Slack / Private Message Drop — page 700

[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 transcription leader at the 5' end. That 3 nucleotide mutation had been bugging me for ages. [2021-04-13 14:51:45] [Andrew Rambaut] 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 14:52:14] [Andrew Rambaut] Had a lovely afternoon of geeky genomic virology. [2021-04-13 14:52:46] [Eddie Holmes] Intermediate host has a complex bat-pangolin recombinant? [2021-04-13 14:55:06] [Andrew Rambaut] 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 mutations in chronic infections - so again that might explain the fitness jump to get there). [2021-04-13 14:56:51] [Andrew Rambaut] There could be other NTD point mutations that provide a similar effect. [2021-04-13 15:01:42] [Eddie Holmes] I think that's what I was I trying to say - that the intermediate host is a different species....but has a virus with a complex recombinant history, like SIVcpz. [2021-04-13 15:04:08] [Eddie Holmes] Or that WIV weren't finished in their engineering job [2021-04-13 15:09:17] [Robert Garry] 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. [2021-04-13 15:10:00] [Eddie Holmes] Good point [2021-04-13 15:29:11] [Andrew Rambaut] I think clearly WIV were really shit at creating SC2 [2021-04-13 15:30:37] [Andrew Rambaut] GX pango still not nearly as similar as RaTG13: [shared file(s): image.png] [2021-04-13 15:32:58] [Andrew Rambaut]