Lab Leak Theory - New article shows link to patented gene in SARS-CoV-2 Furin Cleavage site
Lab leak theories are suddenly very much the MODE (RNA gives us the clue)
I was first alerted to this article by Jikky Kjj, a lab mouse who randomly types on a keyboard. The article referred to has been published today in Frontiers in Virology - Emerging and Reemerging Viruses and is along the same lines as my article from January.
The authors discuss the difference in mutations between SARS-CoV-2 and the bat RaTG13 coronavirus. This bat virus is the closest known relative to SARS-CoV-2 with a 96.2% identical genome. Of all the differences, only one exceeds 3 nucleotides and that is the furin cleavage site (FCS) which contains 12 nucleotides, coding four amino acids. As discussed in previous articles, the FCS insertion is likely to play a critical role in SARS-CoV-2 replication and pathogenesis, i.e. easier to transmit and more deadly.
So what is so interesting about the FCS in this new article? Well, the FCS is not found in any other b-lineage betacoronavirus or any sarbecovirus in nature. The authors say that a peculiar feature of the sequence is it’s two consecutive CGG codons. When they undertook a BLAST search (a NIH tool which compares nucleotides or protein sequences) they found a 100% reverse match in a proprietary sequence found in US patent 9,587,003 filed on 4 February 2016. And who was the applicant of this patent? If you’ve read my previous article or the unsubtle subtitle of this post, you’ll know that the applicant and current assignee of that patent was and is Moderna Therapeutics.
On closer examination the authors realised that the match extended beyond the 12 nucleotide insertion, mentioned above, to a 19 long sequence.
All of the above is very rare and they tried to work out how rare. Using conventional biostatistical analysis they estimated that the probability of the sequence randomly being present in a 30,000 nucleotide viral genome was 3.21 ×10 −11 (a ridiculously small number). They didn’t find the sequence in any other viral genome, except SARS-CoV-2, in the BLAST database.
If this sequence is patented, it must do something useful, so what does it actually do? According to the authors, when read in the forward direction, it is a 100% amino acid match to MSH3 which is a DNA mismatch repair protein. It’s role is to maintain the stability of the genome and can have a role in the suppression of cancerous tumours. In vivo experiments show that induction of DNA mismatch repair deficiency can enhance viral suppression and increase the severity of viral disease (in these experiments they were looking at influenza). Furthermore, it has been proposed that the mismatch repair deficiency can play a role in prolonging SARS-CoV-2 RNA shedding (this paper looked at a cancer patient who tested positive for 54 days).
The paper states that the absence of the sequence from the BLAST database makes recombination in an intermediate host an unlikely explanation for its presence in SARS-CoV-2. They concluded by saying “The presence in SARS-CoV-2 of a 19-nucleotide RNA sequence encoding an FCS at amino acid 681 of its spike protein with 100% identity to the reverse complement of a proprietary MSH3 mRNA sequence is highly unusual. Potential explanations for this correlation should be further investigated”.
This paper gives further teeth to the lab leak theory and raises questions that should and could have been answered right at the beginning of this pandemic, probably saving countless lives. Why is Moderna’s patented sequence in SARS-CoV-2? Moderna were clearly experimenting with various cancer treatments, using this sequence, but what is the connection between those experiments and SARS-CoV-2? Were they being undertaken in the same laboratory and/or by the same individuals? Is it possible that, through contamination, the sequence ended up in SARS-CoV-2 or is the only way for that to happen through direct manipulation of a coronavirus? If direct manipulation of a virus is the only answer then why was this insertion added when it was known to increase transmission and severity of disease? Why has this information been supressed? Why are no other scientists discussing this?
One other point to note about the article is that is was edited by Xin Yin from the Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, China. Furthermore, it was reviewed by Jitao Chang from the same academy. Is this China throwing Moderna under a bus? Why would China allow this information to be released if not for some ulterior motive?
A great article which points us ever closer to the answer of where SARS-CoV-2 came from but leaves so many unanswered questions that we should demand answer to.
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Excellent share. Thank you. Wished I could take it over to my alma marter integrative genomics lab but I might get the PoPo called on me again lol.
Thank you for simplifying--as much as possible--a difficult subject many of us would like to understand.