Slack / Private Message Drop — page 349

general classes, The ones that get the most attention and are likely key for interspecies transfer are of course the RBD mutations. There is strong evidence for immune selection in the RBD and in the N-terminal domain epitopes. The third hotspot for mutation is in and around the FCS. Whether or not this region is under immune selection is anyone's guess, but there is no doubt the region contributes to transmissibility. A fourth mutant class that is also likely to be under immune selection are what I've labeled the membrane proximal region [MPER]. There are some important MPER antibodies in HIV field, so these mutations could also be from immune selection. Finally, are the S2 mutations, which group naturally with Doug. I suspect that these S2 mutations are likely not epitopes (but it's possible). Rather I think that Doug and A82V before it from EBOV are teaching that the adjacent mutation in two of the lions Q613R, plus other mutations that look to be mostly in the metastable regions of S2 could influence refolding to the 6-helix bundle possibly affecting infection efficiency. Note - I'll change the human eventually to someone unlike @Covidfaker who actually was infected with SC2. [shared file(s): image.png] [2020-12-30 15:09:28] [Robert Garry] Red spheres: the UK variant, Blue spheres: ZA variant, Magenta: both UK/ZA, Yellow spheres: animals. [2020-12-30 15:30:58] [Andrew Rambaut] Now if you had just produced that in time to be your Christmas card [2020-12-30 15:51:25] [Eddie Holmes] Fantastic. [2020-12-30 15:52:41] [Eddie Holmes] For the Christmas card I would replace the alpha helices with strings of face masks. [2020-12-30 15:53:58] [Robert Garry] And, change the color scheme to more reds and greens! [2020-12-31 05:28:23] [Robert Garry] @Kristian Andersen seems to be all excited about a SC2 he sequenced from a San Diego patient. Still shocking for me to see the HRRARS variation. Seems it only knocks out 1/3 of the predicted O-linked sites: [shared file(s): image.png] [2020-12-31 06:29:21] [Robert Garry] [thread - ID: 2020-12-28 14:44:55] @Eddie Holmes It's the GD pangolin - there's that little bit in the RBD where the pangolin blue line is above the green RaTG13 line in Spike. Not as well resolved as in Lam2020, which threw me off, but I guess that's a window thing. Will be fascinating to see which bat CoV spike the new Cambodian CoV spike lines up with. Biggest deal still to me similarity with the RaTG13 in orf1b. [2020-12-31 07:10:05] [Kristian Andersen] I'm not sure "excited" is the right word - "exhausted" might be more fitting :stuck_out_tongue_winking_eye:. I'm sure all the UK folks must be rolling their eyes - "seriously, the US goes nuts over A SINGLE SEQUENCE?! Really". But yeah P681H is very interesting indeed - and yes, only knocks out one predicted site. Separately, I don't know what to do about B.1.1.7. Surges in the US typically have Rt ~1.2, while declines are Rt ~0.8. It seems pretty clear that Rt for B.1.1.7 may be increased by roughly 50% (at least in whatever context it finds itself in in the UK) soooo :chart_with_upwards_trend: