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I wouldn't rule-out a phase change. The UK and ZA variants feel like some nonlinear processes occurring. Epistasisis a real thing. Did Doug somehow open the floodgates enabling Nelly, Eeek and Pooh and multiple combinations?On the "up" side it seems to me that at least that a pattern of hotspots for mutations (Xmas card) are starting toemerge. New sampling of the combos as you document above does seem like an ongoing and perhaps acceleratingprocess. Looking ahead I worry about the fertile ground of Africa which has been largely spared being more susceptible to a Phase II variant.
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> I am trying to decide if this is a 'phase-change' in the evolution of the virus (i.e., driven by standing immunity)I have been wondering about this myself - definitely feels like it. The areas where we have seen these popping uphave had a lot of COVID-19 going around, so a fair bit of standing immunity. I absolutely hope not though - it's apretty scary thought and I have no idea how driving vaccines into a raging pandemic will change that landscape.> Pooh - love it :wink:. Bob, how does the RRRAR affect the predicted O-Glyc? Presumably knock out one of the predicted sites? And just to get back to a question we talked about a couple of days ago - (a) might E484K just be overall better atevading immunity or is it just that it (b) changes an important epitope? I have been thinking about this a lot... I had been leaning towards the former, but now I'm getting increasingly concerned it's the latter. Mostly based on this paper: https://www.biorxiv.org/content/10.1101/2021.01.06.425392v2.full.pdf. Is it possible that the combo of Doug, Eeek, and Nelly simply leads to a virus that have such a high affinity for ACE2 that the spike-ACE2 interaction more effectively outcompetes spike-NAb binding? Not inconceivable - I mean, take a look at the difference in binding affinity here: [shared file(s): Screen Shot 2021-01-09 at 10.01.04 AM.png]
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We're talking orders of magnitude difference in binding affinity - that's not nothing....
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Looks like Eeek even though it doesn't seem to contact ACE2 nevertheless can enhance binding when coupled with Nelly. Surprising but perhaps not shocking.
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2021-01-09 10:23
Kristian G. Andersen
Yup - enhances it by quite a bit
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Poor preserved 2/3 predicted O-glycans just like Pooh.
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Immune escape plus enhanced fitness is ......worrisome.
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That's to put it mildly...
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Also, this is basically the final confirmation that @Andrew Rambaut was absolutely correct in ringing the big redalarm bell:https://twitter.com/LindorffLarsen/status/1347916349704646656?s=20Looks like the doubling rate might be a little less in DK than UK, but clearly same trajectory.