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
Also, they are clearly adapting different ways to interact with ACE2, meaning that mutations that might be predicted to give better binding in one lineage has unpredictable effects in others.
But what is pretty striking is that ancestral spike of the SARS2 lineage (that inc S2 and RaTG13) could bind to human, pangolin and R affinis ACE2s.

So there are plenty more out there with pandemic potential

So much for SARS CoV2's much vaunted 'unique adaptation to humans'

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More from @stuartjdneil

21 Jul
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
Read 19 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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