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Slack / Private Message Drop, pp.699-700 [SLACK_000913] · slack_pm:msg:07339

Date: 2021-04-13 14:49
Type: chat message · slack
recipient: Kristian G. Andersen, Robert F. Garry, Edward C. Holmes
speaker: Andrew Rambaut
Topics: Furin cleavage site and molecular features

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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.

In context

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2021-04-13 14:40 Robert F. Garry open

Looking at it this way you can see the relationships in the sarbecos pretty clearly. [shared file(s): image.png]
2021-04-13 14:41 Robert F. Garry open

@Eddie Holmes On it! But hopefully others are as well.
2021-04-13 14:42 Andrew Rambaut open

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).
2021-04-13 14:45 Andrew Rambaut open

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.
2021-04-13 14:49 Andrew Rambaut

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.
2021-04-13 14:51 Andrew Rambaut open

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
2021-04-13 14:52 Andrew Rambaut open

Had a lovely afternoon of geeky genomic virology.
2021-04-13 14:52 Edward C. Holmes open

Intermediate host has a complex bat-pangolin recombinant?
2021-04-13 14:55 Andrew Rambaut open

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).

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