Wuhan Lab-Leak Theory: “Rare” Genetic Sequence Doesn’t Mean the COVID Virus Was Engineered

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The theory that the COVID-19 pandemic was triggered by the Sars-CoV-2 virus being leaked from the Wuhan Institute of Virology in China was recently given new life following an explosive article in the Wall Street Journal (WSJ) in which the authors claimed “the most compelling reason to favor the lab leak hypothesis is firmly based in science.” But does the science really support the claim that the virus was engineered in a laboratory?

Understanding the origin of a viral outbreak can provide scientists with important information about viral lineages and allow steps to be put in place to avoid similar outbreaks in the future. As such, the origin of Sars-CoV-2 has been debated from the beginning of the pandemic and remains an active topic of discussion among scientists.

It has long been known that viruses similar to the original Sars-CoV that causes Sars are found in bats. These viruses are well studied in China, where the 2002 Sars outbreak originated. But related viruses have been found globally.

Unsurprisingly, coronaviruses are again involved in a pandemic, the third such event in the 21st century – first Sars, then Mers, now COVID-19. While a natural origin seems likely – and many have long warned about the danger of wildlife circulating viruses – scientists shouldn’t jump to conclusions.

An important way scientists can determine the origin of a virus is by looking at its genome. In the WSJ article, the authors, Prof Richard Muller, an astrophysicist, and Dr Steven Quay, physician and chief executive of Atossa Therapeutics, claim Sars-CoV-2 has “genetic fingerprints” of a lab-origin virus. They say that the presence of a particular genetic sequence (CGG-CGG) is a sign that the virus originated in a lab.

To understand the claims being made, we must first understand the genetic code. When a virus infects a cell, it hijacks the cellular machinery, providing instructions (genome) to produce more copies of itself. This genome comprises a long series of molecules called nucleotides, each of which is represented by the letters A, C, G or U.

A group of three nucleotides (known as a codon) provides the instruction for a cell to make an amino acid, the most basic molecular building block of living things. Most amino acids are encoded by several different codons. CGG is one of six possible codons that instruct the cell to add the amino acid arginine.

The authors of the WSJ article argue that Sars-CoV-2 originated in a lab based on the presence of a “CGG-CGG” sequence. They claim this is a “readily available and convenient” codon pair that scientists prefer to use to produce the amino acid arginine. But to anyone with an understanding of the techniques required for genetic modification, this double-CGG is usually no more difficult or easy to produce than any other pair of codons that encode arginines.

No reason CGG-CGG had to be made in lab

The authors claim that the CGG codon appears less frequently than the other five possible codons in betacoronaviruses (the family of coronaviruses to which Sars-CoV-2 belongs). If we look at related coronaviruses, the CGG codon encodes about 5% of all arginines in Sars-CoV compared with about 3% of all arginines in Sars-CoV-2. Though CGG is less common than other codons, the authors’ argument fails to provide a reason that the double-CGG sequence could not exist naturally.

The authors argue that recombination (when viruses that infect the same host share genetic material) was the most likely way in which Sars-CoV-2 was able to obtain the double-CGG sequence. They note that the double-CGG codon pair is not found in other members of this “class” of coronavirus, so natural recombination could not possibly generate a double-CGG. However, viruses do not just depend on preassembled segments of genetic material to evolve and expand their host range.

The authors also claim that mutation (random copying errors) is unlikely to generate the double-CGG sequence. But viruses evolve at a rapid rate, so much so that the accumulation of mutations is a common inconvenience of virological studies. Recombination is one way in which viruses evolve, but the authors’ dismissal of mutation as a source of viral change is an inaccurate description of reality.

The final claim that the first sequenced Sars-CoV-2 virus was ideally suited to the human host neglects evidence of viral circulation in local animal populations, animal-to-animal transmission, and the rapid evolution that is driving the increasing transmissibility of the newer variants. If the virus was ideally adapted to humans, why is so much further evolution evident?

Disappointingly, many other media articles appear to have accepted and repeated the claims from the WSJ piece. The origin of Sars-CoV-2 may remain unresolved, but there is no evidence presented in the WSJ piece that scientifically supports the concept of a lab leak of a genetically engineered virus.

Written by

  • Keith Grehan – Postdoctoral Researcher, Molecular Biology, University of Leeds
  • Natalie Kingston – Research Fellow, Virology, University of Leeds

Originally published on The Conversation.The Conversation

9 Comments on "Wuhan Lab-Leak Theory: “Rare” Genetic Sequence Doesn’t Mean the COVID Virus Was Engineered"

  1. Gordon Jenkins | July 7, 2021 at 7:09 pm | Reply

    Perhaps Spin Doctors really are worth the extra expense.

    • Gordon Jenkins | July 7, 2021 at 7:27 pm | Reply

      Let’s not forget the two Wuhan Biologists, who were working at Canada’s Level 4 Lab in Winnipeg, Manitoba, sending samples directly to the Wuhan Lab and “disappeared” with the Canadian Government refusing accountability and disclosure to the Canadian Parliament. The two Michaels waiting in China for release. Political Hot Potato in desperate need of China-Positive Spin to make it all go away.

  2. Putting the WSJ article aside, the codon argument is just one arm of the “lab-leak” theory. Even if the Sars-CoV-2 virus RNA is completely natural and non-engineered, it still might have leaked from a lab in which it was stored after being cultivated. Many will demand proof of such “slanderous ideas” but those that have paid attention understand that any evidence has likely been destroyed already by the CCP.

  3. p. gutierrez | July 8, 2021 at 9:29 pm | Reply

    You use the term “finger prints” of lab origin. When I read Dr. Quays article ‘Bayesian Analysis of SARS-CoV-2 Origin’ version 3 March 29, 2021 ( https://zenodo.org/record/4642956), the real genomic ‘fingerprints’ are the restriction sites that he found in the RaTG13 genome. Pages 132 and 133 state, “Examination of RaTG13 identified two Esp3I cleavage (restriction) sites in the Spike Protein gene …..The 5′ restriction site in RaTG13 begins at aa residue 455L, identified by Andersen et al, Nature, 2020, as the start of the ‘receptor-binding domain (RBM) ACE2 contact residues’…..The 3’ restriction site in RaTG13 is at residue 980L. (the end of heptad repeat 1 domain)….. This is a frequency of these site at their exact location being here from a natural process of approximately one in a billion.”
    For a restriction site (a laboratory ‘fingerprint’) to be found at the beginning of the RBM (receptor binding motif), is pretty amazing. The Covid-19 RRAR cleavage site is within the bounds of these two ESPI restriction sites, supposing RaTG13 is the backbone coronavirus for Covid-19. Restriction digestion may have been used to cut DNA at those sites for removal, and fragments of other DNA may have been pieced together like building blocks via ligation. Dr. Quay (on page 131) sites Ralph Baric’s 2005 article, “Development of Mouse Hepatitis Virus…..”, as to how this may have been done.—————-
    In her report # 1, Dr. Li-Men Yan found EcoRI and BstEII restriction sites (‘genomic fingerprints’) in Wuhan person 1 Covid-19 genome. “Two restriction sites are present at either end of the RBM of SARS-CoV-2, providing convenience for replacing the RBM within the spike gene. A. Nucleotide sequence of the RBM of SARS-CoV-2 (Wuhan-Hu-1). An EcoRI site is found at the 5′-end of the RBM and a BstEII site at the 3′-end.” Quote from Yan’s article, “Unusual Features of the SARS-CoV-2 Genome Suggesting Sophisticated Laboratory Modification….”. Coincidence, both Quay and Yan found restriction sites (‘genomic fingerprints’) at the start of the RBM, in different genomes. If true, more possible evidence of S gene laboratory tampering. Many good scientists say that the Covid-19 RBM is pangolin origin. It would have been easy to insert the (downstream) cleavage site, at the same time as a possible RBM swap.—————-
    In their February 2020 paper, “Functional assessment of cell entry and receptor
    usage for SARS-CoV-2 and other lineage B betacoronaviruses”, Vincent Munster and Michael Letko, of the NIAID in Montana, stated, “We replaced the RBD (receptor binding domains) of full-length clade 2 and 3 spike with the consensus clade 1 RBD and tested pseudotypes on cells expressing ACE2…… For SARS-CoV spike, silent mutations were introduced around codons 308 and 519 to form KpnI and XhoI (restriction) digest sites (to facilitate RBD replacements)……Spike (gene) RBDs were appended with regions of the target spike (gene) backbone to facilitate In-Fusion cloning and synthesized as double stranded DNA fragments….. RBD inserts were resuspended in water and In-Fusion cloned into gel-purified, digested spike backbone vectors (Takara).” State of the art S gene engineering, clone RBDs into S gene backbone vectors from other bats, cut and paste. If you want to reverse engineer how the Covid-19 RRAR cleavage site may have originated, consult the experts. And, test the five Wuhan Hunan Seafood environmental samples genomes available in GISAID, for restriction sites (‘genomic fingerprints’).

  4. Matt Ledbetter | July 10, 2021 at 8:19 am | Reply

    It also might be worth mentioning that Science Tech Daily is headquartered in Zhang Jingan, China.

  5. Theories, theories everywhere and not a DOI to link.

    I can’t wait to see which field YouTube will offer a double secret PhD in next, and how many will die from the advice of borderline schizophrenics who knew nothing on the topic a month ago.

  6. Using a virus as a weapon of war is within the tolerance of the People’s Liberation Army.

  7. There are several flaws in this discussion of Quay’s work. It is worth noting that Quay is a world leading expert in genetics with 100s of papers and 1000s of citations, whereas the authors of this discussion are humble post docs. The closing argument here, that the virus is still rapidly mutating to increase infectivity is false, as Quay has made clear. SARS CoV 2 was 99.6% adapted to infect human ACE2 from the first cases of the pandemic, which as Quay points out is incredibly unlikely for a pathogen emerging from nature. Quay also points out that ONLY 1% of all mutations of SARS-COV2 since the start of the pandemic are relevant to the infectivity of the virus (99% of mutations occurring in parts of the virus unrelated to infectivity). Quay is obviously aware of the arguments presented here re random mutations, but has assigned probabilities and liklehoods to these, and assessed them to be extremely unlikely.

  8. Ching Ching Ching | July 28, 2021 at 8:45 pm | Reply

    Well , why not exterminate some bats 🦇 if it’s been a f**kin problem for so long ?

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