I think, in parallel, Shi Zhengli studied Ra4991 with great interest and, most likely, it was somehow passaged either in various cell cultures, or in humanized mice, or in civets. Most likely, in parallel, this was done in the presence of some kind of mutagen, for example, ribavirin drugs or the same remdesivir that Barik actively studied and could hardly ignore Shi Zhengli.
- Why add remdesivir?
- Such antiviral drugs cause a large number of mutations. Thus, they cause this virus to change very quickly and strongly. In nature, this would take years.
- Why did you decide that they were using remdesivir? Is this drug listed in any of their articles under "methods"?
- I know that this is the scientific brainchild of Ralph Barik, he studied remdesivir for many years. In parallel, as I know, Shi Zhengli was working on her Chinese peptide designed to block the fusion of the spike protein with the membrane, after the junction between the spike protein subunits is cleaved by furin or another enzyme. The stated goal of EcoHealth was to create a universal coronavirus vaccine, says Peter Dashak himself. In November 2019, in an interview, he said that spike proteins are easy to manipulate, so why create a vaccine only against SARS, if you can try to create a universal drug.
- Is this a hypothesis of the DRASTIC team?
- Yes, now we are working on it. The idea arose at the very beginning, when we were arguing whether RaTG13 could be the progenitor of SARS-CoV-2. In the scientific literature, cases have been described where it has been shown that with ribavirin, a similar pattern of mutations is observed, as between RaTG13 and SARS-CoV-2. One type of mutations prevails over the other, which clearly shows that they are not accidental, as usually happens in nature, but that they are caused by something. Some kind of additional agent. Ribavirin is a nucleoside analog, and so is remdesivir. They can cause a particular pattern of mutations.
- That is, if you transplant coronavirus from one Petri dish to another, adding a drug, then the transition will take not 40–70 years, as calculated by scientists, but less?
- Yes. In a test tube, it is possible to accumulate 4% of the differences between RaTG13 and SARS-CoV-2 in a couple of years of passaging, and the addition of a mutagen shortens this period several times. In 2019, Barik's laboratory showed how 100 mutations in coronavirus can be obtained using a mutagen in just 30 passages.
- Do you think such experiments were carried out at the Wuhan Institute of Virology before?
- Quite possible. Initially, they could experiment with Ra4991 in order to adapt it to mice, as Barik did with the first SARS (the same MA15, which they then dissected together with Shi Zhenli in 2015) - simply because it is most convenient to work with mice. Well, God himself ordered the use of "humanized" mice, which were bred by the same Barik, who have a human ACE2 receptor, and generally chimeric lungs, thymus, bone marrow, etc. Then, when it got far enough away from the original Ra4991, they renamed it RaTG13. I think this was one branch of work, and SARS-CoV-2 could be a parallel branch in other animals or cell cultures. This work may have been done by some other team or even another laboratory.
- Why did you decide that they were using remdesivir? Is this drug listed in any of their articles under "methods"?
- I know that this is the scientific brainchild of Ralph Barik, he studied remdesivir for many years. In parallel, as I know, Shi Zhengli was working on her Chinese peptide designed to block the fusion of the spike protein with the membrane, after the junction between the spike protein subunits is cleaved by furin or another enzyme. The stated goal of EcoHealth was to create a universal coronavirus vaccine, says Peter Dashak himself. In November 2019, in an interview, he said that spike proteins are easy to manipulate, so why create a vaccine only against SARS, if you can try to create a universal drug.
- Is this a hypothesis of the DRASTIC team?
- Yes, now we are working on it. The idea arose at the very beginning, when we were arguing whether RaTG13 could be the progenitor of SARS-CoV-2. In the scientific literature, cases have been described where it has been shown that with ribavirin, a similar pattern of mutations is observed, as between RaTG13 and SARS-CoV-2. One type of mutations prevails over the other, which clearly shows that they are not accidental, as usually happens in nature, but that they are caused by something. Some kind of additional agent. Ribavirin is a nucleoside analog, and so is remdesivir. They can cause a particular pattern of mutations.
- That is, if you transplant coronavirus from one Petri dish to another, adding a drug, then the transition will take not 40–70 years, as calculated by scientists, but less?
- Yes. In a test tube, it is possible to accumulate 4% of the differences between RaTG13 and SARS-CoV-2 in a couple of years of passaging, and the addition of a mutagen shortens this period several times. In 2019, Barik's laboratory showed how 100 mutations in coronavirus can be obtained using a mutagen in just 30 passages.
- Do you think such experiments were carried out at the Wuhan Institute of Virology before?
- Quite possible. Initially, they could experiment with Ra4991 in order to adapt it to mice, as Barik did with the first SARS (the same MA15, which they then dissected together with Shi Zhenli in 2015) - simply because it is most convenient to work with mice. Well, God himself ordered the use of "humanized" mice, which were bred by the same Barik, who have a human ACE2 receptor, and generally chimeric lungs, thymus, bone marrow, etc. Then, when it got far enough away from the original Ra4991, they renamed it RaTG13. I think this was one branch of work, and SARS-CoV-2 could be a parallel branch in other animals or cell cultures. This work may have been done by some other team or even another laboratory.
At some point, they also inserted a furin site there (of eight amino acids, necessary for a pathogen to penetrate into a human cell - Izvestia), and maybe also a spike protein from another virus - for example, what was found in pangolins back in early 2019. But this is an even stranger story.
- What is its weirdness?
- Because in one of the datasets published long before the pandemic, for some reason, a receptor-binding domain appears, identical to what we see in SARS-CoV-2, but identical at the amino acid level. Maybe someone saw him and wanted to experiment? Maybe it was a joint work between the Guangdong scientists who published this pangolin dataset, with some Wuhan people who might have been working on passing Ra4991, which eventually turned into SARS-СoV-2?
- And at some point, this generally harmless virus became so infectious that it entered the lungs of an employee of the Wuhan Institute of Virology or a sequencing center?
- I think it was so. Most likely, the furin site was the catalyst, which lowers the dose required for infection by several times or an order of magnitude. Since it was previously believed that coronaviruses do not pass well on humans, they worked, most likely, in BSL2 conditions (the second level of laboratory safety: mask + gloves. - Izvestia), not bothering much with safety precautions.
The sequencing center is a parallel version. Indeed, for work, it was required to constantly sequencing (read the genomes of viruses. - Izvestia) samples. We see that RaTG13, for example, has been sequenced at least twice: once in 2017 and once in 2018.
- Why sequence the same thing twice?
- This is an interesting question. It seems to us that they periodically did sequencing to see what mutations accumulated during the passage in animal cells. Because today whole genome sequencing does not take long. Well, a couple of months at most, if you are in no hurry. And they did it once in the summer of 2017, once in the summer of 2018. This immediately arouses suspicion. Some work was probably in progress. Perhaps all this was done in order to eventually make some kind of pan-coronavirus vaccine. https://iz.ru/export/google/amp/1180484
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