Slack / Private Message Drop — page 327

[Eddie Holmes] Was sent this - you may have seen it already: [shared file(s): KRISP_Minister_President_Briefing_Media.pdf] [2020-12-19 15:24:02] [Eddie Holmes] [thread - ID: 2020-12-19 01:52:11] @Andrew Rambaut Agreed. Seems the 2 NSW cases are likely from different families as they have different surnames. Also, they are not in the community here. We have a new outbreak in NSW which we think is linked to flight crew and that is lineage B.1. Phew. [2020-12-19 17:14:10] [Robert Garry] Off channel most of the day - Jeanette had a minor procedure yesterday and I had a few home items. Yes I can take a look. Both E484K and N501Y are pretty dramatic. One think for sure is that there is considerable plasticity in the RBD-ACE2 interactons. [2020-12-19 17:36:37] [Eddie Holmes] Vince is such a plonker. [2020-12-19 18:02:41] [Kristian Andersen] Does he _ever_ get it right? [2020-12-19 19:53:31] [Eddie Holmes] Not that I've seen. [2020-12-20 07:28:32] [Robert Garry] [thread - ID: 2020-12-20 07:28:32] https://www.biorxiv.org/content/10.1101/2020.11.16.384743v1.full.pdf A couple of initial thoughts on the RBD changes. First, just to reiterate the dirty little "secret" of structural biologists - everything including cryoEM and X-ray crystallography are models - the resolutions are average and locally there is a lot of "fitting." That being said this figure from the Bullocks mink paper shows the residues in question E484 not to far from f486 obviously. Remarkable that N501 shows up in both the mink and the mouse. [shared file(s): image.png] [2020-12-20 07:28:36] [Robert Garry] https://www.nature.com/articles/s41586-020-2772-0 [2020-12-20 07:54:02] [Robert Garry] Benton et al. is going to be the key to interpreting the NTD deletions and probably the other elephant mutations as well. A pretty good interpretation of D614G therein. More importantly it clear that *both* NTD and the RBD need to undergo dramatic shifts that are driven by ACE2 binding to accommodate the S1/S2 and S2' cleavages and ultimately the large scale rearrangement of S2 into the 6 helix bundle. This doesn't rule out an NTD "receptor." I need to get to the office to look at the structures in Benton in a bit more detail to see what del69-70 etc do to the Benton structures, but it won't surprise me if they don't "destabilize" the trimer ala Doug. [2020-12-20 07:59:39] [Andrew Rambaut] [thread - ID: 2020-12-20 07:28:32] @Robert Garry I don't think 501Y turns up in mink. [2020-12-20 08:12:29]