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1. 2020-12-23 04:22 Robert F. Garry open
   The other elephant mutations outside RBD including the dels in the NTD and the P681H near the FCS could indeed be enabling, enhancing replication in their own right or perhaps they are also immune escapes.
2. 2020-12-23 04:35 Robert F. Garry open
   I think this is all relevant to PO2 - it's pretty clear that the changes in SC2 493 and 501 or SC1 479 and 487 enabledspecies jumps - per PO1 there are bat sarbecovs that have an SC2 N501 and we know these infect human cells.We know enough about the epitopes and MAb binding and escape to back up Andrew's point on virological that immune escape is driving the changes in the elephants - the problem happens when immune escape creates variants that are more transmissible or heaven forbid are vaccine resistant.
3. 2020-12-23 04:40 Robert F. Garry open
   Finally to end my rant - let's not give Baric or Fouchier the idea of making SC1 N493Q + T487Y. That to me wouldbe scary with the possibility of SC2 transmissibility and SC1 CFR.
4. 2020-12-23 04:46 Andrew Rambaut open
   One more intersting observation: Some of the South African variant viruses (possibly all of them - it seems their bioinformatics pipeline doesn't call deletions very well) have a deletion at sites 11288-11296 (amino acid 3675-3677 in ORF1ab - thus the in nsp6). Exactly the same deletion is seen in the UK B.1.1.7 lineage. I don't know the significance of this. Any thoughts?
5. 2020-12-23 05:05 Robert F. Garry
   https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7195303/ From this modeling NSP6 looks like a viroporin to me - would have to look at the exact deletion, but most viroporins are involved in virion entry and cytopathogenesis.Same wheelhouse as the RBD and FCS mutations.
6. 2020-12-23 05:21 Robert F. Garry open
   Covs have other viroporins (E protein) that are virion associated, but NSP6 is likely remodeling cell membranes insome way to benefit virus replication.
7. 2020-12-23 05:22 Andrew Rambaut open
   Mmm. So definitely could be associated with a change in virus behaviour. Cool
8. 2020-12-23 05:41 Robert F. Garry open
   I'll map the deletion on the model, which is prob pretty accurate, when I get to the office after dropping off the dog. Ifit's in one of the loops would likely affect regulation and yes change virus behavior.
9. 2020-12-23 05:45 Andrew Rambaut open
   Seems to crop up with a small bunch in Australia with spike S477N, and a few others here and there.

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