Discussion: Chinese Academy of Sciences (CAS) in Wuhan has been working with bats and coronavirus for many years - DNA manipulations, cloning....

[tetano]

Whether Covid escaped from a lab or not, it’s time to talk about biosecurity


The debate on the origins of the Covid-19 pandemic has recently focused on the potential for the Sars-CoV-2 virus to have escaped from the Wuhan Institute of Virology, located in the Chinese city of Wuhan, the centre of the pandemic. This institute houses a maximum containment laboratory, more commonly known as a biosafety level 4 (BSL-4) lab, designed to handle dangerous pathogens for which there are no available treatments or vaccines.

The controversy has brought renewed attention to biosafety, biosecurity, “gain-of-function” and other “dual-use” research, along with consideration of the level of oversight that such labs should be operating under. Although this debate has become polarised and politicised, we should not lose sight of the importance of these issues, even if it turns out this lab had nothing to do with the emergence of the novel coronavirus. Concerns about whether labs are conducting their research safely, securely and responsibly are not new, or of relevance solely to labs in China – as revealed by a comprehensive study on global BSL-4 labs that we recently completed.


..

https://www.theguardian.com/commentisfree/2021/jun/15/covid-escaped-lab-or-not-biosecurity-laboratories

[Pathfinder]

Ex-CDC chief Robert Redfield explains belief COVID came from China lab

By Yaron SteinbuchJune 15, 2021 | 11:40am | Updated

Former CDC Director Robert Redfield defended the theory that COVID-19 escaped from a Chinese lab, arguing the deadly bug’s efficient human-to-human spread contradicted the behavior of other deadly coronaviruses with similar profiles — and was simply not “biologically plausible.”

“I said before that I didn’t think it was biologically plausible that COVID-19 went from a bat to some unknown animal into man and now had become one of the most infectious viruses,” Redfield said during an interview with Fox News.

“That’s not consistent with how other coronaviruses have come into the human species. And, it does suggest that there’s an alternative hypothesis that it went from a bat virus, got into a laboratory, where in the laboratory, it was taught, educated, it evolved, so that it became a virus that could efficiently transmit human to human,” he added.
...
He argued that COVID-19’s efficient human-to-human spread contradicted the behavior of other deadly bugs, such as SARS and MERS, which first infected people through animal contact but spread at a much slower pace, Fox News reported.
...
Redfield expressed disappointment in what he described as a “lack of openness” in the scientific community to “pursue both hypotheses.”

“I’m just giving my best opinion as a virologist, and I don’t think it’s plausible that this virus went from a bat to an animal — we still don’t know that animal — and then went into humans and immediately had learned how to be human-to-human transmissible to the point of now causing one of the greatest pandemics we’ve had in the history of the world,” Redfield told Fox News.
...
Redfield also voiced doubt about the integrity of the World Health Organization, which concluded in a joint report with China that a lab leak was “extremely unlikely.”

He argued the WHO was “too compromised” by Beijing’s influence to carry out a truly transparent probe.

“Clearly, they were incapable of compelling China to adhere to the treaty agreements that they have on global health, because they didn’t do that. Clearly, they allowed China to define the group of scientists that could come and investigate,” Redfield told the news outlet. “That’s not consistent with their role.”
...

https://nypost.com/2021/06/15/ex-cdc-chief-explains-belief-covid-19-came-from-china-lab/

[tetano]

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.

Origin investigations are complicated because outbreaks among animals that aren't the main hosts of a particular virus, such as civets in the case of SARS, are often sporadic. Researchers must find the right animal before it dies or clears the infection. And, even if the animal tests positive, viruses found in saliva, faeces or blood are often degraded, making it difficult to sequence the pathogen’s whole genome.

https://www.nature.com/articles/d41586-021-01529-3

[Pathfinder]

OPINION COMMENTARY

Beijing Protests a Lab Leak Too Much

Strong evidence the virus escaped: the Communist Party’s vicious attacks on anyone who speaks out.

By Perry Link
Updated June 13, 2021 11:42 am ET

I am as eager as anyone to follow the world’s virologists as they try to determine how Covid-19 emerged in Wuhan, China. But as a longtime student of Chinese Communist political language, I will need considerable persuading that the disease came from bats or a wet market. The linguistic evidence is overwhelming that Chinese leaders believe the Wuhan Institute of Virology was the source.

Many years ago a distinguished Chinese writer, Wu Zuxiang, explained to me that there is truth in Communist Party pronouncements, butyou have to read them “upside down.”If a newspaper says “the Party has made great strides against corruption in Henan,” then you know that corruption has recently been especially bad in Henan. If you read about the heroic rescue of eight miners somewhere, you can guess that a mine collapse might have killed hundreds who aren’t mentioned. Read upside-down, there is a sense in which the official press never lies. It cannot lie. It has to tell you what the party wants you to believe, and if you can figure out the party’s motive—which always exists—then you have a sense of the truth.

A few years ago another outstanding Chinese writer, Su Xiaokang, brought me one step deeper. You Westerners, he explained, are too **** up on the question of whether propaganda is true or not. For the regime, truth and falsity are beside the point. A statement might be true, false or partly true. What matters is only whether it works. Does it advance the interests of the party?The top leaders hand out words and phrases for their minions to use, like trowels in a garden. The minions dig with them.
...

https://www.wsj.com/articles/beijing-protests-a-lab-leak-too-much-11623598397

---------------------------------------------------------------

Princeton University
Department of East Asian Studies

Perry Link
Professor Emeritus of East Asian Studies, specializes in 20th-century Chinese literature. He received his B.A. from Harvard in 1966 and his Ph.D. from Harvard in 1976...

https://eas.princeton.edu/people/perry-link

[sharon sanders]

...Many years ago a distinguished Chinese writer, Wu Zuxiang, explained to me that there is truth in Communist Party pronouncements, but you have to read them “upside down.”If a newspaper says “the Party has made great strides against corruption in Henan,” then you know that corruption has recently been especially bad in Henan. If you read about the heroic rescue of eight miners somewhere, you can guess that a mine collapse might have killed hundreds who aren’t mentioned. Read upside-down,..

My experience since 2006. Exactly.

[Shiloh]

Did COVID-19 Leak From A Lab? A Reporter Investigates — And Finds Roadblocks
June 17, 20211:54 PM ET
42-Minute Listen

Transcript

TERRY GROSS, HOST:

This is FRESH AIR. I'm Terry Gross. In order to prevent another disaster pandemic, it would be helpful to know with greater certainty how this one started. Many of us assumed that was a settled issue. The virus jumped from an animal to a human, and it spread. The theory that the virus had escaped from a lab in Wuhan, China, seemed to have been dismissed as an explanation advocated by Trump and his allies to blame China for what Trump liked to call the China virus. But last month, President Biden announced he asked the intelligence community to redouble their efforts to examine whether COVID-19 emerged from human contact with an infected animal or from a laboratory accident. Answering that question is also one of the goals of the COVID Commission Planning Group, a nonpartisan group directed by Philip Zelikow, who also directed the 9/11 Commission.

This week, world leaders at the G-7 summit called for a new investigation into the origins of the virus. My guest, journalist Katherine Eban, has been leading her own investigation into the lab leak theory and whether it's credible. She says, when Trump floated the lab leak hypothesis last April, his divisiveness and lack of credibility made the lab leak theory largely off-limits. She reports that those who pushed for transparency say toxic politics and hidden agendas kept us in the dark. But now that Trump is out of office, she says it should be possible to reject his xenophobic agenda and still ask, why did the outbreak begin in the city with a lab housing one of the world's most extensive collections of bad viruses and doing some of the most aggressive research?

Eban's article, "The Lab-Leak Theory," is now on the Vanity Fair website and will be in a subsequent issue of the print magazine. She spent months investigating the story, conducting dozens of interviews and reviewing hundreds of pages of U.S. government documents, including internal memos, meeting minutes and emails. Eban as a contributing editor at Vanity Fair. She previously joined us to discuss her book, "Bottle Of Lies," about fraud in the generic drug industry.

Katherine Eban, welcome to FRESH AIR. Why did you start the story? What made you think that the lab leak theory had any credibility?

KATHERINE EBAN: So my editor and I were just, you know, putting our heads together and talking about now that COVID-19, at least in the U.S., was coming under some control, what were the big remaining questions of the pandemic? And one of the big remaining questions has been its origin, you know, not because of conspiracy theories, which we were intent on unpacking, but because a host animal has not been found that would support a zoonotic origin. And because of Chinese government suppression and lack of transparency, questions have not been put to rest over whether this could possibly be a lab-originated virus.

And I coupled that with the fact that the World Health Organization, on a report that it had partnered with experts on, put out this document about a couple of months ago at this point, basically saying there's no support for the lab leak theory. And the director of the World Health Organization himself said, actually, that theory is still on the table, and we don't really think that this report got to the bottom of it. So taken all of that together, it seemed to me ripe for a deep dive to look at, what are the credible questions that have not yet been answered around a possible lab leak origin?

GROSS: You write, there's reason to doubt the lab leak hypothesis, but for most of the past year, the lab leak scenario was treated not simply as unlikely or even inaccurate, but as morally out of bounds. Would you explain?

EBAN: Yeah. So the the possible hypothesis that this had originated in a laboratory became completely entangled in Trumpian politics. So in April 2020, Trump came out pretty prematurely, essentially contradicted his own intelligence agencies and put forward the idea of a lab leak. And this was from the same president, of course, who was making racist slurs against Asians and calling this the Kung Flu and had contributed to this terrible rise in violence against Asians and, here in this country, Asian Americans. So the fact that he put that out there seemed to sort of brand it as a conspiracy theory and created a kind of antibody response within the government, as one of my sources put it, you know, where people felt they were absolutely determined to fight against what they saw as a conspiracy of this magnitude.

GROSS: So let's lay out what the two main theories are. Theory one is that it jumped - the virus jumped from an animal like a bat to a human. Tell us a little bit about the scientific basis of that theory and a little bit about what the evidence is that that might be what happened...

Read more: https://www.npr.org/transcripts/1007539626

[Emily]

Discussion of permanent ban from Twitter after posting video about NIH funding of Wuhan lab GOF funding.

https://www.bitchute.com/video/XP9b2l2rwRLO/

[Shiloh]

Sensemaking the 'Lab Leak', Rebel Wisdom: https://www.youtube.com/watch?v=BWQikatEYbI


Making The Lab Leak Case, Bret Weinstein & Yuri Deigin: https://www.youtube.com/watch?v=jTFjzeKsOJU

[tetano]

The remarkable diversity of bat coronaviruses

by Vincent Racaniello

All human viruses, including SARS-CoV-2, arose from spillovers from other animals. Results of a recent study of bat samples collected in a small region of Yunnan Province, China revealed additional close relatives of SARS-CoV-2 and SARS-CoV.

After the identification of SARS-CoV-2 in early 2020, wildlife sampling and retrospective genome sequencing revealed highly related viruses in animals. The virus RaTG13, from Rhinolophus affinis, shares the highest overall genome identity with SARS-CoV-2, 96.10%. The virus RmYN02 from the bat R. malayanus is the closest relative of SARS-CoV-2 in the ORF1ab open reading frame. Pangolin viruses from Guangdong have identical amino acids at six key residues in the receptor binding domain (RBD) needed for binding to human ACE2. A more distantly related coronavirus was isolated from a bat in Japan, and two viruses from Cambodia have 92.6% genome identity with SARS-CoV-2 and share five of six critical amino acids in the RBD. Finally a bat coronavirus from Thailand is closely related to RmYN02. These observations demonstrate that bats from a broad part of Asia harbor close relatives of SARS-CoV-2.

Fecal samples, oral swabs, and urine samples collected from mainly horseshoe bats in a small area of Yunnan Province between May 2019 – November 2020 were analyzed by RNA sequencing. The results revealed 9 novel betacoronaviruses and 17 alphacoronaviruses. Four of the betacoronaviruses were related to SARS-CoV-2 and three were related to SARS-CoV. Rhinolophus pusillus virus RpYN06 was the closest relative of SARS-CoV-2 in most of the genome with the exception of the spike gene. The other three SARS-CoV-2 related coronaviruses encode a spike gene that could weakly bind to the hACE2 receptor in vitro. Patches of high sequence identity in different regions of the genome illustrate the work of extensive recombination events.

While all the viruses identified in this study, as well as the previously discovered RmYN01 and RmYN02, were identified in a 1100 hectare part of Yunnan province, the results of ecological modeling show that many species of rhinolophid bats are present in much of Southeast Asia and southern China. Numerous other bat species and other wildlife inhabit this area, many of which can be infected by SARS-CoV-2. Hence much more wildlife sampling is needed to track potential spillovers of viruses into humans.

These findings also demonstrate that a very large part of Asia might harbor the direct ancestor of SARS-CoV-2. Remember that HIV/AIDS was first detected in Los Angeles in 1981 but the virus spilled over from a chimpanzee to a human in Africa in ~1920.

https://www.virology.ws/2021/06/17/the-remarkable-diversity-of-bat-coronaviruses/

[JJackson]

This Cell preprint was more extensively discussed in TWiV 771

https://www.microbe.tv/twiv/twiv-771/

[Pathfinder]

UK scientist at centre of debate over origin of Covid pandemic 'recuses himself' from inquiry
...
By
Anne Gulland,
GLOBAL HEALTH SECURITY DEPUTY EDITOR
22 June 2021 • 12:55pm

A controversial British-born scientist has recused himself from an inquiry into the origins of the Covid pandemic amid concern over his links to a Wuhan laboratory tied to the ‘lab leak’ theory.

Dr Peter Daszak, president of the US-based EcoHealth Alliance, has “recused himself” from the inquiry by leading medical journal the Lancet after he failed to declare ties to the Wuhan Laboratory of Virology, which was conducting research into coronavirus in bats.

Dr Daszak was also a member of the WHO investigation into the source of the pandemic that issued its report earlier this year.

On the commission’s website it states that Dr Daszak has “recused himself from Commission work on the origins of the pandemic” but gives no further information.
...
Before he recused himself from the Lancet commission, which is supported by the United Nations Sustainable Development Solutions Network, Dr Daszak was one of a 12-strong international team looking at the origins of the pandemic and how future outbreaks could be prevented.
...
The Lancet Group said in a statement: “Lancet Commissions bring together leading international experts with a broad range of relevant expertise to address the most pressing issues in global health and clinical medicine.

“Commissioners are invited through a collaboration between the Chairs of the Commission and journal editors. All final decisions about Commissioners and other contributors are made by the Commission Chair.”

https://www.telegraph.co.uk/global-health/science-and-disease/uk-scientist-centre-pandemic-origins-debate-removed-inquiry/

[Pathfinder]

Addendum: competing interests and the origins of SARS-CoV-2

• Editors of The Lancet

Published:June 21, 2021DOI:https://doi.org/10.1016/S0140-6736(21)01377-5

In February, 2020, 27 public health experts co-authored a Correspondence in The Lancet (“Statement in support of the scientists, public health professionals, and medical professionals of China combatting COVID-19”),1 supporting health professionals and physicians in China during the early stages of the COVID-19 pandemic. In this letter, the authors declared no competing interests. Some readers have questioned the validity of this disclosure, particularly as it relates to one of the authors, Peter Daszak. In line with guidance from the International Committee of Medical Journal Editors, medical journals ask authors to report financial and non-financial relationships that may be relevant to interpreting the content of their manuscript.2 There may be differences in opinion as to what constitutes a competing interest. Transparent reporting allows readers to make judgments about these interests. Readers, in turn, have their own interests that could influence their evaluation of the work in question. With these facts in mind, The Lancet invited the 27 authors of the letter to re-evaluate their competing interests. Peter Daszak has expanded on his disclosure statements for three pieces relating to COVID-19 that he co-authored or contributed to in The Lancet—the February, 2020, Correspondence,1 as well as a Commission Statement3 and a Comment4 for the Lancet COVID-19 Commission. The updated disclosure statement from Peter Daszak is:


“PD's remuneration is paid solely in the form of a salary from EcoHealth Alliance, a 501(c)(3) non-profit organisation. EcoHealth Alliance's mission is to develop science-based solutions to prevent pandemics and promote conservation. Funding for this work comes from a range of US Government funding agencies and non-governmental sources. All past and current funders are listed publicly, and full financial accounts are filed annually and published. EcoHealth Alliance's work in China was previously funded by the US National Institutes of Health (NIH) and the United States Agency for International Development (USAID). Neither PD nor EcoHealth Alliance have received funding from the People's Republic of China. PD joined the WHO–China joint global study on the animal origins of SARS-CoV-2 towards the end of 2020 and is currently a member. As per WHO rules, this work is undertaken as an independent expert in a private capacity, not as an EcoHealth Alliance staff member. The work conducted by this study was published in March, 2021. EcoHealth Alliance's work in China includes collaboration with a range of universities and governmental health and environmental science organisations, all of which are listed in prior publications, three of which received funding from US federal agencies as part of EcoHealth Alliance grants or cooperative agreements, as publicly reported by NIH. EcoHealth Alliance's work in China is currently unfunded. All federally funded subcontractees are assessed and approved by the respective US federal agencies in advance and all funding sources are acknowledged in scientific publications as appropriate. EcoHealth Alliance's work in China involves assessing the risk of viral spillover across the wildlife–livestock–human interface, and includes behavioural and serological surveys of people, and ecological and virological analyses of animals. This work includes the identification of viral sequences in bat samples, and has resulted in the isolation of three bat SARS-related coronaviruses that are now used as reagents to test therapeutics and vaccines. It also includes the production of a small number of recombinant bat coronaviruses to analyse cell entry and other characteristics of bat coronaviruses for which only the genetic sequences are available. NIH reviewed the planned recombinant virus work and deemed it does not meet the criteria that would warrant further specific review by its Potential Pandemic Pathogen Care and Oversight (P3CO) committee. All of EcoHealth Alliance's work is reviewed and approved by appropriate research ethics committees, Institutional Animal Care and Use Committee, Institutional Review Boards for biomedical research involving human subjects, P3CO oversight administrators, and biosafety committees, as listed on all relevant publications.”
...

https://www.thelancet.com/journals/l...inkback-header

[Pathfinder]

Hattip Shiloh

Recovery of deleted deep sequencing data sheds more light on the early Wuhan SARS-CoV-2 epidemic - preprint
https://flutrackers.com/forum/forum/...demic-preprint

Excerpt:
...
Discussion

I have identified and recovered a deleted set of partial SARSCoV-2 sequences from the early Wuhan epidemic. Analysis of these sequences leads to several conclusions. First, the Huanan Seafood Market sequences that were the focus of the joint WHO China report (WHO 2021) are not representative of all SARSCoV-2 in Wuhan early in the epidemic. The deleted data as well as existing sequences from Wuhan-infected patients hospitalized in Guangdong show early Wuhan sequences often carried the T29095C mutation and were less likely to carry T8782C /C28144T than sequences in the joint WHO-China report (WHO 2021). Second, given current data, there are two plausible identities for the progenitor of all known SARS-CoV-2. One is proCoV2 described by Kumar et al. (2021), and the other is a sequence that carries three mutations (C8782T, T28144C, and C29095T) relative to Wuhan-Hu-1. Crucially, both putative progenitors are three mutations closer to SARS-CoV-2’s bat coronavirus relatives than sequences from the Huanan Seafood Market. Note also that the progenitor of all known SARS-CoV-2 sequences could still be downstream of the sequence that infected patient zero depending on the transmission dynamics of the first infections.

The fact that such an informative data set was deleted has implications beyond those gleaned directly from the recovered sequences. Samples from early outpatients in Wuhan are a gold mine for anyone seeking to understand spread of the virus.

Even my analysis of the partial sequences is revealing, and it clearly would have been more scientifically informative to fully sequence the samples rather than surreptitiously delete the partial sequences. There is no plausible scientific reason for the deletion: the sequences are perfectly concordant with the samples described in Wang et al. (2020a,b), there are no corrections to the paper, the paper states human subjects approval was obtained, and the sequencing shows no evidence of plasmid or sample-to-sample contamination. It therefore seems likely the sequences were deleted to obscure their existence. Particularly in light of the directive that labs destroy early samples (Pingui 2020) and multiple orders requiring approval of publications on COVID-19 (China CDC 2020; Kang et al. 2020a), this suggests a less than wholehearted effort to trace early spread of the epidemic.
...
Future studies should devote equal effort to going beyond the annotations in GISAID to carefully trace the location of patient infection and sample sequencing. The potential importance of such work is revealed by the observation that many of the sequences closest to SARS-CoV-2’s bat coronavirus relatives are from early patients who were infected in Wuhan, but then sequenced in and attributed to Guangdong.
...
More broadly, the approach taken here suggests it may be possible to learn more about the origin or early spread of SARSCoV-2 even without an international investigation. Minimally, it should be immediately possible for the NIH to determine the date and purported reason for deletion of the data set analyzed here, since the only way sequences can be deleted from the SRA is by an e-mail request to SRA staff (SRA 2021). In addition, I suggest it could be worthwhile to review e-mail records to identify other SRA deletions, which are already known to include SRR11119760 and SRR11119761 (USRTK 2020). Importantly, SRA deletions do not imply any malfeasance: there are legitimate reasons for removing sequencing runs, and the SRA houses >13-million runs making it infeasible for its staff to validate the rationale for all requests. However, the current study suggests that at least in one case, the trusting structures of science have been abused to obscure sequences relevant to the early spread of SARS-CoV-2 in Wuhan. A careful re-evaluation of other archived forms of scientific communication, reporting, and data could shed additional light on the early emergence of the virus.
...
https://www.biorxiv.org/content/10.1...051v1.full.pdf

[Pathfinder]

The Debate over Origins of SARS-CoV-2

June 22, 2021
...
Caltech's David Baltimore, president emeritus and Distinguished Professor of Biology, is a virologist who received the Nobel Prize for his research into viral genetics. Baltimore was an organizer of the first Asilomar Conference on Recombinant DNA held in 1975 to discuss ethics and regulation of biotechnology. We sat down with him to discuss the debate over the origins of SARS-CoV-2.

What are the arguments that suggest SARS-CoV-2 is a naturally evolved virus? What is the evidence that suggests that it may have originated in and accidentally released from a laboratory in Wuhan, China?

The argument that it's a naturally evolved virus is from the belief that through the time of evolution, any sequence of RNA or DNA could evolve.

Biologists have seen what evolution can create: the whole natural world around us. We believe that evolution can do anything. But the fact that evolution might have been able to generate SARS-CoV-2 doesn't mean that that's how it came about. I think we very much need to find out what was happening in the Wuhan Institute of Virology. I think that we can't say for sure yet whether the SARS-CoV-2 virus came from natural origins or if it was genetically manipulated somehow.

Recently you were quoted as saying: "When I first saw the furin cleavage site in the viral sequence, with its arginine codons, I said to my wife it was the smoking gun for the origin of the virus. These features make a powerful challenge to the idea of a natural origin for SARS2." Can you unpack this quote for us?

Let me be clear, even though I used the phrase "smoking gun," I don't really think there's a smoking gun in the genome itself.

Now, within the SARS-CoV-2 genome there is an insertion of 12 nucleotides that is entirely foreign to the beta-coronavirus class of virus that SARS-CoV-2 is in. There are many other viruses in this class, including the closest relative of SARS-CoV-2 by sequence, and none of them have this sequence. The sequence is called the furin cleavage site.

To back up a little bit: In order to infect a cell, the spike protein on the surface of viruses like SARS-CoV-2 needs to first be cut, or cleaved. The cut needn't be terribly exact, but it needs to be cut. Different viruses attract different kinds of cellular "scissors," so to speak, to make this cut; the furin cleavage site attracts the furin protein providing the most efficient way to make a cut. You don't need a furin cleavage site to cut the protein, but it makes the virus more efficiently infectious.

So where did it come from in SARS-CoV-2? There are other viruses that have furin cleavage sites, other coronaviruses, though not the family of beta-coronaviruses. So this sequence's nucleotides could have hopped from some other virus. No one has identified a virus that has exactly this sequence, but it could have come from something close, then evolved into the sequence that we see today.

I'm perfectly willing to believe that happened, but I don't think it's the only way that that sequence could have appeared. The other way is that somebody could have put it in there. You can't distinguish between the two origins from just looking at the sequence. So, naturally, you want to know were there people in the virology laboratory in Wuhan who were manipulating viral genetic sequences? It's really a question of history: What happened?

When I first saw the sequence of the furin cleavage site—as I've said, other beta coronaviruses don't have that site—it seemed to me a reasonable hypothesis that somebody had put it in there. Now, I don't know if that's true or not, but I do know that it's a hypothesis that must be taken seriously.
...

https://www.caltech.edu/about/news/the-debate-over-origins-of-sars-cov-2

[Emily]

https://iv.iiarjournals.org/content/35/3/1313.full

On the Origin of SARS-CoV-2: Did Cell Culture Experiments Lead to Increased Virulence of the Progenitor Virus for Humans?
BERND KAINA
Institute of Toxicology, University Medical Center, Mainz, Germany
In Vivo May 2021, 35 (3) 1313-1326; DOI: 10.21873/invivo.12384

Abstract

....This article summarizes the unique properties of SARS-CoV-2 and focusses on a specific sequence encoding the spike protein. Possible scenarios of virus evolution are discussed, with particular emphasis on the hypothesis that the virus could have emerged unintentionally through routine culture or gain-of-function experiments in a laboratory, where it was optimally adapted to human cells and caused cryptic infections among workers who finally spread the virus causing the pandemic.

...

It is important to note that all SARS-like coronaviruses known so far do not harbor this insert, while MERS-CoV, which docks to the DPP4 receptor, has an insert in this position of the protein consisting of four amino acids (Pro-Arg-Ser-Val) (Figure 2C). Furin cleavage sites are also found in other viruses in attachment proteins, including HIV, where the protease plays a role in entering the cell. However, a close similarity was found with the sequence of MERS-CoV. In Figure 2D, the nucleotide sequence around the PCS is compared between SARS-CoV-2 and MERS-CoV. Interstingly, on position 678 threonine is encoded by the same triplet ACT in SARS-CoV-2 and MERS-CoV, and on position 681 prolin is encoded again by the same triplet CCT and on position 682 arginine by CGG and CGC. Thus, there is not only a strong identity on the amino acid level, but also on the nucleotide level between SARS-CoV-2 and MERS-CoV. Given the code redundancy, the probability for an identical sequence encoding threonine (pos 678; which can be encoded by ACA, ACG, ACC and ACT) is 0.25×0.25=0.0625, and that of proline (pos 681; encoded by CCT, CCC, CCA and CCG) is again 0.0625. The overall probability harboring the same nucleotide sequence in these two positions is 0.0039. In position 682 with arginine coded by the sequence CGG (SARS-CoV-2) and CGC (MERS-CoV) we are again faced with a coincidence (nucleotides CG) of low probability [arginine is en coded by the codons CG (G,C,A,T), AGG, AGA]. In conclusion, there is a remarkable identity on amino acid and nucleotide level in and around the PCS between SARS-CoV-2 and MERS-CoV. This supports the hypothesis that the PCS/furin cleavage site was gained by a recombination event(s) involving these virus sequences. This notion is important in considering possible zoonotic events, placing laboratory events in the realm of the highly possible.

In this context, it is important to note that a sequence comparison of SARS-CoV-2 with other viruses revealed a 117-nucleotide sequence in the virus genome that is 94.6% identical to a human intron sequence of the netrin G1 gene. Several other viruses also contain human sequences, but they are much shorter (e.g., SARS-CoV contains a 41-nucleotide sequence). MERS-CoV does not contain a human sequence (40). The presence of a human sequence in SARS-CoV-2 supports the hypothesis that the progenitor was propagated in human cells where it gained the sequence by a recombination event...

[sharon sanders]

bump this