SARS2 and HIV-1 redux

In Feb of 2020, a preprint showing that the SARS2 spike protein has 4 regions of homology with HIV-1 (bit.ly/3rmBtYD) was forced to retract.

So where are these regions in the 3D protein structure?

😲All 4 regions are missing!

Surgically ...
Missing residues usually indicate flexible loops.

So where are these loops? What are they doing?

The first 3 are from the HIV-1 gp120 gene which allows it to bind to host cells containing the CD4 receptor: mostly immune cells like T-cells and macrophages.

O no, what if ...
Someone alerted Fauci to the same problem:
bit.ly/3qtU06e

What if the spike protein can interact with the CD4 receptor? Bad news.

Here are the regions in the structure. Spike forms a homo-trimer. The regions (red, yellow, and blue) come together at a peripheral point.
Below is a zoomed-in version for subunit A, with the 3 missing loops drawn in by hand. Note how close their connectors (shown as solid spheres) are in 3D.

So 3 regions with homology to the CD4 binding domain of HIV-1:
- are missing in the structure
- come together in 3D
Should we conclude that the SARS2 spike protein can interact with CD4?

Of course not

If the powers-that-be hadn't forced the retraction of the preprint, we would have had an answer by now

Interestingly, #Fauci knew about this in Feb 2020:
bit.ly/3qtU06e

Who alerted?
There is already evidence that SARS2 can affect CD4+ T helper cells, lymphocytes that coordinate the adaptive immune response.

Thank you @Rossana38510044 !

bit.ly/3FEuJe0

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More from @tony_vandongen

Jan 12,
I recently have claimed, waggishly, that Omicron can:

- Read scientific papers bit.ly/34L0Tro

- Predict the effect of mutations bit.ly/34MhMlu

Pretty smart virus ...

Does this challenge the natural origin hypothesis?

Let's review the weirdness of Omicron
Weirdness #1.

It has 62 new mutations compared to its predecessors.
Previous variants (alpha through mu) have between 18 and 29 mutations.

So, 62 is a lot.

Too many to arise from a natural process?

Probably not. It would just take more time to accumulate that many. Image
Weirdness #2.

There are no intermediate versions of Omicron that have a subset of the 62 mutations.

Probably the biggest problem for the natural origin idea.

Accumulation takes a long time, and Omicron is more infectious than the measles. How could it hide this long?
Read 17 tweets
Jan 11,
Frist, Omicron learned how to read bit.ly/3texqjz

But it gets weirder ...

Omicron also uses different mechanisms for mutations that change amino acids and those that are 'silent'.

It somehow seems to know what the effect of the mutation is going to be. Amazing.
Let's compare silent and functional mutation statistics for Omicron and the the other variants of concern.

First, silent mutations. Variants have on average 7.1 silent mutations, with a STD of 2.4

Assuming a Gaussian distribution, Omicron looks like it fit right in:
The same analysis for the 'functional', amino acid changing, or 'non-synonymous' (NS) mutations.

Average # of NS mutations for other variants is 23.1 with STD of 10.

Here, Omicron clearly does not belong to the group of other VOCs.
Read 18 tweets
Dec 14, 2021
Omicron: Silent Mutations Redux.

Omicron appears to have very few "silent" (S) mutations, compared to the large number of “functional” (NS) amino acid-changing mutations

The ratio dN/dS in Omicron is 41/4 = 10.25

Is there something wrong with that?
If you make random substitutions of nucleotides in the genomes of corona viruses you get a dN/dS ratio of ~3.5

This is to be expected, because changing the 3rd base of a codon usually doesn’t change the amino acid.

That is not that different from 10.25 in Omicron, is it?
For a proper perspective. lets look at the dN/dS ratio for all the corona virus predecessors of Omicron.

The table below shows the "percentage of non-synonymous mutations" in the genomes of Alpha through Iota.

Many zeros, highest is 12%, average is 1.5% Image
Read 14 tweets
Dec 8, 2021
A Moderna patent (US 9587003) filed in 2017 contains a DNA sequence that ended up being the unexpected insertion of the notorious Furin Cleavage Site (FCS) in SARS-CoV-2.

Its devastating effect on infectivity and transmission in the pandemic are well-documented.
Interestingly, Ralph Baric in the University of North Carolina (UNC) has tested vaccines for Moderna, and is also the world's expert in engineering hybrid versions of corona viruses.

No that couldn't possibly be connected ...
There are 2 baffling aspects op the FCS insert: the presence of a Proline (P) which is suboptimal, and the CGG-CGG codon pair encoding two Arginine residues, which extraordinary rare (1 in 2 million).

Both features are found in this patent.
Read 5 tweets

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