. To expect an objective opinion from an individual like this is beyond the pale.

“Chief among these scientists was a biologist named Peter Daszak, president of EcoHealth Alliance, a non-profit research group that ran a large international program to survey natural pathogens with the potential to cause a pandemic. Daszak had been collaborating for years with Shi Zhengli, the director of the Wuhan Institute of Virology and a renowned bat virologist. Daszak co-authored nearly a dozen papers with Shi and funneled at least $600,000 of U.S. government grants her way.

When the pandemic happened to break out on the doorstep of the lab with the largest collection of coronaviruses in the world, fueling speculation that the WIV might be involved, Daszak and 26 other scientists signed a letter that appeared in The Lancet on February 19, 2020. "We stand together to strongly condemn conspiracy theories suggesting that COVID-19 does not have a natural origin," it stated.

We now know, thanks to a Freedom of Information Act request, that Daszak orchestrated the letter to squelch talk of a lab leak. He drafted it, reached out to fellow scientists to sign it, and worked behind the scenes to make it seem that the letter represented the views of a broad range of scientists. "This statement will not have the EcoHealth Alliance logo on it and will not be identifiable as coming from any one organization or person," he wrote in his pitch to the co-signatories. Scientists whose work had overlapped with the WIV agreed not to sign it so they could "put it out in a way that doesn't link it back to our collaboration."

Peter recently was a member of the WHO team that went to Wuhan and “inspected” the situation. Again reaching the same conclusion that it is very unlikely that the Covid-19 virus does not have a natural origin.

This investigation was a canard.

“The report was jointly authored by 17 WHO-appointed experts and 17 Chinese scientists. The sites they visited, and the wording of the report, required sign-off from the Chinese government. And, crucially, the study was not the forensic investigation that some scientists have called for — going through freezers, databases, records of field sampling, and lab notes to probe the controversial theory that the virus escaped in an accident at a lab in the city of Wuhan.”

https://www.buzzfeednews.com/article/peteraldhous/who-covid-origins-china-report-lab-accident.

It doesn ‘t get much worse.. This is like letting the defense write the closing statement for the prosecution.

It has been over a year since the recognized emergence of the Covid – 19 virus. No progress, none, has been made in finding the elusive “missing link”.

No one has been able to take an existing virus and show how via random mutation and natural selection you could get the Covid – 19 virus.

Everyone will jump on me here but – I do not have the details but the most compelling argument for a Nature origin for the virus is that the Covid – 19 virus genome meanders in a way that suggests that it was not just cut and pasted in a lab. This is interesting but not proof. All this suggests is that it took a long time for the Covid – 19 virus to emerge. Note – It would take much, much longer in Nature than if it were nurtured in a lab.

In closing I offer something of interest.

Virus Optimized for humans Last updated on March 30, 2021, at 2:21 p.m. ET

The WHO Report On COVID-19's Origins Shows We May Never Know Where The Coronavirus Came From

“For SARS-CoV-2 to get into human cells, the spike protein on its surface must latch onto a receptor on the cells called ACE2. After the first complete genetic sequence of the virus was posted online by Chinese scientists in January 2020, a team led by Nikolai Petrovsky, an immunologist who works on vaccine development at Flinders University near Adelaide in Australia, started running computer simulations of how well the coronavirus spike protein could bind to ACE2 receptors from different species.

“When we got to the end of the project, what stumped us was that binding to human ACE2 was higher than for any species we tested,” Petrovsky told BuzzFeed News. “For us, that was very hard to explain based on a natural origins theory.”

https://www.buzzfeednews.com/article/peteraldhous/who-covid-origins-china-report-lab-accident
 
  • #43
atyy
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Paul Bieniasz on Twitter: From @edwardcholmes and colleagues: Novel SARS-CoV-2 related viruses in rhinolophid bats, one of which is the closest relative of SARS-CoV-2 in most of the virus genome.

https://www.cell.com/cell/fulltext/S0092-8674(21)00709-1
Identification of novel bat coronaviruses sheds light on the evolutionary origins of SARS-CoV-2 and related viruses
Hong Zhou, Jingkai Ji, Xing Chen, Yuhai Bi, Juan Li, Qihui Wang, Tao Hu, Hao Song, Runchu Zhao, Yanhua Chen, Mingxue Cui, Yanyan Zhang, Alice C. Hughes, Edward C. Holmes, Weifeng Shi
Despite the discovery of animal coronaviruses related to SARS-CoV-2, the evolutionary origins of this virus are elusive. We describe a meta-transcriptomic study of 411 bat samples collected from a small geographical region in Yunnan province, China, between May 2019 and November 2020. We identified 24 full-length coronavirus genomes, including four novel SARS-CoV-2 related and three SARS-CoV related viruses. Rhinolophus pusillus virus RpYN06 was the closest relative of SARS-CoV-2 in most of the genome, although it possessed a more divergent spike gene. The other three SARS-CoV-2 related coronaviruses carried a genetically distinct spike gene that could weakly bind to the hACE2 receptor in vitro. Ecological modeling predicted the co-existence of up to 23 Rhinolophus bat species, with the largest contiguous hotspots extending from South Laos and Vietnam to southern China. Our study highlights the remarkable diversity of bat coronaviruses at the local scale, including close relatives of both SARS-CoV-2 and SARS-CoV.
 
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  • #44
Ygggdrasil
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It has been over a year since the recognized emergence of the Covid – 19 virus. No progress, none, has been made in finding the elusive “missing link”.

No one has been able to take an existing virus and show how via random mutation and natural selection you could get the Covid – 19 virus.

Those are pretty high bars of evidence and mirror some common complaints from those who disbelieve evolution (e.g. about missing links and not being able to show step by step how certain traits or organisms could evolve).

Nature has a nice news article exploring arguments for and against the lab leak hypothesis. Regarding the "missing link":
"Outbreak-origin investigations often take years, and some culprits remain unknown. It took 14 years to nail down the origin of the SARS epidemic, which began with a virus in bats that spread to humans, most likely through civets. To date, a complete Ebola virus has never been isolated from an animal in the region where the world’s largest outbreak occurred between 2013 and 2016."​

As to how it could evolve:
"Just because the virus spreads among humans doesn't mean it was designed to do so. It also flourishes among mink and infects a host of carnivorous mammals. And it wasn’t optimally transmissible among humans for the better part of last year. Rather, new, more efficient variants have evolved around the world. To name one example, the highly transmissible variant of SARS-CoV-2 first reported in India (B.1.617.2, or Delta) has mutations in the nucleotides encoding its furin cleavage site that appear to make the virus better at infecting cells8."​

The whole article is worth a read if you are interested in the topic: https://www.nature.com/articles/d41586-021-01529-3
 
  • #45
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Paul Bieniasz on Twitter: From @edwardcholmes and colleagues: Novel SARS-CoV-2 related viruses in rhinolophid bats, one of which is the closest relative of SARS-CoV-2 in most of the virus genome.

https://www.cell.com/cell/fulltext/S0092-8674(21)00709-1
Identification of novel bat coronaviruses sheds light on the evolutionary origins of SARS-CoV-2 and related viruses
Hong Zhou, Jingkai Ji, Xing Chen, Yuhai Bi, Juan Li, Qihui Wang, Tao Hu, Hao Song, Runchu Zhao, Yanhua Chen, Mingxue Cui, Yanyan Zhang, Alice C. Hughes, Edward C. Holmes, Weifeng Shi
Despite the discovery of animal coronaviruses related to SARS-CoV-2, the evolutionary origins of this virus are elusive. We describe a meta-transcriptomic study of 411 bat samples collected from a small geographical region in Yunnan province, China, between May 2019 and November 2020. We identified 24 full-length coronavirus genomes, including four novel SARS-CoV-2 related and three SARS-CoV related viruses. Rhinolophus pusillus virus RpYN06 was the closest relative of SARS-CoV-2 in most of the genome, although it possessed a more divergent spike gene. The other three SARS-CoV-2 related coronaviruses carried a genetically distinct spike gene that could weakly bind to the hACE2 receptor in vitro. Ecological modeling predicted the co-existence of up to 23 Rhinolophus bat species, with the largest contiguous hotspots extending from South Laos and Vietnam to southern China. Our study highlights the remarkable diversity of bat coronaviruses at the local scale, including close relatives of both SARS-CoV-2 and SARS-CoV.

It is unclear what your comment is addressing. I suspect it might be my statement – “It has been over a year since the recognized emergence of the Covid – 19 virus. No progress, none, has been made in finding the elusive “missing link”.

You might be supporting the argument that there are many different bat sources and coronavirus genomes. It may take longer than thought to find the missing link.

From your quote – (terms are vague – “related” “closest”)

Evidence for lots of bats

1. “including four novel SARS-CoV-2 related and three SARS-CoV related viruses.
2. “Rhinolophus pusillus virus RpYN06 was the closest relative of SARS-CoV-2 in most of the genome, although it possessed a more divergent spike gene. The other three SARS-CoV-2 related coronaviruses carried a
3. “The other three SARS-CoV-2 related coronaviruses carried a genetically distinct spike gene that could weakly bind to the hACE2 receptor in vitro.”
4. “Our study highlights the remarkable diversity of bat coronaviruses at the local scale, including close relatives of both SARS-CoV-2 and SARS-CoV.

All of this work seems to be negated by

“In contrast, given the immeasurably low affinity of bat RaTG13 S for human ACE2, it seems unlikely that at least this class of presumed precursor bat viruses would infect humans.”

https://www.nature.com/articles/s41467-021-21006-9
 
  • #46
51
14
Those are pretty high bars of evidence and mirror some common complaints from those who disbelieve evolution (e.g. about missing links and not being able to show step by step how certain traits or organisms could evolve).

Nature has a nice news article exploring arguments for and against the lab leak hypothesis. Regarding the "missing link":
"Outbreak-origin investigations often take years, and some culprits remain unknown. It took 14 years to nail down the origin of the SARS epidemic, which began with a virus in bats that spread to humans, most likely through civets. To date, a complete Ebola virus has never been isolated from an animal in the region where the world’s largest outbreak occurred between 2013 and 2016."​

As to how it could evolve:
"Just because the virus spreads among humans doesn't mean it was designed to do so. It also flourishes among mink and infects a host of carnivorous mammals. And it wasn’t optimally transmissible among humans for the better part of last year. Rather, new, more efficient variants have evolved around the world. To name one example, the highly transmissible variant of SARS-CoV-2 first reported in India (B.1.617.2, or Delta) has mutations in the nucleotides encoding its furin cleavage site that appear to make the virus better at infecting cells8."​

The whole article is worth a read if you are interested in the topic: https://www.nature.com/articles/d41586-021-01529-3
Ygggdrasil, I want to commend your indefatigable commitment to providing others with useful information. What is most commendable is that you never attach others, like me, as quacks and such.

I know my comments are sophomoric but they are offered as vehicles to expanded thought.

You have repeatedly objected to

Virus Optimized for humans Last updated on March 30, 2021, at 2:21 p.m. ET
The WHO Report On COVID-19's Origins Shows We May Never Know Where The Coronavirus Came From

“For SARS-CoV-2 to get into human cells, the spike protein on its surface must latch onto a receptor on the cells called ACE2. After the first complete genetic sequence of the virus was posted online by Chinese scientists in January 2020, a team led by Nikolai Petrovsky, an immunologist who works on vaccine development at Flinders University near Adelaide in Australia, started running computer simulations of how well the coronavirus spike protein could bind to ACE2 receptors from different species.

“When we got to the end of the project, what stumped us was that binding to human ACE2 was higher than for any species we tested,” Petrovsky told BuzzFeed News. “For us, that was very hard to explain based on a natural origins theory.”

https://www.buzzfeednews.com/article/peteraldhous/who-covid-origins-china-report-lab-accident

You are claiming that different variants of the virus show that the original SARS-CoV-2 was not the optimal configuration.

As the virus has progressed different variants have emerged. In some way perhaps they are more optimal. I do not know how optimization is being measured so I don't know how to compare it to ??

My thought is the mutations you are talking about are a subset of the major mutation. Example - Go from A to B via mutation. B is the major mutation. Then you have the subset b1,b2,b3,...

So what is the major mutation? It is the increase in the positive charge of the S protein on the surface where it binds to the ACE2 receptor.

Analysis the S protein binding to the host ACE2 receptor showed a 30% higher binding energy for SARS-CoV-2 than for the SARS-CoV S protein.

Our findings reveal that the SARS-CoV-2 S protein is slightly more positively charged than that of SARS-CoV since it contains four more positively charged residues and five less negatively charged residues (Table 1). Even if the difference in charge between SARS-CoV-2 and SARS-CoV S proteins is rather small, this effect can be amplified by the high number of S proteins that are present on a virus particle. This difference in chargebetween SARS-CoV-2 and SARS-CoV S proteins can have a significant impact in cell adhesion and crossing of
the BBB28,29


Considerations around the SARS-CoV-2 Spike Protein with Particular Attention to COVID-19 Brain Infection

and Neurological Symptoms
Published online 2020 Jul 6
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7374936/

Further support

Spike Proteins of SARS-CoV and SARS-CoV-2 Utilize Different Mechanisms to Bind With Human ACE2​

https://www.frontiersin.org/articles/10.3389/fmolb.2020.591873/full

So how did the increase in positive charge come about? This is an area that needs investigation.
 
  • #47
chemisttree
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Or bat——> Wuhan Lab ———> Lab Workers——-> the world
 
  • #48
atyy
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Or bat——> Wuhan Lab ———> Lab Workers——-> the world
This is unlikely for the following reasons (unless the WIV has provided misleading information).

Could WIV staff have been accidentally infected with SARS-CoV-2? Shi Zhengli of the Wuhan lab reported around July 2020 that antibody tests on her staff were negative, which is not consistent with accidental infection of her staff with SARS-CoV-2.

Could her staff have been infected with another virus, which then underwent natural selection in humans to become SARS-CoV-2? They have attempted to comprehensively examine sequences in their samples, and thus far the closest virus in their samples to SARS-CoV-2 is RaTG13, about 96% similar, corresponding to 30 or more years of natural evolution. Furthermore, RaTG13 was never "live" in their lab. They have "live" viruses, but these have only about 80% similarity to SARS-CoV-2.

This information was in an interview with Shi Zhengli, and similar information was in the WHO report on SARS-CoV-2 origins.
https://science.sciencemag.org/content/369/6503/487.summary
https://www.sciencemag.org/sites/default/files/Shi Zhengli Q&A.pdf
https://www.who.int/publications/i/...bal-study-of-origins-of-sars-cov-2-china-part
 
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  • #49
chemisttree
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Interesting, if true.
We know of the inaccuracies discovered in early Chinese-made antibody test kits, so being negative, again if true, isn’t solid evidence at all.

What is true is that the lab was performing gain of function research that included creating a chimeric CoV backbone virus with human adapted spike protein. The addition of a furin cleavage site segment would complete the package... or at least the roadmap to create SARS-COV2. There is some discussion as to likely natural pathways for this furin cleavage site to have been added but to my knowledge, there has been no evidence of it found in naturally in Bats... which should be a requirement for us to believe these various theories.

That’s just too close to ignore.
 
  • #50
atyy
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Interesting, if true.
We know of the inaccuracies discovered in early Chinese-made antibody test kits, so being negative, again if true, isn’t solid evidence at all.

It's true that we don't know the details of the serology test they used. However, the lab has experience with serology testing, including test development, which they had used to provide serological evidence of bat SARS-Related Coronavirus Infection in people in China. They also mention serology testing for Ebola virus, Nipah virus and bat SARSr-CoV Rp3 in an addendum to a research paper. So they have demonstrated competence with serology testing.

What is true is that the lab was performing gain of function research that included creating a chimeric CoV backbone virus with human adapted spike protein. The addition of a furin cleavage site segment would complete the package... or at least the roadmap to create SARS-COV2. There is some discussion as to likely natural pathways for this furin cleavage site to have been added but to my knowledge, there has been no evidence of it found in naturally in Bats... which should be a requirement for us to believe these various theories.

That’s just too close to ignore.

That's too far. Those experiments are done with SARS-CoV backbones, and SARS-CoV has about 80% similarity to SARS-CoV-2. The WIV did have RaTG13, which even at 96% similarity is extremely unlikely to have been the basis for lab generation of SARS-CoV-2. The WIV has also reported that it did not have RaTG13 live, and its live viruses have only about 80% similarity to SARS-CoV-2.
 
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