1/6 All right, today I got conclusive proof that Eddie Holmes sucks at aligning genomes. And if that’s not enough, I found the last nail in his “PAA insertion” coffin.
But first things first: he is a coauthor of a recent preprint with the following gem of an alignment (yellow):
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See him putting the R in Rc-o319 alignment one aa ahead of others? That should immediately trigger a WTF moment in anyone even modestly familiar with genome alignments. Next, that urge should translate into checking the underlying nucleotides, which will quickly
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confirm that the RSAN shouldn’t be shifted in Rc-o319 compared to its relatives but should neatly align with RSVN just above it, because it is the N in Rc-o319 that got duplicated (duplicate codons AAC AAC are a dead giveaway) — see my alignment above.
Embarrassing!!! 😂
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Now, regarding that final nail in the PAA insertion coffin. Today, casually browsing through GISAID as I usually do on Friday nights, I ran into a new hot bat virus I haven’t met before: PrC31 from Yunnan.
And after checking out its alignment to my favorite RmYN02,
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I couldn’t contain my excitement: the new kid on the block very nicely anchors the PAA in RmYN02 and PVA in RacCSxxx to its PIL fragment, which, in turn, aligns to SIL in ZC45/ZXC21 and others.
Translated to English, this means PAA is not a freaking insertion, Eddie!
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Could someone please screenshot this for Eddie, as he had me blocked the first time I told him his PAA alignment was wrong 😂😂😂
Ok, here goes nothing. Remember this little thing called a furin cleavage site? You know, the one that made SARS2 into a real promiscuous little virus? Well, as some have pointed out before, the strategy of inserting a furin cleavage site was not only
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investigated by coronavirologists previously as a tool to expand virus tropism, but also by other virologists as a tool to actually ATTENUATE a virus. In other words, a vaccine strategy.
Getting goosebumps yet? I am.
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So how could this be a vaccine strategy? Well, the idea, as I understand it, was to take a virus, insert some FCSs into it in key places, but do so in a cell culture that do NOT normally have furin, and thus the virus won’t get cut in such cells. But then if you infect
Ok, the prize for the craziest and most dangerous gain-of-function research goes out to Italian virologists who took SARS2 and passaged it in vitro in the presence of neutralizing antibodies. It quickly obliged and mutated to escape them. Yay for a novel, more dangerous SARS3! 🤦♂️
Oh, and it developed a glycan sequon in vitro — take that, @K_G_Andersen! 😁
Ok, does this conclusively disprove the PAA "insertion" in RmYN02? I re-ran the CLUSTAL W alignment with ALL genomes used in Zhou et al. (middle block below) and it shows NO trace of an insertion in RmYN02. I get the same result if I omit SARS2 from query (bottom block). 1/4
Here is the original figure from Zhou et al. claiming a PAA insertion. Btw, I couldn't find their nucleotide alignment in the paper, even in the Supplementary.
1/n Here’s what still irks me in the EcoHealth/WIV narrative about RaTG13/4991. So in 2011 and 2012 Shi Zhengli goes on 2 expeditions to a bat cave near Kunming, the capital of Yunnan. There she finds CoV strains RsSHC014 and Rs3367 which share 85% and 96% with the first SARS-CoV
2/n This discovery is worthy of a Nature paper in 2013 and many subsequent accolades to its authors. Btw the first author of the 2013 Nature paper is Ge Xingyi, whose name features prominently on many other joint CoV papers. The team then proceeds to extract a live sample of
3/n Rs3367 which they then christen “WIV1” and later use as a backbone for several chimeric constructs. But for their 2015 joint chimera with Baric they used RsSHC014 as a backbone (85% similar to SARS).
Hmm. A 2017 paper by Ge et al. (same Ge of the 2016 paper reporting the discovery of 4991/RaTG13) describing a Yunnan rat CoV with a RRAR furin site (same as in SARS-CoV-2).
1/4 Peter Daszak blocked me. He never did reply to my questions about his outrageous claim that zoonotic jumps “occur every day”.
2/4 I mean, he extrapolated rather weak results from their study (where 6 out of 218 farmers had antibodies to a bat CoV present in bats that lived nearby) to “1-7 million people per year exposed to bat origin SARS-related CoVs“.
3/4 The extrapolation from 6 to 1-7M notwithstanding, the study itself was weak. First, antibody levels were pretty low. Here’s the antibody graph from their study: compare the farmers’ levels (panel B, leftmost) with those of 2 SARS patients (rightmost):