Private channel session 131

20 messages over 1h 55m, 2020-06-06 – 2020-06-06.

A “conversation” here is an activity session — a run of messages with under 60 minutes of silence inside it. The channel had no native conversation boundaries.

2020-06-06 02:28 Robert F. Garry open PDF p.56

https://elifesciences.org/articles/58603 a-subunit (ENaC-a) how looks in other species? Would be interesting to know a is?
2020-06-06 02:29 Robert F. Garry open PDF p.57

SARS-CoV-2 strategically mimics proteolytic activation of human ENaC
2020-06-06 02:29 Robert F. Garry open PDF p.57

human epithelial sodium channel -subunit (ENaC-)
2020-06-06 02:38 Robert F. Garry open PDF p.57

Sorry - messed up the links above - the elife paper does a considerable amt of arm waving over an 8 amino acid homology -the furin site - but "interesting" that the furin site in both SARS-CoV-2 and ENaC- has predicted O-linked glycans PLUS ENaC- has another proline, serine, threonine rich stretch - a likely mucin domain - OC43 and HKU1 Spike also have this.
2020-06-06 02:51 Robert F. Garry open PDF p.57

"RTT plot for Ebola is super interesting" Agree - how do the RBDs align on the different branches?
2020-06-06 03:10 Edward C. Holmes open PDF p.57

Got it. I don't suppose we know much about how ENaC- how looks in other species? Would be interesting to know what species OC43 and HKU1 originated in.
2020-06-06 03:20 Edward C. Holmes open PDF p.57

Going through our scenarios, if true would the ENaC- + furin link argue for undetected circulation in humans? Possibly to get in animal passage? Could it explain why the furin site is sometimes lost in cell culture? It is clearly doing something. Bill's theory explains how it was created, but it would also be nice to understand how it ismaintained.
2020-06-06 03:28 Andrew Rambaut open PDF p.57

Sorry - I am being dumb here. Can you layout exact what the proposed connection with ENaC- is?
2020-06-06 03:29 Edward C. Holmes open PDF p.57

shared file(s): elife-58603-v1.pdf
2020-06-06 03:29 Edward C. Holmes open PDF p.57

Figure 1
2020-06-06 03:30 Andrew Rambaut open PDF p.57

But not suggesting this was the source of the insertion recombination?
2020-06-06 03:30 Andrew Rambaut open PDF p.57

Just why it might be doing in humans.
2020-06-06 03:31 Edward C. Holmes open PDF p.57

No. But it explains why it is beneficial. A bit of undetected circulation in humans would solve a lot of problems.
2020-06-06 03:37 Andrew Rambaut open PDF p.57

I see it now. Interesting.
2020-06-06 03:38 Andrew Rambaut open PDF p.58

But then we have the source of the nucleotides to think about?
2020-06-06 03:42 Andrew Rambaut open PDF p.58

Just when I think I have this thing straight in my mind.
2020-06-06 03:53 Andrew Rambaut open PDF p.58

@Robert Garry Do you have the nucleotide sequence for this? Could it be the actual source of the insertion?
2020-06-06 04:21 Andrew Rambaut open PDF p.58

This is interesting: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5312086/
2020-06-06 04:21 Andrew Rambaut open PDF p.58

shared file(s): image.png
2020-06-06 04:24 Andrew Rambaut open PDF p.58

Suggests a progressive accumulation of the polybasic site in passaging.