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Tom Peacock

@PeacockFlu

1 Jan

Happy New Year!

New Omicron preprint from us about replication in primary cells, receptor usage and entry routes (can be found here while screening on biorxiv):
drive.google.com/file/d/1vam2PV…

Here are a couple of highlights

We looked at replication of Omicron in different cell types including primary human nasal epithelial cells (hNECs) – it consistantly replicates really really fast in these cells – even faster than Delta (which itself replicates faster than anything before!)

We could see the same doing competition assays (using variant specific RT-qPCR probes). No matter which isolates we used we could see Omicron replicates incredibly fast in primary nasal cells.

Read 11 tweets

Tom Peacock

@PeacockFlu

21 Dec 21

Lots of reports of Omicron sequences carrying Delta-like mutations (eg P681R or L452R). Although a subset of these might end up being real, the vast majority will most likely turn out to be contamination or coinfection. No clear signals of anything real or nasty happening (yet).

To be sure a signal like this is real you really want multiple sequencing labs finding the same recombinant/homoplasy independently (or at least on different sequencing runs) - ideally you would look into the raw seq files as well and show no mixed bases.

As far as I understand it these are appearing now for two reasons:
1) Lots of Delta and Omicron circulating in the same areas
2) Some older sequencing primer sets being less effective at picking up parts of Omicron so low level contamination with Delta being selectively picked up

Read 4 tweets

Tom Peacock

@PeacockFlu

8 Dec 21

I've been thinking about this for a while but with B.1.637.1 being assigned I've decided to write a thread about 'second generation variants'.
- What are they?
- Why should we be bothered about them?
- How should we look for them?
github.com/cov-lineages/p…

Disclaimer – B.1.637.1 is almost definitely nothing to be worried about – its an interesting lineage that has some convergent evolution with Delta – seqs might increase in the coming weeks but this is mostly due to it being an S-gene target failure virus (false positive for BA.1)

@PangoNetwork

So what are 2nd gen variants? I’m defining them as variant lineages (ie long branch lengths, no intermediates) that are derived from previous variant lineages. B.1.637.1 is the first clear example of one of these that been assigned by @PangoNetwork

Read 13 tweets

Tom Peacock

@PeacockFlu

23 Nov 21

Just spotted: very small cluster of variant associated with Southern Africa with very long branch length and really awful Spike mutation profile including RBD - K417N, N440K, G446S, S477N, T478K, E484A, Q493K, G496S, Q498R, N501Y, Y505H

github.com/cov-lineages/p…

Full Spike profile: A67V, Δ69-70, T95I, G142D/Δ143-145, Δ211/L212I, ins214EPE, G339D, S371L, S373P, S375F, K417N, N440K, G446S, S477N, T478K, E484A, Q493K, G496S, Q498R, N501Y, Y505H, T547K, D614G, H655Y, N679K, P681H, N764K, D796Y, N856K, Q954H, N969K, L981F

For those interested this has an NTD insertion at the NTD insertion hotspot (at aa214) which shows high likelihood of being host-derived (from host TMEM245 mRNA)

Read 9 tweets

Tom Peacock

@PeacockFlu

11 Oct 21

We think we can see some evidence of circulating SARS-CoV-2 isolates which have picked up short sequences of human mRNAs and inserted them into thier genomes so we wrote a virological post about it.

virological.org/t/putative-hos…

While substitutions and deletions are common and well described for SARS2, insertions are rarer, though several widespread lineages have unique insertions. Mu/B.1.621, A.2.5, B.1.214.2, and AT.1 all have insertions in Spike

We looked at where insertions cluster in Spike and found they mostly fall in the NTD or near the S1/S2 site. This is very similar to where deletions are found.

Read 10 tweets

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