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.
Lastly the PARP domain enhances interaction with ZAP cofactors TRIM25 and KHNYN.

So compartmentalization of ZAP-L to intracellular membranes is a key mechanistic requirement of its antiviral activity against CpG containing viral RNAs

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More from @stuartjdneil

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
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
20 Jan
With is manuscript from ⁦@PaulBieniasz⁩ and co, that from ⁦@RealMcCoyLab this AM⁩, data from ⁦@10queues⁩ yesterday and the prelim data from South Africa,

The variants we are seeinv have evolved to escape antibody.
biorxiv.org/content/10.110…
How and where to be determined.

Thus far it’s a mixed bag about how much they are resistant to serum from wave 1, and vaccinee serum while slightly reduced in potency, still works. (Good news!)
But these mutations, partic 501Y (Uk, Sa and Brazil) and 484K (SA and Brazil) do completely abolish the activity of some specific individual RBD antibodies.

More alarmingly the SA variant is insensitive to about half of wave 1 sera tested.
Read 8 tweets
1 Jan
I am becoming deeply troubled over the cavalier way the UK vaccine roll out is being changed on the hoof.

We have 2 approved vaccines that work to induce protective immunity.

They are both safe

I understand the haste to get them into as many people as possible.
But the phase iii data doesn’t exist to support their use in combination.

They are not quite the same immunogen. So homologous and heterologous boosting may accentuate different responses. And it might matter which order.

We do not know anything about this.
Next the timing

AZ boosting at 3 months turns out to boost higher Ab levels - another ‘serendipitous’ thing to fall out of the trial. Fine. But how protective is one shot?

And changing the Pfizer regimen, based reanalyzing the data to look for an answer they want. Probably true
Read 5 tweets

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