Slack / Private Message Drop — page 344

Oh, it's time for prayer. [2020-12-26 15:22:08] [Kristian Andersen] Oh man, that IS good. Eddie, we finally made it! (even if he misspelled my name - but I'm sure it must be me). [2020-12-28 09:52:28] [Robert Garry] @Andrew Rambaut Another interesting addendum re the ferret transmission paper linked in channel above. Besides the N501T and FCS mutation from the aerosol transmission study was also L260F in nsp6 - yes, it's in the other large external loop so potentially regulatory. [shared file(s): image.png] [2020-12-28 11:10:03] [Robert Garry] I guess the question of "epistasis" between RBD and FCS and/or nsp6 mutations arises, but in my mind is more likely that all enhance replication independently. [2020-12-28 11:22:08] [Robert Garry] In addition the the three human SC2 to animal transfers noted (mice, mink, ferrets) there have also been well-documented human to cat :scream_cat: transfers and as well as it seems humans to dogs. https://www.nature.com/articles/s41421-020-00210-9 This has apparently been more newsworthy in China and there is this nice publication from G Gao of a crystal structure of SC2 spike with catACE2. The nucleotide and protein database in PubMed is not working well today :rage: for whatever reason, but of the few cat SC2 sequences it is said that there are not changes in the RBD of the SC2 in cats. This makes VERY good sense. The main contact residues for S: Q493 and N501, which seem to mediate species transfers, are identical in human and cat ACE2, H34, Y41/K353. [2020-12-28 12:30:00] [Robert Garry] FWIW - the same story in dogs https://www.nature.com/articles/s41586-020-2334-5 [not sure how I missed this one]. Both the cat and dog S sequences are 99% similar to Wu-1 S. The dog seq is identical except for D614G. [2020-12-28 13:25:04] [Robert Garry] https://www.biorxiv.org/content/10.1101/2020.11.16.384917v1.full.pdf A little more about cats. Serial passage does select for a few variants: The ones that get fixed are S H655Y andE S67S. According to the authors: "S H655Y is near the polybasic cleavage site, residin between the receptor binding domain and the fusion peptide, and is thought to modulate Spike glycoprotein fusion efficiency 55,56,59 262 . E S67S has not been documented elsewhere." It's not that near the FCS, but I take the point... [2020-12-28 14:05:59] [Robert Garry] Continuing my learning exercise for today. https://academic.oup.com/cid/article/71/9/2428/5811871 Infection of hamsters occurs effectively, and there are moderate symptoms. I haven't found much sequence data except Spike in this paper. There was only one mutation in one "serial" [contact] animal. S H655Y just like in the serial cats in the previous example, which is probably not a coincidence. Hamsters have Q34 instead of H34, but have Y41/K353 like humans. [2020-12-28 14:41:21] [Robert Garry] Tiger: https://mra.asm.org/content/9/22/e00468-20 Identical in S to Wu-1 except D614G. [2020-12-28 14:41:46] [Eddie Holmes] Tigers keep getting infected. Very interesting.