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Slack / Private Message Drop, p.339 [SLACK_000553] · slack_pm:msg:03567

Date: 2020-12-22 10:33
Type: chat message · slack
recipient: Robert F. Garry, Edward C. Holmes, Andrew Rambaut
speaker: Kristian G. Andersen

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Yeah, so this "We present evidence that the Spike H69/V70 is a fitness enhancing change that may be stabilising other S gene mutations" from Gupta's recent preprint is what worries me the most and I'm wondering if E484K (or N417K) could play a similar role in the SA lineage that H69/V70 is playing in the UK lineage. Add Nelly on top ofthat, and you might end up with what we're observing now.

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2020-12-22 08:52 Robert F. Garry open

Those are the same and it's the alignment in PO1.
2020-12-22 08:54 Robert F. Garry open

SC1 479 and SC2 493 interact with ACE2 similarly - however SC1 487 and SC2 501 interactions with ACE2 are completely different... *Correction - not completely different - just different*
2020-12-22 09:21 Robert F. Garry open

The pattern of prolines in SC1 and SC2 RBDs are distinct - look at PO1 - which creates a very different interaction with ACE2 - but we're seeing in real time the adaptation of SC2 to receptors in humans, minks and mice pretty muchas you'd draw it up. The twist that it may be immune selection driving better receptor binding is not expected at leastby me. Tuning up receptor binding affinity happened in SARS1 per the JVI paper above, but more subtle and [probably?] not an immune component there in 2002 and 2005.
2020-12-22 09:38 Kristian G. Andersen open

Interesting difference between SC1 and SC2 is that it was pretty darn quick in the former - essentially happened right after the jump from intermediate hosts. Slower for SC2, but it's probably because it was pretty darn good atbinding already.
2020-12-22 10:33 Kristian G. Andersen

Yeah, so this "We present evidence that the Spike H69/V70 is a fitness enhancing change that may be stabilising other S gene mutations" from Gupta's recent preprint is what worries me the most and I'm wondering if E484K (or N417K) could play a similar role in the SA lineage that H69/V70 is playing in the UK lineage. Add Nelly on top ofthat, and you might end up with what we're observing now.
2020-12-22 10:33 Kristian G. Andersen open

https://www.biorxiv.org/content/10.1101/2020.12.14.422555v3.full.pdf

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