I caught the fairly depressing exchanges between Rand Paul and Fauci in the hearing yesterday, and there was a very stark conflation of different things to imply wrong-doing on behalf of Fauci and NIAID, and worse, that they are complicit in the origin of SARS CoV-2. 1/n
It’s worth breaking this down because it's being used by Sen Paul and right-wing libertarians not to shed on the origins of the virus, but to exert revenge on Fauci and the medical establishment for the choices necessary to combat the virus that curtailed personal freedoms. 2/n
EcoHealth Alliance was in receipt of federal funding to identify natural reservoirs of bat coronaviruses with pandemic potential, which they disbursed to collaborating labs including the Shi lab at WIV. 3/n
Under the stated aims of this funding, field workers would swab bats across China and SE Asia, identify novel CoV sequences in the lab and address whether such viruses could pose a pandemic risk. 4/n
In order to do so, they would clone the spike proteins from the identified sequences and use them to pseudotype lentiviral vectors in order to screen for human AEC2 use. 5/n
They'd then clone the most likely candidates into a molecular clone of the closest bat virus relative of SARS CoV-1 called SARSr-CoV-WIV1. This is a natural virus that can already efficiently use human ACE2 and replicate both in human lung epithelial cells and ACE2-Tg-Mice. 6/n
These chimeric viruses would then be used to see if the Spikes of these novel Bat CoVs would be sufficient to replace the function of the WIV1 spike protein and allow similar human cell tropism, pathology in mice and sensitivity to antibodies. 7/n
At the time of the grant award, the NIH had a moratorium on GoF research involving viruses with pandemic potential after generation of broad tropic aerosol transmissible H5N1 avian by two labs (one in the US, the other in the Netherlands) a couple of years earlier. 8/n
The EcoHealth grant was judged by the vetting committee to not involve GoF because the investigators were REPLACING a function in a virus that ALREADY HAD human tropism rather than giving a function to one that could not infect humans. 9/n
Understandably this is a grey area. While I personally think the research was justifiable, there are legitimate concerns that such work needs to be contained in BSL3 and above, and we know some aspects (we do not know which despite innuendo) were performed at BSL2 in WIV. 10/n
But whether I or anyone thinks in retrospect that this is or is not GoF, the NIH did not, so in that respect Fauci is NOT lying. 11/n
But herein lies the disingenuousness of Rand Paul and those feeding him lines. 12/n
NONE of what is described above can possibly have been the source of SARS CoV-2. That virus is not WIV1 or any other known molecularly cloned bat CoV with a heterologous spike cloned into it. And conflating this with the origins of SARS2 is knowingly disinformative. 13/n
And then to juxtapose with the quote that: “all the evidence for the [source of the virus] points to the lab” when at the moment no such evidence exists beyond conjecture is fundamentally dishonest. And I would hope even those promoting a lab leak would acknowledge that. 14/n
Do we need a far better investigation of the origin and early events in Wuhan: Yes
Do the Chinese need to honestly engage in this: Yes
Does the lab(s) have to be ruled in or out ASAP: yes.
15/n
But all lab leak scenarios rest on the isolation and culture of either the immediate precursor of SARS-CoV-2 or the construction of a molecular clone from such a hitherto unidentified/undisclosed virus that... 16/n
could serve as a template for GoF experiments not covered by the NIH funding or required for its stated aims and thusfar denied by the WIV and EcoHealth. 17/n
So unlike Fauci, I do think Sen Paul knows what he is talking about, because he is deliberately and dishonestly conflating these issues. 18/n
And irrespective of the above, all the genetic and epi evidence thusfar gathered is still entirely consistent with a natural spillover, and we cannot allow any inquiries into a lab origin to compromise parallel investigations of a zoontic origin. 18/n
zenodo.org/record/5075888…

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More from @stuartjdneil

21 Jul
Very nice preprint from @jbloom_lab examining the evolution of ACE2 usage in bat sarbecoviruses.

Bottom line: it's complicated.

biorxiv.org/content/10.110…
Broad mammalian ACE2 usage including human is an ancestral trait of asian sarbecoviruses that is subsequently lost (and regained) in some lineages.
This implies that in many horseshoe bat sub-sp these viruses have evolved to use another (unidentified) receptor, the necessity for which may have been driven by +ve selection in bat ACE2s
Read 5 tweets
23 Jun
This is a significant new development.

@jbloom_lab has managed to recover a bunch of early CoV2 sequences deposited early in the epidemic in Wuhan and subsequently deleted that are ancestral to the Huanan market sequences, and make a strong case for wider circulation in Wuhan
The deletion of these sequences (1) suggests there may be more and @jbloom_lab seems confident he can track further ones down, (2) a very clear attempt by someone in China to hide the extent of the early Wuhan epidemic

Such sequences are invaluable in reconstructing the origin
Entirely consistent with the authorities trying to hide that they knew earlier than they said and were trying to keep a lid on it.
Read 4 tweets
23 Jun
New preprint from ⁦@DorotaKmiec⁩ with the aid of Maria Jose Lista, ⁦@MattiaFicarelli⁩ and supervised by ⁦@Swanson_Chad⁩ and myself characterizing the long isoform of ZAP and it’s targeting of CpGs in viral RNA. biorxiv.org/content/10.110…
We found that the long zap isoform alone has antiviral activity against a CpG enriched HIV-1 or SARS CoV-2 despite both long and short isoforms having the same RNA binding site
This is due to the PARP domain on the ZAP-L and it’s c-terminal farnesylation motif which mediates weak assoc of a proportion of ZAP-L with membranes

And appending this to ZAP-S is sufficient to confer some (but not all) activity.
Read 4 tweets
7 Jun
Ok, lets examine this in order. I’m going to piece this together based on what I’ve gleaned from you guys so you’ll have to correct me if I misrepresent something.
But before that lets reiterate what SARS CoV-2 is not. It is not the result of passage or directed evolution of RaTG13, and cannot be derived from the so-called GoF work the WIV was doing with the TOOLS WE KNOW THEY HAD
In 2012 the miners get sick in Yunnan and 3 die of ARDS. The WIV theses suggest that they may have been infected with a bat CoV. Serology apparently suggests that they have Abs against bat CoV N protein.
Read 22 tweets
23 May
So may as well add my 2pth-worth

The data PHE released yesterday alongside other data suggesting B.1.617.2 is outcompeting other variants in India makes a good case for this virus having enhanced transmissibility compared to B.1.1.7.
No evidence yet of enhanced pathogenesis either, but these data will take longer to accumulate.
This may well be in part due to changes in spike, BUT, as for B.1.1.7, it is not yet clear if variations in other parts of the genome play a role in relative transmission differences. And I doubt immune-evasion explains transmissibility
Read 14 tweets
20 May
So this is an interesting thread, but there is nothing new here that adds any further evidence

1: they sequenced a bunch of bat CoVs from the cave by taking bat shit or anal swabs - probably into RNA later. these sequences should be published but, seems they were partial.
They used the WIV1 backbone to do the experiments that they published in PLOS which in pains me to reiterate CANNOT be the source of SARS2 itself
And lastly analyzed blood samples of the miners for antibodies to CoVs.
Read 4 tweets

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