Is SARS2 designed as a consensus sequence?
Like it was proposed in the DEFUSE grant?

Let's see how close we can get to SARS2 using a consensus based on other coronaviruses.

Answer: extremely close. How was the graph obtained?
It should be read from top to bottom because the data are cumulative. Every time a new sequence is added, the consensus is updated, and the number of mismatches goes down.

RaTG13 has 1176 mismatches with SARS2. But most of those are not shared with BANAL52. So the new consensus of BANAL52 and RaTG13 has only 447 mismatches. As we keep adding sequences to the consensus, the number of mismatches drops to 3 by the time we get to GX_PV2. The consensus is now 29900/29903 or 99.999% identical to SARS2

The SARS2 sequence in a bacterium from a patient in Henan, China collected in 2019 may turn out to be a "storm in a glass of water" (Dutch idiom meaning "much ado about nothing").

The author that uploaded the sequence admitted it resulted from "contamination".

What gives? It means the SARS2 sequence was not from the 2019 patient in Henan. And it was not a precursor of SARS2.

So what is it?

It was a DNA construct the lab that submitted the bacterial sequences was working on.

It is synthetic: completely made up on a PC .

The identification of a SARS2 spike protein gene in bacterial genomes isolated from patients in 2019 in Henan province raises many questions. The protein sequence is identical to that in SARS2 except that the furin cleavage site is missing.

https://twitter.com/MartinaSisters/status/1614725052875898882?s=20&t=VnUZzsOp_LAziHcKIYeYsg

The SARS2 spike protein existed in 2019 in patients 500 km away from Wuhan?

How did it end up in bacteria? Maybe it didn't. Possibly a sample contamination issue.

Was it a progenitor of SARS2? Finally, the missing link?

No.

How did Eddie Holmes cause the C19 pandemic?

There are 40,000 wet markets in China.
statista.com/statistics/124…

Eddie visits one of these, the Huanan market in Wuhan, in 2014 and took pictures of raccoon dogs (blue arrow).

5 years later the C19 pandemic breaks out in Wuhan. What are the odds that Eddie's visit to this particular wet market and the outbreak there 5 years later are a coincidence? Obviously 1 in 40,000. Or vanishingly small.

If it is not a coincidence, is there a causal relationship?
Did Eddie cause the pandemic?

Let's see ...

The notion of SARS2 being a "quasi-species swarm" has surfaced again.

Here is a tread explaining what it is: bit.ly/3F4R9GN

If the paradigm applies to SARS2, there are several consequences.

1. Sequences may not be reliable.
2. Vaccines could be ineffective. 1. Since a host (bat, human) harbors a large number of different variants, an isolated cDNA clone is just one of the variants.

NGS sequencing can produce a non-existing sequence that is a combination of many mutations from different variants.

Kindergarten Molecular Biology.

Posting our preprint purporting that SARS2 may have come from a lab elicited a firestorm of critical tweets, some which are helpful in improving our paper.

But there is a lot of confusion, which I will try to address

https://twitter.com/WashburneAlex/status/1583145276151189504?s=20&t=8z9AmI2TOpeN-ipkYJe4dg

Our manuscript hinges on a finding that some "type IIS" restriction enzymes are evenly dispersed in the SARS2 genome.

So what are "type IIS" enzymes and why are they special for engineering viruses? If you don't know, go read the brilliant:

https://twitter.com/Kevin_McKernan/status/1583584111335469056?s=20&t=8z9AmI2TOpeN-ipkYJe4dg

A list of circumstantial pieces of evidence supporting a lab-linked origin for #COVID19:

1. 2018: WIV, EHA & UNC propose to DARPA to construct a SARS virus by insertion of a Furin Cleavage Site (FCS) in the spike protein, and humanize it by serial passaging. A blueprint for SC2.

https://twitter.com/CharlesRixey/status/1517687687813246976

2. Wuhan Institute of Virology (WIV) takes a database offline containing ~2,000 viral sequences on Sep 12, 2019.

3. Oct 2019: WIV staff members are hospitalized with pneumonia-like symptoms.

4. End of 2019: A WIV staff member disappears and hasn’t been seen since.

Do you want to solve the SARS2 origin?
I have some questions we need answers to:

1.Why was the public database with 20,000 viral sequences maintained by the Wuhan Institute of Virology (WIV) deleted on September 12, 2019? The official explanation was that it had been hacked over 3,000 times. Really? In September of 2019? By whom? And why?
Interestingly, before it was taken down, the entire database was downloaded 200 times. These people knew it was going to disappear and made copies.

SARS2 vs BANAL247 revisited. Alignment of N-terminal domains of SARS2 and BANAL247, where transversions dominate.

11 C>T mutations out of a total of 132 = 8%.
No RNA editing.

Why #SARSCoV2 originated from #Omicron

Omicron broke onto the scene in November of 2021 in South Africa. It sported 63 new mutations.

And its ancestor was mysterious: a phylogenetic analysis put its predecessor close to the origin of the pandemic.

But how close? The picture shows a small tree with only close relatives of SARS2. Not surprisingly, Omicron is the closest relative. But it ends up *above* SARS2, which would indicate it preceded it in time. The red dot is a common ancestor Omicron shares with SARS2. Let's call it Omega.

#SARSCoV2 originated from Omicron relative

Before pandemic it went undetected (mild cold)
Produced by serial passaging
Developed as a Live Attenuated Virus
68 mutations from unusual (lab) selection pressure
SARS2 reverted back to original Omicron in humans

Thx @KevinMcH3 This scenario solves a lot problems (it's parsimonious)

1. It explains the unusually large number of mutations in O: they are not mutations. O is wildtype.

2. The lab that created SARS2 didn't have to do any engineering, just serial passaging in cells and humanized mice.

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 ...

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.

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:

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?

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.

https://twitter.com/jhas5/status/1467497456778809351

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 ...