--- type: Conversation title: Private channel session 1654 description: "slack conversation, 47 messages, 2021-11-24." tags: - conversation - slack medium: slack message_count: 47 started_at: "2021-11-24T07:28:16" ended_at: "2021-11-24T09:37:34" duration_seconds: 7758 sources: - { id: slack_pm, resource: /sources/slack-pm.md, title: Slack / Private Message Drop, author: "process:senate-hsgac-release" } generated: { by: randpaul-corpus-pipeline/1.0, at: "2026-08-01T12:42:27Z" } status: stable --- A slack conversation of 47 messages spanning 2h 9m. # Metadata - **Started:** 2021-11-24T07:28:16 - **Ended:** 2021-11-24T09:37:34 - **Duration:** 2h 9m - **Participants:** 3 - **Source:** [slack_pm](/sources/slack-pm.md) - **Pages:** 1024-1028 # Participants * [Andrew Rambaut](/people/andrew-rambaut.md) * [Edward C. Holmes](/people/edward-c-holmes.md) * [Kristian G. Andersen](/people/kristian-g-andersen.md) * [Robert F. Garry](/people/robert-f-garry.md) # Transcript **[2021-11-24T07:28:16] Andrew Rambaut:** This variant is completely insane - https://github.com/cov-lineages/pango-designation/issues/343 **[2021-11-24T07:28:35] Andrew Rambaut:** Mutating itself to death, indeed **[2021-11-24T07:29:12] Andrew Rambaut:** Check this bit... [shared file(s): image.png] **[2021-11-24T07:30:04] Andrew Rambaut:** And a bit of FCS adjacent action... [shared file(s): image.png] **[2021-11-24T07:30:22] Andrew Rambaut:** Plus 69/70 del and the nsp6 del **[2021-11-24T07:36:36] Kristian G. Andersen:** Holy shit - that is quite something. The length of that branch... :scream:. What's the N/S on the branch? **[2021-11-24T07:41:47] Kristian G. Andersen:** Just had a look at the list of mutations - so nuts. Getting rid of a lot of serines (although also adding some new ones...) and adding in lysine - the friggin' genome is going to be made out of lysines at some point! Just nuts. **[2021-11-24T08:22:15] Robert F. Garry:** Oh boy - it's getting more polybasic - that's not good.... **[2021-11-24T08:23:59] Andrew Rambaut:** It must surely be from a immunocompromised chronic infection. Possibly a dual infection with recombination and heavy mutation. But the random traveller in HK has me very worried **[2021-11-24T08:24:34] Andrew Rambaut:** Visited South Africa for 20 days - must be a much more prevalent virus than the sequencing suggests **[2021-11-24T08:24:56] Andrew Rambaut:** Will cause S gene dropout and I think SA is seeing some signal of that apparently **[2021-11-24T08:29:58] Kristian G. Andersen:** HIV patient or animal reservoir - I'll say 70/30 odds. **[2021-11-24T08:32:43] Kristian G. Andersen:** Bob, presumably the N679K combined with P681H makes this a better FCS, correct? It's interesting to see E484A inthere too - presumably E484K was a bit too much. **[2021-11-24T08:33:44] Kristian G. Andersen:** I swear to god - if we see another monster variant gain territory here in November/December, something is driving the emergence. What, I don't know, but "something". **[2021-11-24T08:35:31] Robert F. Garry:** Yes definitely better FCS - the RXXR site really is minimal. Any changes that put postive charges, K, R, H nearbyare going to up the efficacy. It already as discussed has an effective furin landing site in QTQT **[2021-11-24T08:37:21] Robert F. Garry:** LPAI goes from a minimal site to multiple basic residues in HPAI... [shared file(s): image.png] **[2021-11-24T08:37:47] Kristian G. Andersen:** Yup. QTQT is a landing site? **[2021-11-24T08:40:50] Robert F. Garry:** yes both are neutral polar animo acids **[2021-11-24T08:42:32] Andrew Rambaut:** I assume you say it cutie-cutie? **[2021-11-24T08:42:37] Kristian G. Andersen:** I had missed that previously, but that's actually kinda interesting - because: [shared file(s): furin_aa_nov21.png] **[2021-11-24T08:43:15] Kristian G. Andersen:** For the non-SC2 viruses they _either_ have QTQT _or_ the indel - but not both. SC2 has both. **[2021-11-24T08:45:17] Andrew Rambaut:** The RmYN02-like are quite distant to SC2 in this bit of the genome. Is it not more interesting that RaTG13/BANAL-20-52-like viruses acquired the QTQT motif? **[2021-11-24T08:46:41] Kristian G. Andersen:** Yup - almost looks step-wise. **[2021-11-24T08:46:56] Robert F. Garry:** Indeed - that's always puzzled me. **[2021-11-24T08:48:04] Andrew Rambaut:** What would it do without the PRRA insert? **[2021-11-24T08:48:13] Robert F. Garry:** I've think that the enzymes that do the cleavage at R/S also probably benefit by having a "landing pad." **[2021-11-24T08:50:03] Andrew Rambaut:** So if you were going to pick a virus from amongst your large bank of samples in which to try popping a FCS insertion you would pick out one with QTQT? **[2021-11-24T08:52:16] Robert F. Garry:** Not without having all the knowledge in hindsight. **[2021-11-24T08:52:52] Andrew Rambaut:** Fair enough. I won't tweet that then. **[2021-11-24T08:52:59] Robert F. Garry:** Same argument with the O-linked glycans - without having SC2 as the guidepost - you would not know.... **[2021-11-24T08:53:53] Robert F. Garry:** Good - that would just encourage the Leakers... **[2021-11-24T08:54:18] Kristian G. Andersen:** Yeah, very clearly not a conscious choice - just nature doing it's thing. All it took was a virus with a landing site and then stuff comes and goes around that site all the time - just had to be the right sequence that popped in. **[2021-11-24T08:55:08] Robert F. Garry:** Yup - nature - we get to see the brilliance but only afterwards. **[2021-11-24T09:02:01] Kristian G. Andersen:** Some alignments with these sequences combined with relevant SARSr-CoVs - just FYI. [shared file(s): 2021.11.24_alignment_spike_nt.geneious, 2021.11.24_alignment_spike_aa.geneious, 2021.11.24_alignment_spike_aa_minimal_annotated.geneious] **[2021-11-24T09:03:43] Kristian G. Andersen:** This is mind blowing - BANAL-52 is closer to Hu-1 in the spike (in AA space) than the Botswana sequences are.... Holy fuck. **[2021-11-24T09:04:10] Kristian G. Andersen:** 98.4% vs 96.9% **[2021-11-24T09:10:58] Robert F. Garry:** Yeah - what I really want to do is put the PRRA into BANAL-52 and see how it does several species. **[2021-11-24T09:11:45] Kristian G. Andersen:** What the heck is up here - Hu1 on top, Botswana at the bottom [shared file(s): Screen Shot 2021-11-24 at 9.07.10AM.png] **[2021-11-24T09:12:07] Kristian G. Andersen:** In AA space: [shared file(s): Screen Shot 2021-11-24 at 9.07.32 AM.png] **[2021-11-24T09:13:16] Kristian G. Andersen:** Here's the key part of the RBD - contact residues listed in purple above. This makes me believe this could be evolution in a non-human host, so I'll have to change my 70/30 odds to 50/50 based on this alone. This is very interesting. [shared file(s): Screen Shot 2021-11-24 at 9.08.55 AM.png] **[2021-11-24T09:24:22] Robert F. Garry:** Agree - it's freaky! **[2021-11-24T09:24:36] Kristian G. Andersen:** The insertion ("TAGTGCGTGAGCCAGAA") around 630 could be interesting - obviously a short sequence, but it ain't from SC2 itself and the top BLAST results match fungi, cholera, and a fish... **[2021-11-24T09:26:32] Robert F. Garry:** THis insertions are rare - wasn't there a preprint or virological post on those a while back? **[2021-11-24T09:27:42] Kristian G. Andersen:** Yeah - same Tom: https://virological.org/t/putative-host-origins-of-rna-insertions-in-sars-cov-2-genomes/761 **[2021-11-24T09:33:43] Robert F. Garry:** @Andrew Rambaut But saying it out loud only can get you in deep trouble. **[2021-11-24T09:37:24] Andrew Rambaut:** Yes - Tom has identified that insertion in a human mRNA **[2021-11-24T09:37:34] Andrew Rambaut:** Somewhere on twitter