The Evolution of the SARS-COV-2 virus

[Phil Core]

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.

 

[Ygggdrasil]

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):

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.

 

[Ygggdrasil]

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).

 

[Astronuc]

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/technology/exclusive-how-amateur-sleuths-broke-the-wuhan-lab-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

 

[atyy]

Newsweek - https://www.msn.com/en-us/news/technology/exclusive-how-amateur-sleuths-broke-the-wuhan-lab-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%20Zhengli%20Q&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."

 

[Monsterboy]

"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.

 

[Phil Core]

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%20Zhengli%20Q&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 anyone 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

 

[atyy]

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.

 

[Ygggdrasil]

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

 

[Phil Core]

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

 

[Phil Core]

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.

 

[chemisttree]

Or bat——> Wuhan Lab ———> Lab Workers——-> the world

 

[atyy]

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%20Zhengli%20Q&A.pdf
https://www.who.int/publications/i/...bal-study-of-origins-of-sars-cov-2-china-part

 

[chemisttree]

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.

 

[atyy]

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.

 

[Phil Core]

The investigation of the origins of the SARS – CoV-2 virus is one of the most tainted investigation in all of science. It is just coming out now how a part of the scientific community was coerced into endorsing or remaining silent on any alternative except that the virus had a Natural origin.

I question the acumen of anyone who puts any veracity in what the WIV or the WHO states about the origins of the SARS-CoV-2 virus.

The latest WHO dog and pony excursion to the WIV was beyond the pale. Anyone associated with the 315 page report the organization put out should be ashamed. The investigating group was chaperoned and spoon fed the entire time.

I did find – A SARS-like cluster of circulating bat coronaviruses shows potential for human emergence - https://www.nature.com/articles/nm.3985 to be very informative.

It contained not only evidence of suppression of investigation but also insight into gain of function procedures.

Things that should be noted.

1. The article was first published on 09 Nov 2015

2. Where the research was conducted and how it was funded – University of North Carolina //USAID-EPT-PREDICT funding from EcoHealth Alliance

3. It contains this suppressive statement

30 March 2020 Editors’ note, March 2020: We are aware that this article is being used as the basis for unverified theories that the novel Coronavirus causing COVID-19 was engineered. There is no evidence that this is true; scientists believe that an animal is the most likely source of the coronavirus.

“No evidence” and “scientists” (in the large) are strong statements.

Of great interest is the date of the publication of this paper – 09 Nov 2015. This shows that advanced research into CoV viruses had been going on for quite some time.

Current Origin research avoids giving time lines for occurrences. It is as if in late 2019/early 2020 something happened between bats and pangolins and we got the COVID-19 virus.

An emerging lab evolution of the COVID-19 virus is to start with research as indicated above. The next step is to enhance the positive charge of the surface of the spike protein that interfaces with the ACE2 receptors.

Note - In the search for an animal origin for the COVID-19 you want to focus on mammals that have ACE2 structures very similar to humans.

 

[pinball1970]

The investigation of the origins of the SARS – CoV-2 virus is one of the most tainted investigation in all of science. It is just coming out now how a part of the scientific community was coerced into endorsing or remaining silent on any alternative except that the virus had a Natural origin.

I question the acumen of anyone who puts any veracity in what the WIV or the WHO states about the origins of the SARS-CoV-2 virus.

The latest WHO dog and pony excursion to the WIV was beyond the pale. Anyone associated with the 315 page report the organization put out should be ashamed. The investigating group was chaperoned and spoon fed the entire time.

I did find – A SARS-like cluster of circulating bat coronaviruses shows potential for human emergence - https://www.nature.com/articles/nm.3985 to be very informative.

It contained not only evidence of suppression of investigation but also insight into gain of function procedures.

Things that should be noted.

1. The article was first published on 09 Nov 2015

2. Where the research was conducted and how it was funded – University of North Carolina //USAID-EPT-PREDICT funding from EcoHealth Alliance

3. It contains this suppressive statement

30 March 2020 Editors’ note, March 2020: We are aware that this article is being used as the basis for unverified theories that the novel Coronavirus causing COVID-19 was engineered. There is no evidence that this is true; scientists believe that an animal is the most likely source of the coronavirus.

“No evidence” and “scientists” (in the large) are strong statements.

Of great interest is the date of the publication of this paper – 09 Nov 2015. This shows that advanced research into CoV viruses had been going on for quite some time.

Current Origin research avoids giving time lines for occurrences. It is as if in late 2019/early 2020 something happened between bats and pangolins and we got the COVID-19 virus.

An emerging lab evolution of the COVID-19 virus is to start with research as indicated above. The next step is to enhance the positive charge of the surface of the spike protein that interfaces with the ACE2 receptors.

Note - In the search for an animal origin for the COVID-19 you want to focus on mammals that have ACE2 structures very similar to humans.

As an outsider looking in (non scientist) reading the thread can I ask what you think if the investigation had not yet taken place?
Occam razor approach?
Deliberate manufacturer and release?
Study and accidental release?
Natural occurred?

Given what is known about SARS 2002 and what is happening with COVID19 now. Ie the evolutionary pathway, speed of change and effects of those changes?
Alpha to Delta 60% increase in transmission rate for instance?

 

[Phil Core]

Thanks for your response.

I want to apologize. My postings have been rather scattered and hard to follow. Know this, just because you can’t follow something doesn’t mean it is you. More times than not it is the material that has not been constructed correctly.

My last post was all over the place.

The first part of the post relates to problems with information being released by WIH and WHO. The skinny – Very fishy. An interesting article - The Lab-Leak Theory: … - https://www.vanityfair.com/news/202...inside-the-fight-to-uncover-covid-19s-origins

Few are still unaware of how pervasive the influence of the Chinese government is in scientific research. (I cast no aspersions on the Chinese people, it is the Chinese government.)

While the above is interesting it is not the real meat of the discuss.

You have hit on one of the main areas that needs to be investigated – time of evolution.

Nature – relatively long time to get from current samples to SARS-COV-2
Influenced in a lab – relatively shorter time.

For the Nature origin this is the argument.

Parts of the structures of the SARS-COV-2 virus appear in Nature. Therefore since similar structures appear in Nature the origin must be Nature. Further, these parts appear in different organisms, so somehow they had to combine. This somehow and the time it would take for this to happen are part of the reason that the Nature argument is not as strong.

It would take a very long time to go from what we have now in bats and pangolins to arrive at the SARS-COV-2 genome, via the process of random mutation and natural selection. I do not know how to calculate this but a minimum is 30 years. Over this period of time there should be more evidence of the evolution of the virus via random mutation and random mutation.

To account for this a “missing link” is stipulated. How it came about is unknown. When talking about this “missing link” it always seem that the sequence of events would be bat – pangolian – missing link – human. The implication is that the transformation was linear and rather rapid.

I suspect if this actually happened that there would be many alterations of these mutations, not just one, over an extended period of time. As of yet we have made no progress in discovering other organisms since the bat and Pangolin, none. Or other bats or Pangolins with more advanced genomes.

The next statement to counter this is that there a very large number of mammals that could be the missing link and that it is almost impossible to acquire and test all.

I have been able to narrow down the search somewhat to mammal, that comes in contact with humans, and the most important criterion is that this mammals ACE2 receptors has to be very similar to humans. This last constraint considerably reduces the need of testing mammals for every covirus they contain. You just have to test their ACE2 receptors.

The ACE2 constraint manifests due to the increased ability of the SARS - CoV- 2 spiked protein to bind to the ACE2 receptor due to the spiked proteins increased positive surface charge where it binds with the negatively charged surface of the human ACE2 receptor.I will leave the rest for another post.

However, once again you are to be commended for focusing on the time needed for change.

Nature – relatively long time Influenced in a lab – relatively shorter time.

 

[BillTre]

It would take a very long time to go from what we have now in bats and pangolins to arrive at the SARS-COV-2 genome, via the process of random mutation and natural selection. I do not know how to calculate this but a minimum is 30 years. Over this period of time there should be more evidence of the evolution of the virus via

What is all this based on?
You have no references for these kind of assertions as far as I can tell, but you make a lot of assertions.

Where specifically did this: "a minimum is 30 years" come from?
Also, if that in fact is the case, why could this process not have started 30 years ago? There is a lot of time and no obvious starting point.

You really sound like you have an idea you want to find support for, but don't know a lot about what you are talking about.

 

[Phil Core]

30 years is just a guesstimation.

Natural evolution via random mutation and natural selection will take much longer then a Nurtured evolution in a lab.

There are 2 points.

1. The Nature evolution of the SARS - CoV - 2 virus mentioned everywhere avoids addressing how long the process of change would take via random mutation and natural selection. They make it seem like it is rather rapid.

If you want to start with the bat or pangolin genome and via random mutation and natural selection yield the human SARS-Cov-2 virus and have it happen in a few years, I am certainly willing to entertain your idea.

2. If the process has been going on for a long time we should be able to find more virus sample that show the progression via random mutation and natural selection. To date we have been able to find none.

 

[atyy]

1. The Nature evolution of the SARS - CoV - 2 virus mentioned everywhere avoids addressing how long the process of change would take via random mutation and natural selection. They make it seem like it is rather rapid.

If you want to start with the bat or pangolin genome and via random mutation and natural selection yield the human SARS-Cov-2 virus and have it happen in a few years, I am certainly willing to entertain your idea.

There are hypotheses in which estimates are given. For example, Boni et al (2020) propose "Divergence dates between SARS-CoV-2 and the bat sarbecovirus reservoir were estimated as 1948 (95% highest posterior density (HPD): 1879–1999), 1969 (95% HPD: 1930–2000) and 1982 (95% HPD: 1948–2009), indicating that the lineage giving rise to SARS-CoV-2 has been circulating unnoticed in bats for decades."

Also, the combination of bat and pangolin is only one hypothesis. There are other hypotheses, one of which by Lystras (2021) suggests that the furin cleavage site can arise by recombination of sequences already been found in bat Sarbecoviruses.

2. If the process has been going on for a long time we should be able to find more virus sample that show the progression via random mutation and natural selection. To date we have been able to find none.

But that is the same for the lab leak hypothesis. The difference is that we know the diversity in nature is much more than in the lab (and anyway the closest lab samples such as RaTG13 are collected from nature, with no additional lab manipulation), while Shi Zhengli of the WIV has already tried to comprehensively examine her samples for SARS-CoV-2 or for viral sequences that could combine to form SARS-CoV-2, and https://www.sciencemag.org/sites/default/files/Shi%20Zhengli%20Q%26A.pdf (also stated in the WHO origins report as evidence for why the lab leak is unlikely). While it is hard to rule out an incomplete search in the lab, the degree to which a complete search can be attained in the lab is much higher than for the samples found in nature.

[Edited my description and referencing of Lystras (2021) just before @Phil Core replied below]

 

[Phil Core]

There are hypotheses in which estimates are given. For example, Boni et al (2020) propose "Divergence dates between SARS-CoV-2 and the bat sarbecovirus reservoir were estimated as 1948 (95% highest posterior density (HPD): 1879–1999), 1969 (95% HPD: 1930–2000) and 1982 (95% HPD: 1948–2009), indicating that the lineage giving rise to SARS-CoV-2 has been circulating unnoticed in bats for decades."

Also, the combination of bat and pangolin is only one hypothesis. There are other hypotheses, one of which by Lystras et al (2021) suggests that the sequence for the furin cleavage site has already been found in a bat Sarbecovirus.But that is the same for the lab leak hypothesis. The difference is that we know the diversity in nature is much more than in the lab (and anyway the closest lab samples such as RaTG13 are collected from nature, with no additional lab manipulation), while Shi Zhengli of the WIV has already tried to comprehensively examine her samples for SARS-CoV-2 or for viral sequences that could combine to form SARS-CoV-2, and https://www.sciencemag.org/sites/default/files/Shi%20Zhengli%20Q%26A.pdf (also stated in the WHO origins report as evidence for why the lab leak is unlikely). While it is hard to rule out an incomplete search in the lab, the degree to which a complete search can be attained in the lab is much higher than for the samples found in nature.

I appreciate your reply. Actually the prior comment by BillTre is right. I do not know a lot about what I am talking about but I have taken what I can and tried to arrange the information in a reasonable way.

With respect to the RaTG13 sample and the reporting by Shi Zhengli.

While your statement makes sense - "While it is hard to rule out an incomplete search in the lab, the degree to which it can be attained is certainly much higher than for the samples found in nature."

1. I can not put too much credence in anything coming from the WIV.
2. Another possibility is that while Shi Zhengli's lab was the level 4 lab at WIV, additional research was done else where. There are several level 3 and 2 labs at WIV.
3. I can even entertain that the nuturing research was done at a location other than WIV or several locationsI did not repost the details of how the SARS-CoV-2 virus might have evolved in a lab.

This is not the complete sequence, but a train of thoughts that bothers me the most is the claim by Anderson and others that the SARS-CoV-2 virus seems to have been optimized for humans. My claim is that it is possible that the positive charge of the spike proteins surface was increased via nurturing of some sort, which makes the binding affinity between the spike and the human ACE2 receptor stronger.

Andersen notes – “SARS-CoV-2 appears to be optimized for binding to the human receptor ACE2”

https://www.nature.com/articles/s41591-020-0820-9Virus 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 forany 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

This may have been done by increasing the positive charge of the spike protein's surface that interfaces with the human ACE receptors.

Cov vs Cov-2
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/

In addition, we found 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 which may lead to an increased affinity to bind to negatively charged regions of other molecules through nonspecific and specific interactions. 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 charge
between SARS-CoV-2 and SARS-CoV S proteins can have a significant impact in cell adhesion and crossing of the BBB28,29 which will be discussed more in detail later in this Article.

In particular, it has been reported that the increased positive electrostatic potential of the SARS-CoV-2 binding surface is mainly due to an essential mutation of the hydrophobic residue Val404, present in SARS-CoV, to the positively charged residue Lys417 in SARS-CoV-2.31,34 Amin et al. also identified a complementary negative electrostatic potential on the surface of the binding site of ACE2.33

Therefore, an increase of the number of the positive amino acids of the SAR-CoV-2 envelope might increase in a significant manner the adhesion properties of SAR-CoV-2

 

[Pythagorean]

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 https://www.sciencemag.org/sites/default/files/Shi%20Zhengli%20Q%26A.pdf. 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.

That tweet by Kristian Andersen is gone now. Any idea what happened? I found this article but I have no idea the credibility of the outlet: https://www.opindia.com/2021/06/scr...s-coronavirus-engineered-lab-leak-hypothesis/

 

[Pythagorean]

That tweet by Kristian Andersen is gone now. Any idea what happened? I found this article but I have no idea the credibility of the outlet: https://www.opindia.com/2021/06/scr...s-coronavirus-engineered-lab-leak-hypothesis/

looks like he gave an interview about it recently:
https://www.nytimes.com/2021/06/14/science/covid-lab-leak-fauci-kristian-andersen.html

 

[atyy]

looks like he gave an interview about it recently:
https://www.nytimes.com/2021/06/14/science/covid-lab-leak-fauci-kristian-andersen.html

Thanks. Here my sentiments are the same as Jeffrey Barrett's.

 

[atyy]

That tweet by Kristian Andersen is gone now. Any idea what happened? I found this article but I have no idea the credibility of the outlet: https://www.opindia.com/2021/06/scr...s-coronavirus-engineered-lab-leak-hypothesis/

Most of that article is not credible. There has not been a coverup, but as explained in posts #33 (that you quoted) and #40, as well as the Nature news item linked by @Ygggdrasil in post #44, the lab leak hypothesis has been examined, and present evidence https://www.sciencemag.org/sites/default/files/Shi%20Zhengli%20Q&A.pdf that it is unlikely. The evidence was summarized in the WHO report, which was open to following up if new evidence became available.

I don't remember exactly what was in the now-deleted Tweets, but the Nature article reports at least some of their content:

"A Medium article that speculates on a lab origin for SARS-CoV-2 quotes David Baltimore, a Nobel laureate and professor emeritus at the California Institute of Technology in Pasadena, as saying that viruses don’t usually have that particular code for arginine, but humans often do — a “smoking gun”, hinting that researchers might have tampered with SARS-CoV-2’s genome.

Andersen says that Baltimore was incorrect about that detail, however. In SARS-CoV-2, about 3% of the nucleotides encoding arginine are CGG, he says. And he points out that around 5% of those encoding arginine in the virus that caused the original SARS epidemic are CGG, too."

Edit: I see the NY Times interview with Andersen that you linked in post #56 gives the same information.

 

[atyy]

https://www.republik.ch/2021/06/05/herr-drosten-woher-kam-dieses-virus
Interview with Christian Drosten by Marie-José Kolly, Angela Richter und Daniel Ryser

Excerpts below are by Google Translate

"There are actually two laboratory theses. One would be malice that someone has intentionally constructed such a virus. The other would be the research accident, in which an experiment went wrong despite good intentions and curiosity. The malicious thing, to be honest: you have to talk to intelligence officers about it. I cannot judge that."

"Let me explain it with a picture: To check, for example, whether adjustments make the virus more contagious, I would take an existing system, incorporate the change and then compare it with the old system. If I want to know whether a new car radio improves the sound, I take an existing car and replace the radio there. Then I compare. I'm not building a completely new car for it. But that's exactly how it was with Sars-2: The whole car is different."

"This idea of a research accident is extremely unlikely for me because it would be far too cumbersome. The idea of malicious use by some secret service laboratory somewhere: If anything, something like that would probably not come from the Wuhan Virology Institute. This is a reputable academic institute."

 

[Phil Core]

If you mean The proximal origin of SARS-CoV-2 this link still works https://www.nature.com/articles/s41591-020-0820-9

In the beginning of this article you have -

"Our comparison of alpha- and betacoronaviruses identifies two notable genomic features of SARS-CoV-2: (i) on the basis of structural studies7,8,9 and biochemical experiments1,9,10, SARS-CoV-2 appears to be optimized for binding to the human receptor ACE2"

However this is counter by what I consider a somewhat puzzling statement

"While the analyses above suggest that SARS-CoV-2 may bind human ACE2 with high affinity, computational analyses predict that the interaction is not ideal7 and that the RBD sequence is different from those shown in SARS-CoV to be optimal for receptor binding7,11. Thus, the high-affinity binding of the SARS-CoV-2 spike protein to human ACE2 is most likely the result of natural selection on a human or human-like ACE2 that permits another optimal binding solution to arise. This is strong evidence that SARS-CoV-2 is not the product of purposeful manipulation."

Further clarity is given in (7) above

Recognition by the Novel Coronavirus from Wuhan: an Analysis Based on Decade-Long Structural Studies of SARS Coronavirus - https://journals.asm.org/doi/10.1128/JVI.00127-20​

Here it was stated that theoretically an optimal binding configuration was discovered that differs from that found in SARS-CoV-2. However, the binding affinity found in SARS-CoV-2 is still superior to anything found in Nature.

Andersen seems to making the argument that if SARS-CoV-2 was manufactured/influenced in a lab that it would use the theoretically maximum form. From here he jumps to "Thus" and concludes with "strong evidence". I do not find his logic convincing. There could be many reasons why a lab/nurtured virus does not reach theoretical max form.

Andersens best statement is - "However, since we observed all notable SARS-CoV-2 features, including the optimized RBD and polybasic cleavage site, in related coronaviruses in nature, we do not believe that any type of laboratory-based scenario is plausible." (The optimized RBD is actual found in SARS-CoV-2. SARS-Cov binding affinity is at least 30% weaker.)

This amounts to saying we find some of the parts needed for the virus scattered in different mammals therefore the SARS-CoV-2 virus did not originate in a lab.

Note - To date no new candidates for missing link have been found. (7) gives a clue to what one should look for in Nature.

"Different lines of research have shown that which host is susceptible to SARS-CoV infection is primarily determined by the affinity between the viral RBD and host ACE2 in the initial viral attachment step"

You should be looking for a mammal that has ACE2 receptors very close to humans. This should make hunting for it a bit easier.

 

[atyy]

Andersen seems to making the argument that if SARS-CoV-2 was manufactured/influenced in a lab that it would use the theoretically maximum form. From here he jumps to "Thus" and concludes with "strong evidence". I do not find his logic convincing. There could be many reasons why a lab/nurtured virus does not reach theoretical max form.

The most likely reason a lab-nurtured virus does not reach a theoretical optimum would be if it arose from selection in the lab. However, in the part of the paper you referenced, Andersen et al were considering lab-design of the virus. Andersen et al consider the case of selection in the lab separately towards the end of the paper in the section "Selection during passage". While they considered natural selection more likely, they explicitly acknowledged that selection during passage in the lab could not be ruled out without further evidence. Further evidence did come along in the form of reports by Shi https://www.sciencemag.org/sites/default/files/Shi%20Zhengli%20Q%26A.pdf of the WIV in July 2020 (with similar reports referenced in the WHO report) about her group's comprehensive search of viral sequences in the lab, and antibody testing of their staff for infection by SARS-CoV-2 or closely related viruses.

 

[Pythagorean]

Thanks atyy, that article was fishy, but I have been out of the loop and am just catching up now. Didnt even know who Fauci was, title wise.

Does lab leak theory include the case that they were holding the virus; not necissarily experimenting with it, but carried the infection out of the lab? E.g., no evolution occurred in the lab, it was just mishandled as a sample from nature?

 

[atyy]

Does lab leak theory include the case that they were holding the virus; not necissarily experimenting with it, but carried the infection out of the lab? E.g., no evolution occurred in the lab, it was just mishandled as a sample from nature?

Yes, it includes that case. This case is also unlikely for 2 reasons.

1) If it occurred, it would most likely result in staff of the Wuhan Institute of Virology (WIV) being infected. However, Shi Zhengli who heads the lab most associated with the study of coronaviruses, including collection of samples, reported that they had done antibody tests on their staff. These tests can detect past infections by SARS-CoV-2 or similar viruses. These tests were negative.

2) If it occurred, they would have to have a virus with the same or similar sequence to SARS-CoV-2. Shi Zhengli reported that they have gone through all their samples to search for such sequences. The closest they have found is RaTG13, which at 96% similarity is about 30 years or more in terms of natural evolution from SARS-CoV-2. Also, RaTG13 had never been cultured (it seems they've run out of RaTG13 after sequencing it quite fully). The do have viruses "live" in culture, but these have only about 80% similarity to SARS-CoV-2, which is too way too far away.

The above information can be found in her https://www.sciencemag.org/sites/default/files/Shi%20Zhengli%20Q%26A.pdf with Science in July 2020. Among the remaining possibilities are that the above tests and searches were incomplete (just because no tests are 100%), but if they were carried out and yielded the above answers, any lab leak, including accidental release due to mishandling is rendered very unlikely.

Another possibility is that the answers she has given are misleading. However, there are many details given in the interview that make me think these are reports of real data. Furthermore, the lab has openly published its results in excellent scientific papers over many years (eg. RaTG13 that they sequenced more fully recently had already been reported in their previous partial sequencing results) - quite the opposite of doing things in secret. Unless evidence is produced to the contrary, it doesn't make much sense to distrust the information in the interview, while trusting the information they've published and using both trust in the papers and distrust in the interview to cast suspicion on them.

 

[Phil Core]

I do not consider the WHO to be a reliable source of information on the origins of the SARS-CoV-2 virus.

Shi Zhengli would be under extreme pressure to report things favorable to the Chinese government and can not be considered to be a reliable source.

1. A series of gain of function experiments would be involved.
2. These experiments would take a long time
3. It would be hard to hide this in a lab
4. Shi Zhengli would know what type of work was being conducted in her lab
5. She should have know ex ante so why even bother to test

The reported lack of antibodies in June/July of a subset of workers is not sufficient proof of much.

An unconsidered option is that the experiments of interest were conducted in lab/s elsewhere from the known level 4 lab at WIH.

Another unconsidered option is that these experiments were constructed to make it look like the source was Nature. Hence you will not find straight cut and paste alterations.

If the origins of the virus is found to have been influenced in a lab then that research had been going on for some time and at least one if not more of the people involved are extremely skilled.

You can make a no lab case but then you need to make a Nature case. It has been a year and half and no progress has been made here.

I did not completely follow the sequence but you quoted information at one time that seemed to imply to get from what we have - 2 separate parts of the virus - to the SARS-CoV-2 virus would take a min of 30 years - via random mutation and natural selection. There should be a substantial sequence of viruses leading up to the SARS-CoV-2 virus. None have been found.

The best clue I have been able to find for searching in Nature for the origin is - You should be looking for a mammal that has ACE2 receptors very close to humans. This should make hunting for it a bit easier.

 

[Vanadium 50]

I do not consider the WHO to be a reliable source of information on the origins of the SARS-CoV-2 virus.

Shi Zhengli would be under extreme pressure to report things favorable to the Chinese government and can not be considered to be a reliable source.

Is there any source you consider reliable? For that matter, is there any evidence whatsoever that would convince you to change your mind?

 

[Phil Core]

Is there any source you consider reliable? For that matter, is there any evidence whatsoever that would convince you to change your mind?

If you want to claim that the recent investigation by the WHO in Wuhan and the 300+ page report are examples of scientific rigor, I concede.

If your case for the Natural/In The Wild Origin is as outline in (1) – (5), I find the logic flawless and not a subject for further inquiry.

Nature
1. Genome sequenced
2. Partial matches – bat – Pangolian
3. Somehow the viral content of these mammals mixed?
4. Or perhaps there was an intermediary?
5. Somehow jump made to human via unknown host

 

[Vanadium 50]

I don't think you answered my questions. Is there any source you consider reliable? For that matter, is there any evidence whatsoever that would convince you to change your mind?