Private channel session 1001

26 messages over 2h 44m, 2021-02-19 – 2021-02-19.

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.

2021-02-19 12:35 Robert F. Garry open PDF p.526

To @Andrew Rambaut point above. I'm pretty sure there has been a global shift in the fitness landscape. I'm not too sure where the major selection is at the population level or the individual level or BOTH. However, I do think that the mutations at nsp12 P323 are contributing mightily to the volatility. I'm just shaking my head in disbelief. Like ascreaming read flag this amino acid is literally sitting in the groove of the RdRp complex. It surely has to affecttranscription fidelity. A deletion in nsp8 also may be a factor. [shared file(s): image.png]
2021-02-19 12:35 Robert F. Garry open PDF p.526

Same feeling I got when I saw the PRRA....
2021-02-19 12:47 Robert F. Garry open PDF p.526

Looks like it showed up early around about the time of the first DouG sightings.
2021-02-19 13:12 Kristian G. Andersen open PDF p.526

What's the coordinates of that mutation in ORF1a space Bob?
2021-02-19 13:24 Robert F. Garry open PDF p.526

I think it's C14408T P4715L.
2021-02-19 13:27 Kristian G. Andersen open PDF p.526

ORF1b P314L? Interesting - pretty much defines Doug...
2021-02-19 13:31 Robert F. Garry open PDF p.527

Yeah - DouG literally opened up the stem but the nsp12 mutation may be affecting polymerase fidelity (surprising if itdidn't). Could be why @Eddie Holmes reports the volutility in trying to grow postDouG variants in cell culture.
2021-02-19 13:32 Robert F. Garry open PDF p.527

P323L I think.
2021-02-19 13:34 Kristian G. Andersen open PDF p.527

Here's Nextstrain - 323 is listed as only "K". [shared file(s): Screen Shot 2021-02-19 at 1.33.44 PM.png]
2021-02-19 13:34 Kristian G. Andersen open PDF p.527

https://nextstrain.org/ncov/global?c=gt-ORF1b_314
2021-02-19 14:17 Robert F. Garry open PDF p.527

Yeah -that it... It's DouG's world but his naughty polymerase girlfriend PearL may be causing a lot of disruption onher own.
2021-02-19 14:26 Kristian G. Andersen open PDF p.527

You know - none of these spike mutations may make SARS-CoV-2 more transmissible...
2021-02-19 14:30 Robert F. Garry open PDF p.527

You could be right - Thinking back and Bob C and Tom Geisbert will know better, but I think that all of the mutations that make LASV replicate in guinea pigs are in polymerase.
2021-02-19 14:34 Kristian G. Andersen open PDF p.527

I believe in flu, the polymerase is key too.
2021-02-19 14:38 Robert F. Garry open PDF p.527

Exactly!
2021-02-19 14:39 Robert F. Garry open PDF p.527

Although occasionally a little FCS can get involved in the fun.
2021-02-19 14:45 Andrew Rambaut open PDF p.527

I heard from a confidential source that in macaque infections P323L (Phil) came up in 10/10 monkeys.
2021-02-19 14:46 Andrew Rambaut open PDF p.527

And yes Phil is strongly linked with Doug but came up first (in January).
2021-02-19 14:47 Andrew Rambaut open PDF p.527

I think it is probably the first major human adaptation
2021-02-19 14:48 Robert F. Garry open PDF p.528

Remarkable!
2021-02-19 14:50 Robert F. Garry open PDF p.528

I think that all of the natural human-to-animals have been DouG/PhiL, but the fact that a PreDoug virus converted toPhiL in 10/10 monkeys is crazy...
2021-02-19 14:50 Kristian G. Andersen open PDF p.528

So why're we talking about "Doug took over the world"? I'd be _much_ more inclined to think Phil did and brought his friend Doug with him
2021-02-19 14:56 Robert F. Garry open PDF p.528

Just an impression but many [not all] of the places the nonPhiL viruses are lingering seem to be relatively low incidence countries.
2021-02-19 15:11 Robert F. Garry open PDF p.528

RaTG13 and SC1 have the proline at that site.
2021-02-19 15:12 Kristian G. Andersen open PDF p.528

Proves it came from the lab.
2021-02-19 15:19 Robert F. Garry open PDF p.528

Don't tell Yuri, Alina or Billy the one-eyed dead monkey.