Private channel session 1241
33 messages over 2h 0m, 2021-04-13 – 2021-04-13.
A “conversation” here is an activity session — a run of messages with under 60 minutes of silence inside it. The channel had no native conversation boundaries.
-
Joe Grove in Greg Towers group just showed some very interesting data (keep private please - it was on a closed call): [shared file(s): image.png, image.png, image.png, image.png]
-
Essentially Wuhan with a GD Pango NTD has infectivity like B.1.1.7 - despite being the one bit of GD_Pango that isrecombinant and most divergent from SARS-CoV-2
-
@Robert Garry Cited your indel regions as likely reason
-
Will see if he has a preprint or something.
-
:+1: brilliant
-
eDim ain't gonna like those experiments!
-
Sounds like we ought to be looking for more pango viruses?
-
Yes - indeed! Also RpYN06 and PRC31 are essentially GD pango in the NTD so the important bits are definitely out there! [shared file(s): image.png]
-
Have been meaning to put this expanded alignment up as a supplement to Holmes 2021 - should do that at some point.
-
Very interesting. I'll see if any more pangolin viruses are on the go.
-
Looking at it this way you can see the relationships in the sarbecos pretty clearly. [shared file(s): image.png]
-
@Eddie Holmes On it! But hopefully others are as well.
-
Really interesting but I haven't fully got my head around it - basically it means that the bat-like NTD is sub-optimal for humans, B.1.1.7 has converged on whatever the pangolin has as an adaptation to humans (given that B.1.1.7 is the most human adapted virus yet).
-
So 69-70 deletion and the 144 deletion provide greater infectivity (and presumably when combined with 501Y RBD and 681H furin site) result in higher transmissibility.
-
Other thing I got today was that the 3 nucleotide mutation in the middle of N that arose in the early Italian lineage probably create a new sgRNA - the resulting nucleotide sequence is complementary to the sgRNA transcriptionleader at the 5' end. That 3 nucleotide mutation had been bugging me for ages.
-
The cool thing is that explains the N:D3L (also a 3 nucleotide mutation) in B.1.1.7 - Sheffield showed this probably enhances the recombination with the leader two - so it may be compensating to create more N
-
Had a lovely afternoon of geeky genomic virology.
-
Intermediate host has a complex bat-pangolin recombinant?
-
I think you could argue that the pangolin is actually less likely to be the intermediate for SC2. The original Wuhan was more bat like in its NTD and it took all the way to B.1.1.7 before it hit its stride (you also see the same mutationsin chronic infections - so again that might explain the fitness jump to get there).
-
There could be other NTD point mutations that provide a similar effect.
-
I think that's what I was I trying to say - that the intermediate host is a different species....but has a virus with acomplex recombinant history, like SIVcpz.
-
Or that WIV weren't finished in their engineering job
-
Probably good to keep in mind that GX pango is very similar to SC2 in much of the NTD except IR2 where some of the magic may be happening.
-
Good point
-
I think clearly WIV were really shit at creating SC2
-
GX pango still not nearly as similar as RaTG13: [shared file(s): image.png]
-
Just noticed that dip in early ORF1a - don't know why I didn't notice that before.
-
Looks very similar to the RBD dip
-
interesting region at the amino acid level as well.
-
Very interesting stuff! Might be worth looking at reversions - do we see more of those in the NTD vs the rest of the spike / genome?
-
I assume RmYN02 doesn't drop away like that.
-
@Kristian Andersen Actually they did some reversions and and mutants as will but but I didn't grab a screenshot so Ican't remember the details. I will see if he will send the slide deck or is going to be preprinting soon.
-
Cool beans! And I should add - we all need more afternoons of geeky genomics!