Slack / Private Message Drop — page 448

[2021-01-24 14:03:59] [Eddie Holmes] Thanks for all that Bob! I'll take a careful look after I've had my golf lesson. [2021-01-24 14:13:47] [Robert Garry] Almost all the "immunosuppression" mutations perhaps not surprising are in indel regions. Putting together an alignment. Couple of "slippery" regions creating deletions. [2021-01-24 14:19:42] [Eddie Holmes] Got a reply from this person with an interesting profile: [shared file(s): Screen Shot 2021-01-25 at 9.18.52 am.png] [2021-01-24 14:22:44] [Eddie Holmes] I may have to write a book about this. Like everyone else. [2021-01-24 14:24:44] [Robert Garry] This was probably part of the Trump Admin deep intel. [2021-01-24 16:36:09] [Kristian Andersen] @Robert Garry - lots of good stuff here. Don't forget we had a chronic infection in San Diego too - no treatment in this guy. https://andersenlab.slack.com/files/U0HFUE9E3/F01HKFKCLHE/fake-reinfection.pdf [shared file(s): fake-reinfection.pdf] [2021-01-24 16:50:57] [Robert Garry] The two mutations to cysteine??? A new cysteine loop would be insane. [2021-01-24 16:52:36] [Kristian Andersen] Yup. No idea if they could make a bridge though. [2021-01-24 16:54:16] [Robert Garry] Also fits the later arising mutants scenario, but still pretty early. [2021-01-24 17:38:09] [Robert Garry] So they are either bridging with each other or forming two new loops with an existing dicysteine. [2021-01-25 07:57:55] [Robert Garry] @Kristian Andersen the R214C and G261C are *definitely* forming a new cysteine bridge. They are close enough in the structure that they WILL shift around to make the bridge. The existing disulfide bonds are C12 - C136, C131C166, C291 -C301. C12 is [apparently] the N -terminus and C12 to up to the orange A26 is "disordered" and therefore not in the structure I used to model spike. There is a newer structure (unstabilized cryo that gets the whole n terminus, including an N17) - I need to redo that models for sure putting in C12. I might even update some of the Virological Figures. Unpaired cysteines are *very rare* in viral glycoproteins. ALL the sarbecovirus spike cysteines are completely conserved from RmYN02, other Bat Covs, Pango Covs thru SARS-CoV to SC2. THIS IS HIGHLY UNUSUAL, BUT ULTRACOOL. Need to look at other CoVS to see the C-C structures in NTD. The role of NTD in SARS CoVs definately understudied. [shared file(s): image.png]